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  1. Fas Ligand-Dependent Inflammatory Regulation in Acute Myocarditis Induced by Trypanosoma cruzi Infection

    PubMed Central

    de Oliveira, Gabriel Melo; Diniz, Rafaela Lopes; Batista, Wanderson; Batista, Marcelo Meuser; Bani Correa, Cristiane; de Araújo-Jorge, Tânia Cremonini; Henriques-Pons, Andréa

    2007-01-01

    Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L−/− mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8+ T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1+ myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4+/low T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10+ cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3+ but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death. PMID:17591955

  2. Idiopathic pulmonary fibrosis fibroblasts become resistant to Fas ligand-dependent apoptosis via the alteration of decoy receptor 3.

    PubMed

    Im, Jintaek; Kim, Kyutae; Hergert, Polla; Nho, Richard Seonghun

    2016-09-01

    Idiopathic pulmonary fibrosis (IPF) is an irreversible lethal lung disease with an unknown etiology. IPF patients' lung fibroblasts express inappropriately high Akt activity, protecting them in response to an apoptosis-inducing type I collagen matrix. FasL, a ligand for Fas, is known to be increased in the lung tissues of patients with IPF, implicated with the progression of IPF. Expression of Decoy Receptor3 (DcR3), which binds to FasL, thereby subsequently suppressing the FasL-Fas-dependent apoptotic pathway, is frequently altered in various human disease. However, the role of DcR3 in IPF fibroblasts in regulating their viability has not been examined. We found that enhanced DcR3 expression exists in the majority of IPF fibroblasts on collagen matrices, resulting in the protection of IPF fibroblasts from FasL-induced apoptosis. Abnormally high Akt activity suppresses GSK-3β function, thereby accumulating the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) in the nucleus, increasing DcR3 expression in IPF fibroblasts. This alteration protects IPF cells from FasL-induced apoptosis on collagen. However, the inhibition of Akt or NFATc1 decreases DcR3 mRNA and protein levels, which sensitizes IPF fibroblasts to FasL-mediated apoptosis. Furthermore, enhanced DcR3 and NFATc1 expression is mainly present in myofibroblasts in the fibroblastic foci of lung tissues derived from IPF patients. Our results showed that when IPF cells interact with collagen matrix, aberrantly activated Akt increases DcR3 expression via GSK-3β-NFATc1 and protects IPF cells from the FasL-dependent apoptotic pathway. These findings suggest that the inhibition of DcR3 function may be an effective approach for sensitizing IPF fibroblasts in response to FasL, limiting the progression of lung fibrosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. Alteration of PTGS2 promoter methylation in chronic periodontitis.

    PubMed

    Zhang, S; Barros, S P; Niculescu, M D; Moretti, A J; Preisser, J S; Offenbacher, S

    2010-02-01

    Levels of prostaglandin E(2) and the prostaglandin-endoperoxide synthase-2 (PTGS2, or COX-2) increase in actively progressing periodontal lesions, but decrease in chronic disease. We hypothesized that chronic inflammation is associated with altered DNA methylation levels within the PTGS2 promoter, with effects on COX-2 mRNA expression. PTGS2 promoter methylation levels from periodontally inflamed gingival biopsies showed a 5.06-fold increase as compared with non-inflamed samples (p = 0.03), and the odds of methylation in a CpG site in the inflamed gingival group is 4.46 times higher than in the same site in the non-inflamed group (p = 0.016). The level of methylation at -458 bp was inversely associated with transcriptional levels of PTGS2 (RT-PCR) (p = 0.01). Analysis of the data suggests that, in chronically inflamed tissues, there is a hypermethylation pattern of the PTGS2 promoter in association with a lower level of PTGS2 transcription, consistent with a dampening of COX-2 expression in chronic periodontitis. These findings suggest that the chronic persistence of the biofilm and inflammation may be associated with epigenetic changes in local tissues at the biofilm-gingival interface.

  4. Alteration of PTGS2 Promoter Methylation in Chronic Periodontitis

    PubMed Central

    Zhang, S.; Barros, S.P.; Niculescu, M.D.; Moretti, A.J.; Preisser, J.S.; Offenbacher, S.

    2011-01-01

    Levels of prostaglandin E2 and the prostaglandin-endoperoxide synthase-2 (PTGS2, or COX-2) increase in actively progressing periodontal lesions, but decrease in chronic disease. We hypothesized that chronic inflammation is associated with altered DNA methylation levels within the PTGS2 promoter, with effects on COX-2 mRNA expression. PTGS2 promoter methylation levels from periodontally inflamed gingival biopsies showed a 5.06-fold increase as compared with non-inflamed samples (p = 0.03), and the odds of methylation in a CpG site in the inflamed gingival group is 4.46 times higher than in the same site in the non-inflamed group (p = 0.016). The level of methylation at −458 bp was inversely associated with transcriptional levels of PTGS2 (RT-PCR) (p = 0.01). Analysis of the data suggests that, in chronically inflamed tissues, there is a hypermethylation pattern of the PTGS2 promoter in association with a lower level of PTGS2 transcription, consistent with a dampening of COX-2 expression in chronic periodontitis. These findings suggest that the chronic persistence of the biofilm and inflammation may be associated with epigenetic changes in local tissues at the biofilm-gingival interface. PMID:20042743

  5. Promoting Resilience in Youth with Chronic Conditions & Their Families.

    ERIC Educational Resources Information Center

    Garwick, Ann E.; Millar, H. E. C.

    This monograph for health care professionals considers the impact that chronic illness and disability have on youth and their families and provides information on adapting principles of family-centered care to promote resilience in adolescents and their families. The monograph stresses the need for community systems of comprehensive services…

  6. Factors promoting acute and chronic diseases caused by yersiniae.

    PubMed Central

    Brubaker, R R

    1991-01-01

    The experimental system constructed with the medically significant yersiniae provides a powerful basic model for comparative study of factors required for expression of acute versus chronic disease. The system exploits the close genetic similarity between Yersinia pestis, the etiological agent of bubonic plague, and enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica. Y. pestis possesses three plasmids, of which one, shared by the enteropathogenic species, mediates a number of virulence factors that directly or indirectly promote survival within macrophages and immunosuppression. The two remaining plasmids are unique and encode functions that promote acute disease by enhancing bacterial dissemination in tissues and resistance to phagocytosis by neutrophils and monocytes. These properties are replaced in the enteropathogenic yersiniae by host cell invasins and an adhesin which promote chronic disease; the latter are cryptic in Y. pestis. Additional distinctions include specific mutational losses in Y. pestis which result in loss of fitness in natural environments plus gain of properties that facilitate transmission and infection via fleabite. Images PMID:1889045

  7. Bile signalling promotes chronic respiratory infections and antibiotic tolerance

    PubMed Central

    Reen, F. Jerry; Flynn, Stephanie; Woods, David F.; Dunphy, Niall; Chróinín, Muireann Ní; Mullane, David; Stick, Stephen; Adams, Claire; O’Gara, Fergal

    2016-01-01

    Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. In order to uncover the molecular mechanism through which bile modulates the respiratory microbiome, a combination of global transcriptomic and phenotypic analyses of the P. aeruginosa response to bile was undertaken. Bile responsive pathways responsible for virulence, adaptive metabolism, and redox control were identified, with macrolide and polymyxin antibiotic tolerance increased significantly in the presence of bile. Bile acids, and chenodeoxycholic acid (CDCA) in particular, elicited chronic biofilm behaviour in P. aeruginosa, while induction of the pro-inflammatory cytokine Interleukin-6 (IL-6) in lung epithelial cells by CDCA was Farnesoid X Receptor (FXR) dependent. Microbiome analysis of paediatric CF sputum samples demonstrated increased colonisation by P. aeruginosa and other Proteobacterial pathogens in bile aspirating compared to non-aspirating patients. Together, these data suggest that bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease. PMID:27432520

  8. ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia

    PubMed Central

    Jiang, Qingfei; Crews, Leslie A.; Barrett, Christian L.; Chun, Hye-Jung; Court, Angela C.; Isquith, Jane M.; Zipeto, Maria A.; Goff, Daniel J.; Minden, Mark; Sadarangani, Anil; Rusert, Jessica M.; Dao, Kim-Hien T.; Morris, Sheldon R.; Goldstein, Lawrence S. B.; Marra, Marco A.; Frazer, Kelly A.; Jamieson, Catriona H. M.

    2013-01-01

    The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes that regulate stem cell maintenance. In this study, whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-γ pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive ADAR1 p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. Lentiviral overexpression experiments demonstrate that ADAR1 p150 promotes expression of the myeloid transcription factor PU.1 and induces malignant reprogramming of myeloid progenitors. Moreover, enforced ADAR1 p150 expression was associated with production of a misspliced form of GSK3β implicated in LSC self-renewal. Finally, functional serial transplantation and shRNA studies demonstrate that ADAR1 knockdown impaired in vivo self-renewal capacity of blast crisis CML progenitors. Together these data provide a compelling rationale for developing ADAR1-based LSC detection and eradication strategies. PMID:23275297

  9. ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.

    PubMed

    Jiang, Qingfei; Crews, Leslie A; Barrett, Christian L; Chun, Hye-Jung; Court, Angela C; Isquith, Jane M; Zipeto, Maria A; Goff, Daniel J; Minden, Mark; Sadarangani, Anil; Rusert, Jessica M; Dao, Kim-Hien T; Morris, Sheldon R; Goldstein, Lawrence S B; Marra, Marco A; Frazer, Kelly A; Jamieson, Catriona H M

    2013-01-15

    The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes that regulate stem cell maintenance. In this study, whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-γ pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive ADAR1 p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. Lentiviral overexpression experiments demonstrate that ADAR1 p150 promotes expression of the myeloid transcription factor PU.1 and induces malignant reprogramming of myeloid progenitors. Moreover, enforced ADAR1 p150 expression was associated with production of a misspliced form of GSK3β implicated in LSC self-renewal. Finally, functional serial transplantation and shRNA studies demonstrate that ADAR1 knockdown impaired in vivo self-renewal capacity of blast crisis CML progenitors. Together these data provide a compelling rationale for developing ADAR1-based LSC detection and eradication strategies.

  10. Milk--the promoter of chronic Western diseases.

    PubMed

    Melnik, Bodo C

    2009-06-01

    Common chronic diseases of Western societies, such as coronary heart disease, diabetes mellitus, cancer, hypertension, obesity, dementia, and allergic diseases are significantly influenced by dietary habits. Cow's milk and dairy products are nutritional staples in most Western societies. Milk and dairy product consumption is recommended by most nutritional societies because of their beneficial effects for calcium uptake and bone mineralization and as a source of valuable protein. However, the adverse long-term effects of milk and milk protein consumption on human health have been neglected. A hypothesis is presented, showing for the first time that milk protein consumption is an essential adverse environmental factor promoting most chronic diseases of Western societies. Milk protein consumption induces postprandial hyperinsulinaemia and shifts the growth hormone/insulin-like growth factor-1 (IGF-1) axis to permanently increased IGF-1 serum levels. Insulin/IGF-1 signalling is involved in the regulation of fetal growth, T-cell maturation in the thymus, linear growth, pathogenesis of acne, atherosclerosis, diabetes mellitus, obesity, cancer and neurodegenerative diseases, thus affecting most chronic diseases of Western societies. Of special concern is the possibility that milk intake during pregnancy adversely affects the early fetal programming of the IGF-1 axis which will influence health risks later in life. An accumulated body of evidence for the adverse effects of cow's milk consumption from fetal life to childhood, adolescence, adulthood and senescence will be provided which strengthens the presented hypothesis.

  11. Tumour promotion versus tumour suppression in chronic hepatic iron overload.

    PubMed

    Bloomer, Steven A; Brown, Kyle E

    2015-06-01

    Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver.

  12. Theory in Chronic Disease Prevention and Health Promotion

    ERIC Educational Resources Information Center

    Hall, Michael; Elise, Eifert

    2016-01-01

    Morbidity and mortality related to chronic diseases are a primary concern of health professionals, including Health Educators. According to the Centers for Disease Control and Prevention, over one half of the adult population in the United States suffer from one or more chronic conditions. Understanding the health risk behaviors that contribute to…

  13. Theory in Chronic Disease Prevention and Health Promotion

    ERIC Educational Resources Information Center

    Hall, Michael; Elise, Eifert

    2016-01-01

    Morbidity and mortality related to chronic diseases are a primary concern of health professionals, including Health Educators. According to the Centers for Disease Control and Prevention, over one half of the adult population in the United States suffer from one or more chronic conditions. Understanding the health risk behaviors that contribute to…

  14. Introduction to Health Promotion for People with Chronic Illness and Disability

    ERIC Educational Resources Information Center

    Chan, Fong; Chiu, Chung-Yi; Bezyak, Jill L.; Keegan, John

    2012-01-01

    Health promotion has received increasing attention in rehabilitation counseling research. Health promotion research contributes to theory building and provides the foundation for empirically supported interventions that can improve the health-related quality of life and employment outcomes of people with chronic illness and disability. In this…

  15. Introduction to Health Promotion for People with Chronic Illness and Disability

    ERIC Educational Resources Information Center

    Chan, Fong; Chiu, Chung-Yi; Bezyak, Jill L.; Keegan, John

    2012-01-01

    Health promotion has received increasing attention in rehabilitation counseling research. Health promotion research contributes to theory building and provides the foundation for empirically supported interventions that can improve the health-related quality of life and employment outcomes of people with chronic illness and disability. In this…

  16. [Mental Health Promotion Among the Chronic Disabled Population in the Community].

    PubMed

    Huang, Hui-Chuan; Wang, Li-Hua; Chang, Hsiu-Ju

    2015-08-01

    Societal ageing and the rising prevalence of chronic disease are important causes that underlie the growth in the number of disabled individuals. The disease-induced psychological distress experienced by this population not only decreases quality of life but also increases demand for healthcare. The healthcare policy for the disabled population currently focuses on community healthcare. Therefore, developing appropriate programs to promote mental health among the disabled population in community settings is a critical issue. The present paper reviews current mental health promotion initiatives that target the disabled population in the community and addresses mental healthcare issues that are prevalent among the chronically disabled; strategies of mental health promotion that use music therapy, reminiscence therapy, and horticultural therapy; and the roles and responsibilities of community professionals in mental healthcare. We offer these perspectives as a reference to promote mental health and to establish holistic community healthcare for chronically disabled individuals.

  17. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

    PubMed Central

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

    2015-01-01

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

  18. Preventing chronic diseases by promoting healthy diet and lifestyle: public policy implications for China.

    PubMed

    Hu, F B; Liu, Y; Willett, W C

    2011-07-01

    Fuelled by rapid urbanization and changes in dietary and lifestyle choices, chronic diseases have emerged as a critical public health issue in China. The Healthy China 2020 programme recently announced by the Chinese government has set an overarching goal of promoting public health and making health care accessible and affordable for all Chinese citizens by year 2020. One of important components of the programme is to reduce chronic diseases by promoting healthy eating and active lifestyles. Chronic diseases not only affect health and quality of life, but also have economical and social consequences. With a limited infrastructure for chronic disease care, China is ill-equipped to deal with the escalating chronic disease epidemic, which threatens to reverse the gains of economic development in recent decades. Population-based intervention studies conducted in China and elsewhere have demonstrated the efficacy and effectiveness of several preventive strategies to reduce risk of chronic diseases in high-risk individuals and the general population. However, translating these findings into practice requires changes in health systems and public policies. To achieve the goals set by the Healthy China 2020 programme, prevention of chronic diseases should be elevated to a national public policy priority.

  19. Human miR223 promoter as a novel myelo-specific promoter for chronic granulomatous disease gene therapy.

    PubMed

    Brendel, Christian; Hänseler, Walther; Wohlgensinger, Vital; Bianchi, Matteo; Tokmak, Serap; Chen-Wichmann, Linping; Kuzmenko, Elena; Cesarovic, Nikola; Nicholls, Flora; Reichenbach, Janine; Seger, Reinhard; Grez, Manuel; Siler, Ulrich

    2013-06-01

    Targeting transgene expression to specific hematopoietic cell lineages could contribute to the safety of retroviral vectors in gene therapeutic applications. Chronic granulomatous disease (CGD), a defect of phagocytic cells, can be managed by gene therapy, using retroviral vectors with targeted expression to myeloid cells. In this context, we analyzed the myelospecificity of the human miR223 promoter, which is known to be strongly upregulated during myeloid differentiation, to drive myeloid-restricted expression of p47(phox) and gp91(phox) in mouse models of CGD and in primary patient-derived cells. The miR223 promoter restricted the expression of p47(phox), gp91(phox), and green fluorescent protein (GFP) within self-inactivating (SIN) gamma- and lentiviral vectors to granulocytes and macrophages, with only marginal expression in lymphocytes or hematopoietic stem and progenitor cells. Furthermore, gene transfer into primary CD34+ cells derived from a p47(phox) patient followed by ex vivo differentiation to neutrophils resulted in restoration of Escherichia coli killing activity by miR223 promoter-mediated p47(phox) expression. These results indicate that the miR223 promoter as an internal promoter within SIN gene therapy vectors is able to efficiently correct the CGD phenotype with negligible activity in hematopoietic progenitors, thereby limiting the risk of insertional oncogenesis and development of clonal dominance.

  20. Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic Hepatitis B Infection

    PubMed Central

    Ghaleh Baghi, Sahand; Alavian, Seyed Moayed; Mehrnoush, Leila; Salimi, Shima

    2015-01-01

    Background: Interleukin-10 (IL-10) is an important anti-inflammatory cytokine. The polymorphisms of its promoter gene have been considered to be related with the chronicity of hepatitis B infection. Objectives: The aim of this study was to evaluate the polymorphisms at different positions in the IL-10 promoter gene in patients with chronic hepatitis B. Patients and Methods: Totally, 166 patients with chronic hepatitis B infection were enrolled. Genotypes at different positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were determined. Results: The C/A genotype at position -592, C/T genotype at position -819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more common in the patients with cirrhosis. The genotypes were significantly different between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A and G/A). Conclusions: Some IL-10 promoter gene polymorphisms predisposed the infected hepatitis B virus cases to cirrhosis in our study population. PMID:26300930

  1. Chronic and Initiation/Promotion Skin Bioassays of Petroleum Refinery Streams.

    PubMed Central

    Skisak, C; Furedi-Machacek, EM; Schmitt, SS; Swanson, MS; Vernot, EH

    1994-01-01

    Nine refinery streams were tested in both chronic and initiation/promotion (I/P) skin bioassays. In the chronic bioassay, groups of 50 C3H/HeJ mice received twice weekly applications of 50 microl of test article for at least 2 years. In the initiation phase of the I/P bioassay, groups of CD-1 mice received an initiating dose of 50 microl of test article for 5 consecutive days, followed by promotion with 50 microl of phorbol-12-myristate-13-acetate (0.01% w/v in acetone) for 25 weeks. In the promotion phase of the I/P bioassay, CD-1 mice were initiated with 50 microl of 7,12-dimethylbenzanthracene (0.1% w/v in acetone) or acetone, followed by promotion with 50 microl of test article twice weekly for 25 weeks. The most volatile of the streams, sweetened naphtha, and the least volatile, vacuum residuum, were noncarcinogenic in both assays. Middle distillates, with a boiling range of 150 degrees-370 degreesC, demonstrated carcinogenic activity in the chronic bioassay and acted as promoters but not initiators in the I/P bioassay. Untreated mineral oil streams displayed initiating activity and were carcinogenic in the chronic bioassay, presumably due to the presence of polycyclic aromatic hydrocarbons of requisite size and structure. A highly solvent-refined mineral oil stream lacked initiating activity. These results indicate that the I/P bioassay, which takes 6 months to complete, may be a good qualitative predictor of the results of a chronic bioassay, at least for petroleum streams. Furthermore, the I/P bioassay can provide insight into possible mechanisms of tumor development. Images p82-a PMID:9719673

  2. Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia

    PubMed Central

    Fiorcari, Stefania; Martinelli, Silvia; Bulgarelli, Jenny; Audrito, Valentina; Zucchini, Patrizia; Colaci, Elisabetta; Potenza, Leonardo; Narni, Franco; Luppi, Mario; Deaglio, Silvia; Marasca, Roberto; Maffei, Rossana

    2015-01-01

    Lenalidomide is an immunomodulatory agent clinically active in chronic lymphocytic leukemia patients. The specific mechanism of action is still undefined, but includes modulation of the microenvironment. In chronic lymphocytic leukemia patients, nurse-like cells differentiate from CD14+ mononuclear cells and protect chronic lymphocytic leukemia cells from apoptosis. Nurse-like cells resemble M2 macrophages with potent immunosuppressive functions. Here, we examined the effect of lenalidomide on the monocyte/macrophage population in chronic lymphocytic leukemia patients. We found that lenalidomide induces high actin polymerization on CD14+ monocytes through activation of small GTPases, RhoA, Rac1 and Rap1 that correlated with increased adhesion and impaired monocyte migration in response to CCL2, CCL3 and CXCL12. We observed that lenalidomide increases the number of nurse-like cells that lost the ability to nurture chronic lymphocytic leukemia cells, acquired properties of phagocytosis and promoted T-cell proliferation. Gene expression signature, induced by lenalidomide in nurse-like cells, indicated a reduction of pivotal pro-survival signals for chronic lymphocytic leukemia, such as CCL2, IGF1, CXCL12, HGF1, and supported a modulation towards M1 phenotype with high IL2 and low IL10, IL8 and CD163. Our data provide new insights into the mechanism of action of lenalidomide that mediates a pro-inflammatory switch of nurse-like cells affecting the protective microenvironment generated by chronic lymphocytic leukemia into tissues. PMID:25398834

  3. [A study on health perception and health promoting behavior in chronic back pain patients].

    PubMed

    Park, Hyoung-Sook; Kang, Young-Sook; Park, Kyung-Yeon

    2006-06-01

    The purpose of this study was to show a relationship between health perception and health promoting behaviors in chronic low back pain patients. The subjects for this study were 213 persons who the visited hospital with low back pain-related problems. The higher the level of the health perception in chronic back pain patients was the higher the rate of the practice of health promoting behaviors (r=0.393, p<.001). The health perception T score was 50.00+/-10.00. As for health promoting behaviors, the T score was 49.99+/-10.00. The subscale of the highest mean score was interpersonal support (2.96+/-0.64) and the subscale of the lowest mean score was exercise (2.13+/-0.99). This study showed that chronic low back pain patients had a lower level of perception of their health, and their practice to improve their health was not enough. Therefore, nurses should educate and encourage chronic low back pain patients in proper exercises and correct posture to strengthen and maintain lumbar extension muscle power.

  4. Clinical Evaluation of a Novel Topical Negative Pressure Device in Promoting Healing in Chronic Wounds

    PubMed Central

    Bradbury, Sarah; Walkley, Neal; Ivins, Nicola; Harding, Keith

    2015-01-01

    Aim: This observational study evaluated the use of a novel, ultraportable, mechanically powered topical negative pressure device in promoting healing in chronic wounds, including venous and mixed etiology leg ulcers and neuropathic foot ulcers. Materials and Methods: Evaluable patients (n=37) received treatment with the SNaP® Wound Care System for up to 6 weeks. The primary objective was percentage change in wound size, with secondary objectives of clinical assessment of wound parameters, ease of use, and impact on quality of life. Results: A 42.64% mean percentage decrease in wound area was observed, with an overall decrease for each wound etiology subgroup. Increased granulation tissue, decreased exudate levels, and decreased wound pain were reported. Quality-of-life scores increased overall, and the device was easy to use, comfortable, portable, and inconspicuous. Conclusion: The SNaP Wound Care System has the potential to promote healing in chronic wounds of different etiologies. PMID:26029485

  5. Chronic pepsin exposure promotes anchorage-independent growth, and migration of a hypopharyngeal squamous cell line

    PubMed Central

    Kelly, Elizabeth A.; Samuels, Tina L.; Johnston, Nikki

    2015-01-01

    Outcome Objectives 1.Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. 2.Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony forming ability in hypopharyngeal cells. Study Design Translation research. Setting Academic research laboratory. Methods Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01mg/ml, 0.1 mg/ml, or 1mg/ml). Precise wounds were created in confluent cell plates and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony forming ability. Results An increased rate of relative wound density was observed in chronic pepsin treated (0.01mg/ml, 0.1mg/ml) cells compared to control (P<0.001), suggesting greater rates of cell migration. Pepsin treated (0.1 mg/ml) cells demonstrated on average, greater cell viability compared to control after exposure to paclitaxel suggesting possible apoptotic resistance, however this was not statistically significant. Chronic pepsin exposure (0.1mg/ml, 1mg/ml) was associated with dose dependent increase in colony forming ability relative to control (P<0.001). Conclusion Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration, and colony forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux. PMID:24376122

  6. Chronic pepsin exposure promotes anchorage-independent growth and migration of a hypopharyngeal squamous cell line.

    PubMed

    Kelly, Elizabeth A; Samuels, Tina L; Johnston, Nikki

    2014-04-01

    (1) Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. (2) Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony-forming ability in hypopharyngeal cells. Translation research. Academic research laboratory. Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01 mg/mL, 0.1 mg/mL, or 1 mg/mL). Precise wounds were created in confluent cell plates, and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin-exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony-forming ability. An increased rate of relative wound density was observed in chronic pepsin-treated (0.01 mg/mL, 0.1 mg/mL) cells compared with control (P < .001), suggesting greater rates of cell migration. Pepsin-treated (0.1 mg/mL) cells demonstrated on average greater cell viability compared with control after exposure to paclitaxel, suggesting possible apoptotic resistance; however, this was not statistically significant. Chronic pepsin exposure (0.1 mg/mL, 1 mg/mL) was associated with a dose-dependent increase in colony-forming ability relative to control (P < .001). Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration and colony-forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.

  7. [Reducing chronic malnutrition among the disadvantaged populations to promote health and development].

    PubMed

    Bacallao, Jorge; Peña, Manuel; Díaz, Adrián

    2012-08-01

    This article advances theoretical and conceptual arguments to justify efforts to reduce chronic malnutrition as a basic component of any strategy for promoting health and development in countries with a high malnutrition prevalence. The arguments rest on four cardinal principles of contemporary social epidemiology, in whose framework reducing chronic malnutrition would be a key strategic component: the social determinants approach, the life course as the clinical-epidemiological paradigm, the concept of heredity and population health, and recognition of the family as a social determinant. Added to these are the close association between nutrition, health, and development, on the one hand, and the political significance of any strategy that makes the fight against chronic malnutrition the most visible focus of programmatic action.

  8. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord.

    PubMed

    Tom, Veronica J; Sandrow-Feinberg, Harra R; Miller, Kassi; Santi, Lauren; Connors, Theresa; Lemay, Michel A; Houlé, John D

    2009-11-25

    Because there currently is no treatment for spinal cord injury, most patients are living with long-standing injuries. Therefore, strategies aimed at promoting restoration of function to the chronically injured spinal cord have high therapeutic value. For successful regeneration, long-injured axons must overcome their poor intrinsic growth potential as well as the inhibitory environment of the glial scar established around the lesion site. Acutely injured axons that regenerate into growth-permissive peripheral nerve grafts (PNGs) reenter host tissue to mediate functional recovery if the distal graft-host interface is treated with chondroitinase ABC (ChABC) to cleave inhibitory chondroitin sulfate proteoglycans in the scar matrix. To determine whether a similar strategy is effective for a chronic injury, we combined grafting of a peripheral nerve into a highly relevant, chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. We tested this combination in two grafting paradigms: (1) a peripheral nerve that was grafted to span a chronic injury site or (2) a PNG that bridged a chronic contusion site with a second, more distal injury site. Unlike GDNF-PBS treatment, GDNF-ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery. Electrical stimulation of axons in the peripheral nerve bridge induced c-Fos expression in host neurons, indicative of synaptic contact by regenerating fibers. Thus, our data demonstrate, for the first time, that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons.

  9. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  10. Supporting knowledge into action: The Canadian Best Practices Initiative for Health Promotion and Chronic Disease Prevention.

    PubMed

    Jetha, Nina; Robinson, Kerry; Wilkerson, Tricia; Dubois, Nancy; Turgeon, Vincent; DesMeules, Marie

    2008-01-01

    Public health practitioners and policy-makers working to address the burden of chronic disease are increasingly seeking to use best practices given the need to make thoughtful program and policy choices with limited resources. While the evidence base in chronic disease prevention is growing through a number of different information sources, there is often a disconnect between the desire to use best practices and their implementation. This is related not only to individual and organizational barriers in terms of time and resources, but also to lack of agreement on what constitutes best practice and what sources of evidence are valid guides for practice. This is compounded by lack of user-friendly and streamlined access to credible best practice evidence and decision making/practice supports. In response to these needs, six years ago Canadian researchers, policy-makers and practitioners came together to begin working on creating a best practice system in Canada for health promotion and chronic disease prevention. This article presents an overview of the development of the Canadian Best Practices Portal and in particular how an evolution in thinking about best practice methodology and evidence will contribute to an enriched knowledge base for health promotion and chronic disease prevention policy, practice and research.

  11. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth

    PubMed Central

    Barbieri, Antonio; Palma, Giuseppe; Rosati, Alessandra; Giudice, Aldo; Falco, Antonia; Petrillo, Antonella; Petrillo, Mario; Bimonte, Sabrina; Benedetto, Maria Di; Esposito, Giuseppe; Stiuso, Paola; Abbruzzese, Alberto; Caraglia, Michele; Arra, Claudio

    2012-01-01

    Abstract Accumulating evidence suggests that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed animals. Tumour growth was significantly reduced in mice treated with the β-antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by Western blot analysis. We found a significant increase in eNOS levels in tumour samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS−/− mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumour growth. PMID:21722303

  12. Effectiveness of gratitude disposition promotion program on depression and quality of life of chronic schizophrenic patients

    PubMed Central

    Jung, Miran; Han, Kuemsun

    2017-01-01

    Context: Gratitude intervention is expectedly an effective intervention to reduce depression and improve the quality of life in schizophrenic patients, but there is a lack of literature on it. Aims: We attempted to develop and test the effectiveness of the gratitude disposition promotion program for chronic schizophrenic patients in Korea. Settings and Design: Nonequivalent control group pre- and post-test design was used in two mental health centers located at Gyeonggi-do in South Korea. Materials and Methods: This paper was a quasi-experimental study and the participants who took part in the gratitude disposition promotion program were 17 of experimental group and 15 of control group. Gratitude disposition (the short gratitude, resentment, and appreciation test), depression (Beck Depression Inventory), and quality of life (developed by Kook) of chronic schizophrenic patients were measured before and after an intervention, as compared to the control. Statistical Analysis: Chi-square test, Fisher's exact test, and t-test were performed for prehomogeneity testing for variables related to the general characteristics. Testing for the effectiveness of gratitude disposition promotion program and hypothesis testing for its effect on depression and quality of life were by ANCOVA and t-test, as verified to significance level of P < 0.05. Results: The participants who received the gratitude disposition promotion program showed significant improvements in gratitude disposition (F = 18.740, P < 0.0001) and in quality of life (F = 9.800, P = 0.004), but no significant difference in depression (F = 3.870, P = 0.059). Conclusions: The gratitude disposition promotion program was an effective clinical intervention program for enhancing gratitude disposition and quality of life of chronic schizophrenic patients in community. PMID:28827866

  13. Effectiveness of gratitude disposition promotion program on depression and quality of life of chronic schizophrenic patients.

    PubMed

    Jung, Miran; Han, Kuemsun

    2017-01-01

    Gratitude intervention is expectedly an effective intervention to reduce depression and improve the quality of life in schizophrenic patients, but there is a lack of literature on it. We attempted to develop and test the effectiveness of the gratitude disposition promotion program for chronic schizophrenic patients in Korea. Nonequivalent control group pre- and post-test design was used in two mental health centers located at Gyeonggi-do in South Korea. This paper was a quasi-experimental study and the participants who took part in the gratitude disposition promotion program were 17 of experimental group and 15 of control group. Gratitude disposition (the short gratitude, resentment, and appreciation test), depression (Beck Depression Inventory), and quality of life (developed by Kook) of chronic schizophrenic patients were measured before and after an intervention, as compared to the control. Chi-square test, Fisher's exact test, and t-test were performed for prehomogeneity testing for variables related to the general characteristics. Testing for the effectiveness of gratitude disposition promotion program and hypothesis testing for its effect on depression and quality of life were by ANCOVA and t-test, as verified to significance level of P < 0.05. The participants who received the gratitude disposition promotion program showed significant improvements in gratitude disposition (F = 18.740, P < 0.0001) and in quality of life (F = 9.800, P = 0.004), but no significant difference in depression (F = 3.870, P = 0.059). The gratitude disposition promotion program was an effective clinical intervention program for enhancing gratitude disposition and quality of life of chronic schizophrenic patients in community.

  14. Tumour necrosis factor-alpha gene promoter polymorphism in chronic obstructive pulmonary disease.

    PubMed

    Higham, M A; Pride, N B; Alikhan, A; Morrell, N W

    2000-02-01

    Tumour necrosis factor(TNF)-alpha levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-alpha gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians. Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood. There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung). It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease.

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

    PubMed Central

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

    2004-01-01

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

  16. Exploring payment schemes used to promote integrated chronic care in Europe.

    PubMed

    Tsiachristas, Apostolos; Dikkers, Carolien; Boland, Melinde R S; Rutten-van Mölken, Maureen P M H

    2013-12-01

    The rising burden of chronic conditions has led several European countries to reform healthcare payment schemes. This paper aimed to explore the adoption and success of payment schemes that promote integration of chronic care in European countries. A literature review was used to identify European countries that employed pay-for-coordination (PFC), pay-for-performance (PFP), and bundled payment schemes. Existing evidence from the literature was supplemented with fifteen interviews with chronic care experts in these countries to obtain detailed information regarding the payment schemes, facilitators and barriers to their implementation, and their perceived success. Austria, France, England, the Netherlands, and Germany have implemented payment schemes that were specifically designed to promote the integration of chronic care. Prominent factors facilitating implementation included stakeholder cooperation, adequate financial incentives for stakeholders, and flexible task allocation among different care provider disciplines. Common barriers to implementation included misaligned incentives across stakeholders and gaming. The implemented payment schemes targeted different stakeholders (e.g. individual caregivers, multidisciplinary organizations of caregivers, regions, insurers) in different countries depending on the structure and financing of each health care system. All payment reforms appeared to have changed the structure of chronic care delivery. PFC, as it was implemented in Austria, France and Germany, was perceived to be the most successful in increasing collaboration within and across healthcare sectors, whereas PFP, as it was implemented in England and France, was perceived most successful in improving other indicators of the quality of the care process. Interviewees stated that the impact of the payment reforms on healthcare expenditures remained questionable. The success of a payment scheme depends on the details of the specific implementation in a particular

  17. Clinical results of the application of a hemoglobin spray to promote healing of chronic wounds

    PubMed Central

    Arenberger, Peter; Engels, Peter; Arenbergerova, Monika; Gkalpakiotis, Spyridon; García Luna Martínez, Francisco Javier; Villarreal Anaya, Americo; Jimenez Fernandez, Laura

    2011-01-01

    A new technological approach for supplying hypoxic chronic wounds with oxygen is a moist wound treatment with aqueous solutions containing tissue compatible oxygen binders. This facilitates diffusion of oxygen, necessary for the healing process, from the surroundings (room air through an open-porous wound padding) into the ulcerous tissue. A product that is still in development is a spray which contains hemoglobin obtained from domestic pigs. Clinical investigations (a clinical trial, treatment observations and single patient uses) are presented, which were performed to create clinical data regarding efficiency and safety of this product. All data have shown that the application of the hemoglobin spray promoted wound healing in all analyzed cases. Data from a clinical study in Mexico and subsequent therapy observations revealed that in 39 out of 42 patients (93%) the treated wounds were healed. 9 patients from a series of therapy observations in Monterrey (Mexico) showed similar observations. All treated wounds were closed. Single patient uses carried out in Witten (Germany; 6 wounds from 8 (75%)) and Prague (Czech Republic; 5 wounds from 5 (100%) were healed) further support these results: The application of hemoglobin spray can promote healing of chronic wounds. Within the framework of the clinical investigation, the treatment observations, and the individual healing experiments the hemoglobin spray was applied more than 2,000 times onto chronic wounds of 82 patients. In all cases, the spray was well tolerated and there were no adverse event that might have been an adverse reaction to the hemoglobin spray. PMID:22242086

  18. Using health trainers to promote self-management of chronic pain: can it work?

    PubMed

    Harris, Janet; Williams, Tim; Hart, Ollie; Hanson, Chris; Johnstone, Gareth; Muthana, Aziz; Nield, Chris

    2014-02-01

    In 2011, the Sheffield Primary Care Trust piloted a Health Trainer (HT) programme targeted specifically to people with chronic pain. The programme aimed to determine whether patients presenting to primary care with chronic pain would benefit from self-management support, thereby reducing the burden on primary care and secondary care services. We conducted a formative mixed-methods evaluation of the pilot programme, focusing on four aspects of implementation: general practitioner (GP) referral to the programme, HT's ability to use cognitive behavioural (CB) approaches, short-term outcomes for clients and adequacy of resources. Qualitative data were collected via interviews with GPs, HTs and the chronic pain team; supervision sessions with HTs; and client case studies. Quantitative data were collected on satisfaction with training, HT's self-reported confidence to implement CB and clients' self-rated well-being before and after participation. A total of 143 clients with pain for 1 year or more were referred, exceeding the projected 90 referrals by over 50%. A total of 70% of the clients came from the most deprived areas of Sheffield, 40% were listed as permanently sick/disabled and only 20% were working. Qualitative analysis indicated that the CB training was delivered as intended. Clients reported that 75% of their goals were either achieved or partly achieved, and at follow-up 43% of them reported maintaining strategies for self-management. Financial resources were supplemented by indirect resources, including GP 'champions' with a special interest in pain, and a multidisciplinary chronic pain team. The prior history of working with community organizations was critical in ensuring credibility in client communities and addressing client needs. A HT programme promoting self-management of chronic pain can be successfully implemented when supported by community organisations. Preliminary data indicate that the programme can be instrumental in helping clients to

  19. Progesterone and Nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex

    PubMed Central

    el-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2014-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation and axonal degeneration. Current therapies are limited to immunomodulators and anti-inflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2+ oligodendrocyte progenitor cells and CA II+ mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin. PMID:25092805

  20. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    PubMed

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

  1. Hair follicle units promote re-epithelialization in chronic cutaneous wounds: A clinical case series study.

    PubMed

    Liu, Jia-Qi; Zhao, Kong-Bo; Feng, Zi-Hao; Qi, Fa-Zhi

    2015-07-01

    Chronic cutaneous wounds are one of the most unfavorable pathophysiological processes in routine practice. However, developments in hair follicle unit therapy may aid the treatment of these wounds. The aim of the present study was to investigate the function of hair follicle units in chronic cutaneous wound re-epithelialization and to develop an effective protocol for wound treatment. A total of 14 patients, of which nine were male and five were female, with a mean age of 60.71 years (range, 19-76 years) and a mean wound area of 74.14 cm(2), were treated in the study. The hair follicle units were dissected from a scalp graft and transplanted into the chronic cutaneous wound bed, after which clinical evaluation was performed. Images of the recipient site were captured at 0, 1, 2, 3, 4, 5, 8 and 14 weeks following transplantation. In addition, histological examinations were conducted postoperatively at week 16. Total wound re-epithelialization was observed in all the patients. Histological analysis revealed that the epidermis and papillary dermis were present in the wound area. Adnexal structures and the reticular dermis were also observed. Therefore, the present study demonstrated the ability of hair follicle units to promote chronic cutaneous wound healing.

  2. Acute and chronic cadmium exposure promotes E-cadherin degradation in MCF7 breast cancer cells.

    PubMed

    Ponce, Esmeralda; Louie, Maggie C; Sevigny, Mary B

    2015-10-01

    Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure-both acute and chronic-contributes to breast cancer progression by interfering with the normal functional relationship between E-cadherin and β-catenin. An MCF7 breast cancer cell line (MCF7-Cd) chronically exposed to 10(-7)  M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10(-6)  M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E-cadherin protein via the ubiquitination pathway. This resulted in fewer E-cadherin/β-catenin complexes and the relocation of active β-catenin to the nucleus, where it interacted with transcription factor TCF-4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of β-catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down-regulating E-cadherin, thus decreasing the number of E-cadherin/β-catenin adhesion complexes, and (2) enhancing the nuclear translocation of β-catenin to increase expression of cancer-promoting proteins (i.e., c-Jun and cyclin D1).

  3. Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke.

    PubMed

    Kim, Eunhee; Woo, Moon-Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D; Bao, Yi; Bailey, Jason A; Corbett, Dale; Ratan, Rajiv R; Lahiri, Debomoy K; Cho, Sunghee

    2015-11-11

    Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long-term functional recovery is an

  4. Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke

    PubMed Central

    Kim, Eunhee; Woo, Moon-Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D.; Bao, Yi; Bailey, Jason A.; Corbett, Dale; Ratan, Rajiv R.; Lahiri, Debomoy K.

    2015-01-01

    Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. SIGNIFICANCE STATEMENT There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long

  5. Preconception care: screening and management of chronic disease and promoting psychological health

    PubMed Central

    2014-01-01

    Introduction A large proportion of women around the world suffer from chronic diseases including mental health diseases. In the United States alone, over 12% of women of reproductive age suffer from a chronic medical condition, especially diabetes and hypertension. Chronic diseases significantly increase the odds for poor maternal and newborn outcomes in pregnant women. Methods A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for preventing and managing chronic diseases and promoting psychological health on maternal, newborn and child health outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Results Maternal prepregnancy diabetic care is a significant intervention that reduces the occurrence of congenital malformations by 70% (95% Confidence Interval (CI): 59-78%) and perinatal mortality by 69% (95% CI: 47-81%). Furthermore, preconception management of epilepsy and phenylketonuria are essential and can optimize maternal, fetal and neonatal outcomes if given before conception. Ideally changes in antiepileptic drug therapy should be made at least 6 months before planned conception. Interventions specifically targeting women of reproductive age suffering from a psychiatric condition show that group-counseling and interventions leading to empowerment of women have reported non-significant reduction in depression (economic skill building: Mean Difference (MD) -7.53; 95% CI: -17.24, 2.18; counseling: MD-2.92; 95% CI: -13.17, 7.33). Conclusion While prevention and management of the chronic diseases like diabetes and hypertension, through counseling, and other dietary and pharmacological intervention, is important, delivering solutions to prevent and respond to women

  6. Chronic Chlorpyrifos Exposure Does Not Promote Prostate Cancer in Prostate Specific PTEN Mutant Mice

    PubMed Central

    Svensson, Robert U.; Bannick, Nadine L.; Marin, Maximo J.; Robertson, Larry W.; Lynch, Charles F.; Henry, Michael D.

    2014-01-01

    Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Exploration of this potential gene-environment interaction would benefit from the development of a suitable animal model. Utilizing a previously described mouse model that is genetically predisposed to prostate cancer through a prostate-specific heterozygous PTEN deletion, termed C57/Luc/Ptenp+/−, we used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in C57/Luc/Ptenp+/− mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. We found no significant differences in numbers of murine prostatic intraepithelial neoplasia lesions or disease progression in chlorpyrifos versus control treated animals up to 32 weeks. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers. PMID:23758150

  7. Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging.

    PubMed

    Dickens, Alex M; Yoo, Seung Wan; Chin, Alfred C; Xu, Jiadi; Johnson, Tory P; Trout, Amanda L; Hauser, Kurt F; Haughey, Norman J

    2017-08-10

    The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage. However, this assumption has never been experimentally tested. Here we take advantage of the leaky tetracycline promoter system in the Tat-transgenic mouse to show that a chronic very low-level expression of Tat is associated with astrocyte activation, inflammatory cytokine expression, ceramide accumulation, reductions in brain volume, synaptic, and axonal damage that occurs over a time frame of 1 year. These data suggest that a chronic low-level production of Tat may contribute to progressive neurological damage in virally suppressed HIV-infected individuals.

  8. Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach

    PubMed Central

    Nanda, Neha; Dhawan, Devinder K.; Bhatia, Alka; Mahmood, Akhtar; Mahmood, Safrun

    2016-01-01

    Background Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. Materials & Methods In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. Results Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. Conclusion These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects. PMID:26998758

  9. Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis.

    PubMed

    Griseri, Thibault; Arnold, Isabelle C; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S; Crocker, Paul R; Powrie, Fiona

    2015-07-21

    The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

    PubMed

    Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

    2016-05-01

    Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

  11. Chronic Opisthorchis viverrini Infection Changes the Liver Microbiome and Promotes Helicobacter Growth

    PubMed Central

    Itthitaetrakool, Upsornsawan; Pinlaor, Porntip; Pinlaor, Somchai; Chomvarin, Chariya; Dangtakot, Rungtiwa; Chaidee, Apisit; Wilailuckana, Chotechana; Sangka, Arunnee; Lulitanond, Aroonlug; Yongvanit, Puangrat

    2016-01-01

    Adults of Opisthorchis viverrini reside in the biliary system, inducing inflammation of bile ducts and cholangitis, leading to hepatobiliary disease (HBD) including cholangiocarcinoma. O. viverrini infection also has major implications for the bacterial community in bile ducts and liver. To investigate this in chronic O. viverrini infection (≥ 8 months p.i.), bacterial genomic DNA from livers of hamsters and from worms was investigated using culture techniques, PCR for Helicobacter spp. and high-throughput next-generation sequencing targeting the V3-V4 hypervariable regions of prokaryotic 16S rRNA gene. Of a total of 855,046 DNA sequence reads, 417,953 were useable after filtering. Metagenomic analyses assigned these to 93 operational taxonomic units (OTUs) consisting of 80 OTUs of bacteria, including 6 phyla and 42 genera. In the chronic O. viverrini-infected group, bacterial community composition and diversity were significantly increased compared to controls. Sequences of Fusobacterium spp. were the most common (13.81%), followed by Streptococcus luteciae (10.76%), Escherichia coli (10.18%), and Bifidobacterium spp. (0.58%). In addition, Helicobacter pylori (0.17% of sequences) was also identified in the liver of chronic O. viverrini infections, but not in normal liver. The presence of H. pylori was confirmed by PCR and by use of an antibody against bacterial antigen, supporting the metagenomics data. The identities of bacteria cultured for enrichment suggested that chronic O. viverrini infection changes the liver microbiome and promotes Helicobacter spp. growth. There may be synergy between O. viverrini and the liver microbiome in enhancing immune response-mediated hepatobiliary diseases. PMID:27806126

  12. Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice.

    PubMed

    Roth, Lynn; Rombouts, Miche; Schrijvers, Dorien M; Lemmens, Katrien; De Keulenaer, Gilles W; Martinet, Wim; De Meyer, Guido R Y

    2015-09-01

    Vulnerable atherosclerotic plaques are prone to plaque rupture leading to acute cardiovascular syndromes and death. Elucidating the risk of plaque rupture is important to define better therapeutic or preventive strategies. In the present study, we investigated the effect of chronic intermittent mental stress on atherosclerotic plaque stability and cardiovascular mortality in apolipoprotein E-deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/)(-)). This mouse model displays exacerbated atherosclerosis with spontaneous plaque ruptures, myocardial infarction and sudden death, when fed a Western-type diet (WD). Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a WD for up to 25 weeks. After 10 weeks WD, mice were divided in a control (n = 27) and mental stress (n = 29) group. The chronic intermittent mental stress protocol consisted of 3 triggers: water avoidance, damp bedding and restraint stress, in a randomly assigned order lasting 6 h every weekday for 15 weeks. Chronic intermittent mental stress resulted in a significant increase in the amount of macrophages in atherosclerotic plaques of the proximal ascending aorta, whereas type I collagen and fibrous cap thickness were decreased. The coronary arteries of mental stress-treated mice showed larger plaques, more stenosis, and an increased degree of perivascular fibrosis. Moreover, myocardial infarctions occurred more frequently in the mental stress group. As compared to the control group, the survival of stressed ApoE(-/-)Fbn1(C1039G+/-) mice decreased from 67% to 52% at 25 weeks WD, presumably due to myocardial infarctions. In conclusion, chronic intermittent mental stress promotes plaque instability, myocardial infarctions, and mortality of ApoE(-/-)Fbn1(C1039G+/-) mice.

  13. SOCS3 genetic variants and promoter hypermethylation in patients with chronic hepatitis B.

    PubMed

    Hoan, Nghiem Xuan; Van Tong, Hoang; Giang, Dao Phuong; Cuong, Bui Khac; Toan, Nguyen Linh; Wedemeyer, Heiner; Bock, C Thomas; Kremsner, Peter G; Song, Le Huu; Velavan, Thirumalaisamy P

    2017-02-04

    The clinical manifestations of hepatitis B viral infection (HBV) include chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The contribution of negative regulator suppressor of cytokine signaling-3 (SOCS3) promoter variants in HBV disease and SOCS3 hypermethylation in tumor tissues were investigated. The SOCS3 promoter region was screened for polymorphisms in 878 HBV patients and in 272 healthy individuals. SOCS3 promoter methylation was examined by bisulfite sequencing. SOCS3 mRNA expression was quantified in 37 tumor and adjacent non-tumor liver tissue specimens. The minor allele rs12953258A was associated with increased susceptibility to HBV infection (OR=1.3, 95%CI=1.1-1.6, adjusted P=0.03). The minor allele rs111033850C and rs12953258A were observed in increased frequencies in HCC and LC patients compared to CHB patients (HCC: OR=1.7, 95%CI=1.1-2.9, adjusted P=0.046; LC: OR=1.4, 95%CI=1.1-1.9, adjusted P=0.017, respectively). HBV patients with rs111033850CC major genotype had decreased viral load (P=0.034), whereas the rs12953258AA major genotype contributed towards increased viral load (P=0.029). Tumor tissues revealed increased hypermethylation compared to adjacent non-tumor tissues (OR=5.4; 95%CI= 1.9-17.1; P=0.001). Increased SOCS3 expression was observed in HBV infested tumor tissues than non-HBV related tumor tissues (P=0.0048). SOCS3 promoter hypermethylation was associated with relatively low mRNA expression in tumor tissues (P=0.0023). In conclusion, SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development.

  14. Single nucleotide polymorphism at -1087 locus of interleukin-10 gene promoter is associated with severe chronic periodontitis in nonsmoking patients.

    PubMed

    Crena, Jasmine; Subramanian, Sangeetha; Victor, Dayanand John; Gnana, Prakash Ponnudurai Samuel; Ramanathan, Arvind

    2015-01-01

    Single nucleotide polymorphisms (SNPs) in the promoter region of interleukin (IL)-10 gene, which codes for the anti-inflammatory cytokine IL-10, have been associated with its level of production in chronic periodontitis. The prevalence of promoter SNP genotypes is known in other populations with chronic periodontitis, while its association in the Indian population is not known. Hence, the present study was designed to investigate the prevalence of IL-10 promoter polymorphism in a racially defined group of Indians with severe chronic periodontitis as the Indian population is known to be genetically diverse. Genomic deoxyribonucleic acid was extracted from 46 nonsmoking patients with severe chronic periodontitis and 45 subjects with healthy periodontium. A SNP locus at -1087 of IL-10 was chosen, as this locus has been frequently associated with chronic periodontitis in other population. Genotyping was carried out using allele-specific polymerase chain reaction (AS-PCR), and the frequencies of genotype were analyzed between the groups. The distribution of genotype and allele frequencies showed significant differences between the study groups. The prevalence of genotype AA alleles at -1087 locus of IL-10 was significantly higher in severe chronic periodontitis patients compared to the healthy controls (P = 0.05). The study has identified a positive association between the occurrence of AA allele at -1087 locus of IL-10 gene and severe chronic periodontitis in nonsmoking patients.

  15. Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

    PubMed

    Ulrich, Victoria; Rotllan, Noemi; Araldi, Elisa; Luciano, Amelia; Skroblin, Philipp; Abonnenc, Mélanie; Perrotta, Paola; Yin, Xiaoke; Bauer, Ashley; Leslie, Kristen L; Zhang, Pei; Aryal, Binod; Montgomery, Rusty L; Thum, Thomas; Martin, Kathleen; Suarez, Yajaira; Mayr, Manuel; Fernandez-Hernando, Carlos; Sessa, William C

    2016-06-01

    Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions.

  16. Using language for social interaction: Communication mechanisms promote recovery from chronic non-fluent aphasia.

    PubMed

    Stahl, Benjamin; Mohr, Bettina; Dreyer, Felix R; Lucchese, Guglielmo; Pulvermüller, Friedemann

    2016-12-01

    Clinical research highlights the importance of massed practice in the rehabilitation of chronic post-stroke aphasia. However, while necessary, massed practice may not be sufficient for ensuring progress in speech-language therapy. Motivated by recent advances in neuroscience, it has been claimed that using language as a tool for communication and social interaction leads to synergistic effects in left perisylvian eloquent areas. Here, we conducted a crossover randomized controlled trial to determine the influence of communicative language function on the outcome of intensive aphasia therapy. Eighteen individuals with left-hemisphere lesions and chronic non-fluent aphasia each received two types of training in counterbalanced order: (i) Intensive Language-Action Therapy (ILAT, an extended form of Constraint-Induced Aphasia Therapy) embedding verbal utterances in the context of communication and social interaction, and (ii) Naming Therapy focusing on speech production per se. Both types of training were delivered with the same high intensity (3.5 h per session) and duration (six consecutive working days), with therapy materials and number of utterances matched between treatment groups. A standardized aphasia test battery revealed significantly improved language performance with ILAT, independent of when this method was administered. In contrast, Naming Therapy tended to benefit language performance only when given at the onset of the treatment, but not when applied after previous intensive training. The current results challenge the notion that massed practice alone promotes recovery from chronic post-stroke aphasia. Instead, our results demonstrate that using language for communication and social interaction increases the efficacy of intensive aphasia therapy. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. [Histone acetylation modification of topoisomerase enzyme Ⅱα promoter regulation factors in patients with chronic benzene poisoning].

    PubMed

    Shi, Yifen; Qian, Shanhu; Li, Jiaqi; Yu, Kang

    2016-01-01

    To investigate histone acetylation modification of topoisomerase enzyme Ⅱα (TOPOⅡα) promoter regulation factors in patients with chronic benzene poisoning, to explore the possible regulatory mechanism of TOPOⅡα involved in toxicity of chronic benzene poisoning; The bone marrow samples were from 25 chronic benzene poisoning cases and 25 controls. The Chromatin Immunoprecipitation (ChIP) assay was carried out to study the possible mechanism of TOPOⅡα promoter regulation factors expression changes. TOPOⅡα promoter regulation factors mRNA were detected by RT-PCR technique. (1) Compared with the control, the histone H4 acetylation, histone H3 acetylation level of TOPOⅡα promoter regulation factors SP1, ATF-2, SP3, NF-YA, P53, C-MYB, ICBP90, NF-M in chronic benzene poisoning patients decreased, with the significant difference (P<0.05) , except for C-JUN (P>0.05) ; (2) The mRNA expression of TOPOⅡαpromoter regulation factors SP1, NF-YA, C-MYB, C-JUN and NF-M were significantly lower than in the control with the significant difference (P<0.05) , while the expression of SP3、P53 mRNA increased (P<0.05) , ATF-2、ICBP90 mRNA wasn't changed (P>0.05) . (1) Chronic benzene poisoning TOPO Ⅱα promoter regulation factors histone modification changes accompanied with mRNA level changed. (2) Histone acetylation modification of topoisomerase enzyme Ⅱα promoter regulation factors takes important role in the benezen's Hematopoietic toxicity.

  18. Chronic administration of methamphetamine promotes atherosclerosis formation in ApoE-/- knockout mice fed normal diet.

    PubMed

    Gao, Bo; Li, Lun; Zhu, Pengfei; Zhang, Mingjing; Hou, Lingbo; Sun, Yufei; Liu, Xiaoyan; Peng, Xiaohong; Gu, Ye

    2015-11-01

    Chronic methamphetamine (METH) abuse could induce neurotoxicity due to reactive oxygen species generation and sympathetic activation. Both factors are associated with atherosclerosis, so we tested the hypothesis that chronic METH administration might also promote atherosclerosis formation in Apo E-/- knockout mice fed normal diet. Male ApoE-/- mice (6 weeks-old) were treated with saline (NS) or METH [4 mg/kg/day (M4) or 8 mg/kg/day (M8) through intraperitoneal injection] for 24 weeks. Atherosclerotic lesion area on oil red O stained en face aorta was dose-dependently increased in M4 and M8 groups compared to NS group. Percentage of atherosclerotic lesion area was significantly higher in M8 group compared to NS and M4 groups. Plasma CRP was increased and inflammatory cytokine (ICAM-1, VCAM-1, TNF-α, and INF-γ) expression on aortic root was upregulated in METH groups compared to NS group. Neuropeptide Y (NPY) protein and mRNA expressions in aortic root and myocardial tissue were determined by Western blot and real time PCR, which were significantly upregulated in M4 and M8 groups. Moreover, mRNA expressions of NPY1R, NPY2R and NPY5R in aortic and myocardial tissue were also significantly upregulated in M4 and M8 groups. Raw264.7 cells were treated with NPY, NPY receptor antagonists, METH (10 μM or 100 μM) with or without lipopolysaccharide (LPS), and the expressions of TNF-α, CRP, MCP-1 and reactive oxygen species (ROS) production were significantly increased in METH and LPS + METH groups compared to control and LPS groups. Co-treatment with NPY1R antagonist decreased the expressions of TNF-α, CRP and MCP-1 in NPY and METH treated cells. Chronic METH administration can promote inflammation and atherosclerotic plague formation in ApoE-/- mice fed normal chow. NPY might be involved in the pathogenesis of METH-induced atherogenic effects through NPY Y1 receptor pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Promoting Holistic Well-Being in Chronic Stroke Patients Through Leisure Art-Based Creative Engagement.

    PubMed

    Sit, Janet W H; Chan, Amy W H; So, Winnie K W; Chan, Carmen W H; Chan, Aileen W K; Chan, Helen Y L; Fung, Olivia W M; Wong, Eliza M L

    2014-09-15

    To examine the potential value of a creative art-based activity as a caring modality for promoting holistic well-being among chronic stroke patients, and to explore the feelings and meanings that stroke patients derived from their experience in leisure art-based creative engagement (LACE). Qualitative design. Participants were recruited through purposive and snowball sampling. Individual semi-structured interviews were conducted. Qualitative content analysis was performed. The design and implementation of LACE was guided by Watson's theory of caring. Twenty-four participants completed the study. Four themes emerged from participants' account of experiences with the LACE: (1) appreciation of opportunities, (2) appreciation of self, (3) appreciation of others, and (4) appreciation of life. From the perspective of the participants, engaging in LACE enhances their sense of enjoyment and self-expression. Furthermore, they perceived LACE as an affirmation of life and an empowering process strengthening their connection and appreciation with the self and others. This study adds evidence to existing literature on Watson's theory-guided design and implementation of caring initiatives for community rehabilitation and has laid the groundwork for developing further evidence-based research in leisure art-based caring occasions for promoting holistic well-being in stroke rehabilitation. © 2014 Association of Rehabilitation Nurses.

  20. Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol.

    PubMed

    Lopez, M F; Becker, H C; Chandler, L J

    2014-11-01

    Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol

    PubMed Central

    Lopez, M. F.; Becker, H. C.; Chandler, L. J.

    2014-01-01

    Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. PMID:25266936

  2. A multi-interface adaptive hypermedia system to promote consumer-provider partnership in chronic disease management.

    PubMed

    Lundström, Maria; Warren, Jim; Jones, Sara; Chung, Frank

    2003-01-01

    Much of chronic disease management depends on active partnership of consumer and provider. Our system promotes diabetes management through profiling and adaptive support of both consumer and provider. We use a University Podiatry Clinic and diabetes consumer information portal as inter-related contexts that share profile information.

  3. Chronic alcohol intake promotes tumor growth in a diethylnitrosamine-induced hepatocarcinogenesis mouse model through increased Wnt/Beta-catenin signaling

    USDA-ARS?s Scientific Manuscript database

    Ethanol (EtOH) metabolism is involved in both initiating and promoting mechanisms in hepatocellular carcinoma progression in chronic alcoholics. In this study, we developed a mouse model to test the hypothesis that chronic EtOH consumption promotes tumor growth irrespective of EtOH-related initiati...

  4. [Health promotion and primary prevention strategies to fight chronic disease: a systematic review].

    PubMed

    da Silva, Luciana Saraiva; Cotta, Rosângela Minardi Mitre; Rosa, Carla de Oliveira Barbosa

    2013-11-01

    To analyze health promotion and primary prevention strategies in the global fight against chronic noncommunicable diseases (NCDs) and to reflect on the challenges of overcoming these diseases. In this systematic literature review, studies were analyzed on health programs identified by the Brazilian Health Ministry as the main global community intervention initiatives: the North Karelia Project, in Finland; the Stanford Three-Community Study, Stanford Five-City Project, Minnesota Heart Health and Pawtucket Heart Health Program, in the United States; the CINDI project, in Europe and Canada; CARMEN in South America; Mirame, in Chile; and Tianjin, in China. The LILACS, Medline, and SciELO databases were searched, as well as the Brazilian Health Ministry, Pan American Health Organization, and World Health Organization websites. Only original articles analyzing primary data were included. The outcomes evaluated in the studies were cholesterol, blood pressure, obesity, physical activity level, tobacco use, dietary habits, and other risk factors for NCDs. Seventeen studies were selected. The North Karelia Project, Three Community Study, and Five-City Multifactor Risk Reduction Project contributed to decrease tobacco use, cholesterol levels, and blood pressure levels. The Minnesota Heart Health Program and the Pawtucket Heart Health Program had moderate success in reducing the risk factors for NCD. The CINDI and CARMEN programs demonstrated the importance of integrated actions for decreasing the main risk factors. The Mirame project, which focused on educational interventions for school children, reached 30,000 students in 2001 without requiring a large financial investment. The Tianjin project was able to reduce salt intake, prevalence of arterial hypertension, and obesity by restructuring primary health care services. These successful experiences in community health improvement may serve as models for the implementation of more effective health policies, aiming at the

  5. User Requirements for a Chronic Kidney Disease Clinical Decision Support Tool to Promote Timely Referral.

    PubMed

    Gulla, Joy; Neri, Pamela M; Bates, David W; Samal, Lipika

    2017-05-01

    Timely referral of patients with CKD has been associated with cost and mortality benefits, but referrals are often done too late in the course of the disease. Clinical decision support (CDS) offers a potential solution, but interventions have failed because they were not designed to support the physician workflow. We sought to identify user requirements for a chronic kidney disease (CKD) CDS system to promote timely referral. We interviewed primary care physicians (PCPs) to identify data needs for a CKD CDS system that would encourage timely referral and also gathered information about workflow to assess risk factors for progression of CKD. Interviewees were general internists recruited from a network of 14 primary care clinics affiliated with Brigham and Women's Hospital (BWH). We then performed a qualitative analysis to identify user requirements and system attributes for a CKD CDS system. Of the 12 participants, 25% were women, the mean age was 53 (range 37-82), mean years in clinical practice was 27 (range 11-58). We identified 21 user requirements. Seven of these user requirements were related to support for the referral process workflow, including access to pertinent information and support for longitudinal co-management. Six user requirements were relevant to PCP management of CKD, including management of risk factors for progression, interpretation of biomarkers of CKD severity, and diagnosis of the cause of CKD. Finally, eight user requirements addressed user-centered design of CDS, including the need for actionable information, links to guidelines and reference materials, and visualization of trends. These 21 user requirements can be used to design an intuitive and usable CDS system with the attributes necessary to promote timely referral. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. A novel chronic stress-induced shift in the Th1 to Th2 response promotes colon cancer growth.

    PubMed

    Hou, Ni; Zhang, Xin; Zhao, Lingyu; Zhao, Xiaoge; Li, Zongfang; Song, Tusheng; Huang, Chen

    2013-10-04

    Epidemiological data have shown that stress and other psychological factors might influence cancer onset and progression. However, to date, the mechanisms are not well understood. In the present study, we used chronic exposure to a scream as a novel form of sound stress to explore the influence of the chronic stress burden on colon cancer progression, and changes in the immune system were observed. Chronic exposure to scream sound stress induced freezing behavior in the mice and decreased the bodyweight gain. It also caused changes in the adrenal gland and increased serum corticosterone and norepinephrine levels. Cytokine microarray analysis showed changes in the levels of Th1 and Th2 cytokines. The chronic scream sound stress caused a shift from the Th1 to the Th2 response both in the circulation and in tumor-infiltrated lymphocytes, and it promoted colon cancer progression significantly. Taken together, chronic scream sound stress can be conveniently used as a novel chronic stress model. Chronic stress contributes to colon cancer progression and induces a Th1/Th2 imbalance in the mouse immune system, which is considered critical during cancer progression. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Chronic Mineral Dysregulation Promotes Vascular Smooth Muscle Cell Adaptation and Extracellular Matrix Calcification

    PubMed Central

    Shroff, Rukshana C.; McNair, Rosamund; Skepper, Jeremy N.; Figg, Nichola; Schurgers, Leon J.; Deanfield, John; Rees, Lesley

    2010-01-01

    In chronic kidney disease (CKD) vascular calcification occurs in response to deranged calcium and phosphate metabolism and is characterized by vascular smooth muscle cell (VSMC) damage and attrition. To gain mechanistic insights into how calcium and phosphate mediate calcification, we used an ex vivo model of human vessel culture. Vessel rings from healthy control subjects did not accumulate calcium with long-term exposure to elevated calcium and/or phosphate. In contrast, vessel rings from patients with CKD accumulated calcium; calcium induced calcification more potently than phosphate (at equivalent calcium-phosphate product). Elevated phosphate increased alkaline phosphatase activity in CKD vessels, but inhibition of alkaline phosphatase with levamisole did not block calcification. Instead, calcification in CKD vessels most strongly associated with VSMC death resulting from calcium- and phosphate-induced apoptosis; treatment with a pan-caspase inhibitor ZVAD ameliorated calcification. Calcification in CKD vessels was also associated with increased deposition of VSMC-derived vesicles. Electron microscopy confirmed increased deposition of vesicles containing crystalline calcium and phosphate in the extracellular matrix of dialysis vessel rings. In contrast, vesicle deposition and calcification did not occur in normal vessel rings, but we observed extensive intracellular mitochondrial damage. Taken together, these data provide evidence that VSMCs undergo adaptive changes, including vesicle release, in response to dysregulated mineral metabolism. These adaptations may initially promote survival but ultimately culminate in VSMC apoptosis and overt calcification, especially with continued exposure to elevated calcium. PMID:19959717

  8. Cloning of the human TASK-2 (KCNK5) promoter and its regulation by chronic hypoxia

    SciTech Connect

    Brazier, Stephen P.; Mason, Helen S.; Bateson, Alan N.; Kemp, Paul J. . E-mail: Kemp@cf.ac.uk

    2005-11-04

    The tandem P domain potassium channel family includes five members of the acid-sensing subfamily, TASK. TASK channels are active at resting potential and are inhibited by extracellular protons, suggesting they function as acid sensors and control excitability/ion homeostasis. Indeed, TASK-2 (KCNK5) has been shown to control excitability, volume regulation, bicarbonate handling, and apoptosis in a variety of tissues. With such diverse functions being ascribed to TASK-2, it is important to understand long-term as well as short-term regulation of this important channel. Thus, we have cloned the TASK-2 promoter, demonstrated that its transcriptional activity is dependent upon pO{sub 2}, shown that deletion of overlapping consensus binding sites for NF-{kappa}B/Elk-1 ablates this O{sub 2} sensitivity, and proved that Elk-1 binds preferentially to this site. Furthermore, the consequences of chronic hypoxia on natively expressed TASK-2 are decreased steady-state mRNA and cell depolarization showing that TASK-2 contributes to the excitability of this important lung cell type.

  9. Quinacrine promotes replication and conformational mutation of chronic wasting disease prions.

    PubMed

    Bian, Jifeng; Kang, Hae-Eun; Telling, Glenn C

    2014-04-22

    Quinacrine's ability to reduce levels of pathogenic prion protein (PrP(Sc)) in mouse cells infected with experimentally adapted prions led to several unsuccessful clinical studies in patients with prion diseases, a 10-y investment to understand its mechanism of action, and the production of related compounds with expectations of greater efficacy. We show here, in stark contrast to this reported inhibitory effect, that quinacrine enhances deer and elk PrP(Sc) accumulation and promotes propagation of prions causing chronic wasting disease (CWD), a fatal, transmissible, neurodegenerative disorder of cervids of uncertain zoonotic potential. Surprisingly, despite increased prion titers in quinacrine-treated cells, transmission of the resulting prions produced prolonged incubation times and altered PrP(Sc) deposition patterns in the brains of diseased transgenic mice. This unexpected outcome is consistent with quinacrine affecting the intrinsic properties of the CWD prion. Accordingly, quinacrine-treated CWD prions were comprised of an altered PrP(Sc) conformation. Our findings provide convincing evidence for drug-induced conformational mutation of prions without the prerequisite of generating drug-resistant variants of the original strain. More specifically, they show that a drug capable of restraining prions in one species/strain setting, and consequently used to treat human prion diseases, improves replicative ability in another and therefore force reconsideration of current strategies to screen antiprion compounds.

  10. Development and Validation of an Online Program for Promoting Self-Management among Korean Patients with Chronic Hepatitis B.

    PubMed

    Yang, Jinhyang

    2013-01-01

    The hepatitis B virus is second only to tobacco as a known human carcinogen. However, chronic hepatitis B usually does not produce symptoms and people feel healthy even in the early stages of live cancer. Therefore, chronically infected people should perceive it as a serious health problem and move on to appropriate health behaviour. The purpose of this paper is to develop and validate an online program for promoting self-management among Korean patients with chronic hepatitis B. The online program was developed using a prototyping approach and system developing life cycle method, evaluated by users for their satisfaction with the website and experts for the quality of the site. To evaluate the application of the online program, knowledge and self-management compliance of the subjects were measured and compared before and after the application of the online program. There were statistically significant increases in knowledge and self-management compliance in the user group. An online program with high accessibility and applicability including information, motivation, and behavior skill factors can promote self-management of the patient with chronic hepatitis B. Findings from this study allow Korean patients with chronic hepatitis B to engage in proactive and effective health management in the community or clinical practice.

  11. Chronic Mycobacterium marinum Infection Acts as a Tumor Promoter in Japanese Medaka (Oryzias latipes)

    EPA Science Inventory

    An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several ...

  12. Chronic Mycobacterium marinum Infection Acts as a Tumor Promoter in Japanese Medaka (Oryzias latipes)

    EPA Science Inventory

    An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several ...

  13. Ericksonian hypnosis in chronic care support groups: a Rogerian exploration of power and self-defined health-promoting goals.

    PubMed

    Larkin, Dorothy M

    2007-10-01

    This Rogerian study examined how traditional and Ericksonian hypnotherapeutic support groups facilitated self-defined health-promoting goals and power as knowing participation in change for 49 participants with chronic physical illness. The participants were randomly assigned to either a traditional support group or an Ericksonian hypnotherapeutic support group. Measurements of power and self-defined health-promoting goals were obtained seven times over a 10-week period. The results indicated that both the traditional support groups and the Ericksonian hypnotherapeutic support groups experienced significantly enhanced power and progressed significantly toward their health-promoting goals. Correlations for the self-defined health-promoting goals and power progressively and significantly increased through time. This study supports Barrett's claim that power relates to health.

  14. Chronic aerobic swimming exercise promotes functional and morphological changes in rat ileum

    PubMed Central

    da Cunha Araujo, Layanne Cabral; de Souza, Iara Leão Luna; Vasconcelos, Luiz Henrique César; de Freitas Brito, Aline; Queiroga, Fernando Ramos; Silva, Alexandre Sérgio; da Silva, Patrícia Mirella; de Andrade Cavalcante, Fabiana; da Silva, Bagnólia Araújo

    2015-01-01

    Several studies have reported the gastrointestinal (GI) effects promoted by the physical exercise. Thus, we aimed to evaluate the influence of swimming exercise on the contractile reactivity, lipid peroxidation and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and groups exercised for two (EX2), four (EX4), six (EX6) or eight (EX8) weeks, 5 days/week. Animals were killed; the ileum was removed and suspended in organ baths where the isotonic contractions were recorded. Lipid peroxidation was evaluated by MDA (malondialdehyde) measurement with TBARS (thiobarbituric acid reactive substances) assay and morphology by histological staining. Cumulative concentration-response curves to KCl were attenuated, as the Emax values were changed from 100% (SED) to 63.1±3.9 (EX2), 48.8±3.8 (EX4), 19.4±1.8 (EX6) and 59.4±2.8% (EX8). Similarly, cumulative concentration-response curves to carbamylcholine hydrochloride (CCh) were attenuated, as the Emax values were changed from 100% (SED) to 74.1±5.4 (EX2), 75.9±5.2 (EX4) and 62.9±4.6 (EX6), but not in the EX8 (89.7±3.4%). However, CCh potency was increased in this latter, as the EC50 was altered from 1.0±0.1×10−6 (SED) to 2.1±0.4×10−7 (EX8). MDA concentration was altered only in EX4 (44.3±4.4) compared with SED (20.6±3.6 μmol/l). Circular layer was reduced in SED when compared with the exercised groups. Conversely, longitudinal layer was increased. In conclusion, chronic swimming exercise reduces the ileum contraction, equilibrates the oxidative damage and promotes changes in tissue size to establish an adaptation to the exercise. PMID:26424698

  15. Association of promoter polymorphisms of Fas -FasL genes with development of Chronic Myeloid Leukemia.

    PubMed

    Edathara, Prajitha Mohandas; Gorre, Manjula; Kagita, Sailaja; Vuree, Sugunakar; Cingeetham, Anuradha; Nanchari, Santhoshi Rani; Meka, Phanni Bhushann; Annamaneni, Sandhya; Digumarthi, Raghunadha Rao; Satti, Vishnupriya

    2016-04-01

    Chronic myeloid leukemia (CML) is a monoclonal myeloproliferative disorder of hematopoietic stem cells (HSCs), characterized by reciprocal translocation, leading to the formation of BCR-ABL oncogene with constitutive tyrosine kinase (TK) activity. This oncogene is known to deregulate different downstream pathways which ultimately lead to cell proliferation, defective DNA repair, and inhibition of apoptosis. Fas (Fas cell surface death receptor) is a member of tumor necrosis factor (TNF) superfamily which interacts with its ligand, FasL, to initiate apoptosis. Promoter polymorphisms in Fas-FasL genes are known to influence the apoptotic signaling. Hence, the present study has been aimed to find out the association of the promoter polymorphisms in Fas and FasL genes with the development and progression of CML. Blood samples from 772 subjects (386 controls and 386 cases) were collected and genotyped for Fas-FasL gene polymorphisms through PCR-RFLP method. The association between SNPs and clinical outcome was analyzed using statistical softwares like SPSS version 20, SNPSTATs, and Haploview 2.1. The study revealed a significant association of Fas -670 G>A and FasL -844 T>C polymorphisms with the development of CML while Fas -670 AG was associated with accelerated phase. Combined risk analysis by taking the risk genotypes in cases and controls revealed a significant increase in CML risk with increase in number of risk genotypes (one risk genotype-OR 1.99 (1.44-2.76), p < 0.0001; two risk genotypes-OR 3.33 (1.91-5.81), p < 0.0001). Kaplan-Meier survival analysis of Fas -670 A>G and FasL -844 T>C showed reduced event-free survival in patients carrying the variant genotypes, Fas -670 GG, 32.363 ± 6.33, and FasL -844 CC, 33.489 ± 5.83, respectively. Our findings revealed a significant association of Fas -670 GG, FasL -844 TC, and CC genotypes with increased risk of CML.

  16. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism.

    PubMed

    Raimondo, Stefania; Saieva, Laura; Corrado, Chiara; Fontana, Simona; Flugy, Anna; Rizzo, Aroldo; De Leo, Giacomo; Alessandro, Riccardo

    2015-02-03

    Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder in which leukemic cells display a reciprocal t(9:22) chromosomal translocation that results in the formation of the chimeric BCR-ABL oncoprotein, with a constitutive tyrosine kinase activity. Consequently, BCR-ABL causes increased proliferation, inhibition of apoptosis, and altered adhesion of leukemic blasts to the bone marrow (BM) microenvironment. It has been well documented that cancer cells can generate their own signals in order to sustain their growth and survival, and recent studies have revealed the role of cancer-derived exosomes in activating signal transduction pathways involved in cancer cell proliferation. Exosomes are small vesicles of 40-100 nm in diameter that are initially formed within the endosomal compartment, and are secreted when a multivesicular body (MVB) fuses with the plasma membrane. These vesicles are released by many cell types including cancer cells, and are considered messengers in intercellular communication. We have previously shown that CML cells released exosomes able to affect the tumor microenvironment. CML cells, exposed up to one week, to exosomes showed a dose-dependent increased proliferation compared with controls. Moreover, exosome treatment promotes the formation of LAMA84 colonies in methylcellulose. In a CML xenograft model, treatment of mice with exosomes caused a greater increase in tumor size compared with controls (PBS-treated mice). Real time PCR and Western Blot analysis showed, in both in vitro and in vivo samples, an increase in mRNA and protein levels of anti-apoptotic molecules, such as BCL-w, BCL-xl, and survivin, and a reduction of the pro-apoptotic molecules BAD, BAX and PUMA. We also found that TGF- β1 was enriched in CML-exosomes. Our investigations showed that exosome-stimulated proliferation of leukemia cells, as well as the exosome-mediated activation of an anti-apoptotic phenotype, can be inhibited by blocking TGF-β1

  17. Ibrutinib synergizes with MDM-2 inhibitors in promoting cytotoxicity in B chronic lymphocytic leukemia

    PubMed Central

    Melloni, Elisabetta; Rigolin, Gian Matteo; Casciano, Fabio; Arcidiacono, Maria Vittoria; Celeghini, Claudio; Cuneo, Antonio; Zauli, Giorgio; Secchiero, Paola

    2016-01-01

    Objective The aim of this study was to investigate the anti-leukemic activity of the Bruton tyrosine kinase inhibitor Ibrutinib in combination with the small molecule MDM-2 inhibitor Nutlin-3 in preclinical models. Methods The potential efficacy of the Ibrutinib/Nutlin-3 combination was evaluated in vitro in a panel of B leukemic cell lines (EHEB, JVM-2, JVM-3, MEC-1, MEC-2) and in primary B-chronic lymphocytic leukemia (B-CLL) patient samples, by assessing cell viability, cell cycle profile, apoptosis and intracellular pathway modulations. Validation of the combination therapy was assessed in a B leukemic xenograft mouse model. Results Ibrutinib exhibited variable anti-leukemic activity in vitro and the combination with Nutlin-3 synergistically enhanced the induction of apoptosis independently from the p53 status. Indeed, the Ibrutinib/Nutlin-3 combination was effective in promoting cytotoxicity also in primary B-CLL samples carrying 17p13 deletion and/or TP53 mutations, already in therapy with Ibrutinib. Molecular analyses performed on both B-leukemic cell lines as well as on primary B-CLL samples, while confirming the switch-off of the MAPK and PI3K pro-survival pathways by Ibrutinib, indicated that the synergism of action with Nutlin-3 was independent by p53 pathway and was accompanied by the activation of the DNA damage cascade signaling through the phosphorylation of the histone protein H2A.X. This observation was confirmed also in the JVM-2 B leukemic xenograft mouse model. Conclusions Taken together, our data emphasize that the Ibrutinib/Nutlin-3 combination merits to be further evaluated as a therapeutic option for B-CLL. PMID:27661115

  18. Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata.

    PubMed

    Li, Mingqiang; Nie, Lihong; Hu, Yajie; Yan, Xiang; Xue, Lian; Chen, Li; Zhou, Hua; Zheng, Yu

    2013-12-01

    The present experiments were carried out to investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of rats and effects of chronic intermittent hypoxia (CIH) on its expression. Sprague Dawley adult rats were randomly divided into two groups, including control (Con) group and CIH group. The endogenous production of hydrogen sulfide (H2S) in medulla oblongata tissue homogenates was measured using the methylene blue assay method, 3MST mRNA and protein expression were analyzed by RT-PCR and Western blotting, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of rats was investigated with immunohistochemical technique. CIH elevated the endogenous H2S production in rat medulla oblongata (P<0.01). The RT-PCR and Western blotting analyses showed that 3MST mRNA and protein were expressed in the medulla oblongata of rats and CIH promoted their expression (P<0.01). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N and Amb, but not in FN and NTS, were significantly increased in CIH group (P<0.05). In conclusion, 3MST exists in the neurons of medullary respiratory nuclei and its expression can be up-regulated by CIH in adult rat, suggesting that 3MST-H2S pathway may be involved in regulation of respiration and protection on medullary respiratory centers from injury induced by CIH.

  19. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  20. TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

    PubMed

    Miao, Xu-Hong; Wang, Chun-Guo; Hu, Bao-Quan; Li, Ai; Chen, Cheng-Bin; Song, Wen-Qin

    2010-01-01

    The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal function. (2) The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3) TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

  1. Self-efficacy: a useful construct to promote physical activity in people with stable chronic heart failure.

    PubMed

    Du, HuiYun; Everett, Bronwyn; Newton, Phillip J; Salamonson, Yenna; Davidson, Patricia M

    2012-02-01

    To explore the conceptual underpinnings of self-efficacy to address the barriers to participating in physical activity and propose a model of intervention. The benefits of physical activity in reducing cardiovascular risk have led to evidence-based recommendations for patients with heart disease, including those with chronic heart failure. However, adherence to best practice recommendations is often suboptimal, particularly in those individuals who experience high symptom burden and feel less confident to undertake physical activity. Self-efficacy is the degree of confidence an individual has in his/her ability to perform behaviour under several specific circumstances. Four factors influence an individual's level of self-efficacy: (1) past performance, (2) vicarious experience, (3) verbal persuasion and (4) physiological arousal. Discursive. Using the method of a discursive paper, this article seeks to explore the conceptual underpinnings of self-efficacy to address the barriers to participating in physical activity and proposes a model of intervention, the Home-Heart-Walk, to promote physical activity and monitor functional status. Implementing effective interventions to promote physical activities require appreciation of factors impacting on behaviour change. Addressing concepts relating to self-efficacy in physical activity interventions may promote participation and adherence in the longer term. The increasing burden of chronic disease and the emphasis on self-management strategies underscore the importance of promoting adherence to recommendations, such as physical activity. © 2011 Blackwell Publishing Ltd.

  2. Chronic high levels of the RCAN1-1 protein may promote neurodegeneration and Alzheimer disease.

    PubMed

    Ermak, Gennady; Davies, Kelvin J A

    2013-09-01

    The RCAN1 gene encodes three different protein isoforms: RCAN1-4, RCAN1-1L, and RCAN1-1S. RCAN1-1L is the RCAN1 isoform predominantly expressed in human brains. RCAN1 proteins have been shown to regulate various other proteins and cellular functions, including calcineurin, glycogen synthase kinase-3β (GSK-3β), the mitochondrial adenine nucleotide transporter (ANT), stress adaptation, ADP/ATP exchange in mitochondria, and the mitochondrial permeability transition pore (mtPTP). The effects of increased RCAN1 gene expression seem to depend both on the specific RCAN1 protein isoform(s) synthesized and on the length of time the level of each isoform is elevated. Transiently elevated RCAN1-4 and RCAN1-1L protein levels, lasting just a few hours, can be neuroprotective under acute stress conditions, including acute oxidative stress. We propose that, by transiently inhibiting the phosphatase calcineurin, RCAN1-4 and RCAN1-1L may reinforce and extend protective stress-adaptive cell responses. In contrast, prolonged elevation of RCAN1-1L levels is associated with the types of neurodegeneration observed in several diseases, including Alzheimer disease and Down syndrome. RCAN1-1L levels can also be increased by multiple chronic stresses and by glucocorticoids, both of which can cause neurodegeneration. Although increasing levels of RCAN1-1L for just a few months has no overtly obvious neurodegenerative effect, it does suppress neurogenesis. Longer term elevation of RCAN1-1L levels (for at least 16 months), however, can lead to the first signs of neurodegeneration. Such neurodegeneration may be precipitated by (RCAN1-1L-mediated) prolonged calcineurin inhibition and GSK-3β induction/activation, both of which promote tau hyperphosphorylation, and/or by (RCAN1-1L-mediated) effects on the mitochondrial ANT, diminished ATP/ADP ratio, opening of the mtPTP, and mitochondrial autophagy. We propose that RCAN1-1L operates through various molecular mechanisms, primarily dependent upon

  3. Transplants of Neurotrophin-Producing Autologous Fibroblasts Promote Recovery of Treadmill Stepping in the Acute, Sub-Chronic, and Chronic Spinal Cat.

    PubMed

    Krupka, Alexander J; Fischer, Itzhak; Lemay, Michel A

    2017-05-15

    Adult cats show limited spontaneous locomotor capabilities following spinal transection, but recover treadmill stepping with body-weight-supported training. Delivery of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT-3) can substitute for body-weight-supported training, and promotes a similar recovery in a shorter period of time. Autologous cell grafts would negate the need for the immunosuppressive agents currently used with most grafts, but have not shown functional benefits in incomplete spinal cord injury models and have never been tested in complete transection or chronic injury models. In this study, we explored the effects of autologous fibroblasts, prepared from the individual cats and modified to produce BDNF and NT-3, on the recovery of locomotion in acute, sub-chronic and chronic full-transection models of spinal injury. Fourteen female cats underwent complete spinal transection at T11/T12. Cats were separated into four groups: sham graft at the time of injury, and BDNF and NT-3 producing autologous fibroblasts grafted at the time of injury, 2 weeks after injury, or 6 weeks after injury. Kinematics were recorded 3 and 5 weeks after cell graft. Additional kinematic recordings were taken for some cats until 12 weeks post-graft. Eleven of 12 cats with neurotrophin-producing grafts recovered plantar weight-bearing stepping at treadmill speeds from 0.3 to 0.8 m/sec within 5 weeks of grafting, whereas control cats recovered poor quality stepping at low speeds only (≤ 0.4 m/sec). Further, kinematic measures in cats with grafts were closer to pre-transection values than those for controls, and recovery was maintained up to 12 weeks post-grafting. Our results show that not only are autologous neurotrophin-producing grafts effective at promoting recovery of locomotion, but that delayed delivery of neurotrophins does not diminish the therapeutic effect, and may improve outcome.

  4. Expression and regulation of COP1 in chronic lymphocytic leukemia cells for promotion of cell proliferation and tumorigenicity.

    PubMed

    Fu, Chunling; Gong, Yanqing; Shi, Xuanxuan; Shi, Hengliang; Wan, Yan; Wu, Qingyun; Xu, Kailin

    2016-03-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis. The aberration of proliferation-related gene in CLL cells induces cell arrest at G0/G1 phase, or a small section shows rapid cell growth, which further complicates the pathogenesis of CLL. The constitutively photomorphogenic 1 (COP1), as an E3 ubiquitin ligase, is involved in many biological processes in mammalian cells, but its role in chronic lymphocytic leukemia (CLL) progression remains unclear. In the present study, we analyzed the expression of COP1 in peripheral blood mononuclear cells (PBMCs) from 23 CLL patients and 3 healthy donors. The observed upregulated expression of COP1 in CLL patients was positively correlated with CLL clinical stage and ZAP-70 expression, but not del(13q14) and del(17q-). Overexpression of COP1 significantly promoted cell colony formation and proliferation, especially contributing to the accumulation of cells in S-phase by inhibition of FoxO1 and p21. Moreover, overexpression of COP1 accelerated tumorigenicity of HG3 cells and promoted xenograft growth. Therefore, the present study revealed that COP1 plays an important role in CLL cell proliferation and tumorigenicity, and may be a useful indicator of the chronic lymphocytic leukemia processes.

  5. Elevated endothelial HIF-1α contributes to glomerular injury and promotes hypertensive chronic kidney disease

    PubMed Central

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K.; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2016-01-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1alpha is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with RT-PCR profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by Ang II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. PMID:25987665

  6. Position of the Academy of Nutrition and Dietetics: the role of nutrition in health promotion and chronic disease prevention.

    PubMed

    Slawson, Deborah Leachman; Fitzgerald, Nurgul; Morgan, Kathleen T

    2013-07-01

    It is the position of the Academy of Nutrition and Dietetics that primary prevention is the most effective and affordable method to prevent chronic disease, and that dietary intervention positively impacts health outcomes across the life span. Registered dietitians and dietetic technicians, registered are critical members of health care teams and are essential to delivering nutrition-focused preventive services in clinical and community settings, advocating for policy and programmatic initiatives, and leading research in disease prevention and health promotion. Health-promotion and disease-prevention strategies are effective at reducing morbidity and mortality and improving quality of life, and have a significant impact on the leading causes of disease. By applying these principles within a social ecological theoretical framework, positive influence can be applied across the spectrum of engagement: at intrapersonal, interpersonal, institutional, community, and public policy levels. Through the application of efficacious and cost-effective interventions, registered dietitians and dietetic technicians, registered, can positively impact public health as well as health outcomes for the individuals that they counsel. This position paper supports the "Practice Paper of the Academy of Nutrition and Dietetics: The Role of Nutrition in Health Promotion and Chronic Disease Prevention" published on the Academy's website at: www.eatright.org/positions.

  7. Promoting culturally targeted chronic disease prevention research through an adapted participatory research approach: The Qassim-Stanford Universities project.

    PubMed

    Winter, Sandra J; King, Abby C; Stafford, Randall S; Winkleby, Marilyn A; Haskell, William L; Farquhar, John W

    2011-06-01

    The Kingdom of Saudi Arabia (KSA), similar to other countries in the Eastern Mediterranean, has been experiencing a recent rapid increase in the prevalence of chronic diseases and associated risk factors. To begin to take advantage of the chronic disease prevention and health promotion (CDPHP) knowledge available from other nations, researchers at a newly established University in the Qassim Province of the KSA have partnered with Stanford University in the United States of America. To ensure that CDPHP research and interventions are culturally relevant and appropriate, a participatory research approach has been adopted where local researchers are the target "community." Contextual challenges of conducting CDPHP research in the KSA, at the individual, social/cultural, organizational and environmental/policy levels, are identified, as well as examples of CDPHP intervention strategies that may be culturally appropriate at each level.

  8. [Strategies to promote self-esteem, autonomy and self-care practices for people with chronic wounds].

    PubMed

    Bedin, Liarine Fernandes; Busanello, Josefine; Sehnem, Graciela Dutra; Da Silva, Fernanda Machado; Poll, Márcia Adriana

    2014-09-01

    This is a qualitative study of an exploratory nature that aims to identify the strategies used by nurses in primary care, in situations involving nursing care, to promote self-esteem, autonomy and self-care practices for people with chronic wounds. The study included eight nurses. Data were collected by means of a focus group in July 2012. The thematic analysis technique was used to identify the following categories: Nursing care from the perspective of comprehensiveness; Recovering support networks: family and social movements; Multidisciplinary work; Autonomy and nurses. It was concluded that the presented strategies value, above all, the social environment of these individuals, the family, religion and the nurse's approximation to the realities of people with chronic wounds.

  9. Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma.

    PubMed

    Murata, Miki; Yoshida, Katsunori; Yamaguchi, Takashi; Matsuzaki, Koichi

    2014-11-07

    Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.

  10. Interleukin-6 promoter polymorphism (-174 G/C) in Indian patients with chronic periodontitis.

    PubMed

    Kalburgi, Nagaraj B; Bhatia, Aman; Bilichodmath, Shivaprasad; Patil, Sudhir R; Mangalekar, Sachin B; Bhat, Kishore

    2010-09-01

    Recent studies have focused on genetic polymorphism of the interleukin-6 (IL-6) gene, which has led to a better understanding of the intricate interactions between host response, microorganisms, and genetics. Genotype prevalence appears to vary by the race and ethnicity of the population studied. We used a polymerase chain reaction technique to determine the prevalence of single nucleotide polymorphism in IL-6 at position -174 G>C in a population of 30 South Indians. Blood samples were collected from 15 chronic periodontitis patients and 15 healthy controls. The results showed that the G/G genotype was significantly more frequent in the chronic periodontitis group and that the C/C genotype was significantly more frequent in the control group (P = 0.0069 for both). The G allele was more frequent in chronic periodontitis patients (76.67%), whereas the C allele was more frequent in the control group (73.33%). Among chronic periodontitis patients, the odds ratio for having the G allele, as compared with the controls, was 9.04. In this population, the presence of the G/G genotype of IL-6 (-174) might increase susceptibility to chronic periodontitis, whereas the C/C genotype may have a protective effect.

  11. Chronic care management of globesity: promoting healthier lifestyles in traditional and mHealth based settings

    PubMed Central

    Castelnuovo, Gianluca; Pietrabissa, Giada; Manzoni, Gian Mauro; Corti, Stefania; Ceccarini, Martina; Borrello, Maria; Giusti, Emanuele M.; Novelli, Margherita; Cattivelli, Roberto; Middleton, Nicole A.; Simpson, Susan G.; Molinari, Enrico

    2015-01-01

    Obesity and being overweight could be real chronic conditions above all if there are other complications such as type 2 diabetes, cardiovascular diseases, hypertension, dyslipidemia, hypercholesterolemia, cancer, and various psychosocial and psychopathological disorders. Due to the multifactorial etiology of obesity, evidence-based interventions to improve weight loss, maintain a healthy weight, and reduce related comorbidities combine different treatment approaches: dietetic, nutritional, physical, behavioral, psychological, and, in some situations, pharmacological and surgical. There are significant limitations in this multidisciplinary chronic care management of obesity, most notably those regarding costs and long-term adherence and efficacy. Programs including eHealth platforms and new technologies could overcome limitations connected to the traditional in-patient chronic care management of obesity, thus providing promising opportunities in enhancing weight reduction and reducing complications in terms of long-term efficacy and effectiveness across clinical, organizational, and economic perspectives. PMID:26528215

  12. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination

    PubMed Central

    Le, Caroline P.; Nowell, Cameron J.; Kim-Fuchs, Corina; Botteri, Edoardo; Hiller, Jonathan G.; Ismail, Hilmy; Pimentel, Matthew A.; Chai, Ming G.; Karnezis, Tara; Rotmensz, Nicole; Renne, Giuseppe; Gandini, Sara; Pouton, Colin W.; Ferrari, Davide; Möller, Andreas; Stacker, Steven A.; Sloan, Erica K.

    2016-01-01

    Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes. PMID:26925549

  13. Role of Interleukin-10 Gene Promoter Region Polymorphism in the Development of Chronic Lymphoid Leukemia.

    PubMed

    Ovsepyan, V A; Gabdulkhakova, A Kh; Shubenkiva, A A; Zotina, E N

    2015-12-01

    Relationship between interleukin-10 (IL-10) gene G-1082A (rs1800896) polymorphism and the risk of development and stages of chronic lymphoid leukemia is studied in ethnic Russian residents of the Kirov region of Russia. Associations of allele -1082A and genotypes (-1082AA/-1082AG) with the risk of chronic lymphoid leukemia are detected (OR=1.39, 95%CI=1.09-1.78 and OR=1.66, 95%CI=1.09-2.54, respectively). In addition, association of 1082AA genotype with late stages of the disease by the moment of diagnosis is detected. These data indicate that IL-10 polymorphism G-1082A may be involved in the pathogenesis of chronic lymphoid leukemia.

  14. Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery.

    PubMed

    Ferrer, Lucas M; Monroy, Alexandra M; Lopez-Pastrana, Jahaira; Nanayakkara, Gayani; Cueto, Ramon; Li, Ya-Feng; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng; Choi, Eric T

    2016-04-01

    To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase(-/-) mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase(-/-) mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase(-/-) tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.

  15. IL-18 promoter -137G/C polymorphism correlates with chronic hepatitis B and affects the expression of interleukins.

    PubMed

    Jiang, H; Cao, H; Liu, G; Huang, Q; Li, Y

    2014-01-01

    The relationship between the interleukin (IL)-18 promoter -137G/C polymorphism and plasma levels of IL-18, IL-12, IL-4, and IFN-γ in chronic hepatitis B (CHB) patients and healthy subjects was investigated. The polymorphism was genotyped by a ligase detection reaction-PCR (LDR-PCR), while the cytokines were assayed by ELISA. Compared with healthy subjects, CHB patients exhibited an increased frequency of the G allele, GG genotype and increased IL-4 levels, but decreased levels of IL-18, IL-12, and IFN-γ. A positive correlation for IL-18 ~ IL-12 ~ IFN-γ and a negative correlation for IL-18 ~ IL-4 were found. We conclude that the IL-18 promoter -137G polymorphisms correlated with CHB infection and influenced the expression of IL-18. The studied interleukins represent an immunomodulatory network that plays important roles in host immune responses to CHB infection.

  16. Promoting culturally competent chronic pain management using the clinically relevant continuum model.

    PubMed

    Monsivais, Diane B

    2011-06-01

    This article reviews the culture of biomedicine and current practices in pain management education, which often merge to create a hostile environment for effective chronic pain care. Areas of cultural tensions in chronic pain frequently involve the struggle to achieve credibility regarding one's complaints of pain (or being believed that the pain is real) and complying with pain medication protocols. The clinically relevant continuum model is presented as a framework allowing providers to approach care from an evidence-based, culturally appropriate (patient centered) perspective that takes into account the highest level of evidence available, provider expertise, and patient preferences and values. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Effectiveness of Smartphone Devices in Promoting Physical Activity and Exercise in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review.

    PubMed

    Martínez-García, María Del M; Ruiz-Cárdenas, Juan D; Rabinovich, Roberto A

    2017-10-01

    The objectives of this systematic review were to analyse existing evidence on the efficacy of smartphone devices in promoting physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) and to identify the validity and precision of their measurements. A systematic review was undertaken across nine electronic databases: WOS Core Collection, PubMed, CINAHL, AMED, Academic Search Complete, Cochrane Central Register of Controlled Trials, SciELO, LILACS and ScienceDirect. Randomized and non-randomized controlled clinical trials were identified. To obtain additional eligible articles, the reference lists of the selected studies were also checked. Eligibility criteria and risk of bias were assessed by two independent authors. A total of eight articles met eligibility criteria. The studies were focused on promoting PA (n  =  5) and the precision of device measurements (n = 3). The effectiveness of smartphones in increasing PA level (steps/day) at short and long term is very limited. Mobile-based exercise programs reported improvements in exercise capacity (i.e. incremental Shuttle-Walk-Test) at short and long term (18.3% and 21%, respectively). The precision of device measurements was good-to-excellent (r = 0.69-0.99); however, these data should be interpreted with caution due to methodological limitations of studies. The effectiveness of smartphone devices in promoting PA levels in patients with COPD is scarce. Further high-quality studies are needed to evaluate the effectiveness of smartphone devices in promoting PA levels. Registration number: CRD42016050048.

  18. Discipline and the Chronically Ill Child: What Are the Management Strategies To Promote Positive Patient Outcomes?

    ERIC Educational Resources Information Center

    Richardson, Rita C.

    This paper reviews various discipline models and applies them to obtaining cooperation and compliance with medical treatment of children with chronic and acute medical conditions, especially End-Stage Renal Disease (ESRD). The definition of Other Health Impairments in the Individuals with Disabilities Education Act is cited and related to the…

  19. IL8 Gene Promoter Polymorphism (rs4073) may Contributes to Chronic Periodontitis

    PubMed Central

    Andia, Denise C; de Oliveira, Naila F P; Letra, Ariadne M; Júnior, Francisco H Nociti; Line, Sergio R Ps; de Souza, Ana P

    2011-01-01

    Background The proinflammatory chemokine interleukin-8 (IL8) is important in the regulation of the inflammatory response. Single nucleotide polymorphism (SNP) rs4073 have shown that the A allele up regulates the IL8 levels after stimulation with lipopolysaccharides. We investigated the association of the SNP rs4073 with chronic periodontitis. Methods Genotyping was performed by standard polymerase chain reaction-restriction fragment length polymorphism assay in 289 genomic DNA samples of healthy control and chronic periodontitis patients; analyses were adjusted by the multivariate logistic regression modeling. Real-time PCR performance was used to detect the levels of the IL8 mRNA. Results Analysis points to a statistical significant association of chronic periodontitis with the heterozygous TA genotype (p = 0.001); the results showed an increase in the frequency of the A allele in the diseased group (36% in the control × 48% in the periodontitis group). The higher levels of the IL8 mRNA were found in the periodontitis group, mainly in individuals who presented the TA genotype (p=0.03). Conclusion The SNP rs4073 is associated with chronic periodontitis, in non-smoker Brazilian subjects, since the frequency of A allele is higher in the disease than control group and the TA genotype was associated with increased levels of IL8 mRNA transcripts. PMID:21091348

  20. Relational coordination promotes quality of chronic care delivery in Dutch disease-management programs.

    PubMed

    Cramm, Jane Murray; Nieboer, Anna Petra

    2012-01-01

    Previous studies have shown that relational coordination is positively associated with the delivery of hospital care, acute care, emergency care, trauma care, and nursing home care. The effect of relational coordination in primary care settings, such as disease-management programs, remains unknown. This study examined relational coordination between general practitioners and other professionals in disease-management programs and assessed the impact of relational coordination on the delivery of chronic illness care. Professionals (n = 188; response rate = 57%) in 19 disease-management programs located throughout the Netherlands completed surveys that assessed relational coordination and chronic care delivery. We used a cross-sectional study design. Our study demonstrated that the delivery of chronic illness care was positively related to relational coordination. We found positive relationships with community linkages (r = .210, p < .01), self-management support (r = .217, p < .01), decision support (r = .190, p < .01), delivery system design (r = .278, p < .001), and clinical information systems (r = .193, p < .01). Organization of the health delivery system was not significantly related to relational coordination. The regression analyses showed that even after controlling for all background variables, relational coordination still significantly affected chronic care delivery (β = .212, p ≤ .01). As expected, our findings showed a lower degree of relational coordination among general practitioners than between general practitioners and other core disease-management team members: practice nurses (M = 2.69 vs. 3.73; p < .001), dieticians (M = 2.69 vs. 3.07; p < .01), physical therapists (M = 2.69 vs. 3.06; p < .01), medical specialists (M = 2.69 vs. 3.16; p < .01), and nurse practitioners (M = 2.69 vs. 3.19; p < .001). The enhancement of relational coordination among core disease-management professionals with different disciplines is expected to improve chronic

  1. Statewide community-based health promotion: a North Carolina model to build local capacity for chronic disease prevention.

    PubMed

    Plescia, Marcus; Young, Suzanna; Ritzman, Rosemary L

    2005-11-01

    Public health faces major challenges to building state and local infrastructure with the capacity to address the underlying causes of chronic disease. We describe a structured statewide approach to providing technical assistance for local communities to support and develop health promotion capacity. Over the last two decades, the North Carolina Statewide Health Promotion program has supported local approaches to the prevention and control of chronic disease. In 1999, a major change in the program required local health departments to focus on policy-change and environmental-change strategies for addressing three major risk factors: physical inactivity, poor diet, and tobacco use. State program consultants provided technical assistance and training opportunities to local programs on effective policy-change and environmental-change strategies and interventions, based on needs defined by a statewide monitoring and evaluation system. The percentage of health departments in North Carolina with interventions addressing at least one of three targeted risk factors in 2004 approached 100%; in 2001, this percentage was 62%. Additionally, between 2001 and 2004, the number of health departments reporting policy or environmental outcomes related to these risk factors almost doubled. Requiring local programs to implement policy-change and environmental-change interventions that address the three major behavioral risk factors provides an organized framework for accountability. An established reporting system guides technical assistance efforts and monitors their effectiveness based on standardized objectives that address the full scope of the socioecologic model.

  2. Toll-Like Receptor 4 Agonistic Antibody Promotes Host Defense against Chronic Pseudomonas aeruginosa Lung Infection in Mice

    PubMed Central

    Iwanaga, Naoki; Seki, Masafumi; Fukudome, Kenji; Oshima, Kazuhiro; Miyazaki, Taiga; Izumikawa, Koichi; Yanagihara, Katsunori; Miyazaki, Yoshitsugu; Mukae, Hiroshi; Kohno, Shigeru

    2016-01-01

    Chronic lower respiratory tract infection with Pseudomonas aeruginosa is difficult to treat due to enhanced antibiotic resistance and decreased efficacy of drug delivery to destroyed lung tissue. To determine the potential for restorative immunomodulation therapies, we evaluated the effect of Toll-like receptor 4 (TLR4) stimulation on the host immune response to Pseudomonas infection in mice. We implanted sterile plastic tubes precoated with P. aeruginosa in the bronchi of mice, administered the TLR4/MD2 agonistic monoclonal antibody UT12 intraperitoneally every week, and subsequently analyzed the numbers of viable bacteria and inflammatory cells and the levels of cytokines. We also performed flow cytometry-based phagocytosis and opsonophagocytic killing assays in vitro using UT12-treated murine peritoneal neutrophils. UT12-treated mice showed significantly enhanced bacterial clearance, increased numbers of Ly6G+ neutrophils, and increased concentrations of macrophage inflammatory protein 2 (MIP-2) in the lungs (P < 0.05). Depletion of CD4+ T cells eliminated the ability of the UT12 treatment to improve bacterial clearance and promote neutrophil recruitment and MIP-2 production. Additionally, UT12-pretreated peritoneal neutrophils exhibited increased opsonophagocytic killing activity via activation of the serine protease pathway, specifically neutrophil elastase activity, in a TLR4-dependent manner. These data indicated that UT12 administration significantly augmented the innate immune response against chronic bacterial infection, in part by promoting neutrophil recruitment and bactericidal function. PMID:27091927

  3. Social support: a key variable for health promotion and chronic disease management in Hispanic patients with rheumatic diseases.

    PubMed

    Brooks, Alyssa T; Andrade, Regina E; Middleton, Kimberly R; Wallen, Gwenyth R

    2014-01-01

    Chronic diseases, including rheumatic diseases, can cause immense physical and psychosocial burden for patients. Many Hispanics suffering with arthritis face activity limitations. Social support, or the functional content of relationships, may be important to consider when examining treatment and outcomes for Hispanic individuals. Participants were recruited from an urban community health center (CHC) as part of a larger health behavior study. A cross-sectional, descriptive, mixed methods analysis was conducted to explore the role of social support in the sample. Only Hispanic/Latino patients (n = 46) were included in this analysis. Interviews were conducted in both English and Spanish. The majority of the sample (87%) perceived some presence of social support in their lives. The two most commonly cited types of social support were emotional and instrumental. The two most common sources of social support were family members other than spouses (52.2%) and spouses (32.6%). Body mass index (BMI) was significantly correlated with the number of perceived sources of support. The presence or absence and the role of social support in supporting optimal health outcomes should be considered for Hispanics with chronic rheumatic diseases. Involving family members and spouses in the plan of care for this population could facilitate health promotion and chronic disease management.

  4. Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation.

    PubMed

    Shukla, Pradeep K; Chaudhry, Kamaljit K; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S; Rao, RadhaKrishna

    2016-03-07

    Alcohol consumption is one of the major risk factors for colorectal cancer. However, the mechanism involved in this effect of alcohol is unknown. We evaluated the effect of chronic ethanol feeding on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in mouse colon. Inflammation in colonic mucosa was assessed at a precancerous stage by evaluating mucosal infiltration of neutrophils and macrophages, and analysis of cytokine and chemokine gene expression. Chronic ethanol feeding significantly increased the number and size of polyps in colon of AOM/DSS treated mice. Confocal microscopic and immunoblot analyses showed a significant elevation of phospho-Smad, VEGF and HIF1α in the colonic mucosa. RT-PCR analysis at a precancerous stage indicated that ethanol significantly increases the expression of cytokines IL-1α, IL-6 and TNFα, and the chemokines CCL5/RANTES, CXCL9/MIG and CXCL10/IP-10 in the colonic mucosa of AOM/DSS treated mice. Confocal microscopy showed that ethanol feeding induces a dramatic elevation of myeloperoxidase, Gr1 and CD68-positive cells in the colonic mucosa of AOM/DSS-treated mice. Ethanol feeding enhanced AOM/DSS-induced suppression of tight junction protein expression and elevated cell proliferation marker, Ki-67 in the colonic epithelium. This study demonstrates that chronic ethanol feeding promotes colonic tumorigenesis potentially by enhancing inflammation and elevation of proinflammatory cytokines and chemokines.

  5. Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity.

    PubMed

    Lang, Philipp A; Lang, Karl S; Xu, Haifeng C; Grusdat, Melanie; Parish, Ian A; Recher, Mike; Elford, Alisha R; Dhanji, Salim; Shaabani, Namir; Tran, Charles W; Dissanayake, Dilan; Rahbar, Ramtin; Ghazarian, Magar; Brüstle, Anne; Fine, Jason; Chen, Peter; Weaver, Casey T; Klose, Christoph; Diefenbach, Andreas; Häussinger, Dieter; Carlyle, James R; Kaech, Susan M; Mak, Tak W; Ohashi, Pamela S

    2012-01-24

    Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease. Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus. NK cell-deficient (Nfil3(-/-), E4BP4(-/-)) mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILE-infected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore, we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.

  6. [Using the health literacy concept to promote self-management in a chronic kidney disease patient].

    PubMed

    Sun, Jia-Hui; Lin, Chiu-Chu

    2014-02-01

    Patients with chronic kidney disease (CKD) must learn and use self-management skills to control their disease and delay disease progression. Comprehension of instructions is thus critical to integrating self-management principles into daily life. In this case report, the client had difficulty implementing the behavioral changes necessary to control diet and blood sugar due to the lack of proper and sufficient information. The authors applied health literacy concepts to assess the client's knowledge and skills related to disease control and then provided health teaching at a level appropriate to the client's health literacy level. This individualized care enhanced the client's confidence and motivation to implement self-care activities. Healthcare professionals should help patients overcome barriers to reading and verbal communication to help low-health-literacy patients successfully self-manage their chronic disease. Clients may thus learn to report their symptoms clearly and accurately.

  7. Chronic social isolation suppresses proplastic response and promotes proapoptotic signalling in prefrontal cortex of Wistar rats.

    PubMed

    Djordjevic, Ana; Adzic, Miroslav; Djordjevic, Jelena; Radojcic, Marija B

    2010-08-15

    Successful adaptation to stress involves synergized actions of glucocorticoids and catecholamines at several levels of the CNS, including the prefrontal cortex (PFC). Inside the PFC, hormonal signals trigger concerted actions of transcriptional factors, such as glucocorticoid receptor (GR) and nuclear factor kappa B (NFkappaB), culminating in a balanced, proadaptive expression of their common genes, such as proplastic NCAM and/or apoptotic Bax and Bcl-2. In the present study, we hypothesized that chronic stress may compromise the balance between GR and NFkappaB signals and lead to an altered/maladaptive expression of their cognate genes in the PFC. Our results obtained with Wistar rats exposed to chronic social isolation indicated alterations of the GR relative to the NFkappaB, in favor of the GR, in both the cytoplasmic and the nuclear compartments of the PFC. Although these alterations did not affect the induction of proplastic NCAM gene, they decreased the NCAM sialylation necessary for plastic response and caused marked relocation of the mitochondrial membrane antiapoptotic Bcl-2 protein to its cytoplasmic form. Moreover, the compromised PSA-NCAM plastic response found under chronic stress was sustained after exposure of animals to the subsequent acute stress, whereas the proapoptotic signals were further emphasized. It is concluded that chronic social isolation of Wistar animals leads to a maladaptive response of the PFC, considering the diminishment of its plastic potential and potentiating of apoptosis. Such conditions in the PFC are likely to compromise its ability to interact with other CNS structures, such as the hippocampus, which is necessary for successful adaptation to stress.

  8. Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing.

    PubMed

    Carraro, Silvia; Scheltema, Nienke; Bont, Louis; Baraldi, Eugenio

    2014-12-01

    Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease often originate early in life. In addition to a genetic predisposition, prenatal and early-life environmental exposures have a persistent impact on respiratory health. Acting during a critical phase of lung development, these factors may change lung structure and metabolism, and may induce maladaptive responses to harmful agents, which will affect the whole lifespan. Some environmental factors, such as exposure to cigarette smoke, type of childbirth and diet, may be modifiable, but it is more difficult to influence other factors, such as preterm birth and early exposure to viruses or allergens. Here, we bring together recent literature to analyse the critical aspects involved in the early stages of lung development, going back to prenatal and perinatal events, and we discuss the mechanisms by which noxious factors encountered early on may have a lifelong impact on respiratory health. We briefly comment on the need for early disease biomarkers and on the possible role of "-omic" technologies in identifying risk profiles predictive of chronic respiratory conditions. Such profiles could guide the ideation of effective preventive strategies and/or targeted early lifestyle or therapeutic interventions. ©ERS 2014.

  9. Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord injury.

    PubMed

    Sadowsky, Cristina L; Hammond, Edward R; Strohl, Adam B; Commean, Paul K; Eby, Sarah A; Damiano, Diane L; Wingert, Jason R; Bae, Kyongtae T; McDonald, John W

    2013-11-01

    To examine the effect of long-term lower extremity functional electrical stimulation (FES) cycling on the physical integrity and functional recovery in people with chronic spinal cord injury (SCI). Retrospective cohort, mean follow-up 29.1 months, and cross-sectional evaluation. Washington University Spinal Cord Injury Neurorehabilitation Center, referral center. Twenty-five people with chronic SCI who received FES during cycling were matched by age, gender, injury level, and severity, and duration of injury to 20 people with SCI who received range of motion and stretching. Lower extremity FES during cycling as part of an activity-based restorative treatment regimen. Change in neurological function: motor, sensory, and combined motor-sensory scores (CMSS) assessed by the American Spinal Injury Association Impairment scale. Response was defined as ≥ 1 point improvement. FES was associated with an 80% CMSS responder rate compared to 40% in controls. An average 9.6 CMSS point loss among controls was offset by an average 20-point gain among FES subjects. Quadriceps muscle mass was on average 36% higher and intra/inter-muscular fat 44% lower, in the FES group. Hamstring and quadriceps muscle strength was 30 and 35% greater, respectively, in the FES group. Quality of life and daily function measures were significantly higher in FES group. FES during cycling in chronic SCI may provide substantial physical integrity benefits, including enhanced neurological and functional performance, increased muscle size and force-generation potential, reduced spasticity, and improved quality of life.

  10. Chronic Valproate Treatment Enhances Post-ischemic Angiogenesis and Promotes Functional Recovery in a Rat Model of Ischemic Stroke

    PubMed Central

    Wang, Zhifei; Tsai, Li-Kai; Munasinghe, Jeeva; Leng, Yan; Fessler, Emily Bame; Chibane, Fairouz; Leeds, Peter; Chuang, De-Maw

    2012-01-01

    Background and Purpose Enhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase (HDAC) inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke. Methods Male rats underwent middle cerebral artery occlusion (MCAO) for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function via rotarod test; infarct volume via T2-weighted magnetic resonance imaging; microvessel density via immunohistochemistry; relative cerebral blood flow (rCBF) via perfusion-weighted imaging; protein levels of pro-angiogenic factors via Western blotting; and matrix metalloproteinase (MMP)-2/9 activities via gelatin zymography. Results Post-ischemic VPA treatment robustly improved the rotarod performance of MCAO rats on days 7 and 14 after ischemia, and significantly reduced brain infarction on day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased rCBF in the ipsilateral cortex. The transcription factor hypoxia-inducible factor (HIF)-1α and its downstream pro-angiogenic factors, vascular endothelial growth factor (VEGF) and MMP-2/9, were upregulated after MCAO and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on rotarod performance and microvessel density were abolished by HIF-1α inhibition. Conclusions Chronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve HDAC inhibition and upregulation of HIF-1α and its downstream pro-angiogenic factors VEGF and MMP-2/9. PMID:22811460

  11. Stromal cell-derived factor-1 promotes human adipose tissue-derived stem cell survival and chronic wound healing

    PubMed Central

    LI, QIANG; GUO, YANPING; CHEN, FEIFEI; LIU, JING; JIN, PEISHENG

    2016-01-01

    Adipose tissue-derived stem cells (ADSCs) hold great potential for the stem cell-based therapy of cutaneous wound healing. Stromal cell-derived factor-1 (SDF-1) activates CXC chemokine receptor (CXCR)4+ and CXCR7+ cells and plays an important role in wound healing. Increasing evidence suggests a critical role for SDF-1 in cell apoptosis and the survival of mesenchymal stem cells. However, the function of SDF-1 in the apoptosis and wound healing ability of ADSCs is not well understood. The aim of this study was to analyze the effect of SDF-1 on the apoptosis and therapeutic effect of ADSCs in cutaneous chronic wounds in vitro and in vivos. By flow cytometric analysis, it was found that hypoxia and serum free promoted the apoptosis of ADSCs. When pretreated with SDF-1, the apoptosis of ADSCs induced by hypoxia and serum depletion was partly recovered. Furthermore, in vivo experiments established that the post-implantation cell survival and chronic wound healing ability of ADSCs were increased following pretreatment with SDF-1 in a diabetic mouse model of chronic wound healing. To explore the potential mechanism underlying the effect of SDF-1 on ADSC apoptosis, western blot analysis was employed and the results indicate that SDF-1 may protect against cell apoptosis in hypoxic and serum-free conditions through activation of the caspase signaling pathway in ADSCs. This study provides evidence that SDF-1 pretreatment can increase the therapeutic effect of ADSCs in cutaneous chronic wounds in vitro and in vivo. PMID:27347016

  12. Exercise Training and Recreational Activities to Promote Executive Functions in Chronic Stroke: A Proof-of-Concept Study

    PubMed Central

    Liu-Ambrose, Teresa; Eng, Janice J

    2015-01-01

    Background Stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. Both exercise and recreational activities are promising strategies. We assessed the effect of a six-month exercise and recreation program on executive functions in adults with chronic stroke. Methods A six-month ancillary study within a multi-centre randomized trial. Twenty-eight chronic stroke survivors (i.e., ≥ 12 months since an index stroke) were randomized to one of two experimental groups: intervention (INT; n=12) or delayed intervention (D-INT; n=16). Participants of the INT group received a six-month community-based structured program that included two sessions of exercise training and one session of recreation and leisure activities per week. Participants of the D-INT group received usual care. The primary outcome measure was the Stroop Test, a cognitive test of selective attention and conflict resolution. Secondary cognitive measures included set shifting and working memory. Mood, functional capacity, and general balance and mobility were additional secondary outcome measures. Results Compared with the D-INT group, the INT group significantly improved selective attention and conflict resolution (p=0.02), working memory (p=0.04), and functional capacity (p=0.02) at the end of the six-month intervention period. Improved selective attention and conflict resolution was significantly associated with functional capacity at six months (r=0.39; p=0.04). Conclusions This is the first randomized study to demonstrate that an exercise and recreation program can significantly benefit executive functions in community-dwelling chronic stroke survivors who are mildly cognitively impaired – a population at high-risk for dementia and functional decline. Thus, clinicians should consider prescribing exercise and recreational activities in the cognitive rehabilitation of chronic stroke survivors. Clinical Trial Registration http

  13. Predominance of precore mutations and clinical significance of basal core promoter mutations in chronic hepatitis B virus infection in Indonesia.

    PubMed

    Juniastuti; Utsumi, Takako; Aksono, Eduardus Bimo; Yano, Yoshihiko; Soetjipto; Hayashi, Yoshitake; Hotta, Hak; Rantam, Fedik Abdul; Kusumobroto, Hernomo Ontoseno; Lusida, Maria Inge

    2013-07-01

    Chronic hepatitis B virus (HBV) infection is a major health problem worldwide, with a particularly high prevalence in the Asian-Pacific region. During chronic hepatitis B virus (HBV) infection, mutations commonly occur in the basal core promoter (BCP) and precore (PC) regions of HBV, affecting HBeAg expression, particularly following HBeAg serocon-version. Mutations in the B- and T-cell epitopes of the HBV core have also been observed during disease progression. The clinical significance of HBV genome variability has been demonstrated, however the results are a subject of controversy. Considering the characteristics of the virus associated with geographical location, the profiles of BCP, PC and core mutations and their clinical implications in patients with chronic HBV infection in Surabaya, Indonesia, were investigated. The BCP, PC and core mutations and HBV genotypes were detected by direct sequencing. The HBeAg/anti-HBe status and HBV DNA levels were also assessed. This study enrolled 10 patients with chronic HBV infection (UC) from Dr Soetomo General Hospital and Indonesian Red Cross, Surabaya, East Java, Indonesia, 10 patients with chronic hepatitis B and liver cirrhosis (LC) and 4 patients with chronic hepatitis B and hepatocellular carcinoma (HCC) from Dr Soetomo General Hospital. The PC mutation A1896 was predominant in all the groups (60-100%), together with the PC variant T1858, which was associated with HBV genotype B. The number of detected core mutations (Thr/Ser130) was higher in HCC patients (50%). However, the BCP mutations T1762/A1764 were predominant in LC patients (50-60%). The LC and HCC patients carried HBV isolates with additional mutations, at least at BCP or PC, mainly following HBeAg seroconversion. In the majority of anti-HBe-positive samples, the BCP T1762/A1764 mutations were associated with a high viral load, regardless of the PC 1896 status. In conclusion, the PC mutations were found to be predominant in all the groups. However, the

  14. Predominance of precore mutations and clinical significance of basal core promoter mutations in chronic hepatitis B virus infection in Indonesia

    PubMed Central

    JUNIASTUTI; UTSUMI, TAKAKO; AKSONO, EDUARDUS BIMO; YANO, YOSHIHIKO; SOETJIPTO; HAYASHI, YOSHITAKE; HOTTA, HAK; RANTAM, FEDIK ABDUL; KUSUMOBROTO, HERNOMO ONTOSENO; LUSIDA, MARIA INGE

    2013-01-01

    Chronic hepatitis B virus (HBV) infection is a major health problem worldwide, with a particularly high prevalence in the Asian-Pacific region. During chronic hepatitis B virus (HBV) infection, mutations commonly occur in the basal core promoter (BCP) and precore (PC) regions of HBV, affecting HBeAg expression, particularly following HBeAg serocon-version. Mutations in the B- and T-cell epitopes of the HBV core have also been observed during disease progression. The clinical significance of HBV genome variability has been demonstrated, however the results are a subject of controversy. Considering the characteristics of the virus associated with geographical location, the profiles of BCP, PC and core mutations and their clinical implications in patients with chronic HBV infection in Surabaya, Indonesia, were investigated. The BCP, PC and core mutations and HBV genotypes were detected by direct sequencing. The HBeAg/anti-HBe status and HBV DNA levels were also assessed. This study enrolled 10 patients with chronic HBV infection (UC) from Dr Soetomo General Hospital and Indonesian Red Cross, Surabaya, East Java, Indonesia, 10 patients with chronic hepatitis B and liver cirrhosis (LC) and 4 patients with chronic hepatitis B and hepatocellular carcinoma (HCC) from Dr Soetomo General Hospital. The PC mutation A1896 was predominant in all the groups (60–100%), together with the PC variant T1858, which was associated with HBV genotype B. The number of detected core mutations (Thr/Ser130) was higher in HCC patients (50%). However, the BCP mutations T1762/A1764 were predominant in LC patients (50–60%). The LC and HCC patients carried HBV isolates with additional mutations, at least at BCP or PC, mainly following HBeAg seroconversion. In the majority of anti-HBe-positive samples, the BCP T1762/A1764 mutations were associated with a high viral load, regardless of the PC 1896 status. In conclusion, the PC mutations were found to be predominant in all the groups. However

  15. Single nucleotide polymorphism at −1087 locus of interleukin-10 gene promoter is associated with severe chronic periodontitis in nonsmoking patients

    PubMed Central

    Crena, Jasmine; Subramanian, Sangeetha; Victor, Dayanand John; Gnana, Prakash Ponnudurai Samuel; Ramanathan, Arvind

    2015-01-01

    Objective: Single nucleotide polymorphisms (SNPs) in the promoter region of interleukin (IL)-10 gene, which codes for the anti-inflammatory cytokine IL-10, have been associated with its level of production in chronic periodontitis. The prevalence of promoter SNP genotypes is known in other populations with chronic periodontitis, while its association in the Indian population is not known. Hence, the present study was designed to investigate the prevalence of IL-10 promoter polymorphism in a racially defined group of Indians with severe chronic periodontitis as the Indian population is known to be genetically diverse. Materials and Methods: Genomic deoxyribonucleic acid was extracted from 46 nonsmoking patients with severe chronic periodontitis and 45 subjects with healthy periodontium. A SNP locus at −1087 of IL-10 was chosen, as this locus has been frequently associated with chronic periodontitis in other population. Genotyping was carried out using allele-specific polymerase chain reaction (AS-PCR), and the frequencies of genotype were analyzed between the groups. Results: The distribution of genotype and allele frequencies showed significant differences between the study groups. The prevalence of genotype AA alleles at −1087 locus of IL-10 was significantly higher in severe chronic periodontitis patients compared to the healthy controls (P = 0.05). Conclusion: The study has identified a positive association between the occurrence of AA allele at −1087 locus of IL-10 gene and severe chronic periodontitis in nonsmoking patients. PMID:26430368

  16. Chronic alcohol consumption promotes hepatocarcinogenesis in mice through activation of beta-catenin.

    USDA-ARS?s Scientific Manuscript database

    Alcohol abuse is the most common cause of liver cancer in the United States, Although alcohol effects within the liver have been extensively studied, the mechanism by which alcohol causes liver cancer is complex. One mechanism involves speeding up tumor growth (promotion) by increasing the number of...

  17. Chronic alcohol consumption promotes hepatocarcinogenesis in mice through activation of beta-catenin

    USDA-ARS?s Scientific Manuscript database

    Alcohol abuse is the most common cause of liver cancer in the United States, Although alcohol effects within the liver have been extensively studied, the mechanism by which alcohol causes liver cancer is complex. One mechanism involves speeding up tumor growth (promotion) by increasing the number of...

  18. Promoting Health and Preventing Chronic Degenerative Pathologies for Elders: The Empirical Scenario in Italy

    ERIC Educational Resources Information Center

    Lucchetti, Maria; Mazzoni, Ermanna; Principi, Andrea; Greco, Cosetta

    2007-01-01

    The article provides an overview of health prevention programs implemented by local authorities to target the needs of older people in Italy. Interventions include health promotion and primary prevention, secondary prevention, and tertiary prevention. The most important characteristics of the interventions are described in terms of type, targets,…

  19. HOXA4 Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients

    PubMed Central

    Elias, Marjanu Hikmah; Baba, Abdul Aziz; Husin, Azlan; Sulong, Sarina; Hassan, Rosline; Sim, Goh Ai; Abdul Wahid, S. Fadilah; Ankathil, Ravindran

    2013-01-01

    Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673–12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients. PMID:23484077

  20. Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord injury

    PubMed Central

    Sadowsky, Cristina L.; Hammond, Edward R.; Strohl, Adam B.; Commean, Paul K.; Eby, Sarah A.; Damiano, Diane L.; Wingert, Jason R.; Bae, Kyongtae T.; McDonald, John W.

    2013-01-01

    Objective To examine the effect of long-term lower extremity functional electrical stimulation (FES) cycling on the physical integrity and functional recovery in people with chronic spinal cord injury (SCI). Design Retrospective cohort, mean follow-up 29.1 months, and cross-sectional evaluation. Setting Washington University Spinal Cord Injury Neurorehabilitation Center, referral center. Participants Twenty-five people with chronic SCI who received FES during cycling were matched by age, gender, injury level, and severity, and duration of injury to 20 people with SCI who received range of motion and stretching. Intervention Lower extremity FES during cycling as part of an activity-based restorative treatment regimen. Main outcome measure Change in neurological function: motor, sensory, and combined motor–sensory scores (CMSS) assessed by the American Spinal Injury Association Impairment scale. Response was defined as ≥1 point improvement. Results FES was associated with an 80% CMSS responder rate compared to 40% in controls. An average 9.6 CMSS point loss among controls was offset by an average 20-point gain among FES subjects. Quadriceps muscle mass was on average 36% higher and intra/inter-muscular fat 44% lower, in the FES group. Hamstring and quadriceps muscle strength was 30 and 35% greater, respectively, in the FES group. Quality of life and daily function measures were significantly higher in FES group. Conclusion FES during cycling in chronic SCI may provide substantial physical integrity benefits, including enhanced neurological and functional performance, increased muscle size and force-generation potential, reduced spasticity, and improved quality of life. PMID:24094120

  1. Children in chronic pain: promoting pediatric patients' symptom accounts in tertiary care.

    PubMed

    Clemente, Ignasi; Lee, Seung-Hee; Heritage, John

    2008-03-01

    This paper examines how clinicians promote pediatric patients' symptom accounts at the beginning of visits in three pediatric tertiary care clinics at a university hospital in the United States: pain, gastroenterology and neurology. Quantitative and qualitative data were collected for 69 patient-parent pairs, including videotaped intake visits. Two forms of child account promotion, together with their corresponding distribution across clinics, were identified: (1) Epistemic prefaces were used to upgrade the patient's epistemic status and to establish the child as primary informant; and, (2) non-focused questioning was used to permit children latitude in the formulation of symptoms and experiences. In general, epistemic prefaces were characteristic of the gastroenterology and neurology visits, while non-focused questioning was found overwhelmingly in the pain encounters.

  2. Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation.

    PubMed

    Dambuza, Ivy M; Keeton, Roanne; Hsu, Nai-Jen; Allie, Nasiema; Quesniaux, Valérie F J; Ryffel, Bernhard; Jacobs, Muazzam

    2016-12-20

    The pleiotropic activities of TNF are mediated by two structurally related but functionally distinct type I transmembrane receptors, p55TNFR and p75TNFR expressed in most cell types, that can be cleaved and act as TNF scavengers. Here, we investigated the effect of persistent p55TNFR cell surface expression during aerosol inhalation challenge with virulent M. tuberculosis H37Rv. We demonstrated that persistency of p55TNFR in macrophage cultures increased the synthesis of soluble TNF, p75TNFR and NO, however, had no effects on bacteria killing ability. Furthermore, it did not facilitate enhanced protection to primary acute M. tuberculosis infection in p55(∆NS) mice. Without exacerbated lung inflammation, we found a compensatory increase in p75TNFR shedding and decrease in bioactive TNF in BAL of p55(∆NS) mice after M. tuberculosis challenge. Defective expressions of CD44 and INFγ attributed to an impaired T cell response during persistent p55TNFR expression that caused marginal transient susceptibility during chronic infection. Moreover, persistent p55TNFR expression induced early reactivation during latent tuberculosis infection. These data indicate a prominent role of p55TNFR shedding in Th1 mediated protection against chronic and latent tuberculosis infection.

  3. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration

    PubMed Central

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-01-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1−/− mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1−/− mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1−/− mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD. PMID:25604058

  4. Interleukin (Il)-18 Promotes the Development of Chronic Gastrointestinal Helminth Infection by Downregulating IL-13

    PubMed Central

    Helmby, Helena; Takeda, Kiyoshi; Akira, Shizuo; Grencis, Richard K.

    2001-01-01

    Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we show that Th1 response–associated susceptibility involves prior activation of IL-18 and caspase-1 followed by IL-12 and interferon (IFN)-γ in the intestine. IL-18–deficient mice are highly resistant to chronic T. muris infection and in vivo treatment of normal mice with recombinant (r)IL-18 suppresses IL-13 and IL-4 secretion but does not affect IFN-γ. In vivo treatment of T. muris–infected IFN-γ–deficient mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on IL-13 secretion is independent of IFN-γ. Hence, IL-18 does not function as an IFN-γ–inducing cytokine during chronic T. muris infection but rather as a direct regulator of Th2 cytokines. These results provide the first demonstration of the critical role of IL-18 in regulating Th cell responses during gastrointestinal nematode infection. PMID:11489954

  5. Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation

    PubMed Central

    Dambuza, Ivy M.; Keeton, Roanne; Hsu, Nai-Jen; Allie, Nasiema; Quesniaux, Valérie F. J.; Ryffel, Bernhard; Jacobs, Muazzam

    2016-01-01

    The pleiotropic activities of TNF are mediated by two structurally related but functionally distinct type I transmembrane receptors, p55TNFR and p75TNFR expressed in most cell types, that can be cleaved and act as TNF scavengers. Here, we investigated the effect of persistent p55TNFR cell surface expression during aerosol inhalation challenge with virulent M. tuberculosis H37Rv. We demonstrated that persistency of p55TNFR in macrophage cultures increased the synthesis of soluble TNF, p75TNFR and NO, however, had no effects on bacteria killing ability. Furthermore, it did not facilitate enhanced protection to primary acute M. tuberculosis infection in p55∆NS mice. Without exacerbated lung inflammation, we found a compensatory increase in p75TNFR shedding and decrease in bioactive TNF in BAL of p55∆NS mice after M. tuberculosis challenge. Defective expressions of CD44 and INFγ attributed to an impaired T cell response during persistent p55TNFR expression that caused marginal transient susceptibility during chronic infection. Moreover, persistent p55TNFR expression induced early reactivation during latent tuberculosis infection. These data indicate a prominent role of p55TNFR shedding in Th1 mediated protection against chronic and latent tuberculosis infection. PMID:27995986

  6. Caveolin-1 Promotes the Imbalance of Th17/Treg in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Sun, Nina; Wei, Xiaofang; Wang, Jingluan; Cheng, Zhaozhong; Sun, Weihong

    2016-12-01

    The imbalance of Th17/Treg cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Caveolin-1 (Cav-1) has been regarded as a potential critical regulatory protein in pathological mechanisms of chronic inflammatory respiratory diseases. Therefore, we investigated whether the loss of Cav-1 is involved in the homeostasis of Th17/Treg cells in COPD. We examined the expressions of plasma Cav-1 and circulating Th17, Treg cells, and the related cytokines in patients with COPD. Enzyme-linked immunosorbent assay (ELISA) analyses showed a significant reduction of plasma Cav-1 levels in patients with stable COPD (SCOPD) and acutely exacerbated COPD (AECOPD) compared to smokers without COPD. This loss was associated with an increase in frequency of Treg and decreased in frequency of Th17 cells. To further identify the role of Cav-1, we studied the effects of Cav-1 overexpression or downregulation on frequencies of Treg and Th17 cells in peripheral blood mononuclear cells (PBMCs) from subjects. Interestingly, small interfering RNA (siRNA) downregulation of Cav-1 was accompanied by an augmentation of Treg and reduction of Th17 expression. Together, our study demonstrated that the loss of Cav-1 contributed to the imbalance of Th17/Treg cells in patients with COPD.

  7. Music supported therapy promotes motor plasticity in individuals with chronic stroke.

    PubMed

    Ripollés, P; Rojo, N; Grau-Sánchez, J; Amengual, J L; Càmara, E; Marco-Pallarés, J; Juncadella, M; Vaquero, L; Rubio, F; Duarte, E; Garrido, C; Altenmüller, E; Münte, T F; Rodríguez-Fornells, A

    2016-12-01

    Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

  8. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice.

    PubMed

    Carvalho, Frederic A; Koren, Omry; Goodrich, Julia K; Johansson, Malin E V; Nalbantoglu, Ilke; Aitken, Jesse D; Su, Yueju; Chassaing, Benoit; Walters, William A; González, Antonio; Clemente, Jose C; Cullender, Tyler C; Barnich, Nicolas; Darfeuille-Michaud, Arlette; Vijay-Kumar, Matam; Knight, Rob; Ley, Ruth E; Gewirtz, Andrew T

    2012-08-16

    Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4(+) T cells.

    PubMed

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Li, Jingyun; Cooney, Craig A

    2016-10-17

    CD4(+) T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4(+) T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4(+) T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4(+) T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4(+) T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4(+) T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4(+) T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4(+) T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene.

  10. Prevalence and Characteristics of Basal Core Promoter Mutations in Iran and its Correlation with Acute and Chronic Hepatitis B Infection

    PubMed Central

    Nasrollaheian, Sadegh; Farshidfar, Gholamreza; Kheirabad, Ali Kargar; Gouklani, Hamed

    2016-01-01

    Introduction Manifestations of HBV infection differ in chronic and acute phases. Therefore, identifying the determinants such as mutations has a vital role in the treatment of the disease. A dual transversion in the basal core promoter (BCP) region is common among HBV patients. Thus, the present study was conducted with the objective of determining the prevalence of basal core promoter (BCP) mutations and its correlation with the outcome of HBV infection. Method In this cross-sectional study, samples were obtained from 182 Iranian HBsAg positive patients who were admitted to the Bandar Abbas Blood Transfusion Organization in 2012 and 2013. They were screened by ELISA test using commercial kits to detect serological marker anti-HBc IgM for distinct chronic hepatitis from acute infection. Thereafter, the extracted DNA was used for determination of the BCP mutations by PCR-RFLP technique. Data analyses were performed with SPSS 12 by Mann–Whitney U test, Fisher’s exact probability test, and t-test. Results BCP mutations were observed in 15 samples (8.24%) of the study population, and serological tests determined that, among the BCP mutants, one sample (6.67%) was HBeAg positive, 14 samples (93.33%) were HBeAg negative, and four samples (2.2%) were positive for anti-HBc IgM test. Data analysis indicated a statistically significant association between BCP mutations and acute hepatitis (p=0.002). However, no relationship was detected between the prevalences of the BCP mutations and gender of subjects (p>0.567). Conclusions The prevalence of BCP variants was low in the south of Iran, and this mutation can lead to acute phase of viral hepatitis. PMID:28163866

  11. A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

    PubMed

    Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K

    2014-01-01

    We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.

  12. Adipocyte SIRT1 knockout promotes PPARγ activity, adipogenesis and insulin sensitivity in chronic-HFD and obesity

    PubMed Central

    Mayoral, Rafael; Osborn, Olivia; McNelis, Joanne; Johnson, Andrew M.; Oh, Da Young; Izquierdo, Cristina Llorente; Chung, Heekyung; Li, Pingping; Traves, Paqui G.; Bandyopadhyay, Gautam; Pessentheiner, Ariane R.; Ofrecio, Jachelle M.; Cook, Joshua R.; Qiang, Li; Accili, Domenico; Olefsky, Jerrold M.

    2015-01-01

    Objective Adipose tissue is the primary site for lipid deposition that protects the organisms in cases of nutrient excess during obesogenic diets. The histone deacetylase Sirtuin 1 (SIRT1) inhibits adipocyte differentiation by targeting the transcription factor peroxisome proliferator activated-receptor gamma (PPARγ). Methods To assess the specific role of SIRT1 in adipocytes, we generated Sirt1 adipocyte-specific knockout mice (ATKO) driven by aP2 promoter onto C57BL/6 background. Sirt1flx/flxaP2Cre+ (ATKO) and Sirt1flx/flxaP2Cre- (WT) mice were fed high-fat diet for 5 weeks (short-term) or 15 weeks (chronic-term). Metabolic studies were combined with gene expression analysis and phosphorylation/acetylation patterns in adipose tissue. Results On standard chow, ATKO mice exhibit low-grade chronic inflammation in adipose tissue, along with glucose intolerance and insulin resistance compared with control fed mice. On short-term HFD, ATKO mice become more glucose intolerant, hyperinsulinemic, insulin resistant and display increased inflammation. During chronic HFD, WT mice developed a metabolic dysfunction, higher than ATKO mice, and thereby, knockout mice are more glucose tolerant, insulin sensitive and less inflamed relative to control mice. SIRT1 attenuates adipogenesis through PPARγ repressive acetylation and, in the ATKO mice adipocyte PPARγ was hyperacetylated. This high acetylation was associated with a decrease in Ser273-PPARγ phosphorylation. Dephosphorylated PPARγ is constitutively active and results in higher expression of genes associated with increased insulin sensitivity. Conclusion Together, these data establish that SIRT1 downregulation in adipose tissue plays a previously unknown role in long-term inflammation resolution mediated by PPARγ activation. Therefore, in the context of obesity, the development of new therapeutics that activate PPARγ by targeting SIRT1 may provide novel approaches to the treatment of T2DM. PMID:25973386

  13. Acute but not chronic administration of pioglitazone promoted behavioral and neurochemical protective effects in the MPTP model of Parkinson's disease.

    PubMed

    Barbiero, Janaína K; Santiago, Ronise M; Lima, Marcelo M S; Ariza, Deborah; Morais, Lívia H; Andreatini, Roberto; Vital, Maria A B F

    2011-01-01

    The present study investigated the neurochemical, motor and cognitive effects of pioglitazone in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the first experiment, we administered MPTP, and 1h later administered a single oral dose of pioglitazone (5, 15 and 30 mg/kg). The following day, we performed the open-field test and neurochemical dose response curve. We demonstrated that 30 mg/kg of pioglitazone was capable of restoring striatal dopamine (DA) concentrations and motor behaviors. A second experiment was conducted to test the effects of two protocols (acute and chronic) of pioglitazone (30 mg/kg) administration in the open-field test, two-way active avoidance task and in the DA and metabolites levels. The acute protocol consisted of a single oral administration 1 h after MPTP, whereas the chronic protocol was performed with daily administrations starting 1 h after MPTP and ending 22 days after that. Results showed that neither protocol was able to reverse the cognitive impairment promoted by MPTP. We also demonstrated that acute treatment generated some level of neuroprotection, as confirmed by the absence of DA reduction in the group treated with pioglitazone in comparison to the sham group. By contrast, chronic treatment leaded to a reduction of striatal DA, close to MPTP administration alone. These findings suggest that acute administration of pioglitazone (30 mg/kg) was more efficient in generating beneficial effects on motor behaviors and in striatal DA levels. Nevertheless, we failed to demonstrate that pioglitazone administration improved performance on a dopamine-related cognitive task after MPTP.

  14. IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice.

    PubMed

    Hodge, Deborah L; Berthet, Cyril; Coppola, Vincenzo; Kastenmüller, Wolfgang; Buschman, Matthew D; Schaughency, Paul M; Shirota, Hidekazu; Scarzello, Anthony J; Subleski, Jeff J; Anver, Miriam R; Ortaldo, John R; Lin, Fanching; Reynolds, Della A; Sanford, Michael E; Kaldis, Philipp; Tessarollo, Lino; Klinman, Dennis M; Young, Howard A

    2014-09-01

    We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3' untranslated region (3'UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone macrophages (MZMs) are absent in ARE-Del(-/-) mice. ARE-Del(+/-) mice retain both MZB cells and MZMs and develop no or mild autoimmunity. However, low dose clodronate treatment in ARE-Del(+/-) mice specifically eliminates MZMs and promotes anti-DNA antibody development and glomerulonephritis. Our findings demonstrate the consequences of a chronic IFN-γ milieu on B220(+) cell types and in particular the impact of MZB cell loss on MZM function in autoimmunity. Furthermore, similarities between disease states in ARE-Del(-/-) mice and SLE patients suggest that IFN-γ may not only be a product of SLE but may be critical for disease onset and progression.

  15. Canadian Men's Self-Management of Chronic Diseases: A Literature Analysis of Strategies for Dealing With Risks and Promoting Wellness.

    PubMed

    Zanchetta, Margareth S; Maheu, Christine; Kolisnyk, Olesya; Mohamed, Mohamed; Guruge, Sepali; Kinslikh, Diana; Christopher, Joneet J; Stevenson, Melissa; SanJose, CaroLine; Sizto, Terry; Byam, Aaron

    2015-03-23

    This article reviews the qualitative research on men's self-management of mental and physical chronic diseases, with emphasis on strategies for dealing with risks and promoting wellness. Using Bardin's method of document analysis, it was focused on the findings of Canadian qualitative studies published in French or English from 2005 to 2011. Boltanski's theory on social uses of the body inspired the analysis. Living with a chronic disease threatens men's sense of masculinity and self-image, as well as their perceived ability to fulfill expected social roles. Social images of men's bodies influence how men express their emotions, attributes, and attitudes, or acknowledge the need for and seek social affirmation. Self-management has been documented in Canadian qualitative literature as a complex phenomenon influenced by the social environment, personal capacities, feelings, perceptions, and potentials. The extent of how all these features interact within the scope of men's mental and physical health and illness experiences was partially revealed in this study. The findings underscore the social invisibility of men's bodies, especially those of men facing social inequities. Attending to principles of social justice can ensure that future research on men's health will amplify the range of men's voices and allow them to be heard. Recommendations address also the international scientific community interested in advancing men's health research, especially in those countries that lack a national men's health policy.

  16. IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice

    PubMed Central

    Hodge, Deborah L.; Berthet, Cyril; Coppola, Vincenzo; Kastenmüller, Wolfgang; Buschman, Matthew D.; Schaughency, Paul M.; Shirota, Hidekazu; Scarzello, Anthony J.; Subleski, Jeff J.; Anver, Miriam R.; Ortaldo, John R.; Lin, Fanching; Reynolds, Della A.; Sanford, Michael E.; Kaldis, Philipp; Tessarollo, Lino; Klinman, Dennis M.; Young, Howard A.

    2014-01-01

    We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3′ untranslated region (3′UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) −/− present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del−/− mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone macrophages (MZMs) are absent in ARE-Del−/− mice. ARE-Del+/− mice retain both MZB cells and MZMs and develop no or mild autoimmunity. However, low dose clodronate treatment in ARE-Del+/− mice specifically eliminates MZMs and promotes anti-DNA antibody development and glomerulonephritis. Our findings demonstrate the consequences of a chronic IFN-γ milieu on B220+ cell types and in particular the impact of MZB cell loss on MZM function in autoimmunity. Furthermore, similarities between disease states in ARE-Del−/− mice and SLE patients suggest that IFN-γ may not only be a product of SLE but may be critical for disease onset and progression. PMID:24583068

  17. Integrative behavioral couple therapy for chronic pain: promoting behavior change and emotional acceptance.

    PubMed

    Cano, Annmarie; Leonard, Michelle

    2006-11-01

    Couple therapy has been used with success in treating marital distress, psychological distress, and other problems. Researchers in the pain field have also shown that the inclusion of the spouse in pain treatment may be beneficial to the patient. In this article, we present integrative behavioral couple therapy (IBCT) as one option for therapists treating patients who have pain and marital distress. IBCT improves on traditional behavior therapy because it promotes processes that have been shown to be lacking in pain patients' relationships: emotional acceptance and empathy. After reviewing the use of behavior change and emotional acceptance strategies in couples, we describe a couple for whom IBCT improved functioning.

  18. Loss of discoidin domain receptor 2 promotes hepatic fibrosis after chronic carbon tetrachloride through altered paracrine interactions between hepatic stellate cells and liver-associated macrophages.

    PubMed

    Olaso, Elvira; Arteta, Beatriz; Benedicto, Aitor; Crende, Olatz; Friedman, Scott L

    2011-12-01

    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl(4)) to DDR2(+/+) and DDR2(-/-) mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after chronic CCl(4) administration, DDR2(-/-) livers had increased collagen deposition, gelatinolytic activity, and HSC density. Increased basal gene expression of osteopontin, transforming growth factor-β1, monocyte chemoattractant protein-1, and IL-10 and reduced basal gene expression of matrix metalloproteinase-2, matrix metalloproteinase-13, and collagen type I in quiescent DDR2(-/-) HSCs were amplified further after chronic CCl(4). In concordance, DDR2(-/-) HSCs isolated from chronically injured livers had enhanced in vitro migration and proliferation, but less extracellular matrix degradative activity. Macrophages from chronic CCl(4)-treated DDR2(-/-) livers showed stronger chemoattractive activity toward DDR2(-/-) HSCs than DDR2(+/+) macrophages, increased extracellular matrix degradation, and higher cytokine mRNA expression. In conclusion, loss of DDR2 promotes chronic liver fibrosis after CCl(4) injury. The fibrogenic sinusoidal milieu generated in chronic DDR2(-/-) livers recruits more HSCs to injured regions, which enhances fibrosis. Together, these findings suggest that DDR2 normally orchestrates gene programs and paracrine interactions between HSCs and macrophages that together attenuate chronic hepatic fibrosis.

  19. OS060. Exercise training promotes placental growth and development in an animal model of preeclampsia superimposed on chronic hypertension.

    PubMed

    Genest, D S; Falcao, S; Michel, C; Lacasse, A-A; Vaillancourt, C; Gutkowska, J; Lavoie, J L

    2012-07-01

    Chronic hypertension is an important risk factor for preeclampsia, increasing the prevalence of the disease to 15-25% in pregnant women. Unfortunately there are no known treatments for this disease aside from inducing delivery of the fetus. Nonetheless, several studies have found exercise training to have a protective effect on the risk of developing preeclampsia. To determine the mechanisms implicated in the preventive effect of exercise training on preeclampsia, by focusing on the placenta. Double transgenic mice, overexpressing both human renin and angiotensinogen (R(+)/A(+)), were used to investigate the effect of exercise training on an animal model of preeclampsia superimposed on chronic hypertension. Mice were placed in cages with free access to an exercise wheel 4 weeks prior to and during pregnancy. At gestational day 18, mice were sacrificed and their organs were collected. Real time PCR and Western Blot were performed to evaluate placental genes and proteins, respectively. Circulating sFlt-1(soluble Fms-like tyrosine kinase-1) levels were investigated by ELISA. Placental alterations were assessed by histology and immunohistochemistry, while blood pressure was measured by radiotelemetry. Sedentary R(+)/A(+) mice presented with significantly greater placental pathology, which was normalized with exercise training. This was characterized by a normalization of cytokeratin and histone H3 protein expression, thereby restoring placental development, specifically looking at trophoblasts and trophoblast giant cells, respectively. This exercise training effect appears to normalize placental growth primarily by promoting angiogenesis and development. Indeed, a pro-angiogenic shift could be detected which was characterized by an increase in placental growth factor gene expression, along with a decrease in sFlt-1 gene expression, which produced a decrease in circulating sFlt-1. Sedentary R(+)/A(+) mice also presented with a significant increase in VEGF protein, which

  20. High Levels of Hemoglobin Promote Carotid Adventitial Vasa Vasorum Neoangiogenesis in Chronic Kidney Disease.

    PubMed

    Arcidiacono, Maria Vittoria; Martinez-Alonso, Montserrat; Belart, Montserrat; Vilar, Ana; Martín, Marisa; Craver, Lourdes; Betriu, Àngels; Mauricio, Dídac; Valdivielso, José Manuel; Fernández, Elvira; Borràs, Mercè

    2017-01-01

    Chronic kidney disease (CKD) patients, characterized by traditional and nontraditional risk factors, are prone to develop atheromatosis and thus cardiovascular events and mortality. The angiogenesis of the adventitial vasa vasorum (aVV) surrounding the carotid has been described as the atheromatosis initiator. Therefore, the aim of the study was to (1) evaluate if the carotid aVV in CKD patients increases in comparison to its physiological value of healthy patients; (2) explore which traditional or nontraditional risk factor including inflammation, bone and mineral metabolism, and anemia could be related to the aVV angiogenesis. CKD patients without previous cardiovascular events (44, stages 3-4; 37, stage 5D) and 65 healthy subjects were compared. The carotid aVV and the intima-media thickness (cIMT) were evaluated by ultrasound. CKD patients at stages 3-4 showed higher aVV of the right carotid artery even after adjusting for age. Importantly, a multiple linear regression model showed hemoglobin levels > 12.5 g/dL as the factor for an estimated higher aVV of the right carotid artery. In conclusion, the association of hemoglobin with higher aVV could suggest the role of high hemoglobin in the higher incidence of adverse cardiovascular outcomes in CKD patients.

  1. High Levels of Hemoglobin Promote Carotid Adventitial Vasa Vasorum Neoangiogenesis in Chronic Kidney Disease

    PubMed Central

    Martinez-Alonso, Montserrat; Belart, Montserrat; Vilar, Ana; Martín, Marisa; Craver, Lourdes; Betriu, Àngels; Valdivielso, José Manuel; Fernández, Elvira

    2017-01-01

    Chronic kidney disease (CKD) patients, characterized by traditional and nontraditional risk factors, are prone to develop atheromatosis and thus cardiovascular events and mortality. The angiogenesis of the adventitial vasa vasorum (aVV) surrounding the carotid has been described as the atheromatosis initiator. Therefore, the aim of the study was to (1) evaluate if the carotid aVV in CKD patients increases in comparison to its physiological value of healthy patients; (2) explore which traditional or nontraditional risk factor including inflammation, bone and mineral metabolism, and anemia could be related to the aVV angiogenesis. CKD patients without previous cardiovascular events (44, stages 3-4; 37, stage 5D) and 65 healthy subjects were compared. The carotid aVV and the intima-media thickness (cIMT) were evaluated by ultrasound. CKD patients at stages 3-4 showed higher aVV of the right carotid artery even after adjusting for age. Importantly, a multiple linear regression model showed hemoglobin levels > 12.5 g/dL as the factor for an estimated higher aVV of the right carotid artery. In conclusion, the association of hemoglobin with higher aVV could suggest the role of high hemoglobin in the higher incidence of adverse cardiovascular outcomes in CKD patients. PMID:28133420

  2. Chronic non-communicable diseases, risk and health promotion: social construction of VIGITEL participants.

    PubMed

    Mássimo, Erika de Azevedo Leitão; de Souza, Hercília Najara Ferreira; Freitas, Maria Imaculada de Fátima

    2015-03-01

    The dimension of choice and adherence to healthy lifestyles is in the area of social constructions made in representations of individuals and had not yet been included in the Surveillance of Risk and Protective Factors for Chronic Diseases by Telephone Survey (VIGITEL) analysis systems. This article aims to understand, in individual narratives, representations contained in the trajectories of people's lives selected from the 2010 VIGITEL sample, in Belo Horizonte, Minas Gerais. It is a qualitative study based on Social Representation Theory. Thirty in-depth and open interviews with subjects selected from the 2010 VIGITEL sample were conducted in Belo Horizonte in the State of Minas Gerais. The Structural Analysis of Narrative technique was used to reveal the content of speeches. Age and heredity representations related to NCDs are part of the spectrum of current scientific information. Learning from childhood onwards is the basis of care. The lack of comprehension of the pathophysiology of NCDs, and the depth of representations of illness and death related to communicable diseases, is partly responsible for the difficulty of preventing NCDs.

  3. The olfactory neuron AWC promotes avoidance of normally palatable food following chronic dietary restriction

    PubMed Central

    Olofsson, Birgitta

    2014-01-01

    Changes in metabolic state alter foraging behavior and food preference in animals. Here, I show that normally attractive food becomes repulsive to Caenorhabditis elegans if animals are chronically undernourished as a result of alimentary tract defects. This behavioral plasticity is achieved in two ways: increased food leaving and induction of aversive behavior towards food. A particularly strong food avoider is defective in the chitin synthase that makes the pharyngeal lining. Food avoidance induced by underfeeding is mediated by cGMP signaling in the olfactory neurons AWC and AWB, and the gustatory neurons ASJ and ASK. Food avoidance is enhanced by increased population density and is reduced if the animals are unable to correctly interpret their nutritional state as a result of defects in the AMP kinase or TOR/S6kinase pathways. The TGF-β/DBL-1 pathway suppresses food avoidance and the cellular basis for this is distinct from its role in aversive olfactory learning of harmful food. This study suggests that nutritional state feedback via nutrient sensors, population size and olfactory neurons guides food preference in C. elegans. PMID:24577446

  4. Endurance exercise promotes cardiorespiratory rehabilitation without neurorestoration in the chronic mouse model of parkinsonism with severe neurodegeneration.

    PubMed

    Al-Jarrah, M; Pothakos, K; Novikova, L; Smirnova, I V; Kurz, M J; Stehno-Bittel, L; Lau, Y-S

    2007-10-12

    release-dependent locomotor activity was markedly inhibited in the sedentary parkinsonian mice and was also inhibited in the exercised parkinsonian mice. Finally, neuronal recovery from the loss of nigrostriatal tyrosine hydroxylase expression and dopamine levels in the severe parkinsonian mice after exercise was not evident. Taken all together, these data suggest that 4 weeks of treadmill exercise promoted physical endurance, resulting in cardiorespiratory and metabolic adaptations in the chronic parkinsonian mice with severe neurodegeneration without demonstrating a restorative potential for the nigrostriatal dopaminergic function.

  5. Modeling routes of chronic wasting disease transmission: Environmental prion persistence promotes deer population decline and extinction

    USGS Publications Warehouse

    Almberg, Emily S.; Cross, Paul C.; Johnson, Christopher J.; Heisey, Dennis M.; Richards, Bryan J.

    2011-01-01

    Chronic wasting disease (CWD) is a fatal disease of deer, elk, and moose transmitted through direct, animal-to-animal contact, and indirectly, via environmental contamination. Considerable attention has been paid to modeling direct transmission, but despite the fact that CWD prions can remain infectious in the environment for years, relatively little information exists about the potential effects of indirect transmission on CWD dynamics. In the present study, we use simulation models to demonstrate how indirect transmission and the duration of environmental prion persistence may affect epidemics of CWD and populations of North American deer. Existing data from Colorado, Wyoming, and Wisconsin's CWD epidemics were used to define plausible short-term outcomes and associated parameter spaces. Resulting long-term outcomes range from relatively low disease prevalence and limited host-population decline to host-population collapse and extinction. Our models suggest that disease prevalence and the severity of population decline is driven by the duration that prions remain infectious in the environment. Despite relatively low epidemic growth rates, the basic reproductive number, R0, may be much larger than expected under the direct-transmission paradigm because the infectious period can vastly exceed the host's life span. High prion persistence is expected to lead to an increasing environmental pool of prions during the early phases (i.e. approximately during the first 50 years) of the epidemic. As a consequence, over this period of time, disease dynamics will become more heavily influenced by indirect transmission, which may explain some of the observed regional differences in age and sex-specific disease patterns. This suggests management interventions, such as culling or vaccination, will become increasingly less effective as CWD epidemics progress.

  6. IL-17A and the Promotion of Neutrophilia in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

    PubMed

    Roos, Abraham B; Sethi, Sanjay; Nikota, Jake; Wrona, Catherine T; Dorrington, Michael G; Sandén, Caroline; Bauer, Carla M T; Shen, Pamela; Bowdish, Dawn; Stevenson, Christopher S; Erjefält, Jonas S; Stampfli, Martin R

    2015-08-15

    Nontypeable Haemophilus influenzae (NTHi) causes acute exacerbation of chronic obstructive pulmonary disease (AECOPD). IL-17A is central for neutrophilic inflammation and has been linked to COPD pathogenesis. We investigated whether IL-17A is elevated in NTHi-associated AECOPD and required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. Experimental studies with cigarette smoke and NTHi infection were pursued in gene-targeted mice and using antibody intervention. IL-17A was measured in sputum collected from patients with COPD at baseline, during, and after AECOPD. Exacerbated airway neutrophilia in cigarette smoke-exposed mice infected with NTHi was associated with an induction of IL-17A. In agreement, elevated IL-17A was observed in sputum collected during NTHi-associated AECOPD, compared with samples collected before or after the event. NTHi-exacerbated neutrophilia and induction of neutrophil chemoattractants over the background of cigarette smoke, as observed in wild-type mice, was absent in Il17a(-/-) mice and in mice treated with a neutralizing anti-IL-17A antibody. Further studies revealed that IL-1 receptor (R)1 signaling was required for IL-17A-dependent neutrophilia. Moreover, deficiency or therapeutic neutralization of IL-17A did not increase bacterial burden or delay bacterial clearance. IL-17A is induced during NTHi-associated AECOPD. Functionally, IL-1R1-dependent IL-17A is required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. Targeting IL-17A in AECOPD may thus be beneficial to reduce neutrophil recruitment to the airways.

  7. Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat.

    PubMed

    Whittamore, Jonathan M; Hatch, Marguerite

    2015-11-01

    Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine.

  8. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion.

    PubMed

    Yang, Ying; Ju, Jieyang; Deng, Min; Wang, Jing; Liu, Hui; Xiong, Li; Zhang, Junjian

    2017-01-17

    Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs), were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit.

  9. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

    PubMed Central

    Yang, Ying; Ju, Jieyang; Deng, Min; Wang, Jing; Liu, Hui; Xiong, Li; Zhang, Junjian

    2017-01-01

    Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs), were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit. PMID:28106731

  10. PRISM: Promoting Resilience, Independence and Self Management--a strategy to manage chronic mental illnesses.

    PubMed

    Arya, Dinesh K

    2013-08-01

    Many transformations in how mental health care is delivered have required the development of new ways of providing care, treatment and support to mental health consumers. In the recent past, to support consumers and their carers adequately and appropriately, there has been emphasis on case management and care coordination. There is a need to consider whether over-emphasis on case management should be limited to the minority of mental health consumers who are unable to make competent decisions, whereas majority of consumers should take complete charge of their own treatment. PRISM (Promoting Resilience, Independence and Self Management) is a conceptual framework that potentially offers an opportunity to empower consumers to take charge of their own treatment by using specific tools, including a PRISM Pack, Take Charge Sheet, Protocol for Appropriate Care and use of methods that ensure that the mental health consumer does become a key decision maker with regard to their own care and treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Use of Health Information and Communication Technologies to Promote Health and Manage Behavioral Risk Factors Associated with Chronic Disease: Applications in the Field of Health Education

    ERIC Educational Resources Information Center

    Stellefson, Michael; Alber, Julia M.; Wang, Min Qi; Eddy, James M.; Chaney, Beth H.; Chaney, J. Don

    2015-01-01

    This special issue provides real-world examples of the diverse methods health education researchers are using to expand existing applications of information and communication technologies (ICTs) for health promotion and chronic disease management. The original and review articles presented in this special issue investigate eHealth, mHealth, and…

  12. Use of Health Information and Communication Technologies to Promote Health and Manage Behavioral Risk Factors Associated with Chronic Disease: Applications in the Field of Health Education

    ERIC Educational Resources Information Center

    Stellefson, Michael; Alber, Julia M.; Wang, Min Qi; Eddy, James M.; Chaney, Beth H.; Chaney, J. Don

    2015-01-01

    This special issue provides real-world examples of the diverse methods health education researchers are using to expand existing applications of information and communication technologies (ICTs) for health promotion and chronic disease management. The original and review articles presented in this special issue investigate eHealth, mHealth, and…

  13. Health-Promoting Lifestyle, Perceived Health Competence, Barriers to Health Promotion, and Asthma-Related Knowledge in Persons with Chronic Asthma

    DTIC Science & Technology

    1998-05-15

    5 2 | £ ja | 1) A ft ’S S 00 .3 c .a a o ■■0 1 2 I ON •3 0H I •8 O i i HH Status, perceived benefits of health -promoting... benefits of health - promoting behaviors, and perceived barriers to health-promoting behaviors. The modifying factors include demographic...health, perceived health status, perceived benefits of health -promoting behaviors, perceived barriers to health-promoting behaviors, clients

  14. Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats

    PubMed Central

    Lauterborn, Julie C.; Palmer, Linda C.; Jia, Yousheng; Pham, Danielle T.; Hou, Bowen; Wang, Weisheng; Trieu, Brian H.; Cox, Conor D.; Kantorovich, Svetlana

    2016-01-01

    Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. SIGNIFICANCE STATEMENT Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be

  15. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation

    PubMed Central

    Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R.; D’Alessio, Franco R.; Lambert, Allison A.; Kirk, Gregory; Blankson, Joel; Drummond, M. Bradley; Tsibris, Athe M.

    2016-01-01

    Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway

  16. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    PubMed

    Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

    2016-01-01

    Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway

  17. Practice paper of the Academy of Nutrition and Dietetics abstract: the role of nutrition in health promotion and chronic disease prevention.

    PubMed

    Fitzgerald, Nurgul; Morgan, Kathleen T; Slawson, Deborah Leachman

    2013-07-01

    Food intake, lifestyle behaviors, and obesity are linked to the development of chronic diseases such as type 2 diabetes, certain cancers, and cardiovascular diseases. It is recognized that physical and social environment influences individuals' behaviors, and some population subgroups such as racial/ethnic minorities and individuals with low socioeconomic status or limited literacy or language abilities seem to be especially vulnerable to disparities in disease risk factors, disease prevalence, or health outcomes. Certain life cycle phases appear to be especially important for health promotion and disease prevention as the development of chronic diseases can take several decades. Such complex health issues often require system-wide, multifactorial, and multidisciplinary solutions. Social ecological models, with approaches spanning from individual level to macro policy level, can provide registered dietitians (RDs) and dietetic technicians, registered (DTRs) with a comprehensive framework to promote health and to prevent chronic diseases. Furthermore, the Nutrition Care Process can be utilized in carrying out the health promotion and disease prevention efforts. RDs and DTRs have the training and requisite skills to be leaders and active members of multidisciplinary teams to promote health and prevent chronic diseases across the life span. The position of the Academy of Nutrition and Dietetics states that primary prevention is the most effective, affordable method to prevent chronic disease, and that dietary intervention positively impacts health outcomes across the life span. RDs and DTRs are critical members of health care teams and are essential to delivering nutrition-focused preventive services in clinical and community settings, advocating for policy and programmatic initiatives, and leading research in disease prevention and health promotion. In concordance with the Academy's position, this practice paper provides an overview of practice examples, effective

  18. Chronic Cadmium Treatment Promotes Oxidative Stress and Endothelial Damage in Isolated Rat Aorta

    PubMed Central

    Almenara, Camila C. P.; Broseghini-Filho, Gilson B.; Vescovi, Marcus V. A.; Angeli, Jhuli K.; Faria, Thaís de O.; Stefanon, Ivanita; Vassallo, Dalton V.; Padilha, Alessandra S.

    2013-01-01

    Cadmium is a highly toxic metal that is present in phosphate fertilizers, and the incidence of cadmium poisoning in the general population has increased, mainly due to cigarette smoking. Once absorbed, cadmium accumulates in the tissues, causing harmful effects including high blood pressure, endothelial damage and oxidative stress. Oxidative stress is known to efficiently produce oxidized low-density lipoprotein and consequently atherosclerosis, mainly in the aorta. However, the mechanisms through which endothelial damage is induced by cadmium have not been elucidated. Thus, the aim of this study was to investigate the effects of this metal in the isolated aorta and the possible role of oxidative stress. Rats received 100 mg.L−1 cadmium chloride (CdCl2) in the drinking water or distilled water alone for four weeks. The pressor effect of cadmium was followed throughout the exposure period by tail plethysmography. At the end of the fourth week, the blood cadmium content was established, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine and sodium nitroprusside was analyzed in the context of endothelium denudation and incubation with L-NAME, apocynin, losartan, enalapril, superoxide dismutase (SOD) or catalase. We observed an increased response to phenylephrine in cadmium-treated rats. This increase was abolished by catalase and SOD incubation. Apocynin treatment reduced the phenylephrine response in both treatment groups, but its effect was greater in cadmium-treated rats, and NOX2 expression was greater in the cadmium group. These results suggested that cadmium in blood concentrations similar to those found in occupationally exposed populations is able to stimulate NOX2 expression, contributing to oxidative stress and reducing NO bioavailability, despite enhanced eNOS expression. These findings suggest that cadmium exposure promotes endothelial damage that might contribute to inflammation, vascular injury and the development of

  19. Protein damage from electrophiles and oxidants in lungs of mice chronically exposed to the tumor promoter butylated hydroxytoluene.

    PubMed

    Shearn, Colin T; Fritz, Kristofer S; Thompson, John A

    2011-07-15

    The food additive butylated hydroxytoluene (BHT) promotes tumorigenesis in mouse lung. Chronic BHT exposure is accompanied by pulmonary inflammation and several studies indicate that elevated levels of reactive oxygen species (ROS) are involved in its promoting activity. The link between BHT and elevated ROS involves formation of quinone methide (QM) metabolites; these electrophiles form adducts with a variety of lung proteins including several enzymes that protect cells from oxidative stress. Studies in vitro demonstrated that QM alkylation of cytoprotective enzymes is accompanied by inactivation, so an objective of the present investigation was to determine if inactivation also occurs in vivo. Two groups of mice were exposed to BHT by intraperitoneal injection, one for 10 days and the other for 24 days, and proteins from lung cytosols were examined for damage. Analysis by Western blotting demonstrated that BHT treatment caused substantial increases in protein carbonylation, nitration and adduction by 4-hydroxynonenal, confirming the occurrence of sustained oxidative and nitrosative stress over the treatment period required for tumor promotion. Effects of BHT on the activities and/or levels of a representative group of antioxidant/protective enzymes in mouse lung also were assessed; NAD(P)H:quinone reductase and glutathione reductase were unaffected, however carbonyl reductase activity decreased 50-60%. Superoxide dismutase and glutathione peroxidase activities increased 2- and 1.5-fold, respectively, and glutamate-cysteine ligase catalytic subunit expression increased 32-39% relative to untreated mice. Glutathione S-transferase (GST) activity decreased 50-60% but concentrations of the predominant isoforms, GSTM1 and P1, were not affected. GSTP1 was substantially more susceptible than M1 to adduction and inhibition by treatment with BHT-QM in vitro, suggesting that lower GST activity in mice after BHT treatment is due to adduction of the P1 isoform. The results of

  20. Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model

    PubMed Central

    Fan, Hong-Bin; Chen, Li-Xia; Qu, Xue-Bin; Ren, Chuan-Lu; Wu, Xiu-Xiang; Dong, Fu-Xing; Zhang, Bao-Le; Gao, Dian-Shuai; Yao, Rui-Qin

    2017-01-01

    Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases. PMID:28145507

  1. Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model.

    PubMed

    Fan, Hong-Bin; Chen, Li-Xia; Qu, Xue-Bin; Ren, Chuan-Lu; Wu, Xiu-Xiang; Dong, Fu-Xing; Zhang, Bao-Le; Gao, Dian-Shuai; Yao, Rui-Qin

    2017-02-01

    Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases.

  2. Chitosan-aluminum monostearate composite sponge dressing containing asiaticoside for wound healing and angiogenesis promotion in chronic wound.

    PubMed

    Phaechamud, Thawatchai; Yodkhum, Kotchamon; Charoenteeraboon, Juree; Tabata, Yasuhiko

    2015-05-01

    There are many factors that delay healing in chronic wounds including lowering level of growth factors and increasing exudate level comprising high amount of tissue destructive enzymes. Asiaticoside possesses interesting wound healing and angiogenic activities that are employed to stimulate tissue regeneration in wound healing application. This study attempted to develop chitosan-aluminum monostearate (Alst) composite sponge containing asiaticoside for use as an absorbent medical dressing in chronic wound. N-methyl-2-pyrrolidone (NMP) was used to enhance homogeneity of asiaticoside in the polymer composite matrix. The sponge dressings were prepared by lyophilization and dehydrothermal treatment (DHT). Functional group interaction, crystallinity, and morphology of the prepared sponges were investigated using FT-IR, PXRD, and SEM, respectively. Physicochemical properties, porosity, hydrophilic/hydrophobic properties and mechanical property, were evaluated. Wound dressing properties, water vapor transmission rate (WVTR), fluid absorbency, oxygen permeation (OP), and bio-adhesive property, were investigated. In vitro asiaticoside release study was conducted using immersion method. Cytotoxicity was studied in normal human dermal fibroblast (NHDF) and normal human epidermal keratinocyte (NHEK). Angiogenic activity of asiaticoside was evaluated using chick-chorioallantoic membrane (CAM) assay. FT-IR and PXRD results revealed the amidation after DHT to enhance the crystallinity of the prepared sponges. The prepared sponges had high porosity comprising high Alst-loaded amount that exhibited more compact structure. Alst enhanced hydrophobicity therefore it reduced the fluid absorption and WVTR together with bio-adhesion of the prepared sponge dressings. Porosity of all sponges was more than 85% therefore resulting in their high OP. Enhancing hydrophobicity of the material by Alst and more homogeneity caused by NMP eventually retarded the asiaticoside release for 7 days. The

  3. Influence of matrix metalloproteinase-1 gene -1607 (1G/2G) (rs1799750) promoter polymorphism on circulating levels of MMP-1 in chronic pancreatitis.

    PubMed

    Sri Manjari, K; Nallari, Pratibha; Balakrishna, N; Vidyasagar, A; Prabhakar, B; Jyothy, A; Venkateshwari, A

    2013-08-01

    This study investigated the role of -1607 (1G/2G) (rs1799750) polymorphism of the MMP-1 gene in chronic pancreatitis. We genotyped 100 patients with chronic pancreatitis and 100 control subjects using tetra-primer ARMS-PCR followed by agarose gel electrophoresis. Serum levels of MMP-1 were determined by Elisa. Statistical analysis was applied to test the significance of the results. The genotypic and allelic distribution varied significantly between the disease group and the control subjects [OD = 1.981 (1.236-3.181), p = 0.004]. MMP-1 levels were higher in subjects homozygous for the 2G allele than in subjects with the 1G allele. The present study revealed a significant association of the MMP-1 -1607 1G/2G (rs1799750) gene promoter polymorphism with chronic pancreatitis, and it can be considered a biological marker in the etiology of chronic pancreatitis.

  4. Predictors of a health-promoting lifestyle and behaviors among low-income African American mothers and white mothers of chronically ill children.

    PubMed

    Tucker, Carolyn M; Butler, Ashley M; Loyuk, Imicuk S; Desmond, Frederic F; Surrency, Sharon L

    2009-02-01

    This study used Health Self-Empowerment (HSE) Theory as a framework for examining the predictors of engagement in both a health-promoting lifestyle and individual health-promoting behaviors among low-income African American mothers and non-Hispanic white mothers (N = 96), each of whom is the primary caregiver for a chronically ill adolescent. The individual health-promoting behaviors investigated are eating a healthy diet, exercising consistently, stress management practices, and health responsibility behaviors. The examined HSE Theory-based predictor variables were health self-efficacy, active coping, health motivation, and health self-praise. Multiple regression analyses revealed that these predictor variables together accounted for a significant amount of variance (67%) in level of engagement in a health-promoting lifestyle. Additionally, active coping, health self-praise, health self-efficacy, and health motivation were significant individual predictors of 1 or more individual health-promoting behaviors. Findings from this study suggest that further research should be conducted to assess the usefulness of HSE Theory in predicting level of engagement in health-promoting behaviors and to examine the effectiveness of HSE Theory-based interventions for increasing health-promoting behaviors among women similar to those in this study. The findings also suggest that health care providers should promote active coping, health self-praise, health self-efficacy, and health motivation to increase health-promoting behaviors among patients who are similar to those in this study.

  5. Long noncoding RNA HULC promotes cell proliferation by regulating PI3K/AKT signaling pathway in chronic myeloid leukemia.

    PubMed

    Lu, Yinghao; Li, Yan; Chai, Xiao; Kang, Qian; Zhao, Peng; Xiong, Jie; Wang, Jishi

    2017-04-05

    Aberrant expression of long noncoding RNA (lncRNA) HULC is associated with various human cancers. However, the role of HULC in chronic myeloid leukemia (CML) is unknown. In this study, we found that HULC was remarkably overexpressed in both leukemia cell lines and primary hematopoietic cells derived from CML patients. The increase in HULC expression was positively correlated with clinical stages in CML. Moreover, the knockdown of HULC significantly inhibited CML cell proliferation and induced apoptosis by repressing c-Myc and Bcl-2. Furthermore, inhibition of HULC enhanced imatinib-induced apoptosis of CML cells. Further experiments demonstrated that HULC silencing markedly suppressed the phosphorylation of PI3K and AKT, indicating that enhancement of imatinib-induced apoptosis by HULC inhibition is related with the reduction of c-Myc expression and inhibition of PI3K/Akt pathway activity. Furthermore, HULC could modulate c-Myc and Bcl-2 by miR-200a as an endogenous sponge. Taken together, these results reveal that HULC promotes oncogenesis in CML and suggest a potential strategy for the CML treatment.

  6. Transplantation of hUC-MSCs seeded collagen scaffolds reduces scar formation and promotes functional recovery in canines with chronic spinal cord injury

    PubMed Central

    Li, Xing; Tan, Jun; Xiao, Zhifeng; Zhao, Yannan; Han, Sufang; Liu, Dingyang; Yin, Wen; Li, Jing; Li, Juan; Wanggou, Siyi; Chen, Bing; Ren, Caiping; Jiang, Xingjun; Dai, Jianwu

    2017-01-01

    Spinal cord injury (SCI) can lead to locomotor deficits, and the repair of chronic SCI is considered one of the most challenging clinical problems. Although extensive studies have evaluated treatments for acute SCI in small animals, comparatively fewer studies have been conducted on large-animal SCI in the chronic phase, which is more clinically relevant. Here, we used a collagen-based biomaterial, named the NeuroRegen scaffold, loaded with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a canine chronic SCI model. To generate chronic SCI, the T8 spinal cord segment was removed by complete transection of the spinal cord. Two months later, glial scar tissue was removed and a NeuroRegen scaffold was transplanted into the lesion area. Functionalized NeuroRegen scaffold implantation promoted both locomotor recovery and endogenous neurogenesis in the lesion area. Moreover, some newly generated neurons successfully matured into 5-HT-positive neurons at 1 year post-injury. In addition, many regenerated axon fibers in the lesion area exhibited remyelination and synapse formation at 1 year post-injury in the functionalized NeuroRegen scaffold group. In conclusion, the NeuroRegen scaffold functionalized with hUC-MSCs is a promising potential therapeutic approach to chronic SCI that promotes neuronal regeneration, reduces glial scar formation, and ultimately improves locomotor recovery. PMID:28262732

  7. Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component

    PubMed Central

    2013-01-01

    Background Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. Methods/design This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre

  8. Ways of promoting health to patients with diabetes and chronic kidney disease from a nursing perspective in Vietnam: A phenomenographic study

    PubMed Central

    Pham, Lotta; Ziegert, Kristina

    2016-01-01

    Health promotion plays an important role in the management of diabetes and chronic kidney disease, especially when the prevalence of the disease is rising in Vietnam. Nurses have been identified to be the front figure in health promotion; however, little is written about how nurses in Vietnam work with these issues. Therefore, the aim of this study was to describe nurses’ conceptions about how health is promoted, with special focus on physically activity, for patients with type 2 diabetes (T2DM) and/or end-stage renal disease (ESRD). Individual interviews were done with 25 nurses working at two major hospitals in Hanoi, Vietnam. A phenomenographic approach was used to analyse the interviews. Nurses described how creating positive relationships and supporting patients to take part in their social context promoted health. Health was also promoted by educating patients and relatives about health and disease and by supporting patients to be physically active. The findings indicate that the Vietnamese nursing knowledge about health promotion needs to be gathered, and health promotion needs to be further integrated in the education. Further research is necessary to examine patients’ knowledge and attitudes about health and the efficiency of various health-promoting strategies in the Vietnamese context. PMID:27172515

  9. Association of health self-empowerment with health-promoting behaviors among chronically ill African American and non- Hispanic White adolescents.

    PubMed

    Tucker, Carolyn M; Wippold, Guillermo M; Smith, Tasia M; Desmond, Frederic F; Arthur, Tya M; Butler, Ashley M; Pauly, Rebecca R; Surrency, Sharon L

    2014-11-01

    Health Self-Empowerment Theory (health motivation, health self-efficacy, health self-praise, and active coping) was examined as a predictor of levels of engagement in four health-promoting behaviors (health responsibility behaviors, regular exercise, healthy eating, and stress management behaviors) among low-income African American adolescents and non-Hispanic White American adolescents living with at least one chronic illness. Eighty-seven participants completed measures of the Health Self-Empowerment Theory variables and of level of engagement in each of the four health-promoting behaviors. Regression analyses revealed that the combined Health Self-Empowerment Theory variables significantly predicted level of engagement in the four examined health-promoting behaviors. Additionally, active coping, health self-praise, and health motivation each significantly predicted one or more of the examined health-promoting behaviors. Health self-empowerment may be useful for informing interventions designed to foster engagement in health-promoting behaviors among low-income adolescents living with one or more chronic illnesses

  10. TLR-9 and IL-15 Synergy Promotes the In Vitro Clonal Expansion of Chronic Lymphocytic Leukemia B Cells

    PubMed Central

    Gupta, Rashmi; Boyle, Erin; Nieto, Jennifer; Lee, Hyunjoo; Stein, Joanna; Bandovic, Jela; Stankovic, Tatjana; Barrientos, Jacqueline; Kolitz, Jonathan E.; Allen, Steven L.; Rai, Kanti; Chu, Charles C.; Chiorazzi, Nicholas

    2015-01-01

    Clinical progression of B cell chronic lymphocytic leukemia (B-CLL) reflects the clone’s Ag receptor (BCR) and involves stroma-dependent B-CLL growth within lymphoid tissue. Uniformly elevated expression of TLR-9, occasional MYD88 mutations, and BCR specificity for DNA or Ags physically linked to DNA together suggest that TLR-9 signaling is important in driving B-CLL growth in patients. Nevertheless, reports of apoptosis after B-CLL exposure to CpG oligodeoxynucleotide (ODN) raised questions about a central role for TLR-9. Because normal memory B cells proliferate vigorously to ODN+IL-15, a cytokine found in stromal cells of bone marrow, lymph nodes, and spleen, we examined whether this was true for B-CLL cells. Through a CFSE-based assay for quantitatively monitoring in vitro clonal proliferation/survival, we show that IL-15 precludes TLR-9–induced apoptosis and permits significant B-CLL clonal expansion regardless of the clone’s BCR mutation status. A robust response to ODN+IL-15 was positively linked to presence of chromosomal anomalies (trisomy-12 or ataxia telangiectasia mutated anomaly + del13q14) and negatively linked to a very high proportion of CD38+ cells within the blood-derived B-CLL population. Furthermore, a clone’s intrinsic potential for in vitro growth correlated directly with doubling time in blood, in the case of B-CLL with Ig H chain V region–unmutated BCR and <30% CD38+ cells in blood. Finally, in vitro high-proliferator status was statistically linked to diminished patient survival. These findings, together with immunohistochemical evidence of apoptotic cells and IL-15–producing cells proximal to B-CLL pseudofollicles in patient spleens, suggest that collaborative ODN and IL-15 signaling may promote in vivo B-CLL growth. PMID:26136429

  11. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

    PubMed Central

    Xu, Wang-shu; Sun, Xuan; Song, Cheng-guang; Mu, Xiao-peng; Ma, Wen-ping; Zhang, Xing-hu; Zhao, Chuan-sheng

    2016-01-01

    Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia. PMID:27335557

  12. Novel Comparative Pattern Count Analysis Reveals a Chronic Ethanol-Induced Dynamic Shift in Immediate Early NF-κB Genome-wide Promoter Binding During Liver Regeneration

    PubMed Central

    Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

    2016-01-01

    Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1h post PHx. This set was associated with regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1h binding targets showed ethanol-specific differential expression through 6h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx. PMID:26847025

  13. Systematic Review and Meta-Analysis of Psychological Interventions to Promote Treatment Adherence in Children, Adolescents, and Young Adults With Chronic Illness

    PubMed Central

    McGrady, Meghan

    2014-01-01

    Objective This meta-analysis examined the effectiveness of recent adherence-promoting interventions for youth with chronic health conditions. Methods Peer-reviewed randomized controlled trials of adherence-promoting interventions for youth with a chronic illness published between 2007 and 2013 (n = 23) were reviewed. Intervention delivery (in-person vs. technology-based) and outcome measurement (e.g., self-report) were examined as potential moderators of treatment effects. Results Mean effect sizes were small at posttreatment (d = 0.20, 95% confidence interval (CI): 0.08, 0.31, n = 23) and follow-up (d = 0.29, 95% CI: 0.15, 0.43, n = 9). Intervention delivery and outcome measurement did not account for variation in treatment effects (p > .05). Conclusions The small treatment effects of recent adherence-promoting intervention (APIs) reflect the methodological limitations of the included studies and the need to reexamine the delivery and mechanisms of adherence-promoting interventions. PMID:24952359

  14. The -94Ins/DelATTG polymorphism in NFκB1 promoter modulates chronic hepatitis C and liver disease progression.

    PubMed

    Fakhir, Fatima-Zohra; Lkhider, Mustapha; Badre, Wafaa; Alaoui, Rhimou; Pineau, Pascal; Ezzikouri, Sayeh; Benjelloun, Soumaya

    2016-04-01

    Infection with Hepatitis C Virus (HCV) is one of the most important risk factor of hepatocellular carcinoma (HCC). HCV is suspected to induce HCC primarily through chronic inflammation and promotion of cirrhosis, a well-known pre-neoplastic condition. The NF-κB pathway is a key regulator of immune and inflammatory processes and plays a pivotal role in oncogenesis. Genetic variations affecting the pathway may alter NF-κB activity in response to HCV infection and contribute to liver tumorigenesis. The present study aims to evaluate the association between -94Ins/DelATTG (rs28362491) polymorphism in NF-κB1 gene promoter region and 2758G>A (rs696) single nucleotide polymorphism in the 3'UTR region of NFκBIA and the outcomes of HCV infection. In this case-control study, 559 subjects (343 patients with HCV infection including 237 mild chronic hepatitis patients and 106 patients with Advanced Liver Disease (AdLD), 78 individuals who naturally cleared HCV and 138 healthy subjects) were genotyped for the NFκB1 and NFκBIA SNPs using PCR-RFLP. Logistic regression was used to assess the association between polymorphisms and the outcome and progression of the infection. Variation at rs696 was not associated with HCV resolution or progression (P>0.05). By contrast, the Ins/Ins genotype was associated with a 4-fold increase of AdLD risk when compared to mild chronic hepatitis C (OR=4.69; 95% CI, 2.15-10.19; P=0.0001) and the risk was more pronounced when compared to healthy controls (OR=5.02; 95% CI, 2.30-10.98; P=0.00005). Furthermore, carriage of Ins allele at rs28362491 was significantly associated with higher viral loads (P=0.003). Our results suggest that variation in NFκB1 gene promoter modulates the progression of chronic hepatitis C toward advanced liver disease.

  15. Forkhead box C2 Promoter Variant c.-512C>T Is Associated with Increased Susceptibility to Chronic Venous Diseases

    PubMed Central

    Surendran, Sumi; Girijamma, Athira; Nair, Radhakrishnan; Ramegowda, Kalpana S.; Nair, Divya H.; Thulaseedharan, Jissa V.; Lakkappa, Ravikumar B.; Kamalapurkar, Giridhar; Kartha, Chandrasekharan C.

    2014-01-01

    Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (FoxC2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5′ and 3′ flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5′ flanking region and one in 3′ flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4±1.42 fold increased compared to saphenous veins from 20 normal subjects (p<0.01). FoxC2 protein was also significantly upregulated in varicose veins compared to control samples. The c.-512C>T (rs34221221: C>T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers Dll4 and Hey2 and downregulation of venous marker COUP-TFII. Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in

  16. Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients

    PubMed Central

    Wang, Xiao-Ling; Ren, Jian-Ping; Wang, Xue-Qing; Wang, Xiao-Hong; Yang, Shao-Fang; Xiong, Yi

    2016-01-01

    AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes. METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed. RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ2 = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ2 = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively

  17. Eccentric Ergometer Training Promotes Locomotor Muscle Strength but Not Mitochondrial Adaptation in Patients with Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    MacMillan, Norah J.; Kapchinsky, Sophia; Konokhova, Yana; Gouspillou, Gilles; de Sousa Sena, Riany; Jagoe, R Thomas; Baril, Jacinthe; Carver, Tamara E.; Andersen, Ross E.; Richard, Ruddy; Perrault, Hélène; Bourbeau, Jean; Hepple, Russell T.; Taivassalo, Tanja

    2017-01-01

    Eccentric ergometer training (EET) is increasingly being proposed as a therapeutic strategy to improve skeletal muscle strength in various cardiorespiratory diseases, due to the principle that lengthening muscle actions lead to high force-generating capacity at low cardiopulmonary load. One clinical population that may particularly benefit from this strategy is chronic obstructive pulmonary disease (COPD), as ventilatory constraints and locomotor muscle dysfunction often limit efficacy of conventional exercise rehabilitation in patients with severe disease. While the feasibility of EET for COPD has been established, the nature and extent of adaptation within COPD muscle is unknown. The aim of this study was therefore to characterize the locomotor muscle adaptations to EET in patients with severe COPD, and compare them with adaptations gained through conventional concentric ergometer training (CET). Male patients were randomized to either EET (n = 8) or CET (n = 7) for 10 weeks and matched for heart rate intensity. EET patients trained on average at a workload that was three times that of CET, at a lower perception of leg fatigue and dyspnea. EET led to increases in isometric peak strength and relative thigh mass (p < 0.01) whereas CET had no such effect. However, EET did not result in fiber hypertrophy, as morphometric analysis of muscle biopsies showed no increase in mean fiber cross-sectional area (p = 0.82), with variability in the direction and magnitude of fiber-type responses (20% increase in Type 1, p = 0.18; 4% decrease in Type 2a, p = 0.37) compared to CET (26% increase in Type 1, p = 0.04; 15% increase in Type 2a, p = 0.09). EET had no impact on mitochondrial adaptation, as revealed by lack of change in markers of mitochondrial biogenesis, content and respiration, which contrasted to improvements (p < 0.05) within CET muscle. While future study is needed to more definitively determine the effects of EET on fiber hypertrophy and associated underlying

  18. Eccentric Ergometer Training Promotes Locomotor Muscle Strength but Not Mitochondrial Adaptation in Patients with Severe Chronic Obstructive Pulmonary Disease.

    PubMed

    MacMillan, Norah J; Kapchinsky, Sophia; Konokhova, Yana; Gouspillou, Gilles; de Sousa Sena, Riany; Jagoe, R Thomas; Baril, Jacinthe; Carver, Tamara E; Andersen, Ross E; Richard, Ruddy; Perrault, Hélène; Bourbeau, Jean; Hepple, Russell T; Taivassalo, Tanja

    2017-01-01

    Eccentric ergometer training (EET) is increasingly being proposed as a therapeutic strategy to improve skeletal muscle strength in various cardiorespiratory diseases, due to the principle that lengthening muscle actions lead to high force-generating capacity at low cardiopulmonary load. One clinical population that may particularly benefit from this strategy is chronic obstructive pulmonary disease (COPD), as ventilatory constraints and locomotor muscle dysfunction often limit efficacy of conventional exercise rehabilitation in patients with severe disease. While the feasibility of EET for COPD has been established, the nature and extent of adaptation within COPD muscle is unknown. The aim of this study was therefore to characterize the locomotor muscle adaptations to EET in patients with severe COPD, and compare them with adaptations gained through conventional concentric ergometer training (CET). Male patients were randomized to either EET (n = 8) or CET (n = 7) for 10 weeks and matched for heart rate intensity. EET patients trained on average at a workload that was three times that of CET, at a lower perception of leg fatigue and dyspnea. EET led to increases in isometric peak strength and relative thigh mass (p < 0.01) whereas CET had no such effect. However, EET did not result in fiber hypertrophy, as morphometric analysis of muscle biopsies showed no increase in mean fiber cross-sectional area (p = 0.82), with variability in the direction and magnitude of fiber-type responses (20% increase in Type 1, p = 0.18; 4% decrease in Type 2a, p = 0.37) compared to CET (26% increase in Type 1, p = 0.04; 15% increase in Type 2a, p = 0.09). EET had no impact on mitochondrial adaptation, as revealed by lack of change in markers of mitochondrial biogenesis, content and respiration, which contrasted to improvements (p < 0.05) within CET muscle. While future study is needed to more definitively determine the effects of EET on fiber hypertrophy and associated underlying

  19. Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

    PubMed

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2015-07-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by angiotensin II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease.

  20. Student-facilitated health promotion intervention for chronic disease self-management in at-risk elders reflections from the field.

    PubMed

    Seymour, Connie J; Cannon, Stephen

    2010-01-01

    A student-facilitated and faculty-supervised health promotion program for chronic disease management in at-risk elders was developed based on the belief that individual contact with high-risk elders will facilitate improved health behaviors while enhancing the real-life experiences of students through interdisciplinary collaboration and community-based learning. Subjects were seven students enrolled as health professions academic majors at the university who served as student health advocates in the Healthy Elder Living Program (HELP). The data collected included student reflection questionnaires, field notes from the HELP staff, and communication logs between the HELP coordinator and students. As student health advocates, the students made visits to at-risk elders to reinforce recommendations from health care providers, to review adherence to the Health Promotion Inventory (HPI), and to interact socially with the client through discussion of health- and non-health-related issues. A training model for health promotion was developed based on identification of four common themes of student performance as health advocates. Overall, students demonstrated a greater appreciation for the complexity of social, psychological, and physical aspects of chronic disease as a result of participation in this program for at-risk elders. They were able to apply professional skills learned in the classroom while providing a needed service to elders. At-risk clients also benefited from the HELP intervention, showing improved physical performance and less depression.

  1. Chronic low-level arsenite exposure through drinking water increases blood pressure and promotes concentric left ventricular hypertrophy in female mice.

    PubMed

    Sanchez-Soria, Pablo; Broka, Derrick; Monks, Sarah L; Camenisch, Todd D

    2012-04-01

    Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic-treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic-exposed animals show an RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular-related mortalities. These results suggest that chronic low-level arsenite exposure promotes the development of hypertension and the comorbidity of concentric hypertrophy.

  2. Chronic Low-level Arsenite Exposure through Drinking Water Increases Blood Pressure and Promotes Concentric Left Ventricular Hypertrophy in Female Mice

    PubMed Central

    Sanchez-Soria, Pablo; Broka, Derrick; Monks, Sarah L.; Camenisch, Todd D.

    2013-01-01

    Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding on how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses, as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic exposed animals show a RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular related mortalities. These results suggest that chronic low level arsenite exposure promotes the development of hypertension, and the co-morbidity of concentric hypertrophy. PMID:22215511

  3. Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues.

    PubMed

    Kobayashi, T; Ohta, Y; Yoshino, J; Nakazawa, S

    2001-01-01

    Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing-promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg(-1)x 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing-promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration

  4. [Overview of clinical study on traditional Chinese medicine invigorating spleen and stomach, promoting blood circulation and remove blood stasis in treatment of chronic atrophic gastritis].

    PubMed

    Liu, Ming; Liu, Zhen

    2012-11-01

    In recent years, traditional Chinese medicines invigorating spleen and stomach, promoting blood circulation and removing blood stasis have made fruitful achievements in the treatment of chronic atrophic gastritis (CAG) and remarkable curative effects in eliminating clinical signs, enhancing the mucosal barrier, improving submucosal microcirculation, prompting submucosal atrophic glands and atypical hyperplasia reversal. This essay summarizes reports and literatures for clinical studies on CAG in recent years, and discusses its etiology, pathogenesis and clinical administration of traditional Chinese medicine and western medicine, in order to provide ideas and methods for CAG treatment with traditional Chinese medicines.

  5. A novel pathway in NSCLC cells: miR‑191, targeting NFIA, is induced by chronic hypoxia, and promotes cell proliferation and migration.

    PubMed

    Zhao, Jia; Qiao, Cheng-Rui; Ding, Zheng; Sheng, Yin-Liang; Li, Xiang-Nan; Yang, Yang; Zhu, Deng-Yan; Zhang, Chun-Yang; Liu, Dong-Lei; Wu, Kai; Zhao, Song

    2017-03-01

    MicroRNAs (miRs) have emerged as being important in cancer biology. miR‑191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)‑1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR‑191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in non‑small cell lung cancer (NSCLC) cells in patients in vivo. However, the levels of miR‑191 remained unchanged in SK‑MES‑1, A549 and NCI‑H460 NSCLC cell lines, compared with the level in the normal HBE lung cell line, however, the levels were markedly upregulated in these NSCLC cell lines under conditions of chronic hypoxia. Subsequently, an miR‑191 mimic was transfected into the NSCLC cell lines to examine its effect on the progression of the NSCLC cells in vitro. The data obtained using MTT and Cell counting kit‑8 assays revealed that miR‑191 had no effect on the proliferation of the cells under normal condition, however, their proliferation was promoted under mild hypoxic conditions. In addition, the results of a Transwell migration assay showed that miR‑191 had a promoting effect on NSCLC cell migration under the conditions of chronic hypoxia. Furthermore, the TargetScan bioinformatics server and 3'-untranslated region luciferase reporter assay indicated that the transcription factor, nuclear factor 1α (NFIA) was a target of miR‑191. Subsequent western blot analysis showed that, in chronic‑hypoxia, the protein levels of NFIA and the tumor suppressor, CCAAT-enhancer-binding protein α, were sharply reduced in A549 cells. In conclusion, miR‑191 was induced by chronic hypoxia and promoted the proliferation and migration of NSCLC cells under chronic hypoxic conditions. This promotion may be associated with its targeting of NFIA. The present findings may

  6. The importance of a daily rhythm in a supportive environment--promoting ability in activities in everyday life among older women living alone with chronic pain.

    PubMed

    Cederbom, Sara; Wågert, Petra von Heideken; Söderlund, Anne; Söderbäck, Maja

    2014-01-01

    The aim of this study was to explore how older women living alone with chronic musculoskeletal pain, describe their ability in performing activities in everyday life and what could promote their ability in activities in everyday life as well as their perceived meaning of a changed ability to perform activities in everyday life. Qualitative interviews were conducted with 12 women, and an inductive content analysis was used. The results showed the importance of a daily rhythm of activities. Activities included in the daily rhythm were socializing with family and friends, physical activities, doing own activities as well as activities supported by relatives and the community. The activities described by the women also promoted their ability in activities in everyday life. Other findings were the women's perceived meaning of being independent and maintaining that independency, along with the meaning of accepting and adapting to a changed life situation. This paper concludes that it is important to be sensitive of individual needs regarding the daily rhythm of activities when health-care professionals intervene in the activities in everyday life of older women living alone, promote the women's independency, and enable them to participate in the community. Implications for Rehabilitation A daily rhythm of activities is important for older women who live alone with chronic musculoskeletal pain. The importance of health-care professionals being sensitive to individual needs to promote ability in activities in everyday life and to encourage the everyday activities into a daily rhythm. Facilitate the women's desire and will of independency, despite their needs of help from their environment to manage their everyday life.

  7. Encouraging couples to change: a motivational assessment to promote well-being in people with chronic pain and their partners.

    PubMed

    Miller-Matero, Lisa Renee; Cano, Annmarie

    2015-02-01

    Motivating people with chronic pain to engage in therapy can be difficult, especially when individuals have not experienced adequate pain management. Therefore, it may be useful for clinicians to use a motivational assessment as a part of treatment to help patients achieve immediate benefits. Additionally, because the social context impacts chronic illness, the significant other should be included in the assessment. This article describes a motivational assessment that was developed for people with chronic pain and their partners. The motivational assessment begins with gathering information from questionnaires that each partner completes, conducting a semi-structured interview about the couples' relationship and pain history, and observing the couples converse about pain coping. Next, tailored feedback is provided to each couple regarding their strengths and weaknesses with suggestions for how to improve their relationship and pain coping skills. This tailored feedback engages the couple in this conversation by adhering to the principles of motivational interviewing. A case example of a couple who completed this motivational assessment is described. This assessment resulted in immediate improvements in marital satisfaction, pain severity, and mood for the couple. This article provides a guide to clinicians for using a motivational assessment to help patients with a chronic illness achieve immediate benefits. Wiley Periodicals, Inc.

  8. Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.

    PubMed

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2016-09-01

    Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. The purpose of this study was to evaluate skin barrier function during chronic liver injury. Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.

  9. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia

    PubMed Central

    Farooqui, M; Li, Y; Rogers, T; Poonawala, T; Griffin, R J; Song, C W; Gupta, K

    2007-01-01

    Morphine and its congener opioids are the main therapy for severe pain in cancer. However, chronic morphine treatment stimulates angiogenesis and tumour growth in mice. We examined if celecoxib (a cyclooxygenase-2 (COX-2) inhibitor) prevents morphine-induced tumour growth without compromising analgesia. The effect of chronic treatment with celecoxib (by gavage) and/or morphine (subcutaneously), or PBS on tumour prostaglandin E2 (PGE2), COX-2, angiogenesis, tumour growth, metastasis, pain behaviour and survival was determined in a highly invasive SCK breast cancer model in A/J mice. Two weeks of chronic morphine treatment at clinically relevant doses stimulates COX-2 and PGE2 (4.5-fold compared to vehicle alone) and angiogenesis in breast tumours in mice. This is accompanied by increased tumour weight (∼35%) and increased metastasis and reduced survival. Co-administration of celecoxib prevents these morphine-induced effects. In addition, morphine and celecoxib together provided better analgesia than either agent alone. Celecoxib prevents morphine-induced stimulation of COX-2, PGE2, angiogenesis, tumour growth, metastasis and mortality without compromising analgesia in a murine breast cancer model. In fact, the combination provided significantly better analgesia than with morphine or celecoxib alone. Clinical trials of this combination for analgesia in chronic and severe pain in cancer are warranted. PMID:17971769

  10. Does China's new cooperative medical scheme promote rural elders' access to healthcare services in relation to chronic conditions?

    PubMed Central

    Dai, Baozhen

    2015-01-01

    Background This study examined use of healthcare services by elderly people with a long-term condition living in rural China and participating in that country's New Cooperative Medical Scheme (NCMS). Methods Data were taken from the 2009 China Health and Nutrition Survey. Results The study results showed that education level and annual income were low among rural elders (aged ≥65 years); the illiteracy rate was 58.0% (200/345) and 67.6% (92/136) had an annual income of less than 5000 Chinese yuan renminbi. The elders had low rates of treatment and use of preventive healthcare services while the prevalence of chronic disease was highest among them when compared to other age groups. Among the few elders who received preventive healthcare, most received it at village clinics. Conclusions Preventive healthcare services and chronic disease management are urgently needed by rural elders in China. NCMS should initiate payments to township health centers to enable them to undertake community outreach and education campaigns among rural residents, and train village doctors in standard chronic condition management and prevention, with prioritization of the provision of prevention and management of chronic conditions by village clinics. PMID:25091022

  11. Chronic administration tetrahydroxystilbene glucoside promotes hippocampal memory and synaptic plasticity and activates ERKs, CaMKII and SIRT1/miR-134 in vivo.

    PubMed

    Chen, Tao; Yang, Yuan-Jian; Li, Yan-Kun; Liu, Jing; Wu, Peng-Fei; Wang, Fang; Chen, Jian-Guo; Long, Li-Hong

    2016-08-22

    Polygonum multiflorum Thunb is a traditional Chinese medicine with anti-aging effect. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is generally considered as the main active component in Polygonum multiflorum Thunb. However, the effect of TSG on memory in adult is unclear till now. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a polyphenols compound from Polygonum multiflorum Thunb. The present study aimed to evaluate the effect of chronic administration of TSG on hippocampal memory in normal mice. Behavioral test, electrophysiology and golgi staining were used to evaluate the effect of TSG on hippocampus-dependent memory and synaptic plasticity. Western blotting was used to determine the expression of ERK1/2, CaMKII, and SIRT1. Real-time quantitative PCR was explored to measure miR-134. It was found that TSG enhanced hippocampus-dependent contextual fear memory and novel object recognition, facilitated hippocampal LTP and increased dendrite spine density in the CA1 region of hippocampus. TSG obviously promoted the phosphorylations of ERK1/2, CaMKII, CREB and the expression of BDNF in the hippocampus, with upregulation of silent information regulator 1 (SIRT1) and downregulation of miR-134. Chronic administration of TSG promotes hippocampal memory in normal mice, suggesting that supplementary of TSG might serve as an enhancement of memory. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Mindfulness-Based Stress Reduction in Advanced Nursing Practice: A Nonpharmacologic Approach to Health Promotion, Chronic Disease Management, and Symptom Control.

    PubMed

    Williams, Hants; Simmons, Leigh Ann; Tanabe, Paula

    2015-09-01

    The aim of this article is to discuss how advanced practice nurses (APNs) can incorporate mindfulness-based stress reduction (MBSR) as a nonpharmacologic clinical tool in their practice. Over the last 30 years, patients and providers have increasingly used complementary and holistic therapies for the nonpharmacologic management of acute and chronic diseases. Mindfulness-based interventions, specifically MBSR, have been tested and applied within a variety of patient populations. There is strong evidence to support that the use of MBSR can improve a range of biological and psychological outcomes in a variety of medical illnesses, including acute and chronic pain, hypertension, and disease prevention. This article will review the many ways APNs can incorporate MBSR approaches for health promotion and disease/symptom management into their practice. We conclude with a discussion of how nurses can obtain training and certification in MBSR. Given the significant and growing literature supporting the use of MBSR in the prevention and treatment of chronic disease, increased attention on how APNs can incorporate MBSR into clinical practice is necessary. © The Author(s) 2015.

  13. Chronic obstructive pulmonary disease in stage I non-small cell lung cancer that underwent anatomic resection: the role of a recurrence promoter.

    PubMed

    Kuo, Chih-Hsi; Wu, Ching-Yang; Lee, Kang-Yun; Lin, Shu-Min; Chung, Fu-Tsai; Lo, Yu-Lun; Liu, Chien-Ying; Hsiung, Te-Chih; Yang, Cheng-Ta; Wu, Yi-Cheng

    2014-08-01

    Despite the use of anatomic resection, the post-surgical recurrence rate remains high in early-stage non-small cell lung cancer (NSCLC). Chronic inflammation plays a role in the mechanism that promotes tumor initiation. This study aimed to investigate the association between recurrence outcome and chronic inflammation-related co-morbidities in early-stage resected NSCLC. A review of medical records for recurrence outcome and co-morbidities, in terms of chronic obstructive pulmonary disease (COPD), DM, asthma and cardiovascular diseases, was performed with 181 patients with stage I NSCLC that underwent anatomic resection. Subjects with T descriptors as T2a disease (49.5 vs. 28.0%, p < 0.05) and the presence of COPD (42.4 vs. 20.7%, p < 0.01) had a higher risk of tumor recurrence. Univariate analysis for recurrence-free survival showed T descriptor as T2a (21.5 months vs. NR, p < 0.05) and the presence of COPD (20.5 months vs. NR, p < 0.01) as significant factors predicting reduced survival. The presence of COPD (HR: 1.98; 95% CI, 1.29-.02, p < 0.01) and T descriptor as T2a (HR: 2.01; 95% CI, 1.04-3.91, p < 0.05) remain independent predictors of reduced recurrence-free survival in the Cox regression model. Patients with COPD were at higher risk of brain recurrence (OR: 7.88; 95% CI, 1.50-41.3, p < 0.01). In contrast, patients without COPD showed a tendency toward recurrence in bone and liver (OR: 4.13; 95% CI, 1.08-15.8, p = 0.05). Subjects with COPD and T2a disease had a higher risk of recurrence. The role of COPD as a recurrence promoter merits further prospective investigation.

  14. Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy.

    PubMed

    Lange, Christian Markus; Bojunga, Jörg; Ramos-Lopez, Elizabeth; von Wagner, Michael; Hassler, Angela; Vermehren, Johannes; Herrmann, Eva; Badenhoop, Klaus; Zeuzem, Stefan; Sarrazin, Christoph

    2011-05-01

    Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in hepatitis C virus (HCV) genotype 1 patients. We, therefore, performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms with functional relevance within the vitamin D cascade on chronic hepatitis C and its treatment. Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and 1α-hydroxylase were determined in a cohort of 468 HCV genotype 1, 2, and 3 infected patients who were treated with interferon-alfa based regimens. Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D(3)<10 ng/ml in 25% versus 12%, p<0.00001). 25(OH)D(3) deficiency correlated with SVR in HCV genotype 2 and 3 patients (50% and 81% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.0001). In addition, the CYP27B1-1260 promoter polymorphism rs10877012 had substantial impact on 1,25-dihydroxyvitamin D serum levels (72, 61, and 60 pmol/ml for rs10877012 AA, AC, and CC, respectively, p=0.04) and on SVR rates in HCV genotype 1, 2, and 3 infected patients (77% and 65% versus 42% for rs10877012 AA, AC, and CC, respectively, p=0.02). Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25-hydroxyvitamin D levels and CYP27B1-1260 promoter polymorphism leading to reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotype 1, 2, and 3 infected patients. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  15. A novel community-based model to enhance health promotion, risk factor management and chronic disease prevention.

    PubMed

    Carson, Shannon Ryan; Carr, Caroline; Kohler, Graeme; Edwards, Lynn; Gibson, Rick; Sampalli, Tara

    2014-01-01

    Chronic disease is a highly expensive but preventable problem to the healthcare system. Evidence suggests that impacting modifiable behaviours and risk management factors in the areas of physical inactivity, unhealthy diet, stress and obesity can alleviate the burden of chronic disease problem to a large extent. Despite this recognition, the challenge is embedding these recognized priorities into the community and in primary care in a sustainable and meaningful manner. Primary Health Care in Capital Health responded to this challenge by developing and implementing a free, interprofessional and community-based service, namely, the Community Health Teams (CHTs), that offers health and wellness, risk factor management, wellness navigation and behaviour-based programming. In this paper, the development and implementation of the CHTs are discussed. Preliminary outcomes for the model are significant and promising. Formal and large-scale studies are planned to validate these outcomes with additional research rigour. Copyright © 2014 Longwoods Publishing.

  16. Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats

    PubMed Central

    Hilliard, Lucinda M.; Colafella, Katrina M. Mirabito; Bulmer, Louise L.; Puelles, Victor G.; Singh, Reetu R.; Ow, Connie P. C.; Gaspari, Tracey; Drummond, Grant R.; Evans, Roger G.; Vinh, Antony; Denton, Kate M.

    2016-01-01

    Epidemiological evidence links recurrent dehydration associated with periodic water intake with chronic kidney disease (CKD). However, minimal attention has been paid to the long-term impact of periodic water intake on the progression of CKD and underlying mechanisms involved. Therefore we investigated the chronic effects of recurrent dehydration associated with periodic water restriction on arterial pressure and kidney function and morphology in male spontaneously hypertensive rats (SHR). Arterial pressure increased and glomerular filtration rate decreased in water-restricted SHR. This was observed in association with cyclic changes in urine osmolarity, indicative of recurrent dehydration. Additionally, water-restricted SHR demonstrated greater renal fibrosis and an imbalance in favour of pro-inflammatory cytokine-producing renal T cells compared to their control counterparts. Furthermore, urinary NGAL levels were greater in water-restricted than control SHR. Taken together, our results provide significant evidence that recurrent dehydration associated with chronic periodic drinking hastens the progression of CKD and hypertension, and suggest a potential role for repetitive bouts of acute renal injury driving renal inflammatory processes in this setting. Further studies are required to elucidate the specific pathways that drive the progression of recurrent dehydration-induced kidney disease. PMID:27653548

  17. Phosphatidylethanol accumulation promotes intestinal hyperplasia by inducing ZONAB-mediated cell density increase in response to chronic ethanol exposure.

    PubMed

    Pannequin, Julie; Delaunay, Nathalie; Darido, Charbel; Maurice, Tangui; Crespy, Philippe; Frohman, Michael A; Balda, Maria S; Matter, Karl; Joubert, Dominique; Bourgaux, Jean-François; Bali, Jean-Pierre; Hollande, Frédéric

    2007-11-01

    Chronic alcohol consumption is associated with increased risk of gastrointestinal cancer. High concentrations of ethanol trigger mucosal hyperregeneration, disrupt cell adhesion, and increase the sensitivity to carcinogens. Most of these effects are thought to be mediated by acetaldehyde, a genotoxic metabolite produced from ethanol by alcohol dehydrogenases. Here, we studied the role of low ethanol concentrations, more likely to mimic those found in the intestine in vivo, and used intestinal cells lacking alcohol dehydrogenase to identify the acetaldehyde-independent biological effects of ethanol. Under these conditions, ethanol did not stimulate the proliferation of nonconfluent cells, but significantly increased maximal cell density. Incorporation of phosphatidylethanol, produced from ethanol by phospholipase D, was instrumental to this effect. Phosphatidylethanol accumulation induced claudin-1 endocytosis and disrupted the claudin-1/ZO-1 association. The resulting nuclear translocation of ZONAB was shown to mediate the cell density increase in ethanol-treated cells. In vivo, incorporation of phosphatidylethanol and nuclear translocation of ZONAB correlated with increased proliferation in the colonic epithelium of ethanol-fed mice and in adenomas of chronic alcoholics. Our results show that phosphatidylethanol accumulation after chronic ethanol exposure disrupts signals that normally restrict proliferation in highly confluent intestinal cells, thus facilitating abnormal intestinal cell proliferation.

  18. Potential role of complementary and alternative health care providers in chronic disease prevention and health promotion: an analysis of National Health Interview Survey data.

    PubMed

    Hawk, Cheryl; Ndetan, Harrison; Evans, Marion Willard

    2012-01-01

    To make a preliminary assessment of the potential role of the most frequently used licensed or certified United States complementary and alternative medicine (CAM) providers in chronic disease prevention and health promotion. This was a secondary analysis of the 2007 United States National Health Interview Survey (NHIS), the most recent to include CAM use. The Adult Core Sample, Person and Adult Complementary and Alternative Medicine data files were included. NHIS's complete survey design structure (strata, cluster and survey weights) was applied in generating national population estimates for CAM usage. Chiropractic or osteopathic manipulation (8.4%) and massage (8.1%) were most commonly used; acupuncture was used by 1.4% and naturopathy by 0.3% of respondents. Substantial proportions of respondents reported using CAM for wellness and disease prevention, and informed their medical physician of use. Fifty-four percent were overweight or obese, 22.0% physically inactive, and 17.4% smokers; 18.0% reported hypertension, 19.6% high cholesterol, and 9.1% prediabetes or diabetes. CAM users present with risk factors which are priority public health issues. This implies a need to train CAM providers in evidence-based health promotion counseling. CAM encounters may provide opportunities to coordinate health promotion and prevention messages with patients' primary care providers. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Acute and Chronic Whole-Body Vibration Exercise does not Induce Health-Promoting Effects on The Blood Profile

    PubMed Central

    Theodorou, Anastasios A.; Gerodimos, Vassilis; Karatrantou, Konstantina; Paschalis, Vassilis; Chanou, Konstantina; Jamurtas, Athanasios Z.; Nikolaidis, Michalis G.

    2015-01-01

    Whole-body vibration (WBV) exercise is an alternative, popular and easy exercise that can be followed by general public. Therefore, the aim of the present study was to investigate the influence of acute and chronic WBV exercise on health-related parameters. Twenty-eight women were allocated into a control group (n=11, mean ±SEM: age, 43.5 ±1.5 yr; body mass, 66.1 ±3.1 kg; height, 160.6 ±1.5 cm) and a vibration group (n=17, mean ±SEM: age, 44.0 ±1.0 yr; body mass, 67.1 ±2.2 kg; height, 162.5 ±1.5 cm). After baseline assessments, participants of the experimental group performed WBV training 3 times/week for 8 weeks. Before and after the chronic WBV exercise, the participants of the vibration group performed one session of acute WBV exercise. Blood chemistry measurements (hematology, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, glucose, insulin, triacylglycerols, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B and lipoprotein, thiobarbituric-acid reactive substances, protein carbonyls, total antioxidant capacity, uric acid, albumin and bilirubin) were assessed pre-exercise and post-exercise at the first and eighth week of WBV exercise in both control and vibration groups. The results failed to support any effect of both acute and chronic WBV exercise on biochemical health-related parameters. However, it seems that WBV exercise is a safe way of training without a negative impact on muscle and liver functionality. PMID:26240654

  20. A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures.

    PubMed

    Bailey, H Randolph; Beck, David E; Billingham, Richard P; Binderow, Sander R; Gottesman, Lester; Hull, Tracy L; Larach, Sergio W; Margolin, David A; Milsom, Jeffrey W; Potenti, Fabio M; Rafferty, Janice F; Riff, Dennis S; Sands, Lawrence R; Senagore, Anthony; Stamos, Michael J; Yee, Laurence F; Young-Fadok, Tonia M; Gibbons, Robert D

    2002-09-01

    The aim of this study was to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures. A randomized, double-blind study of intra-anally applied nitroglycerin ointment (Anogesic) was conducted in 17 centers in 304 patients with chronic anal fissures. The patients were randomly assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day), for up to eight weeks. A dose-measuring device standardized the delivery of 374 mg ointment. Healing of fissures (complete reepithelialization) was assessed by physical examination using an observer unaware of treatment allocation. The subjects assessed pain intensity daily by completing a diary containing a visual analog scale for average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation. There were no significant differences in fissure healing among any of the treatment groups; all groups, including placebo had a healing rate of approximately 50 percent. This rate of placebo response was inexplicably higher than previously reported in the literature. Treatment with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P < 0.0002) decrease in average pain intensity compared with vehicle as assessed by patients with a visual analog scale. The decreases were observed by Day 4 of treatment. At 8 weeks the magnitude of the difference between 0.4 percent nitroglycerin and control was a 21 percent reduction in average pain. Treatment was well tolerated, with only 3.29 percent of patients discontinuing treatment because of headache. Headaches were the primary adverse event and were dose related. Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures.

  1. Upregulation of CB₁ receptor binding in the ventromedial prefrontal cortex promotes proactive stress-coping strategies following chronic stress exposure.

    PubMed

    McLaughlin, R J; Hill, M N; Dang, S S; Wainwright, S R; Galea, L A M; Hillard, C J; Gorzalka, B B

    2013-01-15

    Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB(1) receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB(1) receptor binding site density in the PFC. Our goal in these studies was to examine the effects of CUS on the density of CB(1) receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB(1) receptor maximal binding site density (B(max)) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB(1) receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB(1) receptor antagonist AM251 prior to swim stress. Moreover, local CB(1) receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB(1) receptor B(max) observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.

  2. Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10.

    PubMed

    Kaesler, Susanne; Volz, Thomas; Skabytska, Yuliya; Köberle, Martin; Hein, Ulrike; Chen, Ko-Ming; Guenova, Emmanuella; Wölbing, Florian; Röcken, Martin; Biedermann, Tilo

    2014-07-01

    Atopic dermatitis (AD) is a T cell-mediated inflammatory skin disease, with TH2 cells initiating acute flares. This inflamed skin is immediately colonized with Staphylococcus aureus, which provides potent Toll-like receptor (TLR) 2 ligands. However, the effect of TLR2 ligands on the development of TH2-mediated AD inflammation remains unclear. We investigated the progression of TH2 cell-mediated dermatitis after TLR2 activation. Using models for acute AD with TH2 cells initiating cutaneous inflammation, we investigated the consequences of TLR2 activation. Dermatitis, as assessed by changes in ear skin thickness and histology, was analyzed in different BALB/c and C57BL/6 wild-type and knockout mouse strains, and immune profiling was carried out by using in vitro and ex vivo cytokine analyses. We show that TH2 cell-mediated dermatitis is self-limiting and depends on IL-4. Activation of TLR2 converted the limited TH2 dermatitis to chronic cutaneous inflammation. We demonstrate that the concerted activation of TLR2 and IL-4 receptor on dendritic cells is sufficient for this conversion. As an underlying mechanism, we found that the combinatorial sensing of the innate TLR2 ligands and the adaptive TH2 cytokine IL-4 suppressed anti-inflammatory IL-10 and consequently led to the exacerbation and persistence of dermatitis. Our data demonstrate that innate TLR2 signals convert transient TH2 cell-mediated dermatitis into persistent inflammation, as seen in chronic human AD, through IL-4-mediated suppression of IL-10. For the first time, these data show how initial AD lesions convert to chronic inflammation and provide another rationale for targeting IL-4 in patients with AD, a therapeutic approach that is currently under development. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation

    PubMed Central

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

    Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice. PMID:26057238

  4. Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype.

    PubMed

    Lefevre, Gaelle M; Patel, Sanjeevkumar R; Kim, Doyeob; Tessarollo, Lino; Dressler, Gregory R

    2010-10-28

    Methylation of specific lysine residues in core histone proteins is essential for embryonic development and can impart active and inactive epigenetic marks on chromatin domains. The ubiquitous nuclear protein PTIP is encoded by the Paxip1 gene and is an essential component of a histone H3 lysine 4 (H3K4) methyltransferase complex conserved in metazoans. In order to determine if PTIP and its associated complexes are necessary for maintaining stable gene expression patterns in a terminally differentiated, non-dividing cell, we conditionally deleted PTIP in glomerular podocytes in mice. Renal development and function were not impaired in young mice. However, older animals progressively exhibited proteinuria and podocyte ultra structural defects similar to chronic glomerular disease. Loss of PTIP resulted in subtle changes in gene expression patterns prior to the onset of a renal disease phenotype. Chromatin immunoprecipitation showed a loss of PTIP binding and lower H3K4 methylation at the Ntrk3 (neurotrophic tyrosine kinase receptor, type 3) locus, whose expression was significantly reduced and whose function may be essential for podocyte foot process patterning. These data demonstrate that alterations or mutations in an epigenetic regulatory pathway can alter the phenotypes of differentiated cells and lead to a chronic disease state.

  5. Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease.

    PubMed

    Stankovic, Marija; Kojic, Snezana; Djordjevic, Valentina; Tomovic, Andrija; Nagorni-Obradovic, Ljudmila; Petrovic-Stanojevic, Natasa; Mitic-Milikic, Marija; Radojkovic, Dragica

    2016-07-01

    The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR = 2.7, P = 0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR = 4.38, P = 0.005) and severity (P = 0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P < 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P < 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016. © 2016 Wiley Periodicals, Inc.

  6. Hematopoietic stem and progenitor cell activation during chronic dermatitis provoked by constitutively active aryl-hydrocarbon receptor driven by Keratin 14 promoter.

    PubMed

    Murakami, Shohei; Yamamoto, Masayuki; Motohashi, Hozumi

    2014-03-01

    Polycyclic aromatic hydrocarbons (PAHs) activate aryl-hydrocarbon receptor (AhR). Because PAHs are known as a risk factor for allergic diseases, PAH-induced AhR activation is expected to be involved in the development of the pathology. We previously generated transgenic mice expressing a constitutively active AhR (AhR-CA) under the control of Keratin 14 (K14) promoter (AhR-CA mouse). The mice develop chronic dermatitis with immune imbalance toward Th2 predominance, indicating that the AhR activation driven by K14 promoter provokes allergic response. Because hematopoietic cells actively participate in the development of allergic inflammation, it is important to understand the hematopoietic status under allergic conditions. To clarify how the K14 promoter-driven AhR activation influences hematopoiesis, we analyzed bone marrow and spleen of AhR-CA mice. We verified that AhR-CA was expressed in keratinocytes and thymic epithelial cells but not in hematopoietic cells. The AhR-CA mice with full-blown dermatitis exhibited leukocytosis and skewed differentiation of hematopoietic progenitor cells toward granulocyte-monocyte lineages. They also showed a significant expansion of short-term hematopoietic stem cells and multipotent progenitors and a subtle reduction in long-term hematopoietic stem cells (LT-HSCs). Their spleens were enlarged and abundantly accumulated hematopoietic stem and progenitor cells. AhR-CA mice at the early stage of dermatitis did not show leukocytosis or splenomegaly but exhibited the granulocyte-monocyte skewing and the reduction in LT-HSCs. Thus, AhR activation driven by K14 promoter already alters the hematopoietic differentiation and reduces LT-HSCs at the initial stage of dermatitis development. These results suggest that nonhematopoietic exposure to PAHs triggers allergic response and concomitantly affects hematopoiesis.

  7. IL-21 promotes lupus-like disease in chronic graft-versus-host disease through both CD4 T cell- and B cell-intrinsic mechanisms.

    PubMed

    Nguyen, Vinh; Luzina, Irina; Rus, Horea; Tegla, Cosmin; Chen, Ching; Rus, Violeta

    2012-07-15

    T cell-driven B cell hyperactivity plays an essential role in driving autoimmune disease development in systemic lupus erythematosus. IL-21 is a member of the type I cytokine family with pleiotropic activities. It regulates B cell differentiation and function, promotes T follicular helper (T(FH)) cell and Th17 cell differentiation, and downregulates the induction of T regulatory cells. Although IL-21 has been implicated in systemic lupus erythematosus, the relative importance of IL-21R signaling in CD4(+) T cells versus B cells is not clear. To address this question, we took advantage of two induced models of lupus-like chronic graft-versus-host disease by using wild-type or IL-21R(-/-) mice as donors in the parent-into-F1 model and as hosts in the Bm12→B6 model. We show that IL-21R expression on donor CD4(+) T cells is essential for sustaining T(FH) cell number and subsequent help for B cells, resulting in autoantibody production and more severe lupus-like renal disease, but it does not alter the balance of Th17 cells and regulatory T cells. In contrast, IL-21R signaling on B cells is critical for the induction and maintenance of germinal centers, plasma cell differentiation, autoantibody production, and the development of renal disease. These results demonstrate that IL-21 promotes autoimmunity in chronic graft-versus-host disease through both CD4(+) T cell- and B cell-intrinsic mechanisms and suggest that IL-21 blockade may attenuate B cell hyperactivity, as well as the aberrant T(FH) cell pathway that contributes to lupus pathogenesis.

  8. What's in a name? Concordance is better than adherence for promoting partnership and self-management of chronic disease.

    PubMed

    Randall, Sue; Neubeck, Lis

    2016-01-01

    The choice of language health professionals use to discuss self-management of chronic disease is important and influences patients' self-management. The words compliance, adherence and concordance are used to discuss patients' agreement with prescribed treatment plans, but have different tone and meanings. Models of care linked to the words compliance and adherence are underpinned by interactions between patients and healthcare providers that merely reinforce instructions about treatments. The 'patient-professional partnership' is introduced as a model by Bodenheimer et al. (2002, p. 2469) whereby true partnership working should be an opportunity to pool the expertise of both parties to arrive at mutually agreed goals in concordance. The impact these words might have on partnership working is important in defining the patient-health professional relationship, and for the patients' healthcare outcomes and the potential effect on healthcare utilisation.

  9. Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo

    PubMed Central

    Patel, Mehul S.; Lee, Jen; Baz, Manuel; Wells, Claire E.; Bloch, Susannah; Lewis, Amy; Donaldson, Anna V.; Garfield, Benjamin E.; Hopkinson, Nicholas S.; Natanek, Amanda; Man, William D‐C; Wells, Dominic J.; Baker, Emma H.; Polkey, Michael I.

    2015-01-01

    Abstract Background Loss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor‐15 (GDF‐15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF‐15 may contribute to muscle wasting in COPD. Methods We determined the expression of GDF‐15 in the serum and muscle of patients with COPD and analysed the association of GDF‐15 expression with muscle mass and exercise performance. To determine whether GDF‐15 had a direct effect on muscle, we also determined the effect of increased GDF‐15 expression on the tibialis anterior of mice by electroporation. Results Growth differentiation factor‐15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF‐15 was inversely correlated with rectus femoris cross‐sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF‐15 levels were associated with 8‐oxo‐dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over‐expression of GDF‐15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF‐15 on muscle mass (P < 0.001). Conclusions Together, the data suggest that GDF‐15 contributes to the loss of muscle mass in COPD. PMID:27239406

  10. A Modified Collagen Gel Dressing Promotes Angiogenesis in a Pre-Clinical Swine Model of Chronic Ischemic Wounds

    PubMed Central

    Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K.

    2015-01-01

    We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine IL-10 and of β-FGF. An increased expression of CCR2, a M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of TGF-β, VEGF, vWF, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post-wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I:III deposition. Taken together, MCG helped mount a more robust inflammatory response which resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome and post-wound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. PMID:25224310

  11. Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan

    PubMed Central

    Ishizaki, Yuko; Higashino, Hirohiko; Kaneko, Kazunari

    2016-01-01

    The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as “carryover patients,” who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term “transition” in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children’s Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition. PMID:27803894

  12. Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model

    PubMed Central

    Meyer, Christiane; Sevko, Alexandra; Ramacher, Marcel; Bazhin, Alexandr V.; Falk, Christine S.; Osen, Wolfram; Borrello, Ivan; Kato, Masashi; Schadendorf, Dirk; Baniyash, Michal; Umansky, Viktor

    2011-01-01

    Tumor microenvironment is characterized by chronic inflammation represented by infiltrating leukocytes and soluble mediators, which lead to a local and systemic immunosuppression associated with cancer progression. Here, we used the ret transgenic spontaneous murine melanoma model that mimics human melanoma. Skin tumors and metastatic lymph nodes showed increased levels of inflammatory factors such as IL-1β, GM-CSF, and IFN-γ, which correlated with tumor progression. Moreover, Gr1+CD11b+ myeloid-derived suppressor cells (MDSCs), known to inhibit tumor reactive T cells, were enriched in melanoma lesions and lymphatic organs during tumor progression. MDSC infiltration was associated with a strong TCR ζ-chain down-regulation in all T cells. Coculturing normal splenocytes with tumor-derived MDSC induced a decreased T-cell proliferation and ζ-chain expression, verifying the MDSC immunosuppressive function and suggesting that the tumor inflammatory microenvironment supports MDSC recruitment and immunosuppressive activity. Indeed, upon manipulation of the melanoma microenvironment with the phosphodiesterase-5 inhibitor sildenafil, we observed reduced levels of numerous inflammatory mediators (e.g., IL-1β, IL-6, VEGF, S100A9) in association with decreased MDSC amounts and immunosuppressive function, indicating an antiinflammatory effect of sildenafil. This led to a partial restoration of ζ-chain expression in T cells and to a significantly increased survival of tumor-bearing mice. CD8 T-cell depletion resulted in an abrogation of sildenafil beneficial outcome, suggesting the involvement of MDSC and CD8 T cells in the observed therapeutic effects. Our data imply that inhibition of chronic inflammation in the tumor microenvironment should be applied in conjunction with melanoma immunotherapies to increase their efficacy. PMID:21969559

  13. Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan.

    PubMed

    Ishizaki, Yuko; Higashino, Hirohiko; Kaneko, Kazunari

    2016-01-01

    The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as "carryover patients," who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term "transition" in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children's Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition.

  14. Neuroprotective and axonal outgrowth-promoting effects of tetramethylpyrazine nitrone in chronic cerebral hypoperfusion rats and primary hippocampal neurons exposed to hypoxia.

    PubMed

    Zhang, Tao; Gu, Jianbo; Wu, Liangmiao; Li, Ning; Sun, Yewei; Yu, Pei; Wang, Yuqiang; Zhang, Gaoxiao; Zhang, Zaijun

    2017-05-15

    Chronic cerebral hypoperfusion is an important risk factor for vascular dementia and other brain dysfunctions, for which there are currently no effective medications available. We investigated the neuroprotective and axonal outgrowth promoting effects of tetramethylpyrazine nitrone (TBN) in a permanent bilateral occlusion of the common carotid arteries (2VO) rat model and in primary hippocampal neurons exposed to oxygen glucose deprivation (OGD). At 6th week after 2VO, TBN increased the time spent in novel arms in the Y-maze test and improved the discrimination ratio in object reorganization task. TBN attenuated axonal damage, and reduced oxidative DNA injury and lipid peroxidation in white matter. TBN also attenuated the neuronal apoptosis and ameliorated accumulation of astrocytes in parietal cortex and CA1 region of hippocampus. Western blot analyses indicated that TBN increased Bcl-2 expression, decreased Bax and Caspase 3 expressions, and upregulated the phosphorylation levels of high-molecular weight neurofilament (p-NFH), Akt (p-Akt) and glycogen synthase kinase-3β (p-GSK3β) in hippocampus at 6th week after chronic hypoperfusion. In vitro, TBN rescued hippocampal neuronal viability and axonal elongation from OGD damage. The p-Akt and p-GSK3β upregulation by TBN was abolished by a specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002, resulting in suppression of axonal outgrowth. Collectively, the results showed that TBN alleviated white matter lesion and impairment of cortex and hippocampus, attenuated oxidative damage and enhanced axonal outgrowth through the regulation of PI3K/Akt/GSK3β signaling pathway, leading to improved cognitive deficit in a rat chronic hypoperfusion model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Tail nerve electrical stimulation combined with scar ablation and neural transplantation promotes locomotor recovery in rats with chronically contused spinal cord.

    PubMed

    Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; Holmberg, Eric G

    2012-05-25

    To date, few treatment strategies applying cellular transplantation to the chronically injured spinal cord have yielded significant functional improvement in animal experiments. Here we report that significant improvement of locomotor function was achieved in rats with chronic spinal cord injury (SCI) by the application of combination treatments with tail nerve electrical stimulation (TANES), which can activate the central pattern generator, inducing active weight-supported stepping. Contusion injury (25 mm) to spinal cord T10 was produced by using the NYU impactor device in female, adult Long-Evans rats. Rats in 2 of 4 groups with SCI received basic treatments (scar ablation followed by transplantation of lamina propria of olfactory mucosa and cultured olfactory ensheathing cells into the lesion cavity) 6 weeks after SCI. Rats both with and without basic treatments were subjected to TANES one week after secondary surgery or 7 weeks after SCI. Sixteen weeks after secondary surgery or 22 weeks after SCI rats in two groups receiving TANES significantly improved their functional recovery compared with those without TANES, when evaluated with BBB open field rating scale (p<0.01). Among them, however, rats with basic treatments performed better than those without basic treatments. TANES may contribute to the activity-dependent plasticity below the injury level, which is critical for functional recovery. Additionally, TANES may promote axonal regeneration, including those from supraspinal level. Since TANES demonstrated considerable potential for achieving improvement of functional recovery in rat model, it would suggest a new strategy for chronic SCI. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model

    PubMed Central

    Baird, Anne-Marie; Gray, Steven G.; Richard, Derek J.; O’Byrne, Kenneth J.

    2016-01-01

    Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting. PMID:26759080

  17. Gain versus loss framing in adherence-promoting communication targeting patients with chronic diseases: the moderating effect of individual time perspective.

    PubMed

    Zhao, Xiaoquan; Villagran, Melinda M; Kreps, Gary L; McHorney, Colleen

    2012-01-01

    This study investigated the joint effect of message framing and time perspective in adherence-promoting communication targeting patients with chronic diseases. Based on previous framing and time perspective research, it was hypothesized that the gain frame would show an advantage over the loss frame among future-oriented patients; for present-oriented patients, it was hypothesized that the framing effect would be relatively indistinct. In total, 1,108 currently nonadherent patients with chronic disease participated in an experiment where they were randomly assigned to either gain- or loss-framed messages addressing key beliefs underlying their nonadherence or a no-message control condition. Intention and attitude regarding future adherence as well as message perceptions were measured after message presentation. Results of this study generally supported the hypotheses. Message topics-whether the messages addressed patients' perceived need for medications or concerns about side effects-did not moderate the effect of framing or the interaction between framing and time perspective. Theoretical and practical implications are discussed.

  18. Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of IL-1β in chronically sun-exposed human skin.

    PubMed

    Qin, Zhaoping; Okubo, Toru; Voorhees, John J; Fisher, Gary J; Quan, Taihao

    2014-02-01

    Chronic exposure of human skin to solar ultraviolet (UV) irradiation causes premature skin aging, which is characterized by reduced type I collagen production and increased fragmentation of the dermal collagenous extracellular matrix. This imbalance of collagen homeostasis is mediated, in part, by elevated expression of the matricellular protein cysteine-rich protein 61 (CCN1), in dermal fibroblasts, the primary collagen producing cell type in human skin. Here, we report that the actions of CCN1 are mediated by induction of interleukin 1β (IL-1β). CCN1 and IL-1β are strikingly induced by acute UV irradiation, and constitutively elevated in sun-exposed prematurely aged human skin. Elevated CCN1 rapidly induces IL-1β, inhibits type I collagen production, and upregulates matrix metalloproteinase-1, which degrades collagen fibrils. Blockade of IL-1β actions by IL-1 receptor antagonist largely prevents the deleterious effects of CCN1 on collagen homeostasis. Furthermore, knockdown of CCN1 significantly reduces induction of IL-1β by UV irradiation, and thereby partially prevents collagen loss. These data demonstrate that elevated CCN1promotes inflammaging and collagen loss via induction of IL-1β and thereby contributes to the pathophysiology of premature aging in chronically sun-exposed human skin.

  19. Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV Egyptian Patients.

    PubMed

    Bader El Din, Noha Gamal; Salum, Ghada M; Anany, Mohamed A; Ibrahim, Marwa Khalil; Dawood, Reham Mohamed; Zayed, Naglaa; El Abd, Yasmine S; El-Shenawy, Reem; El Awady, Mostafa K

    2015-08-01

    To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus resistance (MxA) gene promoter region in relation to the status of hepatitis C virus (HCV) progression and response to combined interferon (IFN) in chronic HCV Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV genotype 4-infected patients who underwent combined IFN therapy and 50 healthy individuals. All subjects were genotyped for -88 MxA polymorphism by the restriction fragment length polymorphism technique. There was an increasing trend of response to combined IFN treatment as 34.9% of GG, 64.3% of GT, and 66.7% of TT genotypes were sustained responders (P=0.05). The T allele was significantly affecting the response rate more than G allele (P=0.032). Moreover, the hepatic fibrosis score and hepatitis activity were higher in GG genotypes compared with the GT and TT genotypes. The multivariate analysis showed that the MxA GG genotype was an independent factor increasing the no response to IFN therapy (P=0.04, odds ratio [OR] 3.822, 95% confidence interval [CI] 1.056-11.092), also MxA G allele (P=0.0372, OR 2.905, 95% CI 1.066-7.919). MxA -88 polymorphism might be a potential biomarker to predict response to IFN and disease progression in chronic HCV-infected patients.

  20. Effectiveness of a Tai chi Qigong program in promoting health-related quality of life and perceived social support in chronic obstructive pulmonary disease clients.

    PubMed

    Chan, Aileen W K; Lee, Albert; Suen, Lorna K P; Tam, Wilson W S

    2010-06-01

    This paper evaluates the effectiveness of a 3-month Tai chi Qigong (TCQ) program in promoting the psychosocial functional health of clients with chronic obstructive pulmonary disease (COPD) in Hong Kong. This study employed a single-blind, randomized controlled trial. Two hundred and six COPD clients were randomly assigned into three groups, namely, TCQ group, exercise group, and control group. Subjects in the TCQ group received a TCQ program, consisting of two 60-min sessions each week for 3 months. Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise. Subjects in the control group received their usual care. Data collections were performed at baseline, on the sixth week and on the third month. The primary outcomes were health-related quality of life using St. George Respiratory Questionnaire-Hong Kong Chinese version and perceived social support using the Multidimensional Scale of Perceived Social Support-Chinese version. The TCQ group showed greater improvements in the symptom (F4, 404=3.351, P=0.010) and activity domains (F4, 404=2.611, P=0.035). No differences were detected in perceived social support among the three groups. Tai chi Qigong promoted health outcomes with respect to clients' perception of their respiratory symptoms. Moreover, TCQ decreased disturbances to their physical activities.

  1. X gene/core promoter deletion mutation: a novel mechanism leading to hepatitis B 'e' antigen‑negative chronic hepatitis B.

    PubMed

    Zhou, Fei; Xu, Hongzhi; Chen, Meiya; Xiao, Hongmin; Zhang, Zhiping; Lu, Yapi; Ren, Jianlin; Dong, Jing

    2014-08-01

    Mutations in the precore and core promoter regions of hepatitis B 'e' antigen (HBeAg) are implicated in HBeAg‑negative chronic hepatitis B virus (HBV) infection (CHB). The objective of the current study was to investigate novel mutant patterns that lead to HBeAg‑negative CHB. The . PreX-X genomic region from the sera of HBV‑infected patients was amplified, and analysis of the sequences displayed a unique deletion region, 234 nucleotides in length, which was observed in 54 clones and named core promoter deletion (CPD). CPD may have an important role in the cause of HBeAg‑negative CHB. In addition, a novel deletion mutation in the X gene was observed in patients with CHB. This deletion mutant codes a 76‑amino‑acid X factor instead of the X protein. In the present study, a new mutation pattern was discovered that may contribute to the cause of HBeAg-negative CHB, and therefore it is worthy of future studies.

  2. Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.

    PubMed

    Carmel, Jason B; Kimura, Hiroki; Martin, John H

    2014-01-08

    Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.

  3. IL-17 functions through the novel REG3β-JAK2-STAT3 inflammatory pathway to promote the transition from chronic pancreatitis to pancreatic cancer

    PubMed Central

    Loncle, Celine; Bonjoch, Laia; Folch-Puy, Emma; Lopez-Millan, Maria Belen; Lac, Sophie; Molejon, Maria Inés; Chuluyan, Eduardo; Cordelier, Pierre; Dubus, Pierre; Lomberk, Gwen; Urrutia, Raul; Closa, Daniel; Iovanna, Juan L

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) offers an optimal model for discovering “druggable” molecular pathways that participate in inflammation-associated cancer development. Chronic pancreatitis, a common prolonged inflammatory disease, behaves as a well-known premalignant condition that contributes to PDAC development. Although the mechanisms underlying the pancreatitis-to-cancer transition remain to be fully elucidated, emerging evidence supports the hypothesis that the actions of proinflammatory mediators on cells harboring Kras mutations promote neoplastic transformation. Recent elegant studies demonstrated that the IL-17 pathway mediates this phenomenon and can be targeted with antibodies, but the downstream mechanisms by which IL-17 functions during this transition are currently unclear. In this study, we demonstrate that IL-17 induces the expression of REG3β, a well-known mediator of pancreatitis, during acinar-to-ductal metaplasia and in early PanIN lesions. Furthermore, we found that REG3β promotes cell growth and decreases sensitivity to cell death through activation of the gp130-JAK2-STAT3-dependent pathway. Genetic inactivation of REG3β in the context of oncogenic Kras-driven PDAC resulted in reduced PanIN formation, an effect that could be rescued by administration of exogenous REG3β. Taken together, our findings provide mechanistic insight into the pathways underlying inflammation-associated pancreatic cancer, revealing a dual and contextual pathophysiological role for REG3β during pancreatitis and PDAC initiation. PMID:26404002

  4. Wogonoside induces growth inhibition and cell cycle arrest via promoting the expression and binding activity of GATA-1 in chronic myelogenous leukemia cells.

    PubMed

    Li, Hui; Hui, Hui; Xu, Jingyan; Yang, Hao; Zhang, Xiaoxiao; Liu, Xiao; Zhou, Yuxin; Li, Zhiyu; Guo, Qinglong; Lu, Na

    2016-06-01

    GATA-1, a zinc finger transcription factor, has been demonstrated to play a key role in the progression of leukemia. In this study, we investigate the effects of wogonoside, a naturally bioactive flavonoid derived from Scutellaria baicalensis Georgi, on cell growth and cell cycle in chronic myeloid leukemia (CML) cells, and uncover its underlying mechanisms. The experimental design comprised CML cell lines K562, imatinib-resistant K562 (K562r) cells, and primary CML cells, treated in vitro or in vivo, respectively, with wogonoside; growth and cell cycle were then evaluated. We found that wogonoside could induce growth inhibition and G0/G1 cell cycle arrest in both normal and K562r cells. Wogonoside promotes the expression of GATA-1 and facilitates the binding to methyl ethyl ketone (MEK) and p21 promoter, thus inhibiting MEK/extracellular signal-regulated kinase signaling and cell cycle checkpoint proteins, including CDK2, CDK4, cyclin A, and cyclin D1, and increasing p21 expression. Furthermore, in vivo studies showed that administration of wogonoside decreased CML cells and prolonged survival in NOD/SCID mice with CML cell xenografts. In conclusion, these results clearly revealed the inhibitory effect of wogonoside on the growth in CML cells and suggested that wogonoside may act as a promising drug for the treatment of imatinib-resistant CML.

  5. Indoxyl Sulfate Enhance the Hypermethylation of Klotho and Promote the Process of Vascular Calcification in Chronic Kidney Disease

    PubMed Central

    Chen, Jing; Zhang, Xiaoyan; Zhang, Han; Liu, Tongqiang; Zhang, Hui; Teng, Jie; Ji, Jun; Ding, Xiaoqiang

    2016-01-01

    Chronic kidney disease (CKD) is a state of Klotho deficiency. The Klotho expression may be suppressed due to DNA hypermethylation in cancer cells so we have investigated the effects and possible mechanisms by which Klotho expression is regulated in human aortic smooth muscle cells (HASMCs). The vascular Klotho hypermethylation in radial arteries of patients with end-stage renal disease was described. Cultured HASMCs and 5/6-nephrectomized Sprague Dawley (SD) rats treated with indoxyl sulfate (IS) were used as in vitro and in vivo models, respectively. IS increased CpG hypermethylation of the Klotho gene and decreased Klotho expression in HASMCs, and potentiated HASMCs calcification. The expression of DNA methyltransferase (DNMT) 1 and 3a in HASMCs treated with IS was significantly increased and specific inhibition of DNA methyltransferase 1 by 5-aza-2'-deoxycytidine(5Aza-2dc) caused demethylation of the Klotho gene and increased Klotho expression. In rats, injection of IS potentiated vascular calcification, increased CpG hypermethylation of the Klotho gene and decreased Klotho expression in the aortic medial layer and all of these changes could be reverted by 5Aza-2dc treatment. Transcriptional suppression of vascular Klotho gene expression by IS and epigenetic modification of Klotho by IS may be an important pathological mechanism of vascular calcification in CKD. PMID:27766038

  6. Strategies to promote adherence to nutritional advice in patients with chronic kidney disease: a narrative review and commentary

    PubMed Central

    Beto, Judith A; Schury, Katherine A; Bansal, Vinod K

    2016-01-01

    Chronic kidney disease (CKD) requires extensive changes to food and lifestyle. Poor adherence to diet, medications, and treatments has been estimated to vary between 20% and 70%, which in turn can contribute to increased mortality and morbidity. Delivering effective nutritional advice in patients with CKD coordinates multiple diet components including calories, protein, sodium, potassium, calcium, phosphorus, and fluid. Dietary intake studies have shown difficulty in adhering to the scope and complexity of the CKD diet parameters. No single educational or clinical strategy has been shown to be consistently effective across CKD populations. Highest adherence has been observed when both diet and education efforts are individualized to each patient and adapted over time to changing lifestyle and CKD variables. This narrative review and commentary summarizes nutrition education literature and published strategies for providing nutritional advice in CKD. A cohort of practical and effective strategies for increasing dietary adherence to nutritional advice are provided that include communicating with “talking control” principles, integrating patient-owned technology, acknowledging the typical food pattern may be snacking rather than formal meals, focusing on a single goal rather than multiple goals, creating active learning and coping strategies (frozen sandwiches, visual hands-on activities, planting herb gardens), and involving the total patient food environment. PMID:26893578

  7. Leptin promotes endothelial dysfunction in chronic kidney disease through AKT/GSK3β and β-catenin signals.

    PubMed

    Ding, Nannan; Liu, Bing; Song, Jiaguang; Bao, Shougang; Zhen, Junhui; Lv, Zhimei; Wang, Rong

    2016-11-25

    Endothelial dysfunction (ED) is a well-recognized instigator of cardiovascular diseases and develops in chronic kidney disease (CKD) with high rate. Recent studies have implicated that leptin is associated with endothelial dysfunction. We investigated the relationship between leptin and markers of ED in CKD patients and how leptin contributed to endothelial damage. 140 CKD patients and 140 healthy subjects were studied. Serum leptin levels were significantly higher in CKD than in controls and displayed significantly positive association with the increase levels of sICAM-1 and sVCAM-1 but negative correlation with flow-mediated dilatation (FMD) reduction in patients. Our in vitro study demonstrated that leptin induced overexpression of ICAM-1 and VCAM-1, led to f-actin reorganization and vinculin assembly, increased endothelial monolayer permeability for FITC-dextran, and accelerated endothelial cell migration; these changes were markedly reversed when the cells were transfected with AKT or β-catenin shRNA vectors. Notably, high leptin resulted in hyper-phosphorylation of AKT and GSK3β, along with nuclear accumulation of β-catenin. In conclusion, serum leptin was elevated in CKD patients and it might contribute to endothelial dysfunction by disarrangement of f-actin cytoskeleton via a mechanism involving the AKT/GSK3β and β-catenin pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis.

    PubMed

    Ahidjo, Bintou A; Maiga, Mariama C; Ihms, Elizabeth A; Maiga, Mamoudou; Ordonez, Alvaro A; Cheung, Laurene S; Beck, Sarah; Andrade, Bruno B; Jain, Sanjay; Bishai, William R

    2016-09-08

    Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone's antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response. The effectiveness of adjunctive pirfenidone during TB drug therapy was evaluated using a murine model of chronic TB. Mice treated with standard therapy 2HRZ/4HR (H, isoniazid; R, rifampin; and Z, pyrazinamide) were compared with 2 alternative regimens containing pirfenidone (Pf) (2HRZPf/4HRPf and 2HRZPf/4HR). Contrary to our hypothesis, adjunctive pirfenidone use leads to reduced bacterial clearance and increased relapse rates. This treatment failure is closely associated with the emergence of isoniazid monoresistant bacilli, increased cavitation, and significant lung pathology. While antifibrotic agents may eventually be used as part of adjunctive host-directed therapy of TB, this study clearly demonstrates that caution must be exercised. Moreover, as pirfenidone becomes more widely used in clinical practice, increased patient monitoring would be required in endemic TB settings.

  9. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis

    PubMed Central

    Ahidjo, Bintou A.; Maiga, Mariama C.; Ihms, Elizabeth A.; Maiga, Mamoudou; Ordonez, Alvaro A.; Cheung, Laurene S.; Beck, Sarah; Andrade, Bruno B.; Jain, Sanjay

    2016-01-01

    Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone’s antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response. The effectiveness of adjunctive pirfenidone during TB drug therapy was evaluated using a murine model of chronic TB. Mice treated with standard therapy 2HRZ/4HR (H, isoniazid; R, rifampin; and Z, pyrazinamide) were compared with 2 alternative regimens containing pirfenidone (Pf) (2HRZPf/4HRPf and 2HRZPf/4HR). Contrary to our hypothesis, adjunctive pirfenidone use leads to reduced bacterial clearance and increased relapse rates. This treatment failure is closely associated with the emergence of isoniazid monoresistant bacilli, increased cavitation, and significant lung pathology. While antifibrotic agents may eventually be used as part of adjunctive host-directed therapy of TB, this study clearly demonstrates that caution must be exercised. Moreover, as pirfenidone becomes more widely used in clinical practice, increased patient monitoring would be required in endemic TB settings. PMID:27699232

  10. CD11c(+) monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23.

    PubMed

    Arnold, I C; Mathisen, S; Schulthess, J; Danne, C; Hegazy, A N; Powrie, F

    2016-03-01

    In inflammatory bowel diseases, a breakdown in host microbial interactions accompanies sustained activation of immune cells in the gut. Functional studies suggest a key role for interleukin-23 (IL-23) in orchestrating intestinal inflammation. IL-23 can be produced by various mononuclear phagocytes (MNPs) following acute microbial stimulation, but little is known about the key cellular sources of IL-23 that drive chronic intestinal inflammation. Here we have addressed this question using a physiological model of bacteria-driven colitis. By combining conditional gene ablation and gene expression profiling, we found that IL-23 production by CD11c(+) MNPs was essential to trigger intestinal immunopathology and identified MHCII(+) monocytes and macrophages as the major source of IL-23. Expression of IL-23 by monocytes was acquired during their differentiation in the intestine and correlated with the expression of major histocompatibility complex class II (MHCII) and CD64. In contrast, Batf3-dependent CD103(+) CD11b(-) dendritic cells were dispensable for bacteria-induced colitis in this model. These studies reinforce the pathogenic role of monocytes in dysregulated responses to intestinal bacteria and identify production of IL-23 as a key component of this response. Further understanding of the functional sources of IL-23 in diverse forms of intestinal inflammation may lead to novel therapeutic strategies aimed at interrupting IL-23-driven immune pathology.

  11. Biocomposites of copper-containing mesoporous bioactive glass and nanofibrillated cellulose: Biocompatibility and angiogenic promotion in chronic wound healing application.

    PubMed

    Wang, Xiaoju; Cheng, Fang; Liu, Jun; Smått, Jan-Henrik; Gepperth, David; Lastusaari, Mika; Xu, Chunlin; Hupa, Leena

    2016-12-01

    Biocomposites of copper-containing mesoporous bioactive glass (Cu-MBG) and nanofibrillated cellulose (NFC) were designated as potential dressing material for chronic wound healing. The phase composition and mesoporous micro-structure of the synthesized Cu-MBGs were elaborately characterized by combining several techniques, including TEM, SEM, XRD, SXAS and N2 physisorption. High bioactivity of the Cu-MBG was confirmed in stimulated body fluids in vitro. A controlled dissolution of Cu from the glass suggests Cu-MBG a suitable source for Cu release in wound healing dressings. Depending on the content of Cu-MBG in the composite formulation, the composites were fabricated as membranes and aerogels. In biocompatibility assessment of the composites, a dose-dependent cytotoxicity of Cu(2+) on 3T3 fibroblasts was found. Importantly, a critical biological level of Cu(2+) below 10mg/L was suggested for the survival and growth of 3T3 fibroblasts. The Cu(2+) released from the composite aerogel of NFC and Cu-MBG showed a profound angiogenic effect in the 3D spheroid culture system of human umbilical vein endothelial cells. Moreover, the angiogenic gene expression of 3T3 fibroblast was upregulated in the real-time quantitative PCR analysis, which also confirms that the incorporation of Cu-MBG into NFC matrix enhances the proangiogenic potential of the biocomposites. In addition, composites of NFC and Cu-MBG also showed an inhibiting effect on the growth of E. coli.

  12. Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey.

    PubMed

    Sunbul, Mustafa; Sugiyama, Masaya; Kurbanov, Fuat; Leblebicioglu, Hakan; Khan, Anis; Elkady, Abeer; Tanaka, Yasuhito; Mizokami, Masashi

    2013-02-01

    The role of hepatitis B virus (HBV) genetics in the clinical manifestations of infection is being increasingly recognized. Genotype D is one of eight currently recognized major HBV genotypes. The virus is ubiquitous worldwide, but shows different features in different regions. One hundred and ninety-eight patients with chronic HBV infection were enrolled in this study, 38 of whom had been diagnosed with cirrhosis of the liver and/or hepatocellular carcinoma. HBV DNA was isolated from the patients' blood samples and the entire genome and/or the basal core promoter/core promoter region sequenced. Phylogenetic analysis of the complete genomes revealed that subgenotype D1 is the most prevalent subgenotype in Turkey, but there was no definite phylogenetic grouping according to geography for isolates from different regions within Turkey, or for isolates in Turkey relative to other parts of the world. Turkish isolates tended to be genetically similar to European and central Asian isolates. Overall, HBV-infection in Turkey appears to be characterized by early HBeAg seroconversion, a high incidence of the A1896 core promoter mutation and a small viral load. Genotype D characteristic mutations A1757 and T1764/G1766 were found in the BCP region. T1773 was associated with T1764/G1766 and a larger viral load. In conclusion, infection with HBV genotype D in Turkey has a similar clinical outcome to that of Europe and central Asia. Genotypic mutations in genotype D may be linked with disease prognosis in Turkey, but further studies with higher sample numbers and balanced clinical groups are needed to confirm this.

  13. Adipose tissue promotes a serum cytokine profile related to lower insulin sensitivity after chronic central leptin infusion.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity.

  14. Adipose Tissue Promotes a Serum Cytokine Profile Related to Lower Insulin Sensitivity after Chronic Central Leptin Infusion

    PubMed Central

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity. PMID:23056516

  15. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

    PubMed

    Zhu, G; Wang, Y; Li, J; Wang, J

    2015-04-30

    Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Egg white hydrolysate promotes neuroprotection for neuropathic disorders induced by chronic exposure to low concentrations of mercury.

    PubMed

    Rizzetti, Danize Aparecida; Fernandez, Francisca; Moreno, Silvia; Uranga Ocio, José Antonio; Peçanha, Franck Maciel; Vera, Gema; Vassallo, Dalton Valentim; Castro, Marta Miguel; Wiggers, Giulia Alessandra

    2016-09-01

    This study aims to investigate whether the egg white hydrolysate (EWH) acts on the neuropathic disorders associated with long-term Mercury (Hg) exposure in rats. 8- week-old male Wistar rats were treated for 60 days with: a) Control - saline solution (i.m.); b) Mercury - HgCl2 (1st dose 4.6μg/kg, subsequent doses 0.07μg/kg/day, i.m.); c) Hydrolysate - EWH (1g/kg/day, gavage); d) Mercury and Hydrolysate. Mechanical allodynia was assessed using Von Frey Hairs test; heat hyperalgesia by the plantar test; catalepsy by a modification of the "ring test" and spontaneous locomotor activity by a photocell activity chambers. Analyses were performed at 0, 30 and 60 days of treatment. Brain and plasma MDA, plasma NPSH and TNF-α determination and skin immunohistochemistry were performed at 60 days. Hg induced a reduction in mechanical sensitivity threshold at 30 and 60 days and in thermal sensitivity threshold at 60 days. At the end of treatment catalepsy was developed, but there was not significant alteration in spontaneous locomotor activity. Hg also increased brain and plasma MDA, plasma NPSH and TNF-α levels and the number of Merkel cell-neurite complex in the skin. EWH prevented the development of mechanical allodynia, thermal hyperalgesia and catalepsy induced by Hg and the increase in MDA concentration in brain and plasma and in the number of Merkel cell-neurite complex in the skin. In conclusion, EWH promotes neuroprotection against the toxic effects caused by Hg, demonstrating a beneficial therapeutic potential. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. The relationship between perceived promotion of autonomy/dependence and pain-related disability in older adults with chronic pain: the mediating role of self-reported physical functioning.

    PubMed

    Matos, Marta; Bernardes, Sónia F; Goubert, Liesbet

    2016-08-01

    Chronic pain is prevalent among older adults and is usually associated with high levels of functional disability. Social support for the promotion of functional autonomy and dependence has been associated with pain-related disability and self-reported physical functioning. Nevertheless, these relationships need further inquiry. Our aims were to investigate: (1) the relationship between perceived promotion of autonomy/dependence and pain-related disability and (2) the extent to which self-reported physical functioning mediated these relationships. 118 older adults (Mage = 81.0) with musculoskeletal chronic pain completed the Portuguese versions of the revised formal social support for Autonomy and Dependence in Pain Inventory, the pain severity and interference scales of the Brief Pain Inventory, and the physical functioning scale of the Medical Outcomes Study-Short-Form 36 v2. Higher levels of perceived promotion of autonomy were associated with lower pain-related disability; this relationship was partially mediated by self-reported physical functioning (B = -.767, p < .001 decreasing to B' = -.485, p < .01). Higher perceived promotion of dependence was associated with higher pain-related disability; this effect was also partially accounted for by self-reported physical functioning (B = .889, p < .01 decreasing to B' = .597, p < .05). These results highlight the importance of perceived promotion of autonomy and dependence for managing older adults' experience of chronic pain.

  18. Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in the C57BL/6J Diet-Induced Obesity Mouse Model

    PubMed Central

    Duval, Caroline; Teixeira-Clerc, Fatima; Leblanc, Alix F.; Touch, Sothea; Emond, Claude; Guerre-Millo, Michèle; Lotersztajn, Sophie; Barouki, Robert; Aggerbeck, Martine; Coumoul, Xavier

    2016-01-01

    Background: Exposure to persistent organic pollutants (POPs) has been associated with the progression of chronic liver diseases, yet the contribution of POPs to the development of fibrosis in non-alcoholic fatty liver disease (NAFLD), a condition closely linked to obesity, remains poorly documented. Objectives: We investigated the effects of subchronic exposure to low doses of the POP 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor ligand, on NAFLD progression in diet-induced obese C57BL/6J mice. Methods: Male C57BL/6J mice were fed either a 10% low-fat (LFD) or a 45% high-fat (HFD) purified diet for 14 weeks and TCDD-exposed groups were injected once a week with 5 μg/kg TCDD or the vehicle for the last 6 weeks of the diet. Results: Liver histology and triglyceride levels showed that exposure of HFD fed mice to TCDD worsened hepatic steatosis, as compared to either HFD alone or LFD plus TCDD and the mRNA levels of key genes of hepatic lipid metabolism were strongly altered in co-treated mice. Further, increased liver collagen staining and serum transaminase levels showed that TCDD induced liver fibrosis in the HFD fed mice. TCDD in LFD fed mice increased the expression of several inflammation and fibrosis marker genes with no additional effect from a HFD. Conclusions: Exposure to TCDD amplifies the impairment of liver functions observed in mice fed an enriched fat diet as compared to a low fat diet. The results provide new evidence that environmental pollutants promote the development of liver fibrosis in obesity-related NAFLD in C57BL/6J mice. Citation: Duval C, Teixeira-Clerc F, Leblanc AF, Touch S, Emond C, Guerre-Millo M, Lotersztajn S, Barouki R, Aggerbeck M, Coumoul X. 2017. Chronic exposure to low doses of dioxin promotes liver fibrosis development in the C57BL/6J diet-induced obesity mouse model. Environ Health Perspect 125:428–436; http://dx.doi.org/10.1289/EHP316 PMID:27713108

  19. Results from a mailed promotion of medication reviews among Department of Defense beneficiaries receiving 10 or more chronic medications.

    PubMed

    Linton, Andrea; Bacon, Thomas A; Trice, Shana; Devine, Joshua; Cottrell, Linda; McGinnis, Thomas J; McAllister, Everett B

    2010-10-01

    among the case subjects. Response was poor to a mailing that promoted a beneficiary- initiated medication review. The absence of significant changes following the medication review suggests several possibilities: a mailed intervention is ineffective in promoting medication review; medication regimens for study subjects are already optimized to the extent obtainable through a routine medication review; or the study sample size was too small to detect relevant changes. Most drug regimen changes were dosage adjustments for current medications or substitutions within the same therapeutic class. The extent to which comprehensive assessment of a patient's medication regimen, including nonprescription and herbal agents, was performed is unclear. More intensive interventions may be required to ensure that medication regimens are being actively managed among those who use a large number of prescription medications.

  20. Down-regulated Peroxisome Proliferator-activated Receptor γ (PPARγ) in Lung Epithelial Cells Promotes a PPARγ Agonist-reversible Proinflammatory Phenotype in Chronic Obstructive Pulmonary Disease (COPD)*

    PubMed Central

    Lakshmi, Sowmya P.; Reddy, Aravind T.; Zhang, Yingze; Sciurba, Frank C.; Mallampalli, Rama K.; Duncan, Steven R.; Reddy, Raju C.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition and a leading cause of death, with no available cure. We assessed the actions in pulmonary epithelial cells of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor with anti-inflammatory effects, whose role in COPD is largely unknown. We found that PPARγ was down-regulated in lung tissue and epithelial cells of COPD patients, via both reduced expression and phosphorylation-mediated inhibition, whereas pro-inflammatory nuclear factor-κB (NF-κB) activity was increased. Cigarette smoking is the main risk factor for COPD, and exposing airway epithelial cells to cigarette smoke extract (CSE) likewise down-regulated PPARγ and activated NF-κB. CSE also down-regulated and post-translationally inhibited the glucocorticoid receptor (GR-α) and histone deacetylase 2 (HDAC2), a corepressor important for glucocorticoid action and whose down-regulation is thought to cause glucocorticoid insensitivity in COPD. Treating epithelial cells with synthetic (rosiglitazone) or endogenous (10-nitro-oleic acid) PPARγ agonists strongly up-regulated PPARγ expression and activity, suppressed CSE-induced production and secretion of inflammatory cytokines, and reversed its activation of NF-κB by inhibiting the IκB kinase pathway and by promoting direct inhibitory binding of PPARγ to NF-κB. In contrast, PPARγ knockdown via siRNA augmented CSE-induced chemokine release and decreases in HDAC activity, suggesting a potential anti-inflammatory role of endogenous PPARγ. The results imply that down-regulation of pulmonary epithelial PPARγ by cigarette smoke promotes inflammatory pathways and diminishes glucocorticoid responsiveness, thereby contributing to COPD pathogenesis, and further suggest that PPARγ agonists may be useful for COPD treatment. PMID:24368768

  1. Down-regulated peroxisome proliferator-activated receptor γ (PPARγ) in lung epithelial cells promotes a PPARγ agonist-reversible proinflammatory phenotype in chronic obstructive pulmonary disease (COPD).

    PubMed

    Lakshmi, Sowmya P; Reddy, Aravind T; Zhang, Yingze; Sciurba, Frank C; Mallampalli, Rama K; Duncan, Steven R; Reddy, Raju C

    2014-03-07

    Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition and a leading cause of death, with no available cure. We assessed the actions in pulmonary epithelial cells of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor with anti-inflammatory effects, whose role in COPD is largely unknown. We found that PPARγ was down-regulated in lung tissue and epithelial cells of COPD patients, via both reduced expression and phosphorylation-mediated inhibition, whereas pro-inflammatory nuclear factor-κB (NF-κB) activity was increased. Cigarette smoking is the main risk factor for COPD, and exposing airway epithelial cells to cigarette smoke extract (CSE) likewise down-regulated PPARγ and activated NF-κB. CSE also down-regulated and post-translationally inhibited the glucocorticoid receptor (GR-α) and histone deacetylase 2 (HDAC2), a corepressor important for glucocorticoid action and whose down-regulation is thought to cause glucocorticoid insensitivity in COPD. Treating epithelial cells with synthetic (rosiglitazone) or endogenous (10-nitro-oleic acid) PPARγ agonists strongly up-regulated PPARγ expression and activity, suppressed CSE-induced production and secretion of inflammatory cytokines, and reversed its activation of NF-κB by inhibiting the IκB kinase pathway and by promoting direct inhibitory binding of PPARγ to NF-κB. In contrast, PPARγ knockdown via siRNA augmented CSE-induced chemokine release and decreases in HDAC activity, suggesting a potential anti-inflammatory role of endogenous PPARγ. The results imply that down-regulation of pulmonary epithelial PPARγ by cigarette smoke promotes inflammatory pathways and diminishes glucocorticoid responsiveness, thereby contributing to COPD pathogenesis, and further suggest that PPARγ agonists may be useful for COPD treatment.

  2. Chronic Neurotrophin Delivery Promotes Ectopic Neurite Growth From the Spiral Ganglion of Deafened Cochleae Without Compromising the Spatial Selectivity of Cochlear Implants

    PubMed Central

    Landry, Thomas G.; Fallon, James B.; Wise, Andrew K.; Shepherd, Robert K.

    2015-01-01

    Cochlear implants restore hearing cues in the severe– profoundly deaf by electrically stimulating spiral ganglion neurons (SGNs). However, SGNs degenerate following loss of cochlear hair cells, due at least in part to a reduction in the endogenous neurotrophin (NT) supply, normally provided by hair cells and supporting cells of the organ of Corti. Delivering exogenous NTs to the cochlea can rescue SGNs from degeneration and can also promote the ectopic growth of SGN neurites. This resprouting may disrupt the cochleotopic organization upon which cochlear implants rely to impart pitch cues. Using retrograde labeling and confocal imaging of SGNs, we determined the extent of neurite growth following 28 days of exogenous NT treatment in deafened guinea pigs with and without chronic electrical stimulation (ES). On completion of this treatment, we measured the spread of neural activation to intracochlear ES by recording neural responses across the cochleotopically organized inferior colliculus using multichannel recording techniques. Although NT treatment significantly increased both the length and the lateral extent of growth of neurites along the cochlea compared with deafened controls, these anatomical changes did not affect the spread of neural activation when examined immediately after 28 days of NT treatment. NT treatment did, however, result in lower excitation thresholds compared with deafened controls. These data support the application of NTs for improved clinical outcomes for cochlear implant patients. PMID:23436344

  3. Chronic neurotrophin delivery promotes ectopic neurite growth from the spiral ganglion of deafened cochleae without compromising the spatial selectivity of cochlear implants.

    PubMed

    Landry, Thomas G; Fallon, James B; Wise, Andrew K; Shepherd, Robert K

    2013-08-15

    Cochlear implants restore hearing cues in the severe-profoundly deaf by electrically stimulating spiral ganglion neurons (SGNs). However, SGNs degenerate following loss of cochlear hair cells, due at least in part to a reduction in the endogenous neurotrophin (NT) supply, normally provided by hair cells and supporting cells of the organ of Corti. Delivering exogenous NTs to the cochlea can rescue SGNs from degeneration and can also promote the ectopic growth of SGN neurites. This resprouting may disrupt the cochleotopic organization upon which cochlear implants rely to impart pitch cues. Using retrograde labeling and confocal imaging of SGNs, we determined the extent of neurite growth following 28 days of exogenous NT treatment in deafened guinea pigs with and without chronic electrical stimulation (ES). On completion of this treatment, we measured the spread of neural activation to intracochlear ES by recording neural responses across the cochleotopically organized inferior colliculus using multichannel recording techniques. Although NT treatment significantly increased both the length and the lateral extent of growth of neurites along the cochlea compared with deafened controls, these anatomical changes did not affect the spread of neural activation when examined immediately after 28 days of NT treatment. NT treatment did, however, result in lower excitation thresholds compared with deafened controls. These data support the application of NTs for improved clinical outcomes for cochlear implant patients.

  4. A scoping review of the literature on benefits and challenges of participating in patient education programs aimed at promoting self-management for people living with chronic illness.

    PubMed

    Stenberg, Una; Haaland-Øverby, Mette; Fredriksen, Kari; Westermann, Karl Fredrik; Kvisvik, Toril

    2016-11-01

    To give a comprehensive overview of benefits and challenges from participating in group based patient education programs that are carried out by health care professionals and lay participants, aimed at promoting self-management for people living with chronic illness. We searched 8 literature databases. Full text articles meeting the inclusion criteria were retrieved and reviewed. Arksey and O'Malley's framework for scoping studies guided the review process and thematic analysis was undertaken to synthesize extracted data. Of the 5935 titles identified, 47 articles were included in this review. The participants experienced the programs as beneficial according to less symptom distress and greater awareness of their own health, improved self-management strategies, peer support, learning and hope. A substantial evidence base supports the conclusion that group based self-management patient education programs in different ways have been experienced as beneficial, but more research is needed. The insights gained from this review can enable researchers, health care professionals, and participants to understand the complexity in evaluating self-management patient education programs, and constitute a basis for a more standardized and systematic evaluation. The results may also encourage health care professionals in planning and carrying out programs in cooperation with lay participants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. [Observation on effect of yugan granule in treating patients of chronic hepatitis B with basic core promoter mutant hepatitis B virus].

    PubMed

    Xie, Chao-liang; Shao, Ze-yong

    2002-07-01

    To observe the effect of Yugan Granule (YGG) in treating patients of chronic hepatitis B infected with basic core promoter (BCP) mutant HBV. BCP mutation was detected by microwell liquid hybridization combined with enzyme linked immunosorbent assay (ELISA) and 46 patients were confirmed to be the mutant positive (Group A), and 69 the mutant negative (Group B). All patients were treated by YGG and the clinical symptoms and laboratory parameters before and after treatment were observed. The scores of symptoms and serum levels of alanine transaminase (ALT) and total bilirubin (TBil) were decreased markedly in both groups after treatment. The HBeAg negative conversion rate in Group A was 60%, obviously higher than that in Group B (30%, P < 0.05), while HBV-DNA negative conversion rate between the two groups had the insignificant difference. The overall efficacy was similar in the two groups. YGG could remarkably alleviate the symptoms, reduce serum levels of ALT and TBil, and showed the effect of anti-HBV with the same efficacy both to BCP mutant and wild strain HBV infected patients.

  6. Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis

    PubMed Central

    Cascio, Sandra; Finn, Olivera J.

    2016-01-01

    Altered glycosylation of mucin 1 (MUC1) on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target for cancer immunotherapy. The importance of altered MUC1 glycosylation extends also to its role as a promoter of chronic inflammatory conditions that lead to malignant transformation and cancer progression. We review here what is known about the role of specific cancer-associated glycans on MUC1 in protein-protein interactions and intracellular signaling in cancer cells and in their adhesion to each other and the tumor stroma. The tumor form of MUC1 also creates a different landscape of inflammatory cells in the tumor microenvironment by controlling the recruitment of inflammatory cells, establishing specific interactions with dendritic cells (DCs) and macrophages, and facilitating tumor escape from the immune system. Through multiple types of short glycans simultaneously present in tumors, MUC1 acquires multiple oncogenic properties that control tumor development, progression, and metastasis at different steps of the process of carcinogenesis. PMID:27754373

  7. The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice.

    PubMed

    Bauer, A K; Dwyer-Nield, L D; Hankin, J A; Murphy, R C; Malkinson, A M

    2001-12-01

    An inflammatory response accompanies the reversible pneumotoxicity caused by butylated hydroxytoluene (BHT) administration to mice. Lung tumor formation is promoted by BHT administration following an initiating agent in BALB/cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation to this differential susceptibility, we quantitatively characterized inflammation after one 150 mg/kg body weight, followed by three weekly 200 mg/kg ip injections of BHT into male mice of both strains. This examination included inflammatory cell infiltrate and protein contents in bronchoalveolar lavage (BAL) fluid, cyclooxygenase (COX)-1 and COX-2 expression in lung extracts, and PGE(2) and PGI(2) production by isolated bronchiolar Clara cells. BAL macrophage and lymphocyte numbers increased in BALB mice (P<0.0007 and 0.02, respectively), as did BAL protein content (P<0.05), COX-1 and COX-2 expression (P<0.05 for each), and PGI(2) production (P<0.05); conversely, these indices were not perturbed by BHT in CXB4 mice. BALB mice fed aspirin (400 mg/kg of chow) for two weeks prior to BHT treatment had reduced inflammatory cell infiltration. Our results support a hypothesis that resistance to BHT-induced inflammation in CXB4 mice accounts, at least in part, for the lack of effect of BHT on lung tumor multiplicity in this strain.

  8. An Internet-Based Counseling Intervention With Email Reminders that Promotes Self-Care in Adults With Chronic Heart Failure: Randomized Controlled Trial Protocol.

    PubMed

    Nolan, Robert P; Payne, Ada Ym; Ross, Heather; White, Michel; D'Antono, Bianca; Chan, Sammy; Barr, Susan I; Gwadry-Sridhar, Femida; Nigam, Anil; Perreault, Sylvie; Farkouh, Michael; McDonald, Michael; Goodman, Jack; Thomas, Scott; Zieroth, Shelley; Isaac, Debra; Oh, Paul; Rajda, Miroslaw; Chen, Maggie; Eysenbach, Gunther; Liu, Sam; Zbib, Ahmad

    2014-01-30

    Chronic heart failure (CHF) is a public health priority. Its age-standardized prevalence has increased over the past decade. A major challenge for the management of CHF is to promote long-term adherence to self-care behaviors without overtaxing available health care resources. Counseling by multidisciplinary health care teams helps to improve adherence to self-care behaviors and to reduce the rate of death and hospitalization. In the absence of intervention, adherence to self-care is below recommended standards. This trial aims to establish and evaluate a Canadian e-platform that will provide a core, standardized protocol of behavioral counseling and education to facilitate long-term adherence to self-care among patients with CHF. Canadian e-Platform to Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT) is a multi-site, double blind, randomized controlled trial with a 2 parallel-group (e-Counseling + Usual Care vs e-Info Control + Usual Care) by 3 assessments (baseline, 4-, and 12-month) design. We will identify subjects with New York Heart Association Class II or III systolic heart failure from collaborating CHF clinics and then recruit them (n=278) by phone. Subjects will be randomized in blocks within each site (Toronto, Montreal, and Vancouver). The primary outcome will be improved quality of life, defined as an increased number of subjects with an improvement of ≥5 points on the summary score of the Kansas City Cardiomyopathy Questionnaire. We will also assess the following secondary outcomes: (1) diet habits, depression, anxiety, smoking history, stress level, and readiness for change using self-report questionnaires, (2) physical activity level, current smoking status, and vagal-heart rate modulation by physiological tests, and (3) exercise capacity, prognostic indicators of cardiovascular functioning, and medication adherence through medical chart review. The primary outcome will be analyzed using generalized estimation equations

  9. An Internet-Based Counseling Intervention With Email Reminders that Promotes Self-Care in Adults With Chronic Heart Failure: Randomized Controlled Trial Protocol

    PubMed Central

    Payne, Ada YM; Ross, Heather; White, Michel; D'Antono, Bianca; Chan, Sammy; Barr, Susan I; Gwadry-Sridhar, Femida; Nigam, Anil; Perreault, Sylvie; Farkouh, Michael; McDonald, Michael; Goodman, Jack; Thomas, Scott; Zieroth, Shelley; Isaac, Debra; Oh, Paul; Rajda, Miroslaw; Chen, Maggie; Eysenbach, Gunther; Liu, Sam; Zbib, Ahmad

    2014-01-01

    Background Chronic heart failure (CHF) is a public health priority. Its age-standardized prevalence has increased over the past decade. A major challenge for the management of CHF is to promote long-term adherence to self-care behaviors without overtaxing available health care resources. Counseling by multidisciplinary health care teams helps to improve adherence to self-care behaviors and to reduce the rate of death and hospitalization. In the absence of intervention, adherence to self-care is below recommended standards. Objective This trial aims to establish and evaluate a Canadian e-platform that will provide a core, standardized protocol of behavioral counseling and education to facilitate long-term adherence to self-care among patients with CHF. Methods Canadian e-Platform to Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT) is a multi-site, double blind, randomized controlled trial with a 2 parallel-group (e-Counseling + Usual Care vs e-Info Control + Usual Care) by 3 assessments (baseline, 4-, and 12-month) design. We will identify subjects with New York Heart Association Class II or III systolic heart failure from collaborating CHF clinics and then recruit them (n=278) by phone. Subjects will be randomized in blocks within each site (Toronto, Montreal, and Vancouver). The primary outcome will be improved quality of life, defined as an increased number of subjects with an improvement of ≥5 points on the summary score of the Kansas City Cardiomyopathy Questionnaire. We will also assess the following secondary outcomes: (1) diet habits, depression, anxiety, smoking history, stress level, and readiness for change using self-report questionnaires, (2) physical activity level, current smoking status, and vagal-heart rate modulation by physiological tests, and (3) exercise capacity, prognostic indicators of cardiovascular functioning, and medication adherence through medical chart review. The primary outcome will be analyzed using

  10. S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

    PubMed

    Prieto, Daniel; Sotelo, Natalia; Seija, Noé; Sernbo, Sandra; Abreu, Cecilia; Durán, Rosario; Gil, Magdalena; Sicco, Estefanía; Irigoin, Victoria; Oliver, Carolina; Landoni, Ana Inés; Gabus, Raúl; Dighiero, Guillermo; Oppezzo, Pablo

    2017-08-10

    Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL. © 2017 by The American Society of Hematology.

  11. Time to face the challenge of multimorbidity. A European perspective from the joint action on chronic diseases and promoting healthy ageing across the life cycle (JA-CHRODIS).

    PubMed

    Onder, Graziano; Palmer, Katie; Navickas, Rokas; Jurevičienė, Elena; Mammarella, Federica; Strandzheva, Mirela; Mannucci, Piermannuccio; Pecorelli, Sergio; Marengoni, Alessandra

    2015-04-01

    Research on multimorbidity has rapidly increased in the last decade, but evidence on the effectiveness of interventions to improve outcomes in patients with multimorbidity is limited. The European Commission is co-funding a large collaborative project named Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) in the context of the 2nd EU Health Programme 2008-2013. The present manuscript summarizes first results of the JA-CHRODIS, focuses on the identification of a population with multimorbidity who has a high or very high care demand. Identification of characteristics of multimorbid patients associated with a high rate of resource consumption and negative health outcomes is necessary to define a target population who can benefit from interventions. Indeed, multimorbidity alone cannot explain the complexity of care needs and further, stratification of the general population based on care needs is necessary for allocating resources and developing personalized, cost-efficient, and patient-centered care plans. Based on analyses of large databases from European countries a profile of the most care-demanding patients with multimorbidity is defined. Several factors associated with adverse health outcomes and resource consumption among patients with multimorbidity were identified in these analyses, including disease patterns, physical function, mental health, and socioeconomic status. These results underline that a global assessment is needed to identify patients with multimorbidity who are at risk of negative health outcomes and that a comprehensive approach, targeting not only diseases, but also social, cognitive, and functional problems should be adopted for these patients. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  12. Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells

    PubMed Central

    Li, Qianyin; Huang, Zhenglan; Gao, Miao; Cao, Weixi; Xiao, Qin; Luo, Hongwei; Feng, Wenli

    2017-01-01

    The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance. PMID:28257089

  13. Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells.

    PubMed

    Li, Qianyin; Huang, Zhenglan; Gao, Miao; Cao, Weixi; Xiao, Qin; Luo, Hongwei; Feng, Wenli

    2017-03-02

    The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance.

  14. Chronic Deep Cerebellar Stimulation Promotes Long-Term Potentiation, Microstructural Plasticity, and Reorganization of Perilesional Cortical Representation in a Rodent Model

    PubMed Central

    Cooperrider, Jessica; Furmaga, Havan; Plow, Ela; Park, Hyun-Joo; Chen, Zhihong; Kidd, Grahame; Baker, Kenneth B.; Gale, John T.

    2014-01-01

    Control over postinjury CNS plasticity is a major frontier of science that, if conquered, would open new avenues for treatment of neurological disorders. Here we investigate the functional, physiological, and structural changes in the cerebral cortex associated with chronic deep brain stimulation of the cerebellar output, a treatment approach that has been shown to improve postischemia motor recovery in a rodent model of cortical infarcts. Long–Evans rats were pretrained on the pasta-matrix retrieval task, followed by induction of focal cortical ischemia and implantation of a macroelectrode in the contralesional lateral cerebellar nucleus. Animals were assigned to one of three treatment groups pseudorandomly to balance severity of poststroke motor deficits: REGULAR stimulation, BURST stimulation, or SHAM. Treatment initiated 2 weeks post surgery and continued for 5 weeks. At the end, animals were randomly selected for perilesional intracortical microstimulation mapping and tissue sampling for Western blot analysis or contributed tissue for 3D electron microscopy. Evidence of enhanced cortical plasticity with therapeutically effective stimulation is shown, marked by greater perilesional reorganization in stimulation- treated animals versus SHAM. BURST stimulation was significantly effective for promoting distal forepaw cortical representation. Stimulation-treated animals showed a twofold increase in synaptic density compared with SHAM. In addition, treated animals demonstrated increased expression of synaptic markers of long-term potentiation and plasticity, including synaptophysin, NMDAR1, CaMKII, and PSD95. These findings provide a critical foundation of how deep cerebellar stimulation may guide plastic reparative reorganization after nonprogressive brain injury and indicate strong translational potential. PMID:24990924

  15. A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

    PubMed

    Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

    2016-03-01

    Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

  16. Ageing, chronic alcohol consumption and folate are determinants of genomic DNA methylation, p16 promoter methylation and the expression of p16 in the mouse colon

    USDA-ARS?s Scientific Manuscript database

    Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

  17. Aging and chronic alcohol consumption are determinants of p16 gene expression, genomic DNA methylation and p16 promoter methylation in the mouse colon

    USDA-ARS?s Scientific Manuscript database

    Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

  18. Invariant natural killer T cells contribute to chronic-plus-binge ethanol-mediated liver injury by promoting hepatic neutrophil infiltration.

    PubMed

    Mathews, Stephanie; Feng, Dechun; Maricic, Igor; Ju, Cynthia; Kumar, Vipin; Gao, Bin

    2016-03-01

    Neutrophil infiltration is a hallmark of alcoholic steatohepatitis; however, the underlying mechanisms remain unclear. We previously reported that chronic-plus-binge ethanol feeding synergistically induces hepatic recruitment of neutrophils, which contributes to liver injury. In this paper, we investigated the roles of invariant natural killer T (iNKT) cells in chronic-plus-binge ethanol feeding-induced hepatic neutrophil infiltration and liver injury. Wild-type and two strains of iNKT cell-deficient mice (CD1d- and Jα18-deficient mice) were subjected to chronic-plus-binge ethanol feeding. Liver injury and inflammation were examined. Chronic-plus-binge ethanol feeding synergistically increased the number of hepatic iNKT cells and induced their activation, compared with chronic feeding or binge alone. iNKT cell-deficient mice were protected from chronic-plus-binge ethanol-induced hepatic neutrophil infiltration and liver injury. Moreover, chronic-plus-binge ethanol feeding markedly upregulated the hepatic expression of several genes associated with inflammation and neutrophil recruitment in wild-type mice, but induction of these genes was abrogated in iNKT cell-deficient mice. Importantly, several cytokines and chemokines (e.g., MIP-2, MIP-1, IL-4, IL-6 and osteopontin) involved in neutrophil infiltration were upregulated in hepatic NKT cells isolated from chronic-plus-binge ethanol-fed mice compared to pair-fed mice. Finally, treatment with CD1d blocking antibody, which blocks iNKT cell activation, partially prevented chronic-plus-binge ethanol-induced liver injury and inflammation. Chronic-plus-binge ethanol feeding activates hepatic iNKT cells, which play a critical role in the development of early alcoholic liver injury, in part by releasing mediators that recruit neutrophils to the liver, and thus, iNKT cells represent a potential therapeutic target for the treatment of alcoholic liver disease.

  19. Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection.

    PubMed

    Zhong, Y W; Di, F L; Liu, C; Zhang, X C; Bi, J F; Li, Y L; Wu, S Q; Dong, H; Liu, L M; He, J; Shi, Y M; Zhang, H F; Zhang, M

    2016-04-01

    We investigated 168 children and analysed the virological characterization and association with disease progression in children with hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutants. Among 168 patients with HBV infection (aged 0.5-18 years old, mean 10.1), 86 of them had HBV-related liver cirrhosis (LC) and 82 had HBV-related chronic hepatitis B (CHB). A direct sequencing method was employed to determine the HBV genotypes and the mutations in BCP/PC regions. In all, 133 of them were infected with genotype C viruses (79.17%); only 35 patients (20.83%) were infected with genotype B viruses. Both LC patients and CHB patients had significantly higher ratios of genotype C when compared with the ratios of genotype B (83.7%-16.3% versus 74.4%-25.6%). For patients with CHB, the prevalence of BCP/PC wild-type viruses was 52.4%; but this was only 4.7% in patients with LC. The C1653T, T1753C, A1762T/G1764A and G1896A mutations had a significantly higher prevalence in patients with LC. Among all the patients with genotype B viruses, those with LC had lower HBV DNA levels and higher G1899A mutation frequency than patients with CHB. Among all the patients with genotype C viruses, the patients with LC had higher prevalence of C1653T, A1762T/G1764A and G1896A mutation frequency, higher hepatitis B e antigen (HBeAg) -negative rates, lower viral load, lower elevated alanine aminotransferase and lower anti-HBe positive rates than CHB patients. The HBV BCP/PC variants were more common in HBeAg-negative LC patients than in the CHB group (BCP, 53.4% versus 15.6%; PC, 18.6% versus 3.7%, respectively, p < 0.001). Patients with HBV genotype C viruses, high viral load and C1653T, A1762T/G1764A, G1896A mutant viruses, were more susceptible to developing LC.

  20. Single-nucleotide polymorphism in the promoter region of the osteopontin gene at nucleotide -443 as a marker predicting the efficacy of pegylated interferon/ribavirin-therapy in Egyptians patients with chronic hepatitis C.

    PubMed

    Shaker, Olfat Gamil; Sadik, Nermin A H; El-Dessouki, Abeer

    2012-10-01

    Osteopontin (OPN) is an extracellular matrix glycophosphoprotein produced by several types of cells including the immune system. The present study examined the possibility that single-nucleotide polymorphisms (SNP) in the promoter region of the OPN at nt -443 is a marker predicting the therapeutic efficacy of pegylated interferon (peg-IFN-α2b)-ribavirin combination therapy in Egyptian patients with chronic hepatitis C. Blood was collected from 95 patients with chronic hepatitis C who had received peg-IFN-α2b-ribavirin combination therapy and 100 age and sex matched controls. SNP in OPN at nucleotide (nt) -443 and its serum protein level were analyzed. Sustained virological response (SVR) was higher in patients with T/T at nt -443 than in those with C/C or C/T. A univariate logistic regression analysis showed that fibrosis grade, serum OPN protein level and T/T homozygotes of SNP at -443 were significant predictors for response. Receiver operating characteristics (ROC) analysis revealed the diagnostic and prognostic efficacy of serum OPN. It can be concluded that SNP in the promoter region of OPN at nt -443 and serum OPN protein level are predictors of response to the efficacy of peg-IFN-α2b-ribavirin therapy in Egyptian patients with chronic hepatitis C.

  1. Characterization of Epstein-Barr virus (EBV) BZLF1 gene promoter variants and comparison of cellular gene expression profiles in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis.

    PubMed

    Imajoh, Masayuki; Hashida, Yumiko; Murakami, Masanao; Maeda, Akihiko; Sato, Tetsuya; Fujieda, Mikiya; Wakiguchi, Hiroshi; Daibata, Masanori

    2012-06-01

    Epstein-Barr virus (EBV) genotypes can be distinguished based on gene sequence differences in EBV nuclear antigens 2, 3A, 3B, and 3C, and the BZLF1 promoter zone (Zp). EBV subtypes and BZLF1 Zp variants were examined in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis. The results of EBV typing showed that samples of infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis all belonged to EBV type 1. However, sequencing analysis of BZLF1 Zp found three polymorphic Zp variants in the same samples. The Zp-P prototype and the Zp-V3 variant were both detected in infectious mononucleosis and chronic active EBV infection. Furthermore, a novel variant previously identified in Chinese children with infectious mononucleosis, Zp-V1, was also found in 3 of 18 samples of infectious mononucleosis, where it coexisted with the Zp-P prototype. This is the first evidence that the EBV variant distribution in Japanese patients resembles that found in other Asian patients. The expression levels of 29 chronic active EBV infection-associated cellular genes were also compared in the three EBV-related disorders, using quantitative real-time reverse transcription polymerase chain reaction analysis. Two upregulated genes, RIPK2 and CDH9, were identified as common specific markers for chronic active EBV infection in both in vitro and in vivo studies. RIPK2 activates apoptosis and autophagy, and could be responsible for the pathogenesis of chronic active EBV infection.

  2. Aryl Hydrocarbon Receptor Ligands in Cigarette Smoke Induce Production of Interleukin-22 to Promote Pancreatic Fibrosis in Models of Chronic Pancreatitis.

    PubMed

    Xue, Jing; Zhao, Qinglan; Sharma, Vishal; Nguyen, Linh P; Lee, Yvonne N; Pham, Kim L; Edderkaoui, Mouad; Pandol, Stephen J; Park, Walter; Habtezion, Aida

    2016-12-01

    Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of CP. We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4(+) T cells. Levels of interleukin-22 (IL22) were measured by enzyme-linked immunosorbent assay and smoking histories were collected. T cells from healthy nonsmokers and smokers were stimulated and incubated with AhR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo[a]pyrene) or antagonists and analyzed by flow cytometry. Mice were given intraperitoneal injections of caerulein or saline, with or without lipopolysaccharide, to induce CP. Some mice were given intraperitoneal injections of AhR agonists at the start of caerulein injection, with or without an antibody against IL22 (anti-IL22) starting 2 weeks after the first caerulein injection, or recombinant mouse IL22 or vehicle (control) intraperitoneally 4 weeks after the first caerulein injection. Mice were exposed to normal air or cigarette smoke for 6 h/d for 7 weeks and expression of AhR gene targets was measured. Pancreata were collected from all mice and analyzed by histology and quantitative reverse transcription polymerase chain reaction. Pancreatic stellate cells and T cells were isolated and studied using immunoblot, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent analyses. Mice given AhR agonists developed more severe pancreatic fibrosis (based on decreased pancreas size, histology, and increased expression of fibrosis-associated genes) than mice not given agonists after caerulein injection. In mice given saline instead of caerulein, AhR ligands did not induce fibrosis. Pancreatic T cells

  3. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

    PubMed Central

    Guo, Shang-Chun; Tao, Shi-Cong; Yin, Wen-Jing; Qi, Xin; Yuan, Ting; Zhang, Chang-Qing

    2017-01-01

    Chronic wounds have become an economic, social, and public health burden and need advanced treatment. Platelet-rich plasma (PRP) has been used extensively in treatment of chronic wounds because it contains an abundance of growth factors secreted by platelets. The exosomes derived from PRP (PRP-Exos) have been proven to encapsulate principal growth factors from platelets. This study is the first to show that these exosomes may exert the function of PRP. PRP-Exos can effectively induce proliferation and migration of endothelial cells and fibroblasts to improve angiogenesis and re-epithelialization in chronic wounds. We regulated YAP to verify the PRP-Exos-dependent effect on fibroblast proliferation and migration through YAP activation. In vivo, we observed the cutaneous healing process in chronic wounds treated with PRP-Exos in a diabetic rat model. We provide evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. PMID:28042318

  4. Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues.

    PubMed

    Li, Xiang; Wang, Xiaolei; Liu, Rui; Ma, Yan; Guo, Huailan; Hao, Liping; Yao, Ping; Liu, Liegang; Sun, Xiufa; He, Ka; Cao, Wenhong; Yang, Xuefeng

    2013-06-01

    This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD). Male Sprague-Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues. Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study.

    PubMed

    Ley, Brett; Newton, Chad A; Arnould, Isabel; Elicker, Brett M; Henry, Travis S; Vittinghoff, Eric; Golden, Jeffrey A; Jones, Kirk D; Batra, Kiran; Torrealba, Jose; Garcia, Christine Kim; Wolters, Paul J

    2017-08-01

    Patients with hypersensitivity pneumonitis are at risk of developing pulmonary fibrosis, which is associated with reduced survival. In families with multiple affected members, individuals might be diagnosed as having idiopathic pulmonary fibrosis (IPF) or chronic (fibrotic) hypersensitivity pneumonitis, which suggests these disorders share risk factors. We aimed to test whether the genomic risk factors associated with the development and progression of IPF are also associated with the development of fibrosis and reduced survival in people with chronic hypersensitivity pneumonitis. We did an observational study of two independent cohorts of patients with chronic hypersensitivity pneumonitis, one from the University of California San Francisco, CA, USA (UCSF), and one from the University of Texas Southwestern, TX, USA (UTSW). We measured two common single-nucleotide polymorphisms associated with IPF (MUC5B rs35705950 and TOLLIP rs5743890) and telomere length in peripheral blood leucocytes, and assessed their associations with chronic hypersensitivity pneumonitis risk, survival, and clinical, radiographic, and pathological features. We compared findings with those in patients with IPF from the UCSF and UTSW cohorts, and healthy controls from the European population of the 1000 Genomes Project Phase 3, version 1. The cohorts included 145 patients from UCSF and 72 from UTSW. The minor allele frequency (MAF) was greater for MUC5B rs35705950 in patients with chronic hypersensitivity pneumonitis than in healthy controls (24·4% in UCSF and 32·3% in UTSW vs 10·7%, both p<0·0001), but not for TOLLIP rs5743890. The MAFs were similar to those for IPF (UCSF 33·3%, p=0·09; UTSW 32·0%, p=0·95). In the combined UCSF and UTSW chronic hypersensitivity pneumonitis cohort, we saw associations between extent of radiographic fibrosis and MUC5B rs35705950 minor alleles (adjusted odds ratio [OR] 1·91, 95% CI 1·02-3·59, p=0·045) and short telomere length (adjusted OR per unit

  6. Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice.

    PubMed

    de Sousa Rodrigues, Maria Elizabeth; Bekhbat, Mandakh; Houser, Madelyn C; Chang, Jianjun; Walker, Douglas I; Jones, Dean P; Oller do Nascimento, Claudia M P; Barnum, Christopher J; Tansey, Malú G

    2017-01-01

    The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism. C57Bl/6 male mice underwent a combination of HFHF and two weeks of chronic psychological stress. MetS-related conditions were assessed using untargeted plasma metabolomics, and structural and immune changes in the gut and liver were evaluated. Inflammation was measured in plasma, liver, gut, and brain. Our results show a complex interplay of diet and stress on gut alterations, energetic homeostasis, lipid metabolism, and plasma insulin levels. Psychological stress and HFHF diet promoted changes in intestinal tight junctions proteins and increases in insulin resistance and plasma cholesterol, and impacted the RNA expression of inflammatory factors in the hippocampus. Stress promoted an adaptive anti-inflammatory profile in the hippocampus that was abolished by diet treatment. HFHF increased hippocampal and hepatic Lcn2 mRNA expression as well as LCN2 plasma levels. Behavioral changes were associated with HFHF and stress. Collectively, these results suggest that diet and stress as pervasive factors exacerbate MetS-related conditions through an inflammatory mechanism that ultimately can impact behavior. This rodent model may prove useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders.

  7. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    PubMed

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application.

  8. Helicobacter pylori-induced chronic inflammation causes telomere shortening of gastric mucosa by promoting PARP-1-mediated non-homologous end joining of DNA.

    PubMed

    Lee, Wei-Ping; Hou, Ming-Chih; Lan, Keng-Hsin; Li, Chung-Pin; Chao, Yee; Lin, Han-Chieh; Lee, Shou-Dong

    2016-09-15

    Helicobacter pylori infection leads to chronic gastritis and increased risk of gastric cancer. The mechanism involves chronic inflammation. We aimed to determine the mechanism by which H. pylori infection causes telomere shortening in inflammatory gastric mucosa. Gastric biopsy specimens were obtained from 20 patients with chronic gastritis or peptic ulcer caused by H. pylori infection. The specimens showed increased NF-κB and superoxide dismutase activities and elevated expressions of PARP-1 and γ-H2AX, all of which returned to normal levels after anti-H. pylori treatment, suggesting that oxidative DNA damage and PARP-1 overexpression might cause telomere shortening. In this report, we adopted DNA end joining assay and showed that H. pylori-infected gastric mucosa had increased alternative NHEJ (non-homologous end joining), implicating that telomere shortening was caused by inflammation-mediated overproduction of reactive oxygen species and PARP-1, leading to telomere shortening. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Acute but not chronic exposure to abiotic stress results in transient reduction of expression levels of the transgene driven by the 35S promoter.

    PubMed

    Boyko, Alex; Molinier, Jean; Chatter, Waine; Laroche, André; Kovalchuk, Igor

    2010-02-28

    The transgenic plant performance depends on the stable expression of the integrated transgene. In this paper, we have analyzed the stability of the most frequently used constitutive promoter, the cauliflower mosaic virus (CaMV) 35S promoter. We used several independent Nicotiana tabacum lines transgenic for the luciferase (LUC) or green fluorescence protein (GFP) coding genes driven by the same 35S promoter. As an indication of the expression level, we measured the steady state RNA level, protein level and protein activity. Exposure of plants to an acute single dose of UVC, UVB or X-ray radiation resulted in a decrease of the transgene expression level, whereas exposure to high temperature increased it. In most of the cases, the expression changed at one to two hours post exposure and returned to normal at four hours. By contrast, plants germinated and grown in the presence of a low dose of either UVB radiation or CuSO(4) for two weeks did not show any changes in expression level. We conclude that although the expression level of the transgenes driven by the 35S promoter can be transiently altered by the acute exposure, no substantial changes occur upon constant low exposure. Copyright 2009 Elsevier B.V. All rights reserved.

  10. Chronic Cough

    MedlinePlus

    Chronic cough Overview By Mayo Clinic Staff A chronic cough is a cough that lasts eight weeks or longer in adults, or four weeks in children. A chronic cough is more than just an annoyance. A chronic ...

  11. Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

    PubMed

    Dos Reis Lívero, Francislaine Aparecida; da Silva, Luisa Mota; Ferreira, Daniele Maria; Galuppo, Larissa Favaretto; Borato, Debora Gasparin; Prando, Thiago Bruno Lima; Lourenço, Emerson Luiz Botelho; Strapasson, Regiane Lauriano Batista; Stefanello, Maria Élida Alves; Werner, Maria Fernanda de Paula; Acco, Alexandra

    2016-09-01

    Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

  12. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    PubMed

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  13. Chronic vitamin C deficiency promotes redox imbalance in the brain but does not alter sodium-dependent vitamin C transporter 2 expression.

    PubMed

    Paidi, Maya D; Schjoldager, Janne G; Lykkesfeldt, Jens; Tveden-Nyborg, Pernille

    2014-04-29

    Vitamin C (VitC) has several roles in the brain acting both as a specific and non-specific antioxidant. The brain upholds a very high VitC concentration and is able to preferentially retain VitC even during deficiency. The accumulation of brain VitC levels much higher than in blood is primarily achieved by the sodium dependent VitC transporter (SVCT2). This study investigated the effects of chronic pre-and postnatal VitC deficiency as well as the effects of postnatal VitC repletion, on brain SVCT2 expression and markers of oxidative stress in young guinea pigs. Biochemical analyses demonstrated significantly decreased total VitC and an increased percentage of dehydroascorbic acid, as well as increased lipid oxidation (malondialdehyde), in the brains of VitC deficient animals (p < 0.0001) compared to controls. VitC repleted animals were not significantly different from controls. No significant changes were detected in either gene or protein expression of SVCT2 between groups or brain regions. In conclusion, chronic pre-and postnatal VitC deficiency increased brain redox imbalance but did not increase SVCT2 expression. Our findings show potential implications for VitC deficiency induced negative effects of redox imbalance in the brain and provide novel insight to the regulation of VitC in the brain during deficiency.

  14. Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors

    PubMed Central

    Ayadi, Meriam; Bouygues, Anaïs; Ouaret, Djamila; Ferrand, Nathalie; Chouaib, Salem; Thiery, Jean-Paul; Muchardt, Christian; Sabbah, Michèle; Larsen, Annette K

    2015-01-01

    Most solid tumors contain a subfraction of cells with stem/progenitor cell features. Stem cells are naturally chemoresistant suggesting that chronic chemotherapeutic stress may select for cells with increased “stemness”. We carried out a comprehensive molecular and functional analysis of six independently selected colorectal cancer (CRC) cell lines with acquired resistance to three different chemotherapeutic agents derived from two distinct parental cell lines. Chronic drug exposure resulted in complex alterations of stem cell markers that could be classified into three categories: 1) one cell line, HT-29/5-FU, showed increased “stemness” and WNT-signaling, 2) three cell lines showed decreased expression of stem cell markers, decreased aldehyde dehydrogenase activity, attenuated WNT-signaling and lost the capacity to form colonospheres and 3) two cell lines displayed prominent expression of ABC transporters with a heterogeneous response for stem cell markers. While WNT-signaling could be attenuated in the HT-29/5-FU cells by the WNT-signaling inhibitors ICG-001 and PKF-118, this was not accompanied by any selective growth inhibitory effect suggesting that the cytotoxic activity of these compounds is not directly linked to WNT-signaling inhibition. We conclude that classical WNT-signaling inhibitors have toxic off-target activities that need to be addressed for clinical development. PMID:26041882

  15. Chronic systemic administration of salmeterol to rats promotes pulmonary β2-adrenoceptor desensitization and down-regulation of Gsα

    PubMed Central

    Finney, Paul A; Donnelly, Louise E; Belvisi, Maria G; Chuang, Tsu-Tshen; Birrell, Mark; Harris, Andrew; Mak, Judith C W; Scorer, Carol; Barnes, Peter J; Adcock, Ian M; Giembycz, Mark A

    2001-01-01

    The aim of the present study was to examine the effects of chronic infusion of the long-acting agonist salmeterol on pulmonary β2-adrenoceptor function in Sprague-Dawley rats in vivo and to elucidate the molecular basis of any altered state. Systemic administration of rats with salmeterol for 7 days compromised the ability of salmeterol and prostaglandin E2 (PGE2), given acutely by the intravenous route, to protect against ACh-induced bronchoconstriction when compared to rats treated identically with vehicle. β1- and β2-adrenoceptor density was significantly reduced in lung membranes harvested from salmeterol-treated animals, which was associated with impaired salmeterol- and PGE2-induced cyclic AMP accumulation ex vivo. Three variants of Gsα that migrated as 42, 44 and 52 kDa peptides on SDS polyacrylamide gels were detected in lung membranes prepared from both groups of rats but the intensity of each isoform was markedly reduced in rats that received salmeterol. The activity of cytosolic, but not membrane-associated, G-protein receptor-coupled kinase was elevated in the lung of salmeterol-treated rats when compared to vehicle-treated animals. The ability of salmeterol, administered systemically, to protect the airways of untreated rats against ACh-induced bronchoconstriction was short-acting (toff ∼45 min), which contrasts with its long-acting nature when given to asthmatic subjects by inhalation. These results indicate that chronic treatment of rats with salmeterol results in heterologous desensitization of pulmonary Gs-coupled receptors. In light of previous data obtained in rats treated chronically with salbutamol, we propose that a primary mechanism responsible for this effect is a reduction in membrane-associated Gsα. The short-acting nature of salmeterol, when administered systemically, and the reduction in β-adrenoceptor number may be due to metabolism to a biologically-active, short-acting and non-selective β-adrenoceptor agonist. PMID

  16. Hepatitis B virus basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

    PubMed

    Yan, Chun-Hui; Zhao, Cheng-Yu; Ding, Hai; Peng, Ya-Qin; Jin, Peng-Yuan; Yan, Ling; Zhuang, Hui; Li, Tong

    2012-11-01

    The present study was aimed to obtain baseline information of basal core promoter A1762T/G1764A and precore G1896A mutations of hepatitis B virus (HBV) in 192 HBeAg-positive chronically-infected Chinese patients, who were potential candidates for antiviral treatment. The detection of these mutations (including minor mutant subpopulations) was achieved by direct sequencing, whose sensitivity for minor mutant subpopulations identification was confirmed by clone sequencing. Patients enrolled were infected with either genotype B (46.35%) or C (53.65%) HBV identified by routine tests in our laboratory. The A1762T/G1764A or G1896A mutations were detected in 125specimens (125/192, 65.10%), in which 77 (77/125, 61.60%) existed as subpopulations. The A1762T/G1764A mutations were found to be more prevalent in genotype C than that in genotype B HBV [62.14% (64/103) vs. 20.22% (18/89), P<0.0001]. There is no statistically significant link between G1896A and genotypes. The emergence of A1762T/G1764A mutations was also found to be associated with an older age, an elevated ALT/AST level, and a lower HBsAg level in serum [wild-type vs. mutant: 4.57 (3.46-5.42) vs. 3.93 (2.51-5.36), P<0.0001]. In conclusion, HBV basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

  17. A history of chronic morphine exposure during adolescence increases despair-like behaviour and strain-dependently promotes sociability in abstinent adult mice

    PubMed Central

    Lutz, PE; Reiss, D; Ouagazzal, AM; Kieffer, BL

    2013-01-01

    A crucial issue in treating opiate addiction, a chronic relapsing disorder, is to maintain a drug-free abstinent state. Prolonged abstinence associates with mood disorders, strongly contributing to relapse. In particular, substance use disorders occurring during adolescence predispose to depression later in adulthood. Using our established mouse model of opiate abstinence, we characterized emotional consequences into adulthood of morphine exposure during adolescence. Our results indicate that morphine treatment in adolescent mice has no effect on anxiety-like behaviours in adult mice, after abstinence. In contrast, morphine treatment during adolescence increases behavioural despair in adult mice. We also show that morphine exposure strain-dependently enhances sociability in adult mice. Additional research will be required to understand where and how morphine acts during brain maturation to affect emotional and social behaviours into adulthood. PMID:23295400

  18. A history of chronic morphine exposure during adolescence increases despair-like behaviour and strain-dependently promotes sociability in abstinent adult mice.

    PubMed

    Lutz, P E; Reiss, D; Ouagazzal, A M; Kieffer, B L

    2013-04-15

    A crucial issue in treating opiate addiction, a chronic relapsing disorder, is to maintain a drug-free abstinent state. Prolonged abstinence associates with mood disorders, strongly contributing to relapse. In particular, substance use disorders occurring during adolescence predispose to depression later in adulthood. Using our established mouse model of opiate abstinence, we characterized emotional consequences into adulthood of morphine exposure during adolescence. Our results indicate that morphine treatment in adolescent mice has no effect on anxiety-like behaviours in adult mice, after abstinence. In contrast, morphine treatment during adolescence increases behavioural despair in adult mice. We also show that morphine exposure strain-dependently enhances sociability in adult mice. Additional research will be required to understand where and how morphine acts during brain maturation to affect emotional and social behaviours into adulthood. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Reduced cost and mortality using home telehealth to promote self-management of complex chronic conditions: a retrospective matched cohort study of 4,999 veteran patients.

    PubMed

    Darkins, Adam; Kendall, Stephen; Edmonson, Ellen; Young, Michele; Stressel, Pamela

    2015-01-01

    This retrospective analysis of 2009-2012 Veterans Health Administration (VHA) administrative data assessed the efficacy of care coordination home telehealth (CCHT), a model of care designed to reduce institutional care. Outcomes for 4,999 CCHT-non-institutional care (NIC) patients were compared with usual (non-CCHT) care in a matched cohort group (MCG) of 183,872 Veterans. Both cohorts were comprised of patients with complex chronic conditions with statistically similar baseline (pre-CCHT enrollment) healthcare costs, when adjusted for age, sex, chronic disease, emergency room (ER) visits, hospital admissions, hospital lengths of stay, and pharmacy costs. Subsequent analyses after 12 months of CCHT-NIC enrollment showed mean annual healthcare costs for CCHT-NIC patients fell 4%, from $21,071 to $20,206, whereas the corresponding costs for MCG patients increased 48%, from $20,937 to $31,055. Higher mean annual pharmacy expenditure of 22% ($470 over baseline) for CCHT-NIC patients versus 15% for MCG patients ($326 over baseline) was attributable to the medication compliance effect of better care coordination. Several healthcare cost drivers (e.g., ER visits and admissions) had sizable declines in the CCHT-NIC group. Medicare usage review in both cohorts excluded this as a confounding factor in cost analyses. Prefinal case selection criteria analysis of both cohorts yielded a 9.8% mortality rate in CCHT patients versus 16.58% in non-CCHT patients. This study corroborates previous positive VHA analyses of CCHT but contradicts results from recent non-VHA studies, highlighting the efficacy of the VHA's standardized CCHT model, which incorporates a biopsychosocial approach to care that emphasizes patient self-management.

  20. Direct determination of single nucleotide polymorphism haplotype of NFKBIL1 promoter polymorphism by DNA conformation analysis and its application to association study of chronic inflammatory diseases.

    PubMed

    Shibata, Hiroki; Yasunami, Michio; Obuchi, Nobuhisa; Takahashi, Megumi; Kobayashi, Yasushi; Numano, Fujio; Kimura, Akinori

    2006-01-01

    We previously revealed that one of the human leukocyte antigen-linked susceptibility genes for Takayasu's arteritis (TA) was mapped between TNFA and MICB loci and that -63T allele of NFKBIL1, which is between TNFA and MICB loci, was associated with rheumatoid arthritis (RA) in the Japanese population. We have developed a novel typing method based on reference strand-mediated conformation analysis for the upstream sequence of the NFKBIL1 gene, where -422 (T)8/(T)9, -325 C/G, -263 A/G, and -63 T/A polymorphisms were found. Upon the analysis of the patients with TA (n = 84), those with RA (n = 120), and healthy control subjects (n = 217), five common haplotypes named IKBLp*01 through IKBLp*05 were found in the Japanese population. The frequency of IKBLp*03 was significantly increased in the patient with TA (57.1% vs 35.0%, giving an odds ratio of 2.47). In addition, the frequency of IKBLp*01, but not that of other -63T-bearing alleles, was increased in the patients with RA (73.3% vs 58.1%, giving an odds ratio of 1.99), suggesting that the susceptibility to RA was conferred not by -63T alone but by combination of single nucleotide polymorphisms in the NFKBIL1 promoter. A higher promoter activity associated with IKBLp*03 and a lower activity associated with IKBLp*01 may contribute to the susceptibility to TA and RA, respectively.

  1. Chronic ω-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol.

    PubMed

    Ferraz, Anete Curte; Delattre, Ana Marcia; Almendra, Rhiana G; Sonagli, Marina; Borges, Conrado; Araujo, Paula; Andersen, Monica L; Tufik, Sergio; Lima, Marcelo M S

    2011-05-16

    Recent evidence has demonstrated dietary influence on the manifestation of different types of behaviors induced by stressor tasks. The present study examined the impact of ω-3 polyunsaturated fatty acids (PUFAs) supplementation in an early phase of the brain development with the goal of preventing or even attenuating the occurrence of stress-related behaviors such as depressive-like behaviors, anxiety and cognitive dysfunctions in male rats subjected to restraint stress. Our results indicated that the supplementation regimen successfully counteracted the anxiogenic effects of stress as evidenced by the rats' increased exploration time in the aversive arms of the elevated plus maze. The forced swimming test indicated that immobility and swimming were more deeply influenced by PUFAs supplementation, thereby demonstrating an antidepressant effect. Furthermore, cognitive function was shown to be intensely affected by restraint stress, but the effects were surprisingly counteracted by the PUFAs supplementation. Lastly, plasmatic corticosterone levels were demonstrated to be drastically increased by the restraint stress; however, PUFAs supplementation promoted a reduction of this stress-related hormone to levels that were comparable to those observed in the control group. Our results suggested that the mechanisms underlying these effects are possibly associated with the reduction of corticosterone levels promoted by the PUFAs supplementation in the stress-induced animals. Further studies to examine the participation of PUFAs in mediating different behaviors in rats subjected to restraint stress are warranted.

  2. Promoting and supporting self-management for adults living in the community with physical chronic illness: A systematic review of the effectiveness and meaningfulness of the patient-practitioner encounter.

    PubMed

    Rees, Sally; Williams, Anne

    2009-01-01

    There has been a reported rise in the number of people with chronic illness (also referred to as long-term disease) in the Western world. One hundred million people in the United States have at least one chronic condition and in the United Kingdom (UK) as many as 17.5 million adults may be living with chronic disease. New models of care have been developed which recognise the complexities of managing care where there is overlap between the wider community, the health care system and provider organisations, for example, the Chronic Care Model and the Expert Patient Programme. These new models herald a shift away from the idea of chronically ill patients as passive recipients of care towards active engagement, in partnership with health professionals, in managing their own care.Partnership, ideally, involves collaborative care and self-management education. This may support self-care alongside medical, preventative and health maintenance interventions. In this context the nature of the patient-practitioner consultation in promoting self-care takes on a new importance. The overall objective of the review was to determine the best available evidence regarding the promotion and support of self-care management for adults living in the community with chronic illness during the patient-practitioner encounter. Specifically the review sought to determine: What is the effectiveness of the patient-practitioner encounter in promoting and supporting self-care management of people with chronic illness? What are the individual and organisational factors which help or hinder recognition, promotion and support of chronic disease self-care management strategies? What are the similarities and differences between how 'effectiveness' is defined in this context by patients and different practitioners? The review focussed on self-caring adults aged nineteen years and older living in the community, with a physical chronic illness, and not currently being treated as an in-patient. For

  3. T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

    PubMed

    Pain, M; Royer, P-J; Loy, J; Girardeau, A; Tissot, A; Lacoste, P; Roux, A; Reynaud-Gaubert, M; Kessler, R; Mussot, S; Dromer, C; Brugière, O; Mornex, J-F; Guillemain, R; Dahan, M; Knoop, C; Botturi, K; Pison, C; Danger, R; Brouard, S; Magnan, A

    2017-06-01

    Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-β. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-β-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Microbubble-mediated ultrasound promotes accumulation of bone marrow mesenchymal stem cell to the prostate for treating chronic bacterial prostatitis in rats

    PubMed Central

    Yi, Shanhong; Han, Guangwei; Shang, Yonggang; Liu, Chengcheng; Cui, Dong; Yu, Shuangjiang; Liao, Bin; Ao, Xiang; Li, Guangzhi; Li, Longkun

    2016-01-01

    Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared with a healthy control group. A therapeutic-ultrasound apparatus was used to treat the prostate in the presence of circulating microbubbles and BMMSCs. The BMMSC distribution was assessed with in vivo imaging, and the prostate structure with light microscopy. Real-time quantitative RT-PCR, ELISA, and immunohistochemistry were used to assess the expressions of TNF-α and IL-1β. More BMMSCs were found in the prostate in the MMUS group than in the CBP, ultrasound, and BMMSC groups. Inflammatory cell infiltration, fibrous tissue hyperplasia, and tumor-like epithelial proliferation were significantly reduced in the MMUS group, as were the mRNA and protein expressions of TNF-α and IL-1β. Microbubble-mediated ultrasound-induced accumulation of BMMSCs can inhibit inflammation and decrease TNF-α and IL-1β expressions in the prostate of CBP rats, suggesting that this method may be therapeutic for CPB. PMID:26797392

  5. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

    PubMed

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-02-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. © 2014 John Wiley & Sons Ltd.

  6. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

    PubMed Central

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-01-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. PMID:25179236

  7. Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

    SciTech Connect

    Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

    2014-10-01

    Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

  8. Assessing the feasibility of a web-based domestic violence intervention using chronic disease frameworks: reducing the burden of 'treatment' and promoting capacity for action in women abused by a partner.

    PubMed

    Tarzia, Laura; May, Carl; Hegarty, Kelsey

    2016-11-24

    Domestic violence shares many features with chronic disease, including ongoing physical and mental health problems and eroded self-efficacy. Given the challenges around help-seeking for women experiencing domestic violence, it is essential that they be given support to 'self-manage' their condition. The growing popularity of web-based applications for chronic disease self-management suggests that there may be opportunities to use them as an intervention strategy for women experiencing domestic violence, however, as yet, little is known about whether this might work in practice. It is critical that interventions for domestic violence-whether web-based or otherwise-promote agency and capacity for action rather than adding to the 'workload' of already stressed and vulnerable women. Although randomised controlled trials are vital to determine the effectiveness of interventions, robust theoretical frameworks can complement them as a way of examining the feasibility of implementing an intervention in practice. To date, no such frameworks have been developed for the domestic violence context. Consequently, in this paper we propose that it may be useful to appraise interventions for domestic violence using frameworks developed to help understand the barriers and facilitators around self-management of chronic conditions. Using a case study of an online healthy relationship tool and safety decision aid developed in Australia (I-DECIDE), this paper adapts and applies two theories: Burden of Treatment Theory and Normalisation Process Theory, to assess whether the intervention might increase women's agency and capacity for action. In doing this, it proposes a new theoretical model with which the practical application of domestic violence interventions could be appraised in conjunction with other evaluation frameworks. This paper argues that theoretical frameworks for chronic disease are appropriate to assess the feasibility of implementing interventions for domestic violence in

  9. The oncogene DEK promotes leukemic cell survival and is downregulated by both Nutlin-3 and chlorambucil in B-chronic lymphocytic leukemic cells.

    PubMed

    Secchiero, Paola; Voltan, Rebecca; di Iasio, Maria Grazia; Melloni, Elisabetta; Tiribelli, Mario; Zauli, Giorgio

    2010-03-15

    To characterize the role of the oncogene DEK in modulating the response to either Nutlin-3, a small-molecule inhibitor of the MDM2/p53 interaction, or chlorambucil in primary B-chronic lymphocytic leukemia (B-CLL) cells. DEK mRNA and protein levels were evaluated in primary B-CLL samples (n = 21), p53(wild-type) SKW6.4, p53(mutated) BJAB lymphoblastoid cell lines, and normal CD19(+) B lymphocytes-treated Nutlin-3 or chlorambucil (10 micromol/L, each). Knocking down experiments with either p53 or DEK small interfering RNA (siRNA) were done to investigate the potential role of p53 in controlling the expression of DEK and the role of DEK in leukemic cell survival/apoptosis. Both Nutlin-3 and chlorambucil downregulated DEK in primary B-CLL samples (n = 21) and SKW6.4 but not in BJAB cells. Knocking down p53 attenuated the effect of Nutlin-3 on DEK expression, whereas knocking down DEK significantly increased both spontaneous and Nutlin-3-induced apoptosis. Conversely, counteracting DEK downmodulation by using p53 small interfering RNA reduced Nutlin-3-mediated apoptosis. On the other hand, Nutlin-3 potently induced p53 accumulation, but it did not affect DEK levels in normal CD19(+) B lymphocytes. These data show that the downregulation of DEK in response to either Nutlin-3 or chlorambucil represents an important molecular determinant in the cytotoxic response of leukemic cells, and suggest that strategies aimed to downregulate DEK might improve the therapeutic potential of these drugs.

  10. Low extracellular sodium promotes adipogenic commitment of human mesenchymal stromal cells: a novel mechanism for chronic hyponatremia-induced bone loss.

    PubMed

    Fibbi, B; Benvenuti, S; Giuliani, C; Deledda, C; Luciani, P; Monici, M; Mazzanti, B; Ballerini, C; Peri, A

    2016-04-01

    Hyponatremia represents an independent risk factor for osteoporosis and fractures, affecting both bone density and quality. A direct stimulation of bone resorption in the presence of reduced extracellular sodium concentrations ([Na(+)]) has been shown, but the effects of low [Na(+)] on osteoblasts have not been elucidated. We investigated the effects of a chronic reduction of extracellular [Na(+)], independently of osmotic stress, on human mesenchymal stromal cells (hMSC) from bone marrow, the common progenitor for osteoblasts and adipocytes. hMSC adhesion and viability were significantly inhibited by reduced [Na(+)], but their surface antigen profile and immuno-modulatory properties were not altered. In low [Na(+)], hMSC were able to commit toward both the osteogenic and the adipogenic phenotypes, as demonstrated by differentiation markers analysis. However, the dose-dependent increase in the number of adipocytes as a function of reduced [Na(+)] suggested a preferential commitment toward the adipogenic phenotype at the expense of osteogenesis. The amplified inhibitory effect on the expression of osteoblastic markers exerted by adipocytes-derived conditioned media in low [Na(+)] further supported this observation. The analysis of cytoskeleton showed that low [Na(+)] were associated with disruption of tubulin organization in hMSC-derived osteoblasts, thus suggesting a negative effect on bone quality. Finally, hMSC-derived osteoblasts increased their expression of factors stimulating osteoclast recruitment and activity. These findings confirm that hyponatremia should be carefully taken into account because of its negative effects on bone, in addition to the known neurological effects, and indicate for the first time that impaired osteogenesis may be involved.

  11. A psychological intervention to promote acceptance and adherence to non-invasive ventilation in people with chronic obstructive pulmonary disease: study protocol of a randomised controlled trial.

    PubMed

    Volpato, Eleonora; Banfi, Paolo; Pagnini, Francesco

    2017-02-06

    People with chronic obstructive pulmonary disease (COPD) sometimes experience anxiety, depression and comorbid cognitive deficits. Rather than being merely a consequence of symptom-related physical impairments these additional problems may be part of the clinical course of the condition. The relationship between the physical and psychological aspects of the condition is illustrated by the patterns of use of non-invasive ventilation (NIV); NIV is often rejected or used inappropriately, resulting in clinical deterioration and an increase in health care costs. The study aims to analyse the effects of psychological support on the acceptance of, and adherence to, NIV. The primary outcome will be a latent variable related to indices of use of NIV equipment and adherence to treatment regime; while survival rates and psychological variables will constitute the secondary outcomes. A two-arm randomised controlled trial will be conducted. We aim to recruit 150 COPD patients for whom NIV is indicated. The experimental group will receive a brief course of psychological support that will include counselling, relaxation and mindfulness-based exercises. In some cases, it will also include neuropsychological rehabilitation exercises. Support will be delivered via four to eight meetings at the HD Respiratory Rehabilitation Unit, at home or via telemedicine. Controls will receive standard care and watch educational videos related to the management of their disease. This investigation will gain insight about the role of a psychological intervention as part of a treatment plan during the process of adaptation to NIV in COPD patients. ClinicalTrials.gov, ID: NCT02499653 . Registered on 14 July 2015.

  12. An action research on promotion of healthy ageing and risk reduction of chronic disease: a need assessment study among rural elderly Malays, care givers and health professionals.

    PubMed

    Nur Asyura Adznam, S; Shahar, S; Rahman, S A; Yusof, N A M; Arshad, F; Yassin, Z; Salleh, M; Samah, A A; Sakian, N I M

    2009-12-01

    Prior to the development of a healthy ageing and risk reduction of chronic diseases intervention package for older people in Malaysia, a need assessment study was conducted to identify nutritional knowledge status and information needs, as part of an action research process. A cross sectional study was conducted among 267 elderly people, 54 care givers and 66 health professionals in two rural areas of Peninsular of Malaysia (i.e Sabak Bernam, Selangor and Kuala Pilah, Negeri Sembilan). Information on nutritional knowledge was obtained from an interview based questionnaire for older subjects and caregiver and through self administered questionnaire from the health professionals. Anthropometric and functional measurements were also conducted among elderly subjects. It was found that the elderly subjects had poor nutritional knowledge with 43.8% of them classified as having unsatisfactory nutritional knowledge, followed by moderately satisfactory (33.7%), very unsatisfactory (15.7%) and good (6.7%). Talks, counselling sessions with health professionals and electronic media such as television and radio were the most preferred nutrition education sources among elderly subjects and their care givers. The majority of health professionals studied (98.5%) had good nutritional knowledge. Although most of them (93.6%) were involved in management of the elderly, only 45.5% incorporated nutritional information component in this activity. Most of the health professionals used the guidelines for management of elderly patients (63.6%). However, nutritional knowledge was very minimal in these guidelines. Multiple regression analysis indicated that 'level education', involvement in 'social activities', presence of 'hearing problems', the Instrumental Activities of Daily Living (IADL) score, having previous 'nutritional information' and 'participation in healthy eating programme' were the major predictors of nutritional knowledge score among elderly subjects. Based on the above

  13. Chronic Bronchitis

    MedlinePlus

    ... Patients & Visitors Giving For Professionals Treatment & Programs Health Information Doctors & Departments Research & Science Education & Training Home Conditions Chronic Bronchitis Chronic Bronchitis ...

  14. Entecavir promotes CD34⁺ stem cell proliferation in the peripheral blood and liver of chronic hepatitis B and liver cirrhosis patients.

    PubMed

    Lv, Bei; Zhao, Hong; Bai, Xue; Huang, Shaoping; Fan, Zhenyu; Lu, Jihua; Tang, Rong; Yin, Keshan; Gao, Peter; Liu, Baoling; Cheng, Jilin

    2014-11-01

    Entecavir (ETV) has been used for more than 2 decades in treating hepatitis B virus (HBV) infections. It has shown significant anti-HBV effect and has led to histological improvement in the liver of chronic hepatitis B (CHB) patients. In patients treated with ETV for over two years, reversal of cirrhosis to normal tissue has also been observed. However, the mechanisms of these tissue repairing or recovery processes are not yet clear. In order to determine the roles that bone marrow and liver stem/progenitor cells play in these processes, we evaluated the CD34⁺ and CD133⁺ stem/progenitor cells in peripheral blood from 292 patients and liver tissues from 43 patients who had received therapies with and without ETV. A significant increase in both CD34⁺ and CD133⁺ cells was found in CHB and cirrhosis patients compared to the healthy controls. In patients treated with ETV, CD34⁺ cells increased 2 and 4 fold in peripheral blood and liver tissues, respectively, while their CD4⁺ and CD8⁺ cells remained the same. On the other hand, CD133⁺ cells did not change or even slightly decreased with ETV treatment. Results from immunohistochemistry staining, real time RT-PCR, and the enzyme-linked immunosorbent assay also revealed the same level of CD34⁺ cell increase and CD133⁺ cell decrease (or no change) in ETV treated patients, compared to patients without ETV therapies. Liver functions in patients with ETV treatment improved in general, but one liver cirrhosis patient with high expression of CD133 in liver tissue developed hepatocellular carcinoma (HCC). In summary, ETV may have differential effects on various stem cell subtypes. ETV-activated stem cells in bone marrow and liver tissues may contribute to the recovery from injuries caused by HBV infection. They also contribute to the regeneration of normal tissue and the recovery of normal liver function. Meanwhile, ETV does not activate stem cells that may participate in the initiation of HCC.

  15. A multicomponent nutrient bar promotes weight loss and improves dyslipidemia and insulin resistance in the overweight/obese: chronic inflammation blunts these improvements.

    PubMed

    McCann, Joyce C; Shigenaga, Mark K; Mietus-Snyder, Michele L; Lal, Ashutosh; Suh, Jung H; Krauss, Ronald M; Gildengorin, Ginny L; Goldrich, Alisa M; Block, Devan S; Shenvi, Swapna V; McHugh, Tara H; Olson, Don A; Ames, Bruce N

    2015-08-01

    This study determined if twice-daily consumption of a nutrient-dense bar intended to fill gaps in Western diets, without other dietary/lifestyle requirements, favorably shifted metabolic/anthropometric indicators of dysregulation in a healthy direction. Three 8-wk clinical trials in 43 healthy lean and overweight/obese (OW/OB) adults, who served as their own controls, were pooled for analysis. In less inflamed OW/OB [high-sensitivity C-reactive protein (hsCRP) <1.5], statistically significant decreases occurred in weight (-1.1 ± 0.5 kg), waist circumference (-3.1 ± 1.4 cm), diastolic blood pressure (-4.1 ± 1.6 mmHg), heart rate [HR; -4.0 ± 1.7 beats per minute (bpm)], triglycerides (-72 ± 38.2 mg/dl), insulin resistance (homeostatic model of insulin resistance) (-0.72 ± 0.3), and insulin (-2.8 ± 1.3 mU/L); an increase in HDL-2b (+303 ± 116 nM) and realignment of LDL lipid subfractions toward a less atherogenic profile [decreased small LDL IIIb (-44 ± 23.5 nM), LDL IIIa (-99 ± 43.7 nM), and increased large LDL I (+66 ± 28.0 nM)]. In the more inflamed OW/OB (hsCRP >1.5), inflammation was reduced at 2 wk (-0.66 mg/L), and HR at 8 wk (-3.4 ± 1.3 bpm). The large HDL subfraction (10.5-14.5 nm) increased at 8 wk (+346 ± 126 nM). Metabolic improvements were also observed in lean participants. Thus, favorable changes in measures of cardiovascular health, insulin resistance, inflammation, and obesity were initiated within 8 wk in the OW/OB by replacing deficiencies in Western diets without requiring other dietary or lifestyle modifications; chronic inflammation blunted most improvements. © FASEB.

  16. Limited knowledge of chronic kidney disease and its main risk factors among Iranian community: an appeal for promoting national public health education programs

    PubMed Central

    Roomizadeh, Peyman; Taheri, Diana; Abedini, Amin; Mortazavi, Mojgan; Larry, Mehrdad; Mehdikhani, Bahareh; Mousavi, Seyed-Mojtaba; Hosseini, Farid-Aldin; Parnia, Aidin; Nakhjavani, Manouchehr

    2014-01-01

    Background: The aim of this survey was to explore the baseline knowledge of the Iranian community about Chronic Kidney Disease (CKD) definition and its two main risk factors, i.e. diabetes and hypertension. This study also introduced a model of public education program with the purpose of reducing the incidence of CKD in high-risk groups and thereby decreasing the economic burden of CKD in Iran. Methods: This cross-sectional study was conducted on world kidney day 2013 in Isfahan, Iran. Self-administered anonymous questionnaires evaluating the knowledge of CKD and its risk factors were distributed among subjects who participated in a kidney disease awareness campaign. Chi-square test and logistic regression analysis were used to examine the differences in the level of knowledge across different socio-demographic groups. Results: The questionnaires were completed by 748 respondents. The majority of these respondents believed that "pain in the flanks" and "difficulty in urination" was the early symptoms of CKD. Roughly, 10.4% knew that CKD could be asymptomatic in the initial stages. Only 12.7% knew diabetes and 14.4% knew hypertension was a CKD risk factor. The respondents who had a CKD risk factor (i.e. diabetes and/or hypertension) were significantly more likely than respondents without CKD risk factor to select "unmanaged diabetes" [Odds Ratio (OR)= 2.2, Confidence Interval (CI) (95%): 1.4–3.6] and "unmanaged hypertension" [OR= 1.9, CI(95%): 1.2–3.0] as "very likely to result in CKD". No more than 34.6% of all respondents with diabetes and/or hypertension reported that their physician has ever spoken with them about their increased risk for developing CKD. Conclusion: The knowledge of Iranian population about CKD and its risk factors is low. Future public health education programs should put efforts in educating Iranian community about the asymptomatic nature of CKD in its initial stages and highlighting the importance of regular renal care counseling. The

  17. [Calcinosis conjunctivae in chronic blepharitis].

    PubMed

    Auw-Hädrich, C; Reinhard, T

    2008-01-01

    We present a case of a 53-year-old female patient with chronic blepharitis and conjunctival overgrowth of the cornea. Histologically the conjunctival overgrowth contained foreign body granulomas around calcification focuses. This could have been promoted by the application of phosphate-containing eye drops and the presence of chemokines like TNF-alpha, which occur in chronic blepharitis. Thus, we recommend the application of phosphate-free eye drops in patients with chronic blepharitis.

  18. Chronic Exposure of Female Mice to an Environmental Level of Perfluorooctane Sulfonate Suppresses Estrogen Synthesis Through Reduced Histone H3K14 Acetylation of the StAR Promoter Leading to Deficits in Follicular Development and Ovulation.

    PubMed

    Feng, Xuejiao; Wang, Xiaoli; Cao, Xinyuan; Xia, Yankai; Zhou, Rong; Chen, Ling

    2015-12-01

    Perfluorooctane sulfonate (PFOS) at a high dose of 10 mg/kg has been reported to affect the neuroendocrine system and exert toxic effects in rodents. The present study examined the influence of chronic exposure to a low-dose of PFOS (0.1 mg/kg/day) on female reproductive endocrine and function. Herein, we show that adult female mice exposed to PFOS by gavage for 4 months (PFOS-mice) exhibited a prolongation of diestrus without signs of toxic effects. The numbers of mature follicles and corpora luteum were significantly reduced in PFOS-mice with increase of atresic follicles. The levels of serum estrogen (E2) and progesterone at proestrus and diestrus were reduced in PFOS-mice. In comparison with controls, PFOS-mice showed a significant decrease in the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and gonadotrophin-releasing hormone, the number of kisspeptin neurons and the level of kiss1 mRNA in anteroventral periventricular nucleus at proestrus but not at diestrus, which could be corrected with the normalization to E2. PFOS-mice did not generate an LH-surge at proestrus, which could be rescued by the application of E2 or kisspeptin-10. Notably, the level of ovarian steroidogenic acute regulatory (StAR) mRNA was decreased in PFOS-mice with the reduction of histone H3K14 acetylation in StAR promoter relative to control mice, whereas the P450scc expression and histone H3K14 acetylation showed no difference between the groups. The present study provides evidence that the chronic exposure to the low-dose of PFOS through selectively reducing histone acetylation of StAR suppresses the biosynthesis of E2 to impair the follicular development and ovulation.

  19. Polymorphism of tumor necrosis factor-α and interleukin-10 gene promoter region in chronic hepatitis C virus patients and their effect on pegylated interferon-α therapy response.

    PubMed

    Dogra, Gaurav; Chakravarti, Anita; Kar, Premashish; Chawla, Yogesh Kumar

    2011-10-01

    The development and resolution of an inflammatory process is regulated by a complex interplay among cytokines that have pro- and anti-inflammatory effects. Regulatory mechanisms that control the production of cytokines include genetic polymorphism in particular promoter/leader region. Polymorphisms may directly or indirectly affect the binding of transcriptional factors, consequently increasing or decreasing the production of mRNA, thus regulating cytokine production. A total of 70 hepatitis C virus (HCV) RNA-positive patients and 70 healthy control subjects were included in the present study, who were attending the medical outpatient department (OPD) and wards of a tertiary care hospital in New Delhi during 2006-2008. This study was designed to determine the polymorphism of tumor necrosis factor-α and interleukin-10 genes in patients with chronic HCV infection patients and their effect on pegylated interferon-α therapy response. Polymorphism in the tumor necrosis factor-α G/G, G/A, and A/A genotype was significant between HCV patients and healthy controls. Interleukin-10 variants (G/G, G/A) were nonsignificant among HCV patients compared with healthy controls. As this is a preliminary study on small sample size, we believe that our findings may stimulate further studies on larger number of patients from this geographic region.

  20. Chinese patent medicine for chronic obstructive pulmonary disease based on principles of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm: a systematic review of randomized controlled trials.

    PubMed

    Liu, Wei; Yang, Shuang; Fu, Min; Li, Jian; Song, Yaling; Wei, Baolin; Liu, Enshun; Sun, Zengtao

    2015-02-01

    To assess the efficacy and safety of Chinese patent medicine (CPM) with the principle of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm (TQ-PBC-RP) in the management of stable chronic obstructive pulmonary disease (COPD). A systematic review of randomized controlled trials (RCTs) identified from electronic databases and print was conducted. RCTs testing CPMs with TQ-PBC-RP against any type of controlled intervention in patients with stable COPD and assessing clinically relevant outcomes were included. Methodological quality was evaluated with the risk of bias tool according to systematic review handbook 5.0.2. Quality of evidence was estimated by the rating approach developed by the Grading of Recommendations, Assessment, Development, and Evaluation Working Group. Thirteen eligible RCTs with 12 oral CPMs were tested. Significant differences between groups in favor of CPMs were not reported in all trials. Most trials included were deemed to be of low methodological quality with poor evidence quality. Because of large data heterogeneity, statistical pooling was not performed for all outcomes. The effectiveness of CPM in the treatment of stable COPD is not supported by evidence. Currently, evidence from RCTs is scarce and methodologically weak. Considering the popularity of CPMs among patients undergoing COPD, rigorously designed trials are warranted.

  1. Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure.

    PubMed

    Li, Han-Min; Ye, Zhi-Hua; Zhang, Jun; Gao, Xiang; Chen, Yan-Ming; Yao, Xin; Gu, Jian-Xun; Zhan, Lei; Ji, Yang; Xu, Jian-Liang; Zeng, Ying-He; Yang, Fan; Xiao, Lin; Sheng, Guo-Guang; Xin, Wei; Long, Qi; Zhu, Qing-Jing; Shi, Zhao-Hong; Ruan, Lian-Guo; Yang, Jia-Yao; Li, Chang-Chun; Wu, Hong-Bin; Chen, Sheng-Duo; Luo, Xin-La

    2014-12-28

    To study the clinical efficacy of traditional Chinese medicine (TCM) intervention "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") for treating liver failure due to chronic hepatitis B. We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a "tonifying qi and detoxification" ("TQD") group (72 patients); and (3) a "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the "TQD" group were given a TCM formula "tonifying qi and detoxification" and general internal medicine treatment; patients in the "TTK" group were given a TCM formula of "TTK" and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups. At the 48-wk post-treatment time point, the patient fatality rates in the MMC, "TQD", and "TTK" groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P < 0.05). However, there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups (P > 0.05). Patients in the "TTK

  2. Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

    PubMed Central

    Li, Han-Min; Ye, Zhi-Hua; Zhang, Jun; Gao, Xiang; Chen, Yan-Ming; Yao, Xin; Gu, Jian-Xun; Zhan, Lei; Ji, Yang; Xu, Jian-Liang; Zeng, Ying-He; Yang, Fan; Xiao, Lin; Sheng, Guo-Guang; Xin, Wei; Long, Qi; Zhu, Qing-Jing; Shi, Zhao-Hong; Ruan, Lian-Guo; Yang, Jia-Yao; Li, Chang-Chun; Wu, Hong-Bin; Chen, Sheng-Duo; Luo, Xin-La

    2014-01-01

    AIM: To study the clinical efficacy of traditional Chinese medicine (TCM) intervention “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) for treating liver failure due to chronic hepatitis B. METHODS: We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a “tonifying qi and detoxification” (“TQD”) group (72 patients); and (3) a “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the “TQD” group were given a TCM formula “tonifying qi and detoxification” and general internal medicine treatment; patients in the “TTK” group were given a TCM formula of “TTK” and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups. RESULTS: At the 48-wk post-treatment time point, the patient fatality rates in the MMC, “TQD”, and “TTK” groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P < 0.05). However, there were no significant differences in the levels of hepatitis B virus DNA or prothrombin

  3. Using Patient-Reported Outcome Measures (PROMs) to promote quality of care and safety in the management of patients with Advanced Chronic Kidney disease (PRO-trACK project): a mixed-methods project protocol.

    PubMed

    Aiyegbusi, Olalekan Lee; Kyte, Derek; Cockwell, Paul; Marshall, Tom; Dutton, Mary; Slade, Anita; Marklew, Neil; Price, Gary; Verdi, Rav; Waters, Judi; Sharpe, Keeley; Calvert, Melanie

    2017-06-30

    Advanced chronic kidney disease (CKD) has a major effect on the quality of life and health status of patients and requires accurate and responsive management. The use of electronic patient-reported outcome measures (ePROMs) could assist patients with advanced pre-dialysis CKD, and the clinicians responsible for their care, by identifying important changes in symptom burden in real time. We report the protocol for 'Using Patient-Reported Outcome measures (PROMs) to promote quality of care and safety in the management of patients with Advanced Chronic Kidney Disease' (PRO-trACK) project, which will explore the feasibility and validity of an ePROM system for use in patients with advanced CKD. The project will use a mixed-methods approach in three studies: (1) usability testing of the ePROM system involving up to 30 patients and focusing on acceptability and technical performance/stability; (2) ascertaining the views of patient and clinician stakeholders on the optimal use and administration of the CKD ePROM system-this will involve qualitative face-to-face/telephone interviewing with up to 30 patients or until saturation is achieved, focus groups with up to 15 clinical staff, management and IT team members; (3) psychometric assessment of the system, within a cohort of at least 180 patients with advanced CKD, to establish the measurement properties of the ePROM. This project was approved by the West Midlands Edgbaston Research Ethics Committee (Reference 17/WM/0010) and received Health Research Authority (HRA) approval on 24 February 2017.The findings from this project will be provided to clinicians at the Department of Renal Medicine, Queen Elizabeth Hospitals, Birmingham (QEHB), NHS England, presented at conferences and to the Kidney Patients' Association, British Kidney Patient Association and the British Renal Society. Articles based on the findings will be written and submitted for publication in peer-reviewed journals. © Article author(s) (or their employer

  4. Chronic Pain

    MedlinePlus

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on for ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis Pain ...

  5. Chronic Bronchitis

    MedlinePlus

    ... a disease, often call Chronic Obstructive Pulmonary Disease (COPD) . A person with COPD may have either emphysema or chronic bronchitis, but many have both. Some people with COPD may also have asthma . Let’s take a look ...

  6. Chronic migraine.

    PubMed

    Schwedt, Todd J

    2014-03-24

    Chronic migraine is a disabling neurologic condition that affects 2% of the general population. Patients with chronic migraine have headaches on at least 15 days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine. Chronic migraine places an enormous burden on patients owing to frequent headaches; hypersensitivity to visual, auditory, and olfactory stimuli; nausea; and vomiting. It also affects society through direct and indirect medical costs. Chronic migraine typically develops after a slow increase in headache frequency over months to years. Several factors are associated with an increased risk of transforming to chronic migraine. The diagnosis requires a carefully performed patient interview and neurologic examination, sometimes combined with additional diagnostic tests, to differentiate chronic migraine from secondary headache disorders and other primary chronic headaches of long duration. Treatment takes a multifaceted approach that may include risk factor modification, avoidance of migraine triggers, drug and non-drug based prophylaxis, and abortive migraine treatment, the frequency of which is limited to avoid drug overuse. This article provides an overview of current knowledge regarding chronic migraine, including epidemiology, risk factors for its development, pathophysiology, diagnosis, management, and guidelines. The future of chronic migraine treatment and research is also discussed.

  7. Chronic kidney disease

    MedlinePlus

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some ...

  8. Chronic pancreatitis.

    PubMed

    DiMagno, Matthew J; DiMagno, Eugene P

    2012-09-01

    We review important new clinical observations in chronic pancreatitis reported in 2011. Smoking increases the risk of nongallstone acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. Binge drinking during Oktoberfest did not associate with increased hospital admissions for acute pancreatitis. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in chronic pancreatitis is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90 000 United States Pharmacopeia units of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared with endoscopic treatment in patients advanced chronic pancreatitis with a dilated main duct ± pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with chronic pancreatitis but approximately 30% of patients have significant side effects. Patients with nongallstone-related acute pancreatitis or chronic pancreatitis of any cause should cease smoking. Results of this year's investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in chronic pancreatitis, and the mechanisms and treatment of neuropathic pain in chronic pancreatitis.

  9. Chronic Bronchitis

    MedlinePlus

    ... to get into your lungs.Bronchitis causes a cough that produces mucus (sometimes called sputum), trouble breathing, ... main symptom of chronic bronchitis is a persistent cough that doesn’t go away for months. The ...

  10. [Chronic migraine].

    PubMed

    Diener, H C; Holle, D; Müller, D; Nägel, S; Rabe, K

    2013-12-01

    The classification of the International Headache Society (IHS) generally differentiates episodic from chronic headache. Chronic migraine is defined as headache on 15 and more days a month over more than 3 months and headache on 8 days or more fulfils the criteria for migraine or were triptan/ergot-responsive when thought to be migrainous in early stages of the attack. The prevalence of chronic migraine is estimated at 2-4 %. The quality of life is highly compromised in this condition and comorbidities are much more frequent compared to episodic migraine. Data from prospective randomized studies are scarce as most patients with chronic migraine were excluded from previous trials and only few studies were conducted for this condition. The efficacy for prophylactic treatment compared with placebo is proven for topiramate and onabotulinum toxin A.

  11. Health Promotion

    PubMed Central

    Wilson, Ron

    1992-01-01

    How physicians address issues of disease prevention and health promotion is discussed and current standards of screening for disease and counseling practices are reviewed. Collaboration among all health professionals is necessary if preventive medicine is to be effective. PMID:21221259

  12. Chronic prostatitis

    PubMed Central

    2011-01-01

    Introduction Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic abacterial prostatitis/chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, biofeedback, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, prostatic massage, quercetin, radical prostatectomy, sitz baths, transurethral microwave thermotherapy, and transurethral resection. PMID:21736764

  13. Veterans and chronic pain

    PubMed Central

    Wilson, Sarah

    2013-01-01

    Summary points 1. Musculoskeletal problems are the commonest reason for medical discharge in all the British armed forces. By definition, these problems are chronic and resistant to treatment. 2. Pain is also common in veterans who have experienced severe injuries (polytrauma), often accompanied by post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) orpostconcussive syndrome. 3. In veterans seeking treatment for chronic pain, PTSD is common. There is also evidence for elevated levels of alcohol misuse in veterans who have been deployed to conflict. However, most veterans do not have pain, PTSD or alcohol problems. 4. Pain clinicians would benefit from training in meeting veterans’ needs, in order to promote their engagement and successful treatment. This should include countering stereotypes, information about the military and support for the assessment and onward referral of PTSD and alcohol problems. PMID:26516504

  14. Chronic pancreatitis.

    PubMed

    Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

    2017-09-07

    Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

  15. Chronic urticaria.

    PubMed Central

    Leznoff, A.

    1998-01-01

    OBJECTIVE: To review the pathophysiology of chronic urticaria in light of recent evidence for it being an autoimmune disease, and to recommend appropriate management. QUALITY OF EVIDENCE: An extensive literature review was supplemented with a MEDLINE search. Articles from easily available journals were preferred. These consisted of the most recent basic articles on autoimmunity in relation to chronic urticaria and a selection of previous articles on pathophysiology, which illustrate consistencies with recent evidence. The investigation and management protocol is supported by original and relevant literature. MAIN FINDINGS: The histopathology and immunohistology of chronic urticaria and certain clinical studies were a prelude to definitive evidence that most instances of chronic urticaria are autoimmune. Although allergic and other causes are uncommon, these must be sought because identification can lead to cure or specific treatment. Management of the much more common autoimmune urticaria is based on principles derived from the demonstrated pathogenesis and on results of published clinical trials. CONCLUSIONS: In most instances, chronic urticaria is an autoimmune disease, but uncommon allergic or other causes must be considered. PMID:9805172

  16. Dental disease in children with chronic illness

    PubMed Central

    Foster, H; Fitzgerald, J

    2005-01-01

    We focus on the role of the general paediatrician in promoting the importance of good dental health for all children and in particular those children "at risk". We present preventive measures, evidence based where available, that may improve dental care and promote the role of paediatric dental services in the multidisciplinary management of chronic disease. PMID:15970611

  17. Promoting Models

    NASA Astrophysics Data System (ADS)

    Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si

    There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.

  18. Health Promotion

    PubMed Central

    Karmali-Rawji, Shameela; Kassim-Lakha, Shaheen; Taylor, Karmel

    1992-01-01

    Perceived lack or loss of control, stress, a rapidly again population and rising costs of health care necessitate effective health promotion and disease prevention in the elderly. In a collaborative health promotion effort, the private sector, public sector, and community partners have joined to increase the South Asian elders' sense of control over the decisions and circumstances that affect their everyday lives. The project was designed to help elders come to terms with the fragmentation of their extended families, cultural alienation, decreased autonomy, need for information, and greater risk of cardiovascular disease. Imagesp622-a

  19. Promoting Health.

    ERIC Educational Resources Information Center

    Mechanic, David

    1990-01-01

    Argues that culture change or modification of the social structure is necessary for effective health promotion because health behavior is closely tied to basic group structures and processes. Examines the health attitudes of Mormons, low income and minority groups, and developing Islamic nations, emphasizing attitudes towards education and women.…

  20. Chronic myelogenous leukemia (CML)

    MedlinePlus

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  1. Chronic Bronchitis

    MedlinePlus

    ... breathing. You may also have other tests. Chronic bronchitis is a long-term condition that keeps coming back or never goes away completely. If you smoke, it is important to quit. Treatment can help with your symptoms. It often includes ...

  2. Chronic gastritis.

    PubMed

    Sipponen, Pentti; Maaroos, Heidi-Ingrid

    2015-06-01

    Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.

  3. Chronic gastritis

    PubMed Central

    Sipponen, Pentti; Maaroos, Heidi-Ingrid

    2015-01-01

    Abstract Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines. PMID:25901896

  4. Chronic insomnia.

    PubMed

    Neubauer, David N

    2013-02-01

    This article provides an overview of current strategies for evaluating and treating patients who experience chronic insomnia. The US Food and Drug Administration (FDA) has approved several medications for the treatment of insomnia that incorporate a variety of pharmacodynamic and pharmacokinetic properties, thus allowing the development of a customized therapeutic approach. FDA-approved medications include γ-aminobutyric acid-modulating benzodiazepine receptor agonists, a melatonin receptor agonist, and a histamine receptor agonist. Psychological and behavioral techniques combined as cognitive-behavioral therapy also have been shown to be effective in the treatment of chronic insomnia. Insomnia is the most common sleep disturbance and represents a chronic condition for many people. Difficulty falling asleep and maintaining sleep are highly prevalent problems in patients with neurologic disorders. Multiple factors typically contribute to insomnia. Accordingly, a rather broad approach to evaluating patients is warranted. Evidence-based guidelines support the use of cognitive and behavioral strategies and selected medications in the treatment of patients with chronic insomnia.

  5. Health Promotion

    DTIC Science & Technology

    1986-03-11

    Dependents Schools and Section 6 schools. (4) Information on the health consequences of smoking shall be incorporated with the information on alcohol...departments. 2. A Health Promotion Coordinating Committee shall be established to enhance communication among the Military Services, recommend joint policy...about the patient’s tobacco use, including use of smokeless tobacco products; to advise him or her of the risks associated with use, the health bcnefits

  6. Chronic Myelogenous Leukemia

    MedlinePlus

    Chronic myelogenous leukemia Overview Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the blood cells. The term "chronic" in chronic myelogenous leukemia indicates that this cancer ...

  7. Chronic obstructive pulmonary disease

    MedlinePlus

    COPD; Chronic obstructive airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... can do to relieve symptoms and keep the disease from getting worse. If you smoke, now is ...

  8. Chronic motor tic disorder

    MedlinePlus

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  9. Chronic pain - resources

    MedlinePlus

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org National ...

  10. Carbonated beverages and chronic kidney disease.

    PubMed

    Saldana, Tina M; Basso, Olga; Darden, Rebecca; Sandler, Dale P

    2007-07-01

    Carbonated beverage consumption has been linked with diabetes, hypertension, and kidney stones, all risk factors for chronic kidney disease. Cola beverages, in particular, contain phosphoric acid and have been associated with urinary changes that promote kidney stones. We examined the relationship between carbonated beverages (including cola) and chronic kidney disease, using data from 465 patients with newly diagnosed chronic kidney disease and 467 community controls recruited in North Carolina between 1980 and 1982. Drinking 2 or more colas per day was associated with increased risk of chronic kidney disease (adjusted odds ratio = 2.3; 95% confidence interval = 1.4-3.7). Results were the same for regular colas (2.1; 1.3-3.4) and artificially sweetened colas (2.1; 0.7-2.5). Noncola carbonated beverages were not associated with chronic kidney disease (0.94; 0.4-2.2). These preliminary results suggest that cola consumption may increase the risk of chronic kidney disease.

  11. Chronic Myeloproliferative Neoplasms Treatment

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  12. Chronic urticaria.

    PubMed Central

    Burrall, B. A.; Halpern, G. M.; Huntley, A. C.

    1990-01-01

    Urticaria affects 15% to 20% of the population once or more during a lifetime. Chronic urticaria is a frequent recurrent eruption over a period greater than 6 weeks; the cause remains a mystery in more than 75% of cases. Urticaria and angioedema may be produced by immunologic or nonimmunologic means. Urticarial vasculitis, contact urticaria, mastocytosis, physical urticarias, dermatographism, cholinergic urticaria, localized heat urticaria, cold urticaria, aquagenic urticaria, and vibratory angioedema all require specific evaluation and treatment. Chronic idiopathic urticaria is usually controlled by antihistamines; depending on the circadian rhythm of the eruption, sedative or nonsedative antihistamines are prescribed. Some patients will require a combination of H1 and H2 antagonists, or even parenteral corticosteroids. PMID:1970697

  13. Chronic Cough.

    PubMed

    Pacheco, Adalberto; de Diego, Alfredo; Domingo, Christian; Lamas, Adelaida; Gutierrez, Raimundo; Naberan, Karlos; Garrigues, Vicente; López Vime, Raquel

    2015-11-01

    Chronic cough (CC), or cough lasting more than 8 weeks, has attracted increased attention in recent years following advances that have changed opinions on the prevailing diagnostic and therapeutic triad in place since the 1970s. Suboptimal treatment results in two thirds of all cases, together with a new notion of CC as a peripheral and central hypersensitivity syndrome similar to chronic pain, have changed the approach to this common complaint in routine clinical practice. The peripheral receptors involved in CC are still a part of the diagnostic triad. However, both convergence of stimuli and central nervous system hypersensitivity are key factors in treatment success. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  14. Epigenetic mechanisms of chronic pain.

    PubMed

    Descalzi, Giannina; Ikegami, Daigo; Ushijima, Toshikazu; Nestler, Eric J; Zachariou, Venetia; Narita, Minoru

    2015-04-01

    Neuropathic and inflammatory pain promote a large number of persisting adaptations at the cellular and molecular level, allowing even transient tissue or nerve damage to elicit changes in cells that contribute to the development of chronic pain and associated symptoms. There is evidence that injury-induced changes in chromatin structure drive stable changes in gene expression and neural function, which may cause several symptoms, including allodynia, hyperalgesia, anxiety, and depression. Recent findings on epigenetic changes in the spinal cord and brain during chronic pain may guide fundamental advances in new treatments. Here, we provide a brief overview of epigenetic regulation in the nervous system and then discuss the still-limited literature that directly implicates epigenetic modifications in chronic pain syndromes.

  15. Surgical Management of Chronic Wounds.

    PubMed

    Johnston, Benjamin R; Ha, Austin Y; Kwan, Daniel

    2016-02-01

    In this article, we outline the important role the surgeon plays in the management of chronic wounds. Debridement and washout are required for grossly infected wounds and necrotizing soft tissue infections. Cutaneous cancers such as squamous cell carcinomas may contribute to chronic wounds and vice versa; if diagnosed, these should be treated with wide local excision. Arterial, venous, and even lymphatic flows can be restored in select cases to enhance delivery of nutrients and removal of metabolic waste and promote wound healing. In cases where vital structures, such as bones, joints, tendons, and nerves, are exposed, vascularized tissue transfers are often required. These tissue transfers can be local or remote, the latter of which necessitates anastomoses of arteries and veins. Pressure sores are managed by relieving pressure, treating acute trauma or infection, and using rotation fasciocutaneous flaps. Lastly, the surgeon must always consider the possibility of osteomyelitis and retained foreign body as etiology for chronic wounds.

  16. Epigenetic Mechanisms of Chronic Pain

    PubMed Central

    Descalzi, Giannina; Ikegami, Daigo; Ushijima, Toshikazu; Nestler, Eric; Zachariou, Venetia; Narita, Minoru

    2015-01-01

    Neuropathic and inflammatory pain promote a large number of persisting adaptations at the cellular and molecular level, allowing tissue or nerve damage, even if only transient, to elicit changes in cells that contribute to the development of chronic pain and associated symptoms. There is evidence that injury-induced changes in chromatin structure drive stable changes in gene expression and neural function, which may cause several symptoms, including allodynia, hyperalgesia, anxiety, and depression. Recent findings on epigenetic changes in the spinal cord and brain during chronic pain may guide fundamental advances in new treatments. In this review, we provide a brief overview of epigenetic regulation in the nervous system and then discuss the still-limited literature that directly implicates epigenetic modifications in chronic pain syndromes. PMID:25765319

  17. Addressing Chronic Disease Within Supportive Housing Programs

    PubMed Central

    Henwood, Benjamin F.; Stanhope, Victoria; Brawer, Rickie; Weinstein, Lara Carson; Lawson, James; Stwords, Edward; Crossan, Cornelius

    2015-01-01

    Background Tenants of supportive housing have a high burden of chronic health conditions. Objectives To examine the feasibility of developing a tenant-involved health promotion initiative within a “housing first” agency using a community-based participatory research (CBPR) framework. Methods Qualitative analyses of nine research capacity-building group meetings and fifteen individual pre- and post-interviews with those who completed a chronic disease self-management program, resulting in the development of several themes. Results Tenants of supportive housing successfully partnered with health care providers to implement a chronic disease self-management program, noting that “health care becomes ‘relevant’ with housing.” Conclusions Supportive housing organizations are well-situated to implement health promotion initiatives. Such publicly subsidized housing that is accompanied by comprehensive supports must also include self-management training to help people overcome both internal and external barriers to addressing chronic health needs. PMID:23543023

  18. Chronic migraine.

    PubMed

    Valade, D

    2013-05-01

    The second edition of the International Classification of Headache Disorders revised in 2006 (ICHD-2R) gives a definition which requires 15 or more headache days per month over the past 3months with at least eight headache days per month that meet criteria for migraine without aura or that responds to migraine specific treatment. Approximately 2% of the global population suffers of chronic migraine (CM). Frequency of headache and degree of disability distinguish CM from episodic migraine (EM). There is a high frequency of medication overuse. The treatment depends on evaluation with education, lifestyle modifications, and trigger management, behavioral and pharmacologic therapies.

  19. Community networks in chronic disease management.

    PubMed

    Pyne, Diane

    2009-01-01

    Community networks are being established as part of the Chronic Disease Management program in Edmonton, Alberta. These networks are programs and services from profit and not-for-profit organizations that support people with chronic conditions to address lifestyle choices and issues. Evidence-informed standards and criteria have been developed that have to be met to belong to such a network. The community network approach is developing a "community" of resources that are available and committed to assist healthcare professionals and the public with health promotion for people with chronic conditions.

  20. [Zinc and chronic enteropathies].

    PubMed

    Giorgi, P L; Catassi, C; Guerrieri, A

    1984-01-01

    In recent years the nutritional importance of zinc has been well established; its deficiency and its symptoms have also been recognized in humans. Furthermore, Acrodermatitis Enteropathica has been isolated, a rare but severe disease, of which skin lesions, chronic diarrhoea and recurring infections are the main symptoms. The disease is related to the malfunctioning of intestinal absorption of zinc and can be treated by administering pharmacological doses of zinc orally. Good dietary sources of zinc are meat, fish and, to a less extent, human milk. The amount of zinc absorbed in the small intestine is influenced by other nutrients: some compounds inhibit this process (dietary fiber, phytate) while others (picolinic acid, citric acid), referred to as Zn-binding ligands (ZnBL) facilitate it. Citric acid is thought to be the ligand which accounts for the high level of bioavailability of zinc in human milk. zinc absorption occurs throughout the small intestine, not only in the prossimal tract (duodenum and jejunum) but also in the distal tract (ileum). Diarrhoea is one of the clinical manifestations of zinc deficiency, thus many illnesses distinguished by chronic diarrhoea entail a bad absorption of zinc. In fact, in some cases of chronic enteropathies in infants, like coeliac disease and seldom cystic fibrosis, a deficiency of zinc has been isolated. Some of the symptoms of Crohn's disease, like retarded growth and hypogonadism, have been related to hypozinchemia which is present in this illness. Finally, it is possible that some of the dietary treatments frequently used for persistent post-enteritis diarrhoea (i.e. cow's milk exclusion, abuse and misuse of dietary fiber like carrot and carub powder, use of soy formula) can constitute a scarce supply of zinc and therefore could promote the persistency of diarrhoea itself.

  1. Susceptibility to chronic inflammation: an update.

    PubMed

    Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R

    2017-03-01

    Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed. We also discuss newly identified canonical and non-canonical genes associated with chronic inflammation. In the environmental section, we highlight some of the latest updates and evidence in relation to the role that infection, diet and stress play in promoting inflammation. The aim of this review is to provide an overview of the latest research to build on our current understanding of chronic inflammation. It highlights the complexity associated with chronic inflammation, as well as provides insights into potential new targets for therapies that could be used to treat chronic inflammation and consequently prevent disease progression.

  2. Promoting Retention

    PubMed Central

    Hall, LaToya N.; Ficker, Lisa J.; Chadiha, Letha A.; Green, Carmen R.; Jackson, James S.; Lichtenberg, Peter A.

    2016-01-01

    Objectives: The objectives of this study were to evaluate the capability of a research volunteer registry to retain community-dwelling African American older adults, and to explore demographic and health factors associated with retention. Method: A logistic regression model was used to determine the influence of demographics, health factors, and registry logic model activities on retention in a sample of 1,730 older African American adults. Results: Almost 80% of participants active in the volunteer research registry between January 2012 and June 2015 were retained. Employment, being referred to research studies, a higher number of medical conditions, and more follow-up contacts were associated with an increased likelihood of retention. Older age, more months in the registry, and more mobility problems decreased the likelihood of retention. Discussion: These results suggest the Michigan Center for Urban African American Aging Research logic model promotes retention through involving older African American adults in research through study referrals and intensive follow-up. The loss of participants due to age- and mobility-related issues indicate the registry may be losing its most vulnerable participants. PMID:28138501

  3. Effect of interleukin-10 gene promoter polymorphisms -1082 G/A and -592 C/A on response to therapy in children and adolescents with chronic hepatitis C virus infection.

    PubMed

    El-Karaksy, Hanaa M; Sharaf, Sahar A; Mandour, Iman A; Mogahed, Engy A; Rady, Normeen H; El-Mougy, Fatma A

    2016-12-01

    Studying predictors of response to therapy for hepatitis C virus (HCV) infection in children may help avoid the inappropriate use of currently available costly therapy associated with numerous adverse effects. We tested the hypothesis that inheritance of single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) promoter gene might influence response to HCV treatment. The impact of SNPs, -1082 G/A and -592 C/A, in the promoter region of IL-10 gene, on response to HCV therapy was assessed in a cohort of 40 children treated with a combination of pegylated interferon (Peg-IFN) α2b and ribavirin. Sustained virological response was achieved in 48.7%. High viral load was associated with non-response to therapy. There was no association between histopathological degree of inflammation or fibrosis and response to therapy. There was no direct statistically significant association between polymorphisms in the IL-10 gene (-1082G/A and -592 C/A) as regards inflammation or response to therapy in children. As for the SNP -592 C/A; there was a statistically significant association with the score of fibrosis (P<0.004), concluding that the A allele was protective from moderate and severe fibrosis. Meanwhile the SNP -1082G/A did not show any association with the fibrosis score. We could not associate response to therapy for HCV with IL-10 polymorphisms -1082 G/A and -592 C/A. For the SNP -592 C/A, the A allele protected from moderate and severe fibrosis. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  4. Chronic subdural hematoma

    MedlinePlus

    Subdural hemorrhage - chronic; Subdural hematoma - chronic; Subdural hygroma ... A subdural hematoma develops when bridging veins tear and leak blood. These are the tiny veins that run between the ...

  5. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP. PMID:22782018

  6. CHRONIC URTICARIA

    PubMed Central

    Sachdeva, Sandeep; Gupta, Vibhanshu; Amin, Syed Suhail; Tahseen, Mohd

    2011-01-01

    Chronic urticaria (CU) is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the ‘idiopathic’ forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented. PMID:22345759

  7. Chronic Stress in Children and Adolescents.

    ERIC Educational Resources Information Center

    Thoresen, Carl E.; Eagleston, Jean R.

    1983-01-01

    Chronic stress can affect the health of children and adolescents when their resources are insufficient for coping with demands placed upon them. Harmful behavior patterns can lead to poor health. Students should be taught to mobilize their physiological, cognitive, and social resources in ways that promote good health. (PP)

  8. Lymphocyte 'homing' and chronic inflammation.

    PubMed

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  9. Hyperglycemia, tumorigenesis, and chronic inflammation.

    PubMed

    Chang, Shu-Chun; Yang, Wei-Chung Vivian

    2016-12-01

    Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells. Therefore, uncontrolled proinflammatory responses could conceivably create a chronic inflammatory state, promoting a tumor-favorable microenvironment and potentially triggering immune overactivation and cancer growth. To further understand how hyperglycemia contributes to immune overactivation, the tumor microenvironment and the development of chronic inflammation-associated tumors may provide insights into tumor biology and immunology. This paper provides a brief introduction to hyperglycemia-associated diseases, followed by a comprehensive overview of the current findings of regulatory molecular mechanisms of glycosylation on proteoglycans in the extracellular matrix under hyperglycemic conditions. Then, the authors discuss the role of hyperglycemia in tumorigenesis (particularly in prostate, liver, colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia to chronic inflammation. The authors end with a brief discussion on the future perspectives of hyperglycemia/tumorigenesis and potential applications of alternative/effective therapeutic strategies for hyperglycemia-associated cancers.

  10. [Experiences in promoting physical activity].

    PubMed

    Mena-Bejarano, Beatriz

    2006-12-01

    Evaluating the strengths and weaknesses of some experiences emphasising physical activity in promoting health in Bogotá. A documentary review of theoretical models of intervention was first undertaken, followed by examining guidelines proposed in international declarations and in Bogotá related to physical activity. Three-phase analysis was carried. 1) The exploratory phase involved collecting general information regarding programmes pertaining to physical activity aimed at preventing non-transmittable chronic diseases (NTCD) and promoting health. 2) The descriptive phase involved characterising programmes for promoting physical activity according to their objectives, scope and the strategies and methodologies used in such processes. 3) The analytical phase involved a critical analysis of current programmes in terms of their strengths and weaknesses. The programmes analysed here promoted self-management and autonomy by producing support networks and training leaders for guaranteeing their sustainability. The programmes involved people and the community by holding practical and theoretical workshops which did not cover the whole vital human process, but concentrated on specific population groups. They were deficient in broadcasting in the mass-media.

  11. Supporting Self-management of Chronic Pain

    ClinicalTrials.gov

    2017-09-19

    Chronic Pain Syndrome; Chronic Pain; Chronic Pain Due to Injury; Chronic Pain Due to Trauma; Chronic Pain Due to Malignancy (Finding); Chronic Pain Post-Procedural; Chronic Pain Hip; Chronic Pain, Widespread

  12. The Ion Channel TRPA1 Is Required for Chronic Itch

    PubMed Central

    Wilson, Sarah R.; Nelson, Aislyn M.; Batia, Lyn; Morita, Takeshi; Estandian, Daniel; Owens, David M.; Lumpkin, Ellen A.; Bautista, Diana M.

    2013-01-01

    Chronic itch is a debilitating condition that affects one in 10 people. Little is known about the molecules that mediate chronic itch in primary sensory neurons and skin. We demonstrate that the ion channel TRPA1 is required for chronic itch. Using a mouse model of chronic itch, we show that scratching evoked by impaired skin barrier is abolished in TRPA1-deficient animals. This model recapitulates many of the pathophysiological hallmarks of chronic itch that are observed in prevalent human diseases such as atopic dermatitis and psoriasis, including robust scratching, extensive epidermal hyperplasia, and dramatic changes in gene expression in sensory neurons and skin. Remarkably, TRPA1 is required for both transduction of chronic itch signals to the CNS and for the dramatic skin changes triggered by dry-skin-evoked itch and scratching. These data suggest that TRPA1 regulates both itch transduction and pathophysiological changes in the skin that promote chronic itch. PMID:23719797

  13. Topical Review: Resilience Resources and Mechanisms in Pediatric Chronic Pain

    PubMed Central

    Kalapurakkel, Sreeja; Cohen, Lindsey L.; Simons, Laura E.

    2015-01-01

    Objective To apply resilience theory and the extant literature to propose a resilience-risk model for pediatric chronic pain and provide an agenda for research and clinical practice in pediatric chronic pain resilience. Method Literature review to develop a resilience-risk model for pediatric chronic pain. Results The chronic pain literature has identified unique individual and social/environmental resilience resources and pain-related resilience mechanisms that promote pain adaptation. These data support our ecological resilience-risk model for pediatric chronic pain, and the model highlights novel directions for clinical and research efforts for youth with chronic pain. Conclusions The examination of pediatric chronic pain from a strengths-based approach might lead to novel clinical avenues to empower youth to positively adapt and live beyond their pain. PMID:25979085

  14. Male chronic pelvic pain: An update

    PubMed Central

    Smith, Christopher P.

    2016-01-01

    Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and interstitial cystitis/bladder pain syndrome collectively referred to as urologic CPPS (UCPPS) is defined by the absence of identifiable bacterial infection as a cause for the chronic pain and urinary symptoms. Methods: A PubMed search of all recent relevant articles using the keywords/phrases: CPPS, CPPS, and male pelvic pain, was conducted. Results: CPPS has a high worldwide prevalence and its negative impact on quality of life compares with or exceeds common chronic morbidities. Triggers include certain comestibles as well as psychosocial factors that promote catastrophizing and illness focused behavior. Several validated tools are currently available to help diagnose and direct targeted therapy. Treatment should begin with the most simple and least invasive based on the presenting clinical phenotype. Conclusions: Although no gold-standard treatment exists, a multidisciplinary approach with multimodal therapy gives the UCPPS patient the best chance of symptom relief. PMID:26941492

  15. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  16. [Chronic otitis mediaChronic Otitis Media].

    PubMed

    Kohles, N; Schulz, T; Eßer, D

    2015-11-01

    There are 2 different kinds of chronic otitis media: Otitis media chronica mesotympanalis and otitis media chronica epitympanalis (cholesteatoma). The incidence of chronic otitis media as reported in literature differs in a wide range. The incidence rates vary between 0.45 and 46%. Both, otitis media chronica mesotympanalis and cholesteatoma, lead to eardrum perforation due to lengthy and recurring inflammations. Furthermore, chronic otitis media is characterized by frequently recurring otorrhea and conductive hearing loss.

  17. Chronic Kidney Diseases

    MedlinePlus

    ... Room? What Happens in the Operating Room? Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases A ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  18. [Chronic recurrent multifocal osteomyelitis].

    PubMed

    Marrero Calvo, M; Merino Arribas, J; Rodrigo Palacios, J; Bartolomé Albistegui, M; Camino Fernández, A; Grande Sáez, C

    2001-02-01

    Chronic recurrent multifocal osteomyelitis is a rare disorder of unknown etiology, characterized by multiple bone lesions and a variable clinical course. We present a 10 year old boy with chronic recurrent multifocal osteomyelitis who improved after treatment with naproxen.

  19. Employees with Chronic Pain

    MedlinePlus

    ... related, condition. Chronic Pain and the Americans with Disabilities Act Is chronic pain a disability under the ADA? The ADA does not contain a list of medical conditions that constitute disabilities. Instead, the ADA has a general definition of ...

  20. Chronic Kidney Diseases

    MedlinePlus

    ... A Real Lifesaver Kids Talk About: Coaches Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  1. Fighting Chronic Pain

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Fighting Chronic Pain Past Issues / Fall 2007 Table of Contents For ... diagnose, health care professionals and scientists know that chronic pain is very complex. Below are some of the ...

  2. Farriery for chronic laminitis.

    PubMed

    O'Grady, Stephen E

    2010-08-01

    Laminitis is considered chronic once the distal phalanx has displaced within the hoof capsule. Chronic laminitis generally occurs as a direct sequel to acute laminitis. Clinical evaluation of chronic laminitis is best performed with a thorough clinical examination and radiography. The mainstay of hoof care is therapeutic farriery. In this article, the goals and principles of hoof care, the appropriate trim and various shoes that form the bulk of farriery for chronic laminitis, and surgical treatments are discussed.

  3. Chronic inflammation potentiates kidney aging.

    PubMed

    Mei, Changlin; Zheng, Feng

    2009-11-01

    Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-alpha, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney.

  4. The lesson of chronic migraine.

    PubMed

    Bonavita, V; De Simone, R

    2015-05-01

    The hypothesis that central sensitization/allodynia is the common final mechanism responsible for the progression of migraine pain is supported by the possibility of tracing back to allodynic mechanisms the action of the main risk factors for chronic migraine validated by the recent literature. The comorbidity between migraine and idiopathic intracranial hypertension without papilledema is emerging as a new, commonly overlooked risk factor for migraine progression whose putative mechanism might also converge on the sensitization of central pain pathways. If headache progression always occurs at the end of a pathogenetic sequence typical of an individual susceptibility to allodynia, then the primary character of chronic migraine might be debated. Allodynia is not specific to migraine but is implied in the progressive amplification of pain after repeated stimuli, a universal adaptive phenomenon. Being largely conditioned by the individual comorbidity profile, allodynia may only in part be defined as primary in itself. Many migraine comorbid conditions, including a hidden idiopathic intracranial hypertension without papilledema, may emphasize susceptibility to allodynia and promote chronic migraine. These factors and comorbid conditions require to be individually assessed and adequately treated to optimize the therapeutic response.

  5. Chronic Methadone Treatment Shows a Better Cost/Benefit Ratio than Chronic Morphine in Mice

    PubMed Central

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura

    2012-01-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not. PMID:22062352

  6. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.

    PubMed

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer L

    2012-02-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

  7. Chronic autoimmune urticaria.

    PubMed

    Wardhana; Datau, E A

    2012-04-01

    Chronic urticaria is common and patients may present with transient eruption of itchy, eruthematous, edematous swellings of the dermis, which lasts more than six weeks. One type of chronic idiopathic urticaria, and part of it, is the chronic autoimmune urticaria. The chronic autoimmune urticaria is caused by high affinity of IgE receptors (anti-FcRI) and less frequently by anti-IgE autoantibodies, also the role of complement activation, that leads to mast and basophil activation. Despite many recent advances in the understanding of chronic autoimmune urticaria, this condition remains a major challenge in the terms of its etiology, investigations, and management.

  8. Carbonated Beverages and Chronic Kidney Disease

    PubMed Central

    Saldana, Tina M.; Basso, Olga; Darden, Rebecca; Sandler, Dale P.

    2012-01-01

    Background Carbonated beverage consumption has been linked with diabetes, hypertension, and kidney stones, all risk factors for chronic kidney disease. Cola beverages, in particular, contain phosphoric acid and have been associated with urinary changes that promote kidney stones. Methods We examined the relationship between carbonated beverages (including cola) and chronic kidney disease, using data from 465 patients with newly diagnosed chronic kidney disease and 467 community controls recruited in North Carolina between 1980 and 1982. Results Drinking 2 or more colas per day was associated with increased risk of chronic kidney disease (adjusted odds ratio = 2.3; 95% confidence interval = 1.4 –3.7). Results were the same for regular colas (2.1; 1.3–3.4) and artificially sweetened colas (2.1; 0.7–2.5). Noncola carbonated beverages were not associated with chronic kidney disease (0.94; 0.4 –2.2). Conclusions These preliminary results suggest that cola consumption may increase the risk of chronic kidney disease. PMID:17525693

  9. Approaching chronic sinusitis.

    PubMed

    Sarber, Kathleen M; Dion, Gregory Robert; Weitzel, Erik K; McMains, Kevin C

    2013-11-01

    Chronic sinusitis is a common disease that encompasses a number of syndromes that are characterized by sinonasal mucosal inflammation. Chronic sinusitis can be defined as two or more of the following symptoms lasting for more than 12 consecutive weeks: discolored rhinorrhea, postnasal drip, nasal obstruction, facial pressure or pain, or decreased sense of smell. Chronic sinusitis is further classified as chronic sinusitis with polyposis, chronic sinusitis without polyposis, or allergic fungal sinusitis using physical examination, and histologic and radiographic findings. Treatment methods for chronic sinusitis are based upon categorization of the disease and include oral and inhaled corticosteroids, nasal saline irrigations, and antibiotics in selected patients. Understanding the various forms of chronic sinusitis and managing and ruling out comorbidities are key to successful management of this common disorder.

  10. Nutrition for the Prevention of Chronic Diseases.

    PubMed

    Kimokoti, Ruth W; Millen, Barbara E

    2016-11-01

    Chronic non-communicable diseases (NCDs) are the leading causes of morbidity and mortality in the United States and globally, and are attributable largely to poor nutrition and suboptimal lifestyle behaviors. The 2015-2020 Dietary Guidelines for Americans promote healthy eating and lifestyle patterns across the lifespan to reduce risk of NCDs. Physicians are well positioned to provide lifestyle preventive interventions that are personalized to their patients' biological needs and cultural preferences through multidisciplinary team activities or referral to professional nutrition and physical activity experts. They can also advocate for environmental changes in healthcare and community settings that promote healthful lifestyle behaviors.

  11. Synthetic promoters in planta.

    PubMed

    Dey, Nrisingha; Sarkar, Shayan; Acharya, Sefali; Maiti, Indu B

    2015-11-01

    This paper reviews the importance, prospective and development of synthetic promoters reported in planta. A review of the synthetic promoters developed in planta would help researchers utilize the available resources and design new promoters to benefit fundamental research and agricultural applications. The demand for promoters for the improvement and application of transgenic techniques in research and agricultural production is increasing. Native/naturally occurring promoters have some limitations in terms of their induction conditions, transcription efficiency and size. The strength and specificity of native promoter can be tailored by manipulating its 'cis-architecture' by the use of several recombinant DNA technologies. Newly derived chimeric promoters with specific attributes are emerging as an efficient tool for plant molecular biology. In the last three decades, synthetic promoters have been used to regulate plant gene expression. To better understand synthetic promoters, in this article, we reviewed promoter structure, the scope of cis-engineering, strategies for their development, their importance in plant biology and the total number of such promoters (188) developed in planta to date; we then categorized them under different functional regimes as biotic stress-inducible, abiotic stress-inducible, light-responsive, chemical-inducible, hormone-inducible, constitutive and tissue-specific. Furthermore, we identified a set of 36 synthetic promoters that control multiple types of expression in planta. Additionally, we illustrated the differences between native and synthetic promoters and among different synthetic promoter in each group, especially in terms of efficiency and induction conditions. As a prospective of this review, the use of ideal synthetic promoters is one of the prime requirements for generating transgenic plants suitable for promoting sustainable agriculture and plant molecular farming.

  12. Chronic diseases: the silent global epidemic.

    PubMed

    Meetoo, Danny

    In most industrialized nations and many developing countries chronic diseases or non-communicable diseases (NCDs) are the leading cause of death. In 2005, chronic diseases, such as cardiovascular disease, cancer, respiratory disease and diabetes caused 58 million deaths worldwide (World Health Organization, 2005). Despite strong evidence for the magnitude of this burden, the preventability of NCD causes and the threat they pose to already strained healthcare systems, national and global responses have been slow. This article provides a global overview of chronic diseases. It further explores the impact of globalization as an important determinant of NCD epidemics. Finally, in addition to working alongside policy-makers, the fundamental roles of nursing to promote health, prevent disease and alleviate suffering call for expression of caring for humanity and environment through political activism at all levels to bring about reforms of current global economic order.

  13. Exercise as a Polypill for Chronic Diseases.

    PubMed

    Pareja-Galeano, Helios; Garatachea, Nuria; Lucia, Alejandro

    2015-01-01

    Exercise may be described as a polypill to prevent and/or treat almost every chronic disease, with obvious benefits such as its low cost and practical lack of adverse effects. Implementing physical activity interventions in public health is therefore a goal at the medical, social, and economic levels. This chapter describes the importance of health promotion through physical activity and discusses the impacts of exercise on the most prevalent chronic diseases, namely metabolic syndrome-related disorders, cardiovascular diseases, cancer, and Alzheimer's disease. For each of these chronic conditions, we discuss the epidemiological evidence supporting a beneficial role of exercise, provide guidelines for exercise prescription, and describe the biological mechanisms whereby exercise exerts its modulatory effects.

  14. Biofilms in chronic wounds.

    PubMed

    James, Garth A; Swogger, Ellen; Wolcott, Randall; Pulcini, Elinor deLancey; Secor, Patrick; Sestrich, Jennifer; Costerton, John W; Stewart, Philip S

    2008-01-01

    Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference (p<0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.

  15. Developing a Promotional Video

    ERIC Educational Resources Information Center

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  16. Developing a Promotional Video

    ERIC Educational Resources Information Center

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  17. Healthy and wellbeing activities' promotion using a Big Data approach.

    PubMed

    Gachet Páez, Diego; de Buenaga Rodríguez, Manuel; Puertas Sánz, Enrique; Villalba, María Teresa; Muñoz Gil, Rafael

    2016-08-04

    The aging population and economic crisis specially in developed countries have as a consequence the reduction in funds dedicated to health care; it is then desirable to optimize the costs of public and private healthcare systems, reducing the affluence of chronic and dependent people to care centers; promoting healthy lifestyle and activities can allow people to avoid chronic diseases as for example hypertension. In this article, we describe a system for promoting an active and healthy lifestyle for people and to recommend with guidelines and valuable information about their habits. The proposed system is being developed around the Big Data paradigm using bio-signal sensors and machine-learning algorithms for recommendations.

  18. Food Insecurity and Chronic Disease123

    PubMed Central

    Laraia, Barbara A.

    2013-01-01

    Household food insecurity has been previously hypothesized to promote dependence on inexpensive, highly palatable foods that are energy dense. Such dependence, and the cyclical nature of having enough food in the beginning of the month followed by food scarcity at the end of the month, could lead to weight gain over a short period of time. Such dependence on energy-dense foods and weight gain may play a direct role in the development of chronic conditions. Other compounding factors that result from exposure to household food insecurity have been well described, including pathways by which stress promotes visceral fat accumulation and chronic disease. This symposium review paper summarizes the literature on the link between food insecurity and the following: 1) diet, 2) weight gain, and 3) chronic disease, especially among women. This paper also proposes a framework for considering how the lived experience of household food insecurity may potentiate the development of chronic disease by activating the stress response among individuals at critical developmental periods in a food-impoverished environment. PMID:23493536

  19. Implementation of Mexico's Health Promotion Operational Model.

    PubMed

    Santos-Burgoa, Carlos; Rodríguez-Cabrera, Lucero; Rivero, Lilia; Ochoa, Jorge; Stanford, Adriana; Latinovic, Ljubica; Rueda, Gretel

    2009-01-01

    Mexico is undergoing profound health reform, extending health insurance to previously uninsured populations and changing the way health care services are delivered. Legislation enacted in 2003 and implemented in 2004 mandated funding and infrastructure that will allow 52% of Mexico's population to access medical care at no cost by 2010. This ambitious social reform has not been without challenges, particularly financial sustainability. Health promotion, because of its potential to prevent or delay chronic diseases and injuries and their associated costs, is a key component of health care reform. In 2006, the Ministry of Health's General Directorate of Health Promotion developed the Health Promotion Operational Model. Based on Ottawa Charter functions, the model integrates health promotion activities within the overall health care system. The main goal of this model is to build strong human capital and to improve organizational capacity for health promotion starting at the local level by training health care personnel to implement health promotion activities. Organizational development workshops started in 2006, and implementation plans in all 32 Mexican states were in place by end of 2008.

  20. [Chronic wounds: differential diagnosis].

    PubMed

    Situm, Mirna; Kolić, Maja

    2013-10-01

    Wound is a disruption of anatomic and physiologic continuity of the skin. According to the healing process, wounds are classified as acute and chronic wounds. A wound is considered chronic if standard medical procedures do not lead to the expected healing, or if the wound does not heal within six weeks. Chronic wounds are classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic wounds. Diabetic foot and decubitus ulcers stand out as a specific entity among typical wounds. About 80 percent of chronic wounds localized on lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder are mostly neuropathic ulcers. About 95 percent of chronic wounds manifest as one of the above-mentioned entities. Other forms of chronic wounds are atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome). Although atypical wounds are a rare cause of chronic wounds, it should always be taken in consideration during diagnostic procedure.

  1. DNA methylation of SPARC and chronic low back pain

    PubMed Central

    2011-01-01

    Background The extracellular matrix protein SPARC (Secreted Protein, Acidic, Rich in Cysteine) has been linked to degeneration of the intervertebral discs and chronic low back pain (LBP). In humans, SPARC protein expression is decreased as a function of age and disc degeneration. In mice, inactivation of the SPARC gene results in the development of accelerated age-dependent disc degeneration concurrent with age-dependent behavioral signs of chronic LBP. DNA methylation is the covalent modification of DNA by addition of methyl moieties to cytosines in DNA. DNA methylation plays an important role in programming of gene expression, including in the dynamic regulation of changes in gene expression in response to aging and environmental signals. We tested the hypothesis that DNA methylation down-regulates SPARC expression in chronic LBP in pre-clinical models and in patients with chronic LBP. Results Our data shows that aging mice develop anatomical and behavioral signs of disc degeneration and back pain, decreased SPARC expression and increased methylation of the SPARC promoter. In parallel, we show that human subjects with back pain exhibit signs of disc degeneration and increased methylation of the SPARC promoter. Methylation of either the human or mouse SPARC promoter silences its activity in transient transfection assays. Conclusions This study provides the first evidence that DNA methylation of a single gene plays a role in chronic pain in humans and animal models. This has important implications for understanding the mechanisms involved in chronic pain and for pain therapy. PMID:21867537

  2. Natural selection promotes antigenic evolvability.

    PubMed

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  3. Inner strength in women with chronic illness.

    PubMed

    Jenkinson, Amanda; Cantrell, Mary A

    2017-06-01

    Objectives This literature review summarizes research relevant to the meaning of inner strength in females living with a chronic illness. This review also examined studies that have used The Inner Strength Questionnaire to examine inner strength among chronically ill females. Methods Using the search terms inner strength and women, CINAHL, PubMed, and ProQuest Nursing databases were searched for the years 1990-2016. Ten articles met the inclusion criteria. Results Inner strength in women is a mental health construct that women can encompass to positively affect their quality of life while living through challenging life events. The Theory of Inner Strength appears to be a useful a framework for understanding how physical, psychological, and spiritual health can promote well-being, quality of life, and spirituality in women. Discussion The limited number of studies identified suggests the need for further investigations to explore the relationship between inner strength and quality of life among females living with chronic health conditions. The Inner Strength Questionnaire is a unique tool with adequate psychometric properties to measure inner strength in chronically ill women that includes a holistic assessment of living with a chronic illness that encompasses women' social, physical, emotional, and spiritual needs.

  4. Understanding facilitators of and barriers to health promotion practice.

    PubMed

    Robinson, Kerry L; Driedger, Michelle S; Elliott, Susan J; Eyles, John

    2006-10-01

    The health promotion best practices literature is imbued with hope for knowledge mobilization, enhanced practice, and improved population health. Given constrained medical care systems, health promotion is key to reducing the significant burden of chronic disease. However, we have seen little evidence of change. This article investigates facilitators of, and barriers to, three stages of health promotion practice in public health organizations, interagency coalitions, and volunteer committees. The article focuses not on what works but why it does or does not, drawing on five case studies within the Canadian Heart Health Initiative. Results indicate that the presence or absence of appropriately committed and/or skilled people, funds and/or resources, and priority and/or interest are the most common factors affecting all stages of health promotion practice. The article extends the literature on internal and external factors affecting health promotion and highlights strategic influences to consider in support of effective health promotion practice.

  5. Health promotion in smaller workplaces in the United States.

    PubMed

    Harris, Jeffrey R; Hannon, Peggy A; Beresford, Shirley A A; Linnan, Laura A; McLellan, Deborah L

    2014-01-01

    Most American workplaces are smaller, with fewer than 1,000 employees. Many of these employees are low-wage earners and at increased risk for chronic diseases. Owing to the challenges smaller workplaces face to offering health-promotion programs, their employees often lack access to health-promotion opportunities available at larger workplaces. Many smaller employers do not offer health insurance, which is currently the major funding vehicle for health-promotion services. They also have few health-promotion vendors to serve them and low internal capacity for, and commitment to, delivery of on-site programs. The programs they offer, whether aimed at health promotion alone or integrated with health protection, are rarely comprehensive and are understudied. Research priorities for health promotion in smaller workplaces include developing programs feasible for the smallest workplaces with fewer than 20 employees. Policy priorities include incentives for smaller workplaces to implement comprehensive programs and an ongoing system for monitoring and evaluation.

  6. Chronic Inflammation in Skin Malignancies

    PubMed Central

    Tang, Lihua

    2016-01-01

    Chronic inflammation is linked to the development and progression of multiple cancers, including those of the lung, stomach, liver, colon, breast and skin. Inflammation not only drives the oncogenic transformation of epithelial cells under the stress of chronic infection and autoimmune diseases, but also promotes the growth, progression and metastatic spread of cancers. Tumor-infiltrating inflammatory cells are comprised of a diverse population of myeloid and immune cell types, including monocytes, macrophages, dendritic cells, T and B cells, and others. Different myeloid and lymphoid cells within tumor microenvironment exert diverse, often contradicting, effects during skin cancer development and progression. The nature of tumor-immune interaction determines the rate of cancer progression and the outcome of cancer treatment. Inflammatory environment within skin tumor also inhibits naturally occurring anti-tumor immunity and limits the efficacy of cancer immunotherapy. In this article we aim to give an overview on the mechanism by which inflammation interferes with the development and therapeutic intervention of cancers, especially those of the skin.

  7. Battling Chronic Absenteeism

    ERIC Educational Resources Information Center

    Nauer, Kim

    2016-01-01

    While the principal of a New York elementary school (P.S. 48) took on chronic absenteeism from 2011 to 2013, a research team at the Center for New York City Affairs followed her efforts. The school drove down chronic absenteeism almost 10 percentage points. School staff routinely touched base with students, outside "success mentors"…

  8. Battling Chronic Absenteeism

    ERIC Educational Resources Information Center

    Nauer, Kim

    2016-01-01

    While the principal of a New York elementary school (P.S. 48) took on chronic absenteeism from 2011 to 2013, a research team at the Center for New York City Affairs followed her efforts. The school drove down chronic absenteeism almost 10 percentage points. School staff routinely touched base with students, outside "success mentors"…

  9. Chronic odontogenic maxillary sinusitis.

    PubMed

    Ugincius, Paulius; Kubilius, Ricardas; Gervickas, Albinas; Vaitkus, Saulius

    2006-01-01

    The aim of the present study was to estimate average age of the patients in both sexes treated for MS, distribution by sex, amount of dexter and sinister MS with and without the fistulas into the maxillary sinus, with and without the foreign-bodies, length of stay in the Department of Maxillofacial Surgery at Kaunas Hospital of University of Medicine during the period from 1999 till 2004. The retrospective data analysis of the patients' treated from chronic MS was made. 346 patients (213 females and 133 males) were treated for chronic MS. 55 cases of chronic dexter MS with a fistula into maxillary sinus, 98 cases of chronic dexter MS without a fistula, 45 cases of chronic sinister MS with a fistula, 112 cases chronic sinister MS without a fistula, 16 cases of foreign-bodies in dexter maxillary sinus, 20 cases of foreign-bodies in sinister maxillary sinus have been detected. The main age of the female was 46.6+/-15.0, the main age of the men was 42.1+/-14.4. Statictically significant difference in the age difference of the women and the men was found (p=0.0024). It was determined, that females diagnosed and treated with chronic MS were 1.6 times more than males during the period from 1999 till 2004 in Kaunas Hospital of University of Medicine. Females treated for chronic MS were 4.5 years older than males.

  10. Chronic and subacute meningitis.

    PubMed

    Zunt, Joseph R; Baldwin, Kelly J

    2012-12-01

    This article describes the background, clinical presentation, diagnosis, and treatment of selected etiologies of subacute and chronic meningitis. Key diagnostic considerations when evaluating a patient presenting with chronic inflammation of the CNS are discussed, and several specific infectious, neoplastic, and autoimmune etiologies are reviewed in detail. With recent advancement in serologic and CSF diagnostic testing, specific infectious, neoplastic, or autoimmune etiologies of chronic meningitis can be identified. Eliminating previous diagnostic uncertainty of chronic inflammation in the CNS has led to rapid and specific treatment regimens that ultimately improve patient outcomes. Recent advances in imaging have also aided clinicians in both their diagnostic approach and the detection of inflammatory complications such as hydrocephalus, hemorrhage, and ischemic stroke. Meningitis is defined as inflammation involving the meninges of the brain and spinal cord. Meningitis can be categorized as acute, subacute, or chronic based on duration of inflammation. This article focuses on the most common causes of subacute and chronic meningitis. Chronic meningitis is commonly defined as inflammation evolving during weeks to months without resolution of CSF abnormalities. Determining the time course of meningitis is important for creating a differential diagnosis. Most organisms causing acute meningitis rarely persist more than a few weeks. Although numerous etiologies of subacute and chronic meningitis have been identified, this article focuses on the most common etiologies: (1) infectious, (2) autoimmune, and (3) neoplastic.

  11. Coping with Chronic Illness

    MedlinePlus

    Having a long-term, or chronic, illness can disrupt your life in many ways. You may often be tired and in pain. Your illness might affect your ... able to work, causing financial problems. For children, chronic illnesses can be frightening, because they may not ...

  12. Chronic gastritis - an update.

    PubMed

    Varbanova, Mariya; Frauenschläger, Katrin; Malfertheiner, Peter

    2014-12-01

    Helicobacter pylori is the main aetiologic factor for chronic gastritis worldwide. The degree of inflammation and the evolution of this form of chronic gastritis can vary largely depending on bacterial virulence factors, host susceptibility factors and environmental conditions. Autoimmune gastritis is another cause of chronic inflammation in the stomach, which can occur in all age groups. This disease presents typically with vitamin B12 deficiency and pernicious anaemia. The presence of anti-parietal cell antibodies is highly specific for the diagnosis. The role of H. pylori as a trigger for autoimmune gastritis remains uncertain. Other rare conditions for chronic gastritis are chronic inflammatory conditions such as Crohn's disease or on the background of lymphocytic or collagenous gastroenteropathies.

  13. [Chronic pancreatitis, acute pancreatitis].

    PubMed

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  14. Health promotion in Brazil.

    PubMed

    Buss, Paulo Marchiori; de Carvalho, Antonio Ivo

    2007-01-01

    The evolution of health promotion within the Brazilian health system is examined, including an assessment of the intersectoral and development policies that have influenced the process. Particular attention is paid to the legal characteristics of the Unified Health System. Human resources formation and research initiatives in health promotion are outlined, with a summary of the obstacles that need to be overcome in order to ensure the effective implementation of health promotion in the future. Up to the end of the 20th Century health promotion was not used as a term in the Brazilian public heath context. Health promoting activities were concentrated in the area of health education, although targeting the social determinants of health and the principle of intersectoral action were part of the rhetoric. The situation has changed during the last decade, with the publication of a national policy of health promotion, issued by the Ministry of Health and jointly implemented with the States and Municipals Health Secretaries. More recently there has been a re-emergence of the discourse on the social determinants of health and the formation of intersectoral public policies as the basis of a comprehensive health promotion. Health promotion infrastructure, particularly around human resources and financing, requires strengthening in order to ensure capacity and sustainability in health promotion practice.

  15. Social psychogenic stress promotes the development of endometriosis in mouse.

    PubMed

    Guo, Sun-Wei; Zhang, Qi; Liu, Xishi

    2017-03-01

    Exposure to chronic stress before and well after the induction of endometriosis is reported to increase lesion sizes in rats, but it is unclear whether stress, exposed shortly after the induction of endometriosis, would also promote the development of endometriosis, nor is it clear what the underlying possible molecular mechanism is. This study was undertaken to test the hypothesis that chronic stress can promote the development of endometriosis. A prospective randomized mouse experiment was conducted that subjected mice with induced endometriosis to predator stress. In addition, a cross-sectional immunohistochemistry study was performed in ectopic and eutopic endometrial tissue samples from age- and roughly menstrual phase-matched women with ovarian endometriomas. It was found that the chronic psychogenic stress induced epigenetic changes in the hippocampus in mouse independent of endometriosis. It was also found that chronic psychogenic stress induced epigenetic changes in the hippocampus of mice with endometriosis, and seemingly activated the adrenergic signalling in ectopic endometrium, resulting in increased angiogenesis and accelerated growth of endometriotic lesions. Thus, chronic psychogenic stress promotes endometriosis development, raising the possibility that the use of anti-depressants in cases of prolonged and intense stress might forestall the negative impact of stress on the development of endometriosis. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  16. How can research on plants contribute to promoting human health?

    PubMed

    Martin, Cathie; Butelli, Eugenio; Petroni, Katia; Tonelli, Chiara

    2011-05-01

    One of the most pressing challenges for the next 50 years is to reduce the impact of chronic disease. Unhealthy eating is an increasing problem and underlies much of the increase in mortality from chronic diseases that is occurring worldwide. Diets rich in plant-based foods are strongly associated with reduced risks of major chronic diseases, but the constituents in plants that promote health have proved difficult to identify with certainty. This, in turn, has confounded the precision of dietary recommendations. Plant biochemistry can make significant contributions to human health through the identification and measurement of the many metabolites in plant-based foods, particularly those known to promote health (phytonutrients). Plant genetics and metabolic engineering can be used to make foods that differ only in their content of specific phytonutrients. Such foods offer research tools that can provide significant insight into which metabolites promote health and how they work. Plant science can reduce some of the complexity of the diet-health relationship, and through building multidisciplinary interactions with researchers in nutrition and the pathology of chronic diseases, plant scientists can contribute novel insight into which foods reduce the risk of chronic disease and how these foods work to impact human health.

  17. "Act Healthy": Promoting Health Behaviors and Self-Efficacy in the Workplace

    ERIC Educational Resources Information Center

    Schopp, Laura H.; Bike, Denise H.; Clark, Mary J.; Minor, Marian A.

    2015-01-01

    Chronic health conditions and multiple health risk factors afflict Americans and burden employers, but effective, affordable, workplace-based health promotion interventions have not been widely implemented. This is the first study to adapt the empirically validated Chronic Disease Self-Management Program for a general employee population in a…

  18. "Act Healthy": Promoting Health Behaviors and Self-Efficacy in the Workplace

    ERIC Educational Resources Information Center

    Schopp, Laura H.; Bike, Denise H.; Clark, Mary J.; Minor, Marian A.

    2015-01-01

    Chronic health conditions and multiple health risk factors afflict Americans and burden employers, but effective, affordable, workplace-based health promotion interventions have not been widely implemented. This is the first study to adapt the empirically validated Chronic Disease Self-Management Program for a general employee population in a…

  19. [Cellular senescence and chronic inflammation].

    PubMed

    Ohtani, Naoko

    2014-01-01

    It has recently become apparent that obesity is associated with chronic inflammation and several common types of cancer development. Although several events were proposed to be involved in these pathologies, the precise mechanisms underlying obesity-associated inflammation and cancer largely remain unclear. Here, we show that senescence-associated secretory phenotype (SASP) plays crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of a bacterial metabolite that cause DNA damage. The enterohepatic circulation of the bacterial metabolites provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn, secretes various inflammatory and tumour promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Importantly, reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the induction of SASP by the gut bacterial metabolite in HSCs plays key roles in obesity-associated HCC development. Interestingly, moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with nonalcoholic steatohepatitis (NASH), implying that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer.

  20. Negotiating Access to Health Information to Promote Students' Health

    ERIC Educational Resources Information Center

    Radis, Molly E.; Updegrove, Stephen C.; Somsel, Anne; Crowley, Angela A.

    2016-01-01

    Access to student health information, such as immunizations, screenings, and care plans for chronic conditions, is essential for school nurses to fulfill their role in promoting students' health. School nurses typically encounter barriers to accessing health records and spend many hours attempting to retrieve health information. As a result,…

  1. Negotiating Access to Health Information to Promote Students' Health

    ERIC Educational Resources Information Center

    Radis, Molly E.; Updegrove, Stephen C.; Somsel, Anne; Crowley, Angela A.

    2016-01-01

    Access to student health information, such as immunizations, screenings, and care plans for chronic conditions, is essential for school nurses to fulfill their role in promoting students' health. School nurses typically encounter barriers to accessing health records and spend many hours attempting to retrieve health information. As a result,…

  2. Health Promotion Program.

    ERIC Educational Resources Information Center

    McClary, Cheryl

    The Health Promotion Program began with establishment of a one-credit course in health promotion and wellness and the training of family practice residents at the Mountain Area Health Education Center to serve as lab leaders in the course. The course later became part of the university's general education requirements. In addition, a health…

  3. High expression Zymomonas promoters

    DOEpatents

    Viitanen, Paul V.; Tao, Luan; Zhang, Yuying; Caimi, Perry G.; McCole, Laura : Zhang, Min; Chou, Yat-Chen; McCutchen, Carol M.; Franden, Mary Ann

    2011-08-02

    Identified are mutants of the promoter of the Z. mobilis glyceraldehyde-3-phosphate dehydrogenase gene, which direct improved expression levels of operably linked heterologous nucleic acids. These are high expression promoters useful for expression of chimeric genes in Zymomonas, Zymobacter, and other related bacteria.

  4. Promoting Resilience in Children.

    ERIC Educational Resources Information Center

    Rolfe, Sharne A.

    2002-01-01

    This booklet invites reflection on ways in which childhood resilience can be promoted, thereby helping children to adapt effectively in the face of adversity. The attributes of resilient children are described, as is the importance of protective factors in building or promoting resilience. The booklet discusses the complex interplay between risk…

  5. Health Promotion Program.

    ERIC Educational Resources Information Center

    McClary, Cheryl

    The Health Promotion Program began with establishment of a one-credit course in health promotion and wellness and the training of family practice residents at the Mountain Area Health Education Center to serve as lab leaders in the course. The course later became part of the university's general education requirements. In addition, a health…

  6. Promoting Resilience in Children.

    ERIC Educational Resources Information Center

    Rolfe, Sharne A.

    2002-01-01

    This booklet invites reflection on ways in which childhood resilience can be promoted, thereby helping children to adapt effectively in the face of adversity. The attributes of resilient children are described, as is the importance of protective factors in building or promoting resilience. The booklet discusses the complex interplay between risk…

  7. Improving the performance of interorganizational networks for preventing chronic disease: identifying and acting on research needs.

    PubMed

    Willis, Cameron D; Riley, Barbara L; Taylor, Martin; Best, Allan

    2014-01-01

    This article describes the role of interorganizational networks in chronic disease prevention and an action research agenda for promoting understanding and improvement. Through a model of engaged scholarship, leaders with expertise and experience in chronic disease prevention networks helped shape research directions focused on network value, governance, and evolution. The guiding principles for facilitating this research include applying existing knowledge, developing network-appropriate methods and measures, creating structural change, promoting an impact orientation, and fostering cultural change.

  8. Chronic hypersensitivity pneumonitis

    PubMed Central

    Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

  9. Inflammation in Chronic Wounds

    PubMed Central

    Zhao, Ruilong; Liang, Helena; Clarke, Elizabeth; Jackson, Christopher; Xue, Meilang

    2016-01-01

    Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research. PMID:27973441

  10. [Chronic transplant nephropathy].

    PubMed

    Campistol Plana, J M

    2008-01-01

    In 2007 there were important scientific contributions in the field of kidney transplant and specifically in chronic transplant nephropathy (interstitial fibrosis and tubular atrophy). A new nomenclature and classification of chronic kidney disease was probably the most important contribution in this entity. Use of the C4d stain has allowed the concepts of glomerulopathy to be updated and to reveal the frequency of this entity and its impact in kidney transplant. Finally, two experimental studies provide new perspectives on the treatment of chronic kidney disease such as the use of statins or the use of pyridoxamine to block glycation end products.

  11. Patients with chronic pain.

    PubMed

    Salama-Hanna, Joseph; Chen, Grace

    2013-11-01

    Preoperative evaluation of patients with chronic pain is important because it may lead to multidisciplinary preoperative treatment of patients' pain and a multimodal analgesia plan for effective pain control. Preoperative multidisciplinary management of chronic pain and comorbid conditions, such as depression, anxiety, deconditioning, and opioid tolerance, can improve patient satisfaction and surgical recovery. Multimodal analgesia using pharmacologic and nonpharmacologic strategies shifts the burden of analgesia away from simply increasing opioid dosing. In more complicated chronic pain patients, multidisciplinary treatment, including pain psychology, physical therapy, judicious medication management, and minimally invasive interventions by pain specialists, can improve patients' satisfaction and surgical outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Chronic Lyme disease.

    PubMed

    Lantos, Paul M

    2015-06-01

    Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Inflammation in Chronic Wounds.

    PubMed

    Zhao, Ruilong; Liang, Helena; Clarke, Elizabeth; Jackson, Christopher; Xue, Meilang

    2016-12-11

    Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research.

  14. Prostatitis: acute and chronic.

    PubMed

    Ramakrishnan, Kalyanakrishnan; Salinas, Robert C

    2010-09-01

    Prostatitis, one of the most common urological infections afflicting adult men, has recently been divided into 4 different categories based on the National Institutes of Health consensus classification: acute bacterial prostatitis, chronic bacterial prostatitis, chronic nonbacterial prostatitis and pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Most patients with prostatitis are found to have either nonbacterial prostatitis or prostatodynia. Prostatitis poses an international health problem, with epidemiologic studies suggesting a worldwide prevalence of more than 10%. This article reviews current modes of diagnosis and therapy for acute and chronic prostatitis. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  15. Chronic Arsenic poisoning.

    PubMed

    Ahsan, Tasnim; Zehra, Kaneez; Munshi, Alia; Ahsan, Samiah

    2009-02-01

    Chronic Arsenic Toxicity may have varied clinical presentations ranging from non-cancerous manifestations to malignancy of skin and different internal organs. Dermal lesions such as hyper pigmentation and hyperkeratosis, predominantly over palms and soles are diagnostic of Chronic Arsenicosis. We report two cases from a family living in Sukkur who presented with classical skin lesions described in Chronic Arsenicosis. The urine, nail and hair samples of these patients contained markedly elevated levels of arsenic. Also the water samples from their household and the neighbouring households were found to have alarming levels of inorganic Arsenic.

  16. [Chronic constipation in adults].

    PubMed

    Zeitoun, Jean-David; de Parades, Vincent

    2013-09-01

    Chronic constipation is a very common condition, which is responsible for a major socioeconomic burden. Primary management must rule out secondary constipation before recognizing chronic idiopathic constipation, which is the most common diagnosis. Initial treatment frequently associates simple lifestyle modifications, whose efficacy is limited, with osmotic laxatives or bulking agents. If those measures do not relieve symptoms, a switch of laxatives or a combination must be proposed. Pharmacological treatments of constipation represent a new alternative approach in case of failure of previously mentioned measures. In case of chronic constipation reluctant to all conservative therapies, specific tests are required before considering biofeedback intervention or exceptionally a surgical option.

  17. Sustainable chronic disease management in remote Australia.

    PubMed

    Wakerman, John; Chalmers, Elizabeth M; Humphreys, John S; Clarence, Christine L; Bell, Andrew I; Larson, Ann; Lyle, David; Pashen, Dennis R

    2005-11-21

    The Sharing Health Care Initiative (SHCI) demonstration project, which aimed to improve management of chronic diseases, was implemented in four small remote communities in the Katherine region which are serviced by the Katherine West Health Board, a remote Aboriginal-community-controlled health organisation in the Northern Territory. We reviewed the project proposal, final report, evaluation reports and transitional funding proposal, and supplemented these with in-depth interviews with key individuals. We determined factors critical to the sustainability of the SHCI project in relation to context, community engagement, systems flexibility and adaptability, the availability and effect of information systems, and the human nature of health care and policy. The project had a significant impact on community awareness of chronic disease and an improvement in clinic processes. We found that a number of interrelated factors promoted sustainability, including: An implementation strategy sufficiently flexible to take account of local conditions; A high level of community engagement; Appropriate timeframes, timing and congruence between national policy and local readiness to implement a chronic disease project; Effective communication between participating organisations; Project champions (key individuals) in participating organisations; Effective use of monitoring and evaluation data; and Adequate and ongoing funding. The absence of a number of these factors, such as poor communication, inhibited sustainability. Other factors could both promote and inhibit. For example, the impact of key individuals was important, but could be idiosyncratic and have negative effects.

  18. Correction: At-a-glance - The 2017 Canadian Chronic Disease Indicators.

    PubMed

    2017-08-01

    [This corrects the article https://www.canada.ca/en/public-health/services/reports-publications/health-promotion-chronic-disease-prevention-canada-research-policy-practice/vol-37-no-8-2017/at-a-glance-2017-canadian-chronic-disease-indicators.html].

  19. [Sleep promoters and insomnia].

    PubMed

    Poyares, Dalva; Pinto Jr, Luciano Ribeiro; Tavares, Stella; Barros-Vieira, Sergio

    2005-05-01

    The purpose of this updating manuscript is to briefly describe the profile, clinical use and indication of some of the most used sedative and hypnotic compounds. About 2/3 of all hypnotic prescriptions go to chronic use. Benzodiazepines are among the most prescribed drugs worldwide. Women, elderly, psychiatric and medical disease patients are among chronic users of hypnotics. Zolpidem is now the most prescribed hypnotic in most countries. It appears to be safer, compared to benzodazepines, and might be an option for long-term and controlled use ("as needed"). Sedative antidepressants are also among the most prescribed drug for sedation in insomnia patients in USA and UK. Sedative effect and use of trazodone, mirtazapine, doxepine, amitryptilin are described. The authors also discuss the use of melatonin and its sleep properties, and the rational use of sedative antipsychotics for chronic insomnia, particularly in psychiatric patients. Finally, some phytotherapeutic compounds are mentioned.

  20. Health Promotion — The Family Physician's Responsibility

    PubMed Central

    Vinger, Irving

    1972-01-01

    All health professionals are presently spending the majority of their service time helping families inflicted with chronic, incurable illness. We must begin to place our emphasis on prevention. We have recently begun to look at the problem of early detection of illness but there has been a conspicuous lack of labor in the area of primary prevention or health promotion. This seems to be due not to a lack of knowledge or resources but to the lack of a delineation of responsibility. This article places that responsibility primarily with the family physician. PMID:20468805

  1. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    PubMed Central

    Khadilkar, Satish V.; Deshmukh, Shrikant S.; Dhonde, Pramod D.

    2011-01-01

    The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies. PMID:21808468

  2. Chronic Ankle Instability

    MedlinePlus

    ... Risk for Newly Active Baby Boomers The American College of Foot and Ankle Surgeons has a valuable lesson for Baby Boomers now getting back into fitness and sports: Get your ankles checked for chronic instability caused ...

  3. Chronic Pancreatitis in Children

    MedlinePlus

    ... years to appear, but this, too, is highly variable; some patients with chronic pancreatitis will develop diabetes ... of modifying factors include other genes or environmental variables, which is a term that scientists use to ...

  4. Zabofloxacin for chronic bronchitis.

    PubMed

    Kocsis, B; Szabo, D

    2016-09-01

    Treatment of lower respiratory tract infection poses as an ongoing challenge among respiratory tract diseases. Bacterial infections are causes of acute exacerbations in chronic bronchitis and indications for antibacterial therapy. Several antibiotics were applied to treat bacterial infections in chronic bronchitis, among them fluoroquinolones are considered potent, broad-spectrum agents with excellent tissue penetration. This monograph focuses on zabofloxacin, a novel fluoroquinolone agent recently approved and launched in South Korea, and summarizes the drug's antibacterial efficacy, pharmacokinetic properties and toxicity. Recent advances concerning fluoroquinolones in chronic bronchitis will be discussed, along with a comparison between zabofloxacin and moxifloxacin. Zabofloxacin has proved to be noninferior to moxifloxacin against major community-acquired Gram-positive and Gram-negative respiratory tract pathogens and found to be well tolerated in both oral and parenteral administrations. These features can make it a potential antimicrobial agent in therapy of chronic bronchitis and other lower respiratory tract infections.

  5. Chronic granulomatous disease

    MedlinePlus

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... The condition is often discovered very early in childhood. Milder forms may be diagnosed during the teenage ...

  6. Chronic Pain Medicines

    MedlinePlus

    ... doctor or your pharmacist.AcetaminophenAcetaminophen (one brand name: Tylenol) helps many kinds of chronic pain. Remember, many over-the-counter and prescription pain medicines have acetaminophen in them. If you’re not careful, you ...

  7. Chronic Kidney Disease

    MedlinePlus

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  8. Low back pain - chronic

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007422.htm Low back pain - chronic To use the sharing features on this page, please enable JavaScript. Low back pain refers to pain that you feel in your ...

  9. Tips for Chronic Pain

    MedlinePlus

    Patient Education Sheet Tips for Chronic Pain The SSF thanks Stuart S. Kassan, MD, FACP, Clinical Professor of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, for authoring ...

  10. Sleep and Chronic Disease

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Sleep and Sleep Disorders Note: Javascript is disabled or is not ... Data Source Projects and Partners Resources For Clinicians Sleep and Chronic Disease Recommend on Facebook Tweet Share ...

  11. Chronic care coordination.

    PubMed

    Peters, Steve G; Bunkers, Kari S

    2015-10-01

    Chronic care management describes the services provided to patients with two or more chronic conditions that pose risks of exacerbation, clinical deterioration, or death. These services extend beyond the typical face-to-face office visit and require coordination and oversight by a physician or other qualified health-care professional to maintain and modify as necessary a comprehensive and multidisciplinary plan of care. New codes for 2015 describe chronic care management services per calendar month. While the new services acknowledge the role and importance of coordination by primary care providers, they are also appropriate for specialists who oversee the management of all of the chronic conditions of a patient and provide access, education, care coordination, communication, and health information exchange with other providers.

  12. Chronic appendicitis in children.

    PubMed

    Kim, David; Butterworth, Sonia A; Goldman, Ran D

    2016-06-01

    While the diagnosis of acute appendicitis is relatively straightforward, chronic appendicitis is an entity that can be controversial and is often misdiagnosed. How and when should clinicians be investigating chronic appendicitis as a cause of chronic and recurrent abdominal pain in the pediatric population? Chronic appendicitis is a long-standing inflammation or fibrosis of the appendix that presents clinically as prolonged or intermittent abdominal pain. It is often a challenging diagnosis and might result in complications such as intra-abdominal infections or bowel obstruction or perforation. Clinical presentation, along with imaging studies, can help the clinician rule out other conditions, and among those who are diagnosed, for many children, appendectomy results in partial or complete resolution of pain symptoms. Copyright© the College of Family Physicians of Canada.

  13. Chronic Beryllium Disease

    MedlinePlus

    ... LS. Epidemiology of beryllium sensitizations and disease in nuclear workers. Am Rev Respir Dis 1993; 148:985- ... chronic beryllium disease. In: Rossman MD, Preuss OP, Powers MB, eds. Beryllium: Biomedical and Environmental Aspects . Baltimore: ...

  14. Chronic Exertional Compartment Syndrome

    MedlinePlus

    ... through the pain; that can lead to permanent muscle or nerve damage. Sometimes chronic exertional compartment syndrome is mistaken for shin splints, a more common cause of leg pain in young people who do a lot of vigorous weight- ...

  15. Chronic sinusitis (image)

    MedlinePlus

    ... and cartilage and lined with a mucous membrane. Sinusitis occurs when the membranes becomes inflamed and painful, ... a result of a blocked sinus opening. Chronic sinusitis is often caused by inflammation and blockage due ...

  16. Chronic Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  17. Chronic Pelvic Pain

    MedlinePlus

    ... to treat chronic pelvic pain. They include medications, physical therapy, nutritional therapy, and surgery: Lifestyle changes—Good posture ... are helpful in relieving pelvic pain, especially dysmenorrhea . Physical therapy—Acupuncture, acupressure, and nerve stimulation therapies may be ...

  18. Chronic Rhinosinusitis Pathogenesis

    PubMed Central

    Stevens, Whitney W.; Lee, Robert J.; Schleimer, Robert P.; Cohen, Noam A.

    2015-01-01

    There are a variety of medical conditions associated with chronic sinonasal inflammation including chronic rhinosinusitis (CRS) and cystic fibrosis. CRS in particular can be divided into two major subgroups based upon whether nasal polyps are present (CRSwNP) or absent (CRSsNP). Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier and tissue remodeling all contribute to the chronic inflammatory and tissue deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and may be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review with special focus placed on the roles of epithelial cells and the host immune response in cystic fibrosis, CRSsNP and CRSwNP. PMID:26654193

  19. [Chronic mesenteric ischemia revisited].

    PubMed

    do Carmo, Germano; Rosa, António; Ministro, Augusto; Pestana, Cristina

    2013-01-01

    The authors report two clinical cases of rare and complex situations - an aortic dissection and an aortitis -, which had as a common denominator a chronic mesenteric ischemia. They discuss the indications and surgical strategies adopted.

  20. Chronic Hypertension in Pregnancy

    MedlinePlus

    ... AGE Downloaded from http:// circ. ahajournals. org/ by guest on April 13, 2017 Chronic Hypertension in Pregnancy ... e189 Downloaded from http:// circ. ahajournals. org/ by guest on April 13, 2017 TABLE 1. Types of ...

  1. Chronic Fatigue Syndrome

    MedlinePlus

    Chronic fatigue syndrome (CFS) is a disorder that causes extreme fatigue. This fatigue is not the kind of tired feeling that ... activities. The main symptom of CFS is severe fatigue that lasts for 6 months or more. You ...

  2. Chronically unreduced elbow dislocations.

    PubMed

    Lyons, Robert P; Armstrong, April

    2008-02-01

    This article focuses on various methods to treat the chronically unreduced elbow. There are only a few small series published in the literature on which to base treatment options. Anatomic features pertinent to the discussion of the chronically unstable elbow are highlighted. The spectrum of treatment options includes open reduction, internal fixation and ligament reconstruction, external fixation, and elbow arthroplasty. The indications, operative technique, and results of each treatment modality are explored.

  3. 77 FR 47820 - Invention Promoters/Promotion Firms Complaints

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... United States Patent and Trademark Office Invention Promoters/Promotion Firms Complaints ACTION: Proposed... participate in any legal proceedings against invention promoters or promotion firms. Complaints submitted to... promotion firm, explain the basis for the complaint, and include the signature of the complainant....

  4. Chronic pain after childbirth.

    PubMed

    Landau, R; Bollag, L; Ortner, C

    2013-04-01

    With over four million deliveries annually in the United States alone and a constant increase in cesarean delivery rate, childbirth is likely to have a huge impact on the occurrence of acute and possibly chronic postpartum pain. Recent awareness that chronic pain may occur after childbirth has prompted clinicians and researchers to investigate this topic. Current evidence points towards a relatively low incidence of chronic pain after cesarean delivery, with rates ranging between 1% and 18%. To provide a potential mechanistic explanation for the relatively low occurrence of chronic pain after cesarean delivery compared with that after other types of surgery, it has been proposed that endogenous secretion of oxytocin may confer specific protection. Clinical interventions to reduce the incidence and severity of chronic post-surgical pain have not been consistently effective. Likely explanations are that the drugs that have been investigated were truly ineffective or that the effect was too modest because with a low incidence of chronic pain, studies were likely to be underpowered and failed to demonstrate an effect. In addition, since not all women require preventive therapies, preoperative testing that may identify women vulnerable to pain may be highly beneficial. Further research is needed to identify valid models that predict persistent pain to allow targeted interventions to women most likely to benefit from more tailored anti-hyperalgesic therapies.

  5. Hypertension in Chronic Glomerulonephritis

    PubMed Central

    2015-01-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  6. Treatment of Chronic Cough.

    PubMed

    Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

    2017-01-01

    Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

  7. Supportive Care for Chronic Lymphocytic Leukemia

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Supportive Care for Chronic Lymphocytic Leukemia Supportive care for chronic lymphocytic leukemia (CLL) is ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  8. Process Evaluation of an Integrated Health Promotion/Occupational Health Model in WellWorks-2

    ERIC Educational Resources Information Center

    Hunt, Mary Kay; Lederman, Ruth; Stoddard, Anne M.; LaMontagne, Anthony D.; McLellan, Deborah; Combe, Candace; Barbeau, Elizabeth; Sorensen, Glorian

    2005-01-01

    Disparities in chronic disease risk by occupation call for new approaches to health promotion. WellWorks-2 was a randomized, controlled study comparing the effectiveness of a health promotion/occupational health program (HP/OHS) with a standard intervention (HP). Interventions in both studies were based on the same theoretical foundations. Results…

  9. The Value of College Health Promotion: A Critical Population and Setting for Improving the Public's Health

    ERIC Educational Resources Information Center

    Lederer, Alyssa M.; Oswalt, Sara B.

    2017-01-01

    College students are an important priority population, and higher education is an opportune setting for chronic disease prevention and health promotion. Yet many people do not understand why enhancing the well-being of college students is of value. In this commentary, we address 3 common misperceptions about college health promotion: (1) College…

  10. Molecular Determinants of a Symbiotic Chronic Infection

    PubMed Central

    Gibson, Katherine E.; Kobayashi, Hajime

    2009-01-01

    Rhizobial bacteria colonize legume roots for the purpose of biological nitrogen fixation. A complex series of events, coordinated by host and bacterial signal molecules, underlie the development of this symbiotic interaction. Rhizobia elicit de novo formation of a novel root organ within which they establish a chronic intracellular infection. Legumes permit rhizobia to invade these root tissues while exerting control over the infection process. Once rhizobia gain intracellular access to their host, legumes also strongly influence the process of bacterial differentiation that is required for nitrogen fixation. Even so, symbiotic rhizobia play an active role in promoting their goal of host invasion and chronic persistence by producing a variety of signal molecules that elicit changes in host gene expression. In particular, rhizobia appear to advocate for their access to the host by producing a variety of signal molecules capable of suppressing a general pathogen defense response. PMID:18983260

  11. Dermatologic Manifestations of Chronic Hepatitis C Infection.

    PubMed

    Sayiner, Mehmet; Golabi, Pegah; Farhat, Freba; Younossi, Zobair M

    2017-08-01

    Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including dermatologic involvement mostly caused by immune complexes. Mixed cryoglobulinemia has a strong relationship with HCV with 95% of these patients being infected with HCV. Lichen planus is a disease of the squamous epithelium and may affect any part of the skin, with 4% to 24% of patients with lichen planus reported to have chronic HCV infection. Porphyria cutanea tarda is the most common form of porphyria, and it is thought that HCV interferes with iron stores, which can promote porphyria cutanea tarda. Finally, necrolytic acral erythema is a rare, psoriasis-like disease closely associated with HCV. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Novelty and Promotional Items

    EPA Pesticide Factsheets

    Small novelty or promotional products, primarily used for outreach and educational purposes, must effectively convey a message, and their purchase will only be allowed if the item will contribute to the accomplishment of the Agency's mission.

  13. Promoting "Global" Attitudes.

    ERIC Educational Resources Information Center

    Case, Roland

    1996-01-01

    Discusses and illustrates three ways to promote prosocial attitudes towards global issues among students. Includes classroom environments that reinforce desired attitudes; facilitating direct "emotional" experiences that influence attitudes; and engaging students in thoughtful deliberation about global issues. Offers illustrative…

  14. Promoting Your Web Site.

    ERIC Educational Resources Information Center

    Raeder, Aggi

    1997-01-01

    Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)

  15. Psychosocial factors in chronic disability.

    PubMed

    Pearce, J M S

    2002-12-01

    If adopted without adequate cause, the lifestyle of an invalid is a grave misfortune for the patient and for its reflection on current social attitudes that foster such states. Psychological illnesses are frequently invoked and are often a genuine source of suffering and disability. However, patients who may be rewarded by large financial settlements in courts, may also on occasion exaggerate their claims. Modern society has established systems of support, and rulings in court proceedings that conduce to illness behaviour. To some extent the portentous diagnostic labels given to these patients fosters rather than alleviates illness. It is probable that biological factors deriving from the primary event initiate the process. In medical terms, the symptoms and disabilities are often discrepant with the initial illness or injury. The patients' behaviour arises out of a desire to attain the sick role for secondary gain. If society eliminated the stigma of psychological illness, and opposed exaggeration and simulation of illness, then such chronic disability with 'retreat into illness' might disappear. Sometimes an assumed illness becomes an adopted way of life. The unfortunate patients may come to believe they are ill; symptoms then persist after settlement. It is wrong to blame everything on society and to deny the free choice of the individual. Nevertheless, the pressures of society can be difficult to withstand for those not gifted with resilience. We should also recognise and try to eliminate the contribution made by doctors and health workers who mistakenly aid and abet a 'culture' that promotes this state of chronic disability. If adopted without adequate cause, the lifestyle of an invalid is a grave misfortune for the patient and for its reflection on current social attitudes that foster such states. Psychological illnesses are frequently invoked and are often a genuine source of suffering and disability. However, patients who may be rewarded by large financial

  16. [Evaluation of an online health promotion Diploma].

    PubMed

    Salinas, Judith; Muñoz, Carolina; Albagli, Andrea; Vio, Fernando

    2014-02-01

    Health promotion in Chile is essential, considering its current epidemiologic status where chronic diseases are predominant. To report the evaluation of an on-line Diploma in health promotion for Primary Health Care professionals. Two hundred sixty four professionals from all regions of the country (40% rural and 60% urban) took the Diploma. It lasted 8 months with 248 academic hours distributed in 5 modules with a total of 15 units. The program was evaluated with four surveys answered by the students (general description of participants, mid-term, final and follow-up). Students were highly satisfied with the program and especially with its interactive methodology which included tutorials, individual and group assignments, online discussions and a final project. The drawbacks were time restrictions and limited internet access. Ninety percent of students completed the course with an overall mean grade of 5.57 (out of a 1-7 scale). The follow-up survey showed that students implemented the new health promotion knowledge acquired, and put in practice their final assignment in their local counties. Also, most students improved their working conditions. The on-line interactive and participative methodology applied in this Diploma had positive results and the evaluation model can be applied in other health promotion on-line education programs.

  17. History of physical and sexual abuse in women with chronic pelvic pain.

    PubMed

    Rapkin, A J; Kames, L D; Darke, L L; Stampler, F M; Naliboff, B D

    1990-07-01

    The history of physical and sexual abuse in childhood and adulthood was assessed in 31 women with chronic pelvic pain, 142 women with chronic pain in other locations, and 32 controls. Thirty-nine percent of patients with chronic pelvic pain had been physically abused in childhood. This percentage was significantly greater than that observed in other chronic-pain patients (18.4%) or controls (9.4%), though the prevalence of childhood sexual abuse did not differ among the groups (19.4, 16.3, and 12.5%, respectively). Abuse in adulthood was less common and was not significantly more likely to have occurred in patients with chronic pelvic pain than in other chronic-pain patients or controls. These data suggest that pelvic pain is unlikely to be specifically and psychodynamically related to sexual abuse but that the pernicious nature of abuse, whether physical or sexual, may promote the chronicity of painful conditions.

  18. Self-organization in chronic pain: a concept analysis.

    PubMed

    Monsivais, Diane

    2005-01-01

    The purpose of this article is to examine the concept of self-organization in chronic pain using Rodgers' (2000) evolutionary approach. This article describes the antecedents, attributes, and consequences of self-organization in chronic pain. Self-organization in chronic pain may be achieved through the attributes of being believed, accessing credible resources, and taking action and responsibility. Self-organization occurs when the patient with pain develops a transformed identity, new insights, and is an active, in-control participant in care. Chronic pain is a common and costly problem, and recognition of the key attributes of self-organization in this condition is an important step in promoting positive health outcomes. Rehabilitation nurses play a key role in providing credible resources and working with the patient to take action and responsibility.

  19. Health promotion overview: evidence-based strategies for occupational health nursing practice.

    PubMed

    Dombrowski, Jill J; Snelling, Anastasia M; Kalicki, Michelle

    2014-08-01

    Health promotion practice has evolved over the past four decades in response to the rising rates of chronic disease. The focus of health promotion is attaining wellness by managing modifiable risk factors, such as smoking, diet, or physical activity. Occupational health nurses are often asked to conduct worksite health promotion programs for individuals or groups, yet may be unfamiliar with evidence-based strategies. Occupational health nurses should lead interprofessional groups in designing and implementing worksite health promotion programs. This article introduces occupational health nurses to health promotion concepts and discusses evidence-based theories and planning models that can be easily introduced into practice.

  20. Nutrition and Chronic Wounds

    PubMed Central

    Molnar, Joseph Andrew; Underdown, Mary Jane; Clark, William Andrew

    2014-01-01

    Significance: Nutrition is one of the most basic of medical issues and is often ignored as a problem in the management of our chronic wound patients. Unfortunately, malnutrition is widespread in our geriatric patients even in nursing homes in developed countries. Attention to basic nutrition and providing appropriate supplements may assist in the healing of our chronic wounds. Recent Advances: Recent research has revealed the epidemiology of malnutrition in developed countries, the similarities to malnutrition in developing countries, and some of the physiologic and sociologic causes for this problem. More information is now available on the biochemical effects of nutrient deficiency and supplementation with macronutrients and micronutrients. In some cases, administration of isolated nutrients beyond recommended amounts for healthy individuals may have a pharmacologic effect to help wounds heal. Critical Issues: Much of the knowledge of the nutritional support of chronic wounds is based on information that has been obtained from trauma management. Due to the demographic differences of the patients and differences in the physiology of acute and chronic wounds, it is not logical to assume that all aspects of nutritional support are identical in these patient groups. Before providing specific nutritional supplements, appropriate assessments of patient general nutritional status and the reasons for malnutrition must be obtained or specific nutrient supplementation will not be utilized. Future Directions: Future research must concentrate on the biochemical and physiologic differences of the acute and chronic wounds and the interaction with specific supplements, such as antioxidants, vitamin A, and vitamin D. PMID:25371850

  1. [Chronic disease and adolescence].

    PubMed

    Bühlmann, U

    1992-01-25

    Chronic disease is not a strictly defined term and includes a large number of illnesses ranging from physical to mental impairment. It is estimated that between 10% and 20% of adolescents have a chronic disease. Independence and new relations, acceptance of a new body image and sexuality, career plans and cognitive maturation are core topics in development to adulthood. Chronic disease may interfere with these developmental tasks. Most often there is no specific psychopathology, but the type of impairment, its influence on family life and functioning, age at onset, gender, and other factors will interact with psychosocial maturation. Because of the important role of the family, not only the adolescent patient him/herself, but also parents and siblings need to be included in all major decisions. As hospitalizations may be disruptive they must be planned, taking in account the patient's plans and opinions. Chronic disease may lead to death during the period of adolescence. It is believed that the concept of one's own mortality develops at age 14 to 17 years, a fact that will influence care during the terminal stage of a disease. Whatever the problems and questions raised by the family, the developmental stage of the adolescent has always to be considered when dealing with specific issues of chronic disease. Periodic reassessment of psychosocial development is therefore one of the main tasks of the primary care physician. Counselling will address not only the disease but also the developmental tasks of any teenager.

  2. [Chronic migraine: treatment].

    PubMed

    Pascual, Julio

    2012-04-10

    We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A.

  3. Protective Connections and Educational Attainment among Young Adults with Childhood-Onset Chronic Illness

    ERIC Educational Resources Information Center

    Maslow, Gary; Haydon, Abigail A.; McRee, Annie-Laurie; Halpern, Carolyn T.

    2012-01-01

    Background: Youth with childhood-onset chronic illness (COCI) are at risk of poor educational attainment. Specific protective factors that promote college graduation in this population have not been studied previously. In this study, we examine the role protective factors during adolescence play in promoting college graduation among young adults…

  4. Protective Connections and Educational Attainment among Young Adults with Childhood-Onset Chronic Illness

    ERIC Educational Resources Information Center

    Maslow, Gary; Haydon, Abigail A.; McRee, Annie-Laurie; Halpern, Carolyn T.

    2012-01-01

    Background: Youth with childhood-onset chronic illness (COCI) are at risk of poor educational attainment. Specific protective factors that promote college graduation in this population have not been studied previously. In this study, we examine the role protective factors during adolescence play in promoting college graduation among young adults…

  5. Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

    PubMed Central

    Criner, Gerard J.

    2013-01-01

    Chronic bronchitis (CB) is a common but variable phenomenon in chronic obstructive pulmonary disease (COPD). It has numerous clinical consequences, including an accelerated decline in lung function, greater risk of the development of airflow obstruction in smokers, a predisposition to lower respiratory tract infection, higher exacerbation frequency, and worse overall mortality. CB is caused by overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse. Despite its clinical sequelae, little is known about the pathophysiology of CB and goblet cell hyperplasia in COPD, and treatment options are limited. In addition, it is becoming increasingly apparent that in the classic COPD spectrum, with emphysema on one end and CB on the other, most patients lie somewhere in the middle. It is known now that many patients with severe emphysema can develop CB, and small airway pathology has been linked to worse clinical outcomes, such as increased mortality and lesser improvement in lung function after lung volume reduction surgery. However, in recent years, a greater understanding of the importance of CB as a phenotype to identify patients with a beneficial response to therapy has been described. Herein we review the epidemiology of CB, the evidence behind its clinical consequences, the current understanding of the pathophysiology of goblet cell hyperplasia in COPD, and current therapies for CB. PMID:23204254

  6. Chronic thromboembolic pulmonary hypertension.

    PubMed

    Schölzel, B E; Snijder, R J; Mager, J J; van Es, H W; Plokker, H W M; Reesink, H J; Morshuis, W J; Post, M C

    2014-12-01

    Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

  7. Pathophysiology of chronic rhinosinusitis.

    PubMed

    Tomassen, Peter; Van Zele, Thibaut; Zhang, Nan; Perez-Novo, Claudina; Van Bruaene, Nicholas; Gevaert, Philippe; Bachert, Claus

    2011-03-01

    Chronic rhinosinusitis (CRS), a disease presenting with chronic symptoms such as nasal obstruction, rhinorrhea, hyposmia and facial pain, is highly prevalent and has a considerable impact on quality of life and health care expenditures. The disease is characterized by chronic inflammation of the sinonasal mucosa and can present with nasal polyps. Current consensus classifies CRS into CRS with nasal polyps and CRS without nasal polyps. This review illustrates the diversity of pathophysiological observations in CRS and highlights selected etiological hypotheses. A wide spectrum of alterations is described regarding histopathology, pattern of T cells and inflammatory effector cells, remodeling, immunoglobulin production, chemokine and eicosanoid production, and the role of microorganisms. The pathophysiological diversity observed in CRS seems to stand in contrast to its nonspecific clinical presentation, but is of the utmost importance in the development and application of highly individualized treatments. Identification of specific disease subgroups and their etiologies is an important and challenging task for future research.

  8. Chronic Demyelinating Polyneuropathies.

    PubMed

    Allen, Jeffrey A

    2017-10-01

    This article reviews the chronic demyelinating neuropathies, with a focus on the diagnosis and treatment of immune-mediated neuropathies and the features that can help differentiate immune-mediated neuropathies from other chronic demyelinating peripheral nerve conditions. Advances in clinical phenotyping and outcomes assessment have enabled neurologists to improve disease recognition, treatment, and disease monitoring. Our understanding of the immunopathogenesis of demyelinating neuropathies is evolving. Identification of new antibodies and recognition that node of Ranvier dysfunction may be an early pathogenic feature may herald further diagnostic and treatment advancements. The chronic demyelinating polyneuropathies are heterogeneous. The clinical and diagnostic features are sometimes overlapping, and the specific disorders are variable in pathogenesis, treatment, and prognosis. This heterogeneity underscores the importance of achieving diagnostic accuracy and implementing disease-specific treatment approaches.

  9. [Anaemia and chronic diseases].

    PubMed

    Chassagne, Philippe; Amalou, Laetitia; Thillard, Anne-Lyse; Gbaguidi, Xavier; Roca, Frédéric

    2015-03-01

    The prevalence of anemia in old patients is 20%. Anemia is mostly multifactorial associated with multiple comorbidities that are frequently observed in people of 65 years or older. Chronic renal failure, inflammatory diseases, nutrient deficiencies and especially iron deficiency are the most associated conditions with anemia. Anemia represents a prognosis marker of general health in old people. Thus anemia is associated with higher rates of morbidities (such as unplanned hospitalizations) and greatest mortality. Therefore anemia could be considered either as a consequence of chronic diseases or a prognosis marker of their severity. The prognosis of chronic cardiac failure is for example worst in anemic patients. Finally anemia is listed as a component of the frailty.

  10. Chronic Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Opinion statement Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treatment. Most clinical neurologists will be involved in the management of patients with these disorders, and should be familiar with available therapies for CIDP. We review the distinctive clinical, laboratory, and electro-diagnostic features that aid in diagnosis. We emphasize the importance of clinical patterns that define treatment responsiveness and the most appropriate therapies in order to improve prognosis. PMID:23564314

  11. Chronic pelvic floor dysfunction.

    PubMed

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Brassinosteroid-promoted growth.

    PubMed

    Müssig, C

    2005-03-01

    Brassinosteroids (BRs) are highly potent growth-promoting sterol derivatives. BR-deficient or BR-insensitive mutants display dwarfism. Whole plants and excised tissues have been used to analyse the mechanisms involved in BR-promoted growth. BR stimulates cell elongation and cell division, and BR has specific effects on differentiation. Underlying physiological pathways include modification of cell wall properties, effects on carbohydrate assimilation and allocation, and control of aquaporin activities. BR apparently coordinates and integrates diverse processes required for growth, partly via interactions with other phytohormones setting the frame for BR responses. Ultimately, BR-promoted growth is mediated through genomic pathways. Positive regulators of the BR response (such as BZR1 and BES1) and putative downstream components (such as EXO) are involved in the regulation of BR-responsive genes and growth promotion. BR-responsive genes have been identified in several plant species. However, causal links between physiological effects and changes of transcript patterns, for the most part, are still unresolved. This review focuses on physiology and molecular mechanisms underlying BR-promoted growth in the different plant organs. Interactions with other phytohormones are discussed.

  13. [Benign chronic pain].

    PubMed

    Serrie, A; Thurel, C

    1994-09-15

    Recent data indicate that 25 to 30% of the population in industrialized countries suffers from benign chronic pain. Among these patients, 50 to 75% are professionally incapable for varied lengths of time, from a few days to some weeks or months, or even definitively. The aetiology and clinical presentation of chronic benign pain are enormously varied because this definition includes such different pathologies as headache, pain of rheumatologic, postsurgical, organic, and post-zoster origin, lombalgia, radiculalgia, post-amputation pain, neuropathologic pain, causalgia, algoneurodystrophic pain, psychosomatic and idiopathic pain. Since these syndromes and causes of pain could not be discussed individually, they have been grouped according to their neurophysiology and pathophysiology.

  14. [Chronic knee joint discomfort].

    PubMed

    Wittke, R

    2005-06-23

    Chronic pain in the knee joint is frequently a sign of arthrosis in adults. This must be clearly differentiated from other knee problems. Patellofemoral stress syndrome (occurs mostly in young people) and arthritis with effusion in the knee joint after long and mostly unusual stress also allow only a reduced function of the knee joint. However, even when the knee joint is still fully functional, chronic problems could already exist: For example, for joggers, iliotibial band friction syndrome (runner's knee) or after high unphysiological stress, patellar tendinopathy (jumper's knee). These must be differentiated from pes anserinus syndrome and a plica mediopatellaris.

  15. [Chronic interstitial pneumonitis].

    PubMed

    Almeida, Rui; Reis, Guilhermina; Ferreira, Cristina; Oliveira, Ma José; Oliveira, Dulce; Fernandes, Paula; Ferreira, Paula; Frutuoso, Simão; Carreira, Luísa; Alves, Valter; Paiva, António; Guedes, Margarida

    2004-01-01

    Interstitial lung disease includes a group of chronic diseases characterized by alterations in alveolar walls and loss of functional alveolar-capillary units. These are rare diseases in children, mostly with an unknown cause and associated with a high morbidity and mortality due to insufficient therapeutic effectiveness. The authors report a case of a previously healthy 3 years old child who presented with wheezing and severe respiratory insufficiency following a respiratory infection. The investigation performed led to the diagnosis of chronic interstitial pneumonitis. Several treatments have been tried (corticosteroids, hydroxychloroquine, N-acetylcysteine) without any obvious improvement.

  16. [Histaminergic angioedema and chronic urticaria].

    PubMed

    Hacard, Florence; Nosbaum, Audrey; Bensaid, Benoit; Nicolas, Jean-François; Augey, Frédéric; Goujon, Catherine; Bérard, Frédéric

    2015-01-01

    Most angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives. Chronic urticaria is a benign disease, and autoimmune in 40 % of cases. The occurrence of angioedema in chronic urticaria is not a sign of severity. The occurrence of angioedema in chronic urticaria is associated with a longer duration of urticarial disease. NSAIDs and/or systemic corticotherapy are classic triggers of angioedema in chronic urticaria. In the absence of clinical endpoints, there is no need to make further assessment in chronic urticaria good responders to antihistamines.

  17. Probiotics and chronic kidney disease.

    PubMed

    Koppe, Laetitia; Mafra, Denise; Fouque, Denis

    2015-11-01

    Probiotics are the focus of a thorough investigation as a natural biotreatment due to their various health-promoting effects and inherent ability to fight specific diseases including chronic kidney disease (CKD). Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Because many of the multifactorial physiological functions of probiotics are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical. The interest in developing new research initiatives on probiotics in CKD have increased over the last decade with the goal of fully exploring their therapeutic potentials. The efficacy of probiotics to decrease uremic toxin production and to improve renal function has been investigated in in vitro models and in various animal and human CKD studies. However to date, the quality of intervention trials investigating this novel CKD therapy is still lacking. This review outlines potential mechanisms of action and efficacy of probiotics as a new CKD management tool, with a particular emphasis on uremic toxin production and inflammation.

  18. [Apoptosis in chronic lymphocytic leukemia].

    PubMed

    Giordano, M

    2000-01-01

    Chronic lymphocytic leukemia of B cells (B-CLL) is the most prevalent leukemia in the Occidental Hemisphere. It is characterized by a progressive accumulation of monoclonal CD5+ B lymphocytes, with low amounts of surface Ig. Most B-CLL cells are arrested in the G0 phase of the cell cycle; therefore their accumulation in vivo appears to result from the inhibition of apoptosis which has been attributed to over-expression of the anti-apoptotic protein Bcl-2. When cultured in vitro, spontaneous apoptosis occurs, suggesting the existence in vivo of survival-promoting factors. We here show that non-malignant leukocytes, particularly monocytes and NK cells, are able to inhibit B-CLL cells apoptosis, at least in part, through the release of soluble factors. Neutralizing antibodies directed to interferon-gamma or IL-4 only partially abolish the protecting effects of accessory cells suggesting that they are not the main cytokines involved. Increased apoptosis of B-CLL cells is not associated with modifications in the expression of Bcl-2, Fas or Fas ligand. Considering that B-CLL is associated to autoimmune phenomena and recurrent infections due to hypogammaglobulinemia, it should be interesting to correlate the activation of immune responses with disease progression.

  19. Chronic Hepatitis C

    PubMed Central

    Jang, Jae Young

    2011-01-01

    The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma. PMID:21814590

  20. Chronic wasting disease

    USDA-ARS?s Scientific Manuscript database

    Chronic wasting disease (CWD) is an emerging prion disease of deer, elk, and moose in North America. This fatal neurodegenerative disease was first recognized 50 years ago and its distribution was limited to the Rocky Mountains for several decades. In the past few years, CWD has been found in the ea...

  1. Chronic pancreatitis in dogs.

    PubMed

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  2. [Chronic blepharitis and Demodex].

    PubMed

    Rodríguez, A E; Ferrer, C; Alió, J L

    2005-11-01

    Demodex is a mite commonly found in eyelash hair follicles and sebaceous glands of healthy people. Due to the fact this mite has also been reported in many chronic cases of blepharitis, we aimed to investigate the incidence of infestation with this mite in healthy people and in patients with chronic blepharitis, in addition to evaluating the response to the different treatments used for blepharitis. 105 subjects without blepharitis were selected as a control group and 20 subjects diagnosed as having chronic blepharitis were selected as patients. Epilated eyelashes were observed under microscope in both groups of patients. Those with overpopulation of mites were treated with ether lid and eyelash scrubs and 2% mercury oxide ointment. The incidence of Demodex infestation in the control group was 0.08 mites per eyelash, whereas in the patients with chronic blepharitis the incidence was 0.69 mites per eyelash; this difference was statistically significant (p=0.006). All the mites found were Demodex folliculorum except in one patient where the mite was identified as Demodex brevis. After 3-8 weeks of specific treatment the number of mites per eyelash decreased dramatically (0.03, with p=0.001). Two patients were intolerant of the therapy. In this study the incidence of Demodex in patients with blepharitis was very high, when compared with normal subjects, showing a clear association between blepharitis and Demodex infestation. Treatment with mercury oxide ointment was satisfactory in controlling the infection, despite difficulty in its application and occasional toxicity.

  3. Chronic sinusitis in children.

    PubMed

    Calderon, E; O'Neal, M L; Fox, R W; Calderon-Moncloa, J

    1996-01-01

    Chronic sinusitis is now recognized as a common clinical syndrome in adults and children. An astute physician can diagnose chronic sinusitis during the physical exam, but fiber-optic rhinoscopy and x-rays (plain films and computerized tomography) are required to confirm this diagnosis, evaluate the severity of the sinusitis and determine follow-up treatment. Appropriate treatment plans are prescribed for an adequate duration to eliminate infection and inflammatory components of the pathologic process of the sinuses involved. Antibiotics, decongestants, and inhaled or systemic corticosteroids are required in the treatment of patients with chronic sinusitis. When combined with close clinical follow-up, successful resolution is expected. Surgical intervention is needed in the medically refractory and symptomatic cases, or when complications develop. The frequent diagnosis of chronic sinusitis in the past 1-2 decades is, in part, due to the enhanced awareness and clinical skills of the treating physicians, but other concerns about environmental influences such as frequent respiratory tract infections in childhood and air quality issues are considered potentially important.

  4. Chronic Kidney Disease

    MedlinePlus

    ... factors. It is important to diagnose CKD early. Diagnosis & TestsHow can my doctor tell if I have CKD?There are three simple tests that your doctor might do if he or she suspects you might have chronic kidney disease:Blood pressure testUrine albumin (a test to see ...

  5. Chronic manganese intoxication

    SciTech Connect

    Huang, C.C.; Chu, N.S.; Lu, C.S.; Wang, J.D.; Tsai, J.L.; Tzeng, J.L.; Wolters, E.C.; Calne, D.B. )

    1989-10-01

    We report six cases of chronic manganese intoxication in workers at a ferromanganese factory in Taiwan. Diagnosis was confirmed by assessing increased manganese concentrations in the blood, scalp, and pubic hair. In addition, increased manganese levels in the environmental air were established. The patients showed a bradykinetic-rigid syndrome indistinguishable from Parkinson's disease that responded to treatment with levodopa.

  6. Resolvin D1 Reduces Emphysema and Chronic Inflammation

    PubMed Central

    Hsiao, Hsi-Min; Thatcher, Thomas H.; Colas, Romain A.; Serhan, Charles N.; Phipps, Richard P.; Sime, Patricia J.

    2016-01-01

    Chronic obstructive pulmonary disease is characterized, in part, by chronic inflammation that persists even after smoking cessation, suggesting that a failure to resolve inflammation plays an important role in the pathogenesis of the disease. It is widely recognized that the resolution of inflammation is an active process, governed by specialized proresolving lipid mediators, including lipoxins, resolvins, maresins, and protectins. Here, we report that proresolving signaling and metabolic pathways are disrupted in lung tissue from patients with chronic obstructive pulmonary disease, suggesting that supplementation with proresolving lipid mediators might reduce the development of emphysema by controlling chronic inflammation. Groups of mice were exposed long-term to cigarette smoke and treated with the proresolving mediator resolvin D1. Resolvin D1 was associated with a reduced development of cigarette smoke–induced emphysema and airspace enlargement, with concurrent reductions in inflammation, oxidative stress, and cell death. Interestingly, resolvin D1 did not promote the differentiation of M2 macrophages and did not promote tissue fibrosis. Taken together, our results suggest that cigarette smoking disrupts endogenous proresolving pathways and that supplementation with specialized proresolving lipid mediators is an important therapeutic strategy in chronic lung disease, especially if endogenous specialized proresolving lipid mediator signaling is impaired. PMID:26468975

  7. Chronic kidney disease: effects on the cardiovascular system.

    PubMed

    Schiffrin, Ernesto L; Lipman, Mark L; Mann, Johannes F E

    2007-07-03

    Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.

  8. Extrahepatic manifestations in chronic hepatitis C virus carriers.

    PubMed

    Rosenthal, E; Cacoub, P

    2015-04-01

    Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. [The role of chronic tonsillitis in the development of reproductive pathology in women of child-bearing age].

    PubMed

    Slavskiĭ, A N

    2009-01-01

    Women of child-bearing age with decompensated form of chronic tonsillitis should be regarded as being at high risk of endocrine infertility. Early identification and sanitization of the chronic infectious focus (chronic tonsillitis) is necessary to avoid irreversible changes in the functional capacity of the reproductive system. Sanitization of palatine tonsils in patients with chronic tonsillitis and reproductive pathology promotes normalization of their hormonal status. Therefore, a gynecologist examining women with menstrual disturbances should take into consideration their possible association with chronic tonsillitis and refer such patients to otorhinolaryngologist.

  10. Living with chronic headache: a qualitative study exploring goal management in chronic headache.

    PubMed

    Ciere, Yvette; Visser, Annemieke; Jacobs, Bram; Padberg, Marielle; Lebbink, John; Sanderman, Robbert; Fleer, Joke

    2017-08-10

    Effective goal management may potentially prevent or reduce disability in chronic pain. The aim of this study was to gain insight into the nature of goal management in the context of chronic headache (CH). Interviews with 20 patients were conducted, coded, and analyzed using a combined data-driven and theory-driven approach. The dual process model (DPM) was used as a theoretical framework for this study. Participants used a combination of strategies to regain and maintain a balance between personal goals and resources available for goal pursuit. Furthermore, their retrospective reports indicated a development in strategy use of time. Three goal management phases were identified: (1) a "persistence phase," characterized by the use of "resource-depleting" assimilative strategies to remain engaged in goals, (2) a "reorientation phase" in accommodative strategies were used to regain balance, and (3) a "balancing phase" in which a combination of "resource-depleting" and "resource-replenishing" assimilative strategies was used to maintain balance. Goal management is a dynamic process that may contribute to the development of, and recovery from, headache-related disability. Rehabilitation services offered to individuals with CH should target this process to promote optimal functioning. Implications for Rehabilitation Individuals with chronic headache use assimilative and accommodative goal management strategies to be able to pursue personal goals despite the limitations of chronic headache. Before accommodating goals to the limitations of chronic headache, many patients go through a phase of persistence, characterized by the use of resource-depleting assimilative strategies. A reorientation phase, characterized by accommodation of goals to the limitations of chronic headache, allows patients to adopt a more balanced way of pursuing personal goals.

  11. Promoting Classroom Technology Use

    ERIC Educational Resources Information Center

    Rosenfeld, Barbara; Martinez-Pons, Manuel

    2005-01-01

    The purpose of this study was to test two hypotheses: (1) that participation in a course providing theory and practice in the classroom use of technology promotes its use and results in gained competence in technology use; and (2) that functional relations exist among the availability of technology in the classroom, technology utilization, and…

  12. Promoting Healthy Dietary Behaviors.

    ERIC Educational Resources Information Center

    Perry, Cheryl L.; Story, Mary; Lytle, Leslie A.

    This chapter reviews the research on promoting healthy dietary behaviors in all youth, not just those who exhibit problems such as obesity or eating disorders. The first section of this chapter presents a rationale for addressing healthy dietary behavior with children and adolescents, on the basis of the impact of these behaviors on short- and…