Science.gov

Sample records for promotes fas-ligand-dependent chronic

  1. Person-centered Health Promotion in Chronic Disease

    PubMed Central

    Cloninger, C. Robert

    2015-01-01

    Health promotion must be person-centered, not organ- or disease-centered, in order to be effective because physical, mental, social, and spiritual aspects of human functioning are inextricably intertwined. Chronic medical disorders, such as heart disease, chronic obstructive pulmonary disease, diabetes, cancer, asthma, and arthritis, are strongly associated with immature personality, emotional instability, and social dysfunction. All indicators of physical, mental, and social well-being are strongly related to the level of maturity and integration of personality, so personality is a useful focus for the promotion of well-being. Assessment of personality also facilitates the awareness of the clinician and the patient about the patient’s strengths, weaknesses, and goals, thereby contributing to an effective therapeutic alliance. Health, well-being, resilience, and recovery of function all involve increasing levels of the character traits of Self-directedness, Cooperativeness, and Self-transcendence. Person-centered programs that enhance self-regulation of functioning to achieve personally valued goals improve compliance with medical treatment and quality of life in people with chronic disease. Effective therapeutic approaches to health promotion activate a complex adaptive system of feedback interactions among functioning, plasticity, and virtuous ways of thinking and acting. The probability of personality change can be predicted by high levels of Self-transcendence, which give rise to an outlook of unity and connectedness, particularly when combined with the temperament traits of high Novelty Seeking and high Persistence. In summary, person-centered psychobiological treatments that facilitate the development of well-being and personality development are crucial in the prevention, treatment, and rehabilitation of chronic medical diseases. PMID:26339469

  2. 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

  3. Bile signalling promotes chronic respiratory infections and antibiotic tolerance.

    PubMed

    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

  4. 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. PMID:26059599

  5. Chronic Sleep Fragmentation Promotes Obesity in Young Adult Mice

    PubMed Central

    Wang, Yang; Carreras, Alba; Lee, SeungHoon; Hakim, Fahed; Zhang, Shelley X.; Nair, Deepti; Ye, Honggang; Gozal, David

    2013-01-01

    Objectives Short sleep confers a higher risk of obesity in humans. Restricted sleep increases appetite, promotes higher calorie intake from fat and carbohydrate sources, and induces insulin resistance. However, the effects of fragmented sleep (SF), such as occurs in sleep apnea, on body weight, metabolic rates, and adipose tissue distribution are unknown. Design and Methods C57BL/6 mice were exposed to SF for 8 weeks. Their body weight, food consumption, and metabolic expenditure were monitored over time, and their plasma leptin levels measured after exposure to SF for 1 day as well as for 2 weeks. In addition, adipose tissue distribution was assessed at the end of the SF exposure using MRI techniques. Results Chronic SF induced obesogenic behaviors and increased weight gain in mice by promoting increased caloric intake without changing caloric expenditure. Plasma leptin levels initially decreased and subsequently increased. Furthermore, increases in both visceral and subcutaneous adipose tissue volumes occurred. Conclusions These results suggest that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of obesity via activation of obesogenic behaviors and possibly leptin resistance, in the absence of global changes in energy expenditure. PMID:24039209

  6. 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…

  7. CHRONIC DISEASE PREVENTION (CDP) BIBLIOGRAPHIC DATABASE HEALTH PROMOTION AND PREVENTION (HP) DATABASE

    EPA Science Inventory

    This database focuses on chronic disease prevention, health promotion, and health education emphasizing the methodology and application of effective programs and risk reduction interventions. The materials cover such topics as community health education, self-care, maternal and i...

  8. Sustained Elevated Adenosine via ADORA2B Promotes Chronic Pain through Neuro-immune Interaction.

    PubMed

    Hu, Xia; Adebiyi, Morayo G; Luo, Jialie; Sun, Kaiqi; Le, Thanh-Thuy T; Zhang, Yujin; Wu, Hongyu; Zhao, Shushan; Karmouty-Quintana, Harry; Liu, Hong; Huang, Aji; Wen, Yuan Edward; Zaika, Oleg L; Mamenko, Mykola; Pochynyuk, Oleh M; Kellems, Rodney E; Eltzschig, Holger K; Blackburn, Michael R; Walters, Edgar T; Huang, Dong; Hu, Hongzhen; Xia, Yang

    2016-06-28

    The molecular mechanisms of chronic pain are poorly understood and effective mechanism-based treatments are lacking. Here, we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected chronic mechanical and thermal hypersensitivity due to sustained elevated circulating adenosine. Extending from Ada(-/-) mice, we further discovered that prolonged elevated adenosine contributed to chronic pain behaviors in two additional independent animal models: sickle cell disease mice, a model of severe pain with limited treatment, and complete Freund's adjuvant paw-injected mice, a well-accepted inflammatory model of chronic pain. Mechanistically, we revealed that activation of adenosine A2B receptors on myeloid cells caused nociceptor hyperexcitability and promoted chronic pain via soluble IL-6 receptor trans-signaling, and our findings determined that prolonged accumulated circulating adenosine contributes to chronic pain by promoting immune-neuronal interaction and revealed multiple therapeutic targets. PMID:27320922

  9. 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…

  10. [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. PMID:26242434

  11. The human immunodeficiency virus type 1 tat protein enhances Cryptosporidium parvum-induced apoptosis in cholangiocytes via a Fas ligand-dependent mechanism.

    PubMed

    O'Hara, Steven P; Small, Aaron J; Nelson, Jeremy B; Badley, Andrew D; Chen, Xian-Ming; Gores, Gregory J; Larusso, Nicholas F

    2007-02-01

    While Cryptosporidium parvum infection of the intestine has been reported in both immunocompetent and immunocompromised individuals, biliary infection is seen primarily in adult AIDS patients and is associated with development of AIDS cholangiopathy. However, the mechanisms of pathogen-induced AIDS cholangiopathy remain unclear. Since we previously demonstrated that the Fas/Fas ligand (FasL) system is involved in paracrine-mediated C. parvum cytopathicity in cholangiocytes, we also tested the potential synergistic effects of human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat)-mediated FasL regulation on C. parvum-induced apoptosis in cholangiocytes by semiquantitative reverse transcription-PCR, immunoblotting, immunofluorescence analysis, and immunogold electron microscopy. H69 cells do not express CXCR4 and CCR5, which are receptors required for direct HIV-1 viral infection. However, recombinant biologically active HIV-1-associated Tat protein increased FasL expression in the cytoplasm of cholangiocytes without a significant increase in apoptosis. We found that C. parvum-induced apoptosis was associated with translocation of intracellular FasL to the cell membrane surface and release of full-length FasL from infected H69 cells. Tat significantly (P < 0.05) increased C. parvum-induced apoptosis in bystander cells in a dose-dependent manner. Moreover, Tat enhanced both C. parvum-induced FasL membrane translocation and release of full-length FasL. In addition, the FasL neutralizing antibody NOK-1 and the caspase-8 inhibitor Z-IETD-fmk both blocked C. parvum-induced apoptosis in cholangiocytes. The data demonstrated that HIV-1 Tat enhances C. parvum-induced cholangiocyte apoptosis via a paracrine-mediated, FasL-dependent mechanism. Our results suggest that concurrent active HIV replication, with associated production of Tat protein, and C. parvum infection synergistically increase cholangiocyte apoptosis and thus jointly contribute to AIDS-related cholangiopathies. PMID:17118988

  12. 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. PMID:21366840

  13. 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

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

    PubMed

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

    2015-02-01

    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

  15. 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

  16. Human miR223 Promoter as a Novel Myelo-Specific Promoter for Chronic Granulomatous Disease Gene Therapy

    PubMed Central

    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

    2013-01-01

    Abstract 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 p47phox and gp91phox in mouse models of CGD and in primary patient-derived cells. The miR223 promoter restricted the expression of p47phox, gp91phox, 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 p47phox patient followed by ex vivo differentiation to neutrophils resulted in restoration of Escherichia coli killing activity by miR223 promoter–mediated p47phox 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. PMID:23489116

  17. 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

  18. 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

  19. Health Promotion Behaviors and Chronic Diseases of Aging in the Elderly People of Iranshahr*- IR Iran

    PubMed Central

    Mofrad, Zahra Pishkar; Jahantigh, Mozhgan; Arbabisarjou, Azizollah

    2016-01-01

    Introduction and Aim: Aging is considered as the phenomenon of the day in the health arena of the world and Iran. It is anticipated that there will be an explosion of aging population in Iran in about 2031 and 20-25% of the population will be aged over 60 years. With aging, chronic diseases also increase and diminish the functional ability of older people. On the other hand, increased healthcare costs should be also added to this issue. Health promotion is a concept of process that continues throughout life. As much as health promotion is important in children and adults, it is equally important in older people. In fact, the elderlies, as a group, also acquire many benefits from health promotion behaviors. Due to the increasing elderly population, geriatric health promotion and enhancing the health level of older people is proposed as a health priority that should be properly planned. Hence, the present study has been conducted in this regard and aims to identify behaviors of health promotion and chronic diseases of aging in the elderly people of Iranshahr-Iran. Materials and Methods: The present research is a cross-sectional descriptive study whose population consists of 425 elderly people aged 60 years and over, who lived in the city of Iranshahr*, IR Iran. The random cluster sampling method has been used to select the research samples. The required information was collected using a questionnaire which was distributed among the older people through visiting their homes; then, the collected data was statistically analyzed using the statistical software of SPSS version 13. Findings: The research findings show that the mean age of older people is 66.33 ± 7.7 and the highest frequency belongs to the age group of 60 years and the maximum age is 92 years. 69.5% of the older people were in the age group of the young elderly (60-69 years) and 44% of them lived with their married children; also 55.8%, 81.9%, 70.5%, and 74.4% of them were respectively female, illiterate

  20. Cationic Antimicrobial Peptides Promote Microbial Mutagenesis and Pathoadaptation in Chronic Infections

    PubMed Central

    Limoli, Dominique H.; Rockel, Andrea B.; Host, Kurtis M.; Jha, Anuvrat; Kopp, Benjamin T.; Hollis, Thomas; Wozniak, Daniel J.

    2014-01-01

    Acquisition of adaptive mutations is essential for microbial persistence during chronic infections. This is particularly evident during chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients. Thus far, mutagenesis has been attributed to the generation of reactive species by polymorphonucleocytes (PMN) and antibiotic treatment. However, our current studies of mutagenesis leading to P. aeruginosa mucoid conversion have revealed a potential new mutagen. Our findings confirmed the current view that reactive oxygen species can promote mucoidy in vitro, but revealed PMNs are proficient at inducing mucoid conversion in the absence of an oxidative burst. This led to the discovery that cationic antimicrobial peptides can be mutagenic and promote mucoidy. Of specific interest was the human cathelicidin LL-37, canonically known to disrupt bacterial membranes leading to cell death. An alternative role was revealed at sub-inhibitory concentrations, where LL-37 was found to induce mutations within the mucA gene encoding a negative regulator of mucoidy and to promote rifampin resistance in both P. aeruginosa and Escherichia coli. The mechanism of mutagenesis was found to be dependent upon sub-inhibitory concentrations of LL-37 entering the bacterial cytosol and binding to DNA. LL-37/DNA interactions then promote translesion DNA synthesis by the polymerase DinB, whose error-prone replication potentiates the mutations. A model of LL-37 bound to DNA was generated, which reveals amino termini α-helices of dimerized LL-37 bind the major groove of DNA, with numerous DNA contacts made by LL-37 basic residues. This demonstrates a mutagenic role for antimicrobials previously thought to be insusceptible to resistance by mutation, highlighting a need to further investigate their role in evolution and pathoadaptation in chronic infections. PMID:24763694

  1. 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

  2. Chronic cortisol exposure promotes the development of a GABAergic phenotype in the primate hippocampus.

    PubMed

    McMillan, Pamela J; Wilkinson, Charles W; Greenup, Lynne; Raskind, Murray A; Peskind, Elaine R; Leverenz, James B

    2004-11-01

    Glucocorticoids regulate plasticity and survival of hippocampal neurons. Aberrant exposure to this steroid hormone can result in neurodegeneration, perhaps secondary to disruption of calcium homeostasis. Calbindin, a calcium-binding protein that buffers excess calcium, may protect against neurodegeneration resulting from overabundance of intracellular calcium. In this study, we examined whether chronic treatment (1 year) with cortisol enhances hippocampal calbindin expression in primates. Calbindin is a marker for inhibitory neurons and the dentate gyrus is known to adopt an inhibitory phenotype in response to extreme conditions such as seizures. Thus, we hypothesized that chronic cortisol exposure may also promote a GABAergic phenotype. Therefore, we examined the expression of the GABA-synthesizing enzyme glutamic acid decarboxylase. The expression of brain-derived neurotrophic factor, which is responsive to glucocorticoids, was also examined. Our results demonstrate significant increases in calbindin, glutamic acid decarboxylase and brain-derived neurotrophic factor in several regions of the primate hippocampus, including the dentate gyrus and CA3, in response to chronic cortisol exposure. These results suggest that chronic cortisol exposure may shift the balance towards a GABAergic phenotype, perhaps as part of a compensatory feedback mechanism to dampen the initial excitatory effects of glucocorticoids in the hippocampus. PMID:15525338

  3. 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. PMID:25092805

  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. Erythropoietin promotes deleterious cardiovascular effects and mortality risk in a rat model of chronic sports doping.

    PubMed

    Piloto, Nuno; Teixeira, Helena M; Teixeira-Lemos, Edite; Parada, Belmiro; Garrido, Patrícia; Sereno, José; Pinto, Rui; Carvalho, Lina; Costa, Elísio; Belo, Luís; Santos-Silva, Alice; Teixeira, Frederico; Reis, Flávio

    2009-12-01

    Athletes who abuse recombinant human erythropoietin (rhEPO) consider only the benefit to performance and usually ignore the potential short and long-term liabilities. Elevated haematocrit and dehydratation associated with intense exercise may reveal undetected cardiovascular risk, but the mechanisms underlying it remain to be fully explained. This study aimed to evaluate the cardiovascular effects of rhEPO in rats under chronic aerobic exercise. A ten week protocol was performed in four male Wistar rat groups: control--sedentary; rhEPO--50 IU kg(-1), 3 times/wk; exercised (EX)--swimming for 1 h, 3 times/wk; EX + rhEPO. One rat of the EX + rhEPO group suffered a sudden death episode during the week 8. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertrophy, sympathetic and serotonergic overactivation. The suddenly died rat's tissues presented brain with vascular congestion; left ventricular hypertrophy, together with a "cardiac-liver", suggesting the hypothesis of heart failure as cause of sudden death. In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected RBC count increment, suggesting hyperviscosity, but also other serious deleterious cardiovascular and thromboembolic modifications, including mortality risk, which might be known and assumed by all sports authorities, including athletes and their physicians. PMID:19859831

  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. miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.

    PubMed

    Hu, Ruozhen; Kagele, Dominique A; Huffaker, Thomas B; Runtsch, Marah C; Alexander, Margaret; Liu, Jin; Bake, Erin; Su, Wei; Williams, Matthew A; Rao, Dinesh S; Möller, Thomas; Garden, Gwenn A; Round, June L; O'Connell, Ryan M

    2014-10-16

    Chronic inflammation is a contributing factor to most life-shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood, making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a(-/-) mice grew older. Upon analyzing lymphocytes from inflamed versus healthy middle-aged mice, we found elevated numbers of T follicular helper (Tfh) cells, germinal center (GC) B cells, and autoantibodies, all occurring in a miR-155-dependent manner. Further, Cd4-cre Mir155(fl/fl) mice were generated and demonstrated that miR-155 functions in T cells, in addition to its established role in B cells, to promote humoral immunity in a variety of contexts. Taken together, our study discovers that miR-146a and miR-155 counterregulate Tfh cell development that drives aberrant GC reactions during chronic inflammation. PMID:25367574

  10. 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. PMID:26233915

  11. Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury

    PubMed Central

    Peng, Jiyun; Gu, Nan; Zhou, Lijun; B Eyo, Ukpong; Murugan, Madhuvika; Gan, Wen-Biao; Wu, Long-Jun

    2016-01-01

    Microglia and peripheral monocytes contribute to hypersensitivity in rodent models of neuropathic pain. However, the precise respective function of microglia and peripheral monocytes has not been investigated in these models. To address this question, here we combined transgenic mice and pharmacological tools to specifically and temporally control the depletion of microglia and monocytes in a mouse model of spinal nerve transection (SNT). We found that although microglia and monocytes are required during the initiation of mechanical allodynia or thermal hyperalgesia, these cells may not be as important for the maintenance of hypersensitivity. Moreover, we demonstrated that either resident microglia or peripheral monocytes are sufficient in gating neuropathic pain after SNT. We propose that resident microglia and peripheral monocytes act synergistically to initiate hypersensitivity and promote the transition from acute to chronic pain after peripheral nerve injury. PMID:27349690

  12. 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

    2016-01-01

    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. PMID:27137489

  13. Low-grade chronic inflammation perpetuated by modern diet as a promoter of obesity and osteoporosis.

    PubMed

    Ilich, Jasminka Z; Kelly, Owen J; Kim, Youjin; Spicer, Maria T

    2014-06-01

    Some of the universal characteristics of pre-agricultural hominin diets are strikingly different from the modern human diet. Hominin dietary choices were limited to wild plant and wild animal foods, while the modern diet includes more than 70 % of energy consumed from refined sugars, refined vegetable oils, and highly processed cereals and dairy products. The modern diet, with higher intake of fat has also resulted in a higher ratio of omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acids (PUFA), contributing to low-grade chronic inflammation (LGCI) and thus promoting the development of many chronic diseases, including obesity and osteoporosis. In this review, we describe the changes in modern diet, focusing on the kind and amount of consumed fat; explain the shortcomings of the modern diet with regard to inflammatory processes; and delineate the reciprocity between adiposity and inflammatory processes, with inflammation being a common link between obesity and osteoporosis. We present the evidence that overconsumption of n-6 PUFA coupled with under-consumption of n-3 PUFA results in LGCI and, along with the increased presence of reactive oxygen species, leads to a shift in mesenchymal stem cells (precursors for both osteoblasts and adipocytes) lineage commitment toward increased adipogenesis and suppressed osteoblastogenesis. In turn, high n-6 to n-3 PUFA ratios in the modern diet, coupled with increased synthesis of pro-inflammatory cytokines due to adiposity, propagate obesity and osteoporosis by increasing or maintaining LGCI. PMID:24945416

  14. Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development.

    PubMed

    Pietrzyk, Lukasz; Torres, Anna; Maciejewski, Ryszard; Torres, Kamil

    2015-01-01

    Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression). PMID:26028066

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.

    PubMed

    Gruosso, Tina; Mieulet, Virginie; Cardon, Melissa; Bourachot, Brigitte; Kieffer, Yann; Devun, Flavien; Dubois, Thierry; Dutreix, Marie; Vincent-Salomon, Anne; Miller, Kyle Malcolm; Mechta-Grigoriou, Fatima

    2016-01-01

    Anti-cancer drugs often increase reactive oxygen species (ROS) and cause DNA damage. Here, we highlight a new cross talk between chronic oxidative stress and the histone variant H2AX, a key player in DNA repair. We observe that persistent accumulation of ROS, due to a deficient JunD-/Nrf2-antioxidant response, reduces H2AX protein levels. This effect is mediated by an enhanced interaction of H2AX with the E3 ubiquitin ligase RNF168, which is associated with H2AX poly-ubiquitination and promotes its degradation by the proteasome. ROS-mediated H2AX decrease plays a crucial role in chemosensitivity. Indeed, cycles of chemotherapy that sustainably increase ROS reduce H2AX protein levels in Triple-Negative breast cancer (TNBC) patients. H2AX decrease by such treatment is associated with an impaired NRF2-antioxidant response and is indicative of the therapeutic efficiency and survival of TNBC patients. Thus, our data describe a novel ROS-mediated regulation of H2AX turnover, which provides new insights into genetic instability and treatment efficacy in TNBC patients. PMID:27006338

  17. Point mutations in the promoter region of the CYBB gene leading to mild chronic granulomatous disease

    PubMed Central

    Weening, R S; De Boer, M; Kuijpers, T W; Neefjes, V M E; Hack, W W M; Roos, D

    2000-01-01

    Chronic granulomatous disease (CGD) is a clinical syndrome of recurrent bacterial and fungal infections caused by a rare disorder of phagocytic cells. In CGD, the phagocytes are unable to generate oxygen radicals after stimulation of these cells, due to a defect in the NADPH oxidase system. This NADPH oxidase is a multicomponent enzyme of at least four subunits, of which the β-subunit of cytochrome b558, gp91-phox, is encoded by an X-linked gene (called CYBB). We report here five patients from two families; in each family we found a different mutation in the promoter region of CYBB. Both mutations prevented the expression of gp91-phox in the patients' neutrophils and thus caused inability of these cells to generate oxygen radicals. However, the mutations left the gp91-phox expression and the function of the NADPH oxidase in the patients' eosinophils intact. The relatively mild course of the CGD in these patients can probably be attributed to the fact that the eosinophils have retained their oxidative capacity. Furthermore, our results indicate that neutrophils and eosinophils differ in their regulation of gp91-phox expression. PMID:11122248

  18. 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 ...

  19. 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. PMID:26563376

  20. 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

  1. Endothelin-1 Promotes Survival and Chemoresistance in Chronic Lymphocytic Leukemia B Cells through ETA Receptor

    PubMed Central

    Martinelli, Silvia; Castelli, Ilaria; Valenti, Vanessa; Rossi, Davide; Bonacorsi, Goretta; Zucchini, Patrizia; Potenza, Leonardo; Vallisa, Daniele; Gattei, Valter; Poeta, Giovanni Del; Forconi, Francesco; Gaidano, Gianluca; Narni, Franco; Luppi, Mario; Marasca, Roberto

    2014-01-01

    The endothelin axis, comprising endothelins (ET-1, ET-2 and ET-3) and their receptors (ETAR and ETBR), has emerged as relevant player in tumor growth and metastasis. Here, we investigated the involvement of ET-1/ETAR axis in chronic lymphocytic leukemia (CLL). CLL cells expressed higher levels of ET-1 and ETA receptor as compared to normal B cells. ET-1 peptide stimulated phosphoinositide-3-kinase and mitogen-activated protein kinase signaling pathways, improved survival and promoted proliferation of leukemic cells throughout ETAR triggering. Moreover, the blockade of ETAR by the selective antagonist BQ-123 inhibited the survival advantage acquired by CLL cells in contact with endothelial layers. We also found that blocking ETAR via BQ-123 interferes with ERK phosphorylation and CLL pro-survival effect mediated by B-cell receptor (BCR) activation. The pro-apoptotic effect of phosphoinositide-3-kinase δ inhibitor idelalisib and mitogen-activated protein kinase inhibitor PD98059 was decreased by the addition of ET-1 peptide. Then, ET-1 also reduced the cytotoxic effect of fludarabine on CLL cells cultured alone or co-cultured on endothelial layers. ETAR blockade by BQ-123 inhibited the ET-1-mediated protection against drug-induced apoptosis. Lastly, higher plasma levels of big ET-1 were detected in patients (n = 151) with unfavourable prognostic factors and shorter time to first treatment. In conclusion, our data describe for the first time a role of ET-1/ETAR signaling in CLL pathobiology. ET-1 mediates survival, drug-resistance, and growth signals in CLL cells that can be blocked by ETAR inhibition. PMID:24901342

  2. Promoting normal development and self-efficacy in school-age children managing chronic conditions.

    PubMed

    Mickley, Kristyn L; Burkhart, Patricia V; Sigler, April N

    2013-06-01

    Chronic conditions can affect school-age children in more ways than just physically. Normal childhood maturation is critical at this age, yet daily management of chronic symptoms can be challenging. This article describes 4 common childhood chronic illnesses (asthma, seizure disorders, diabetes, and cystic fibrosis), and the impact these conditions have on the developing child. Self-efficacy, the belief that one can effectively perform necessary skills, is essential to self-management of chronic conditions and contributes in a positive way to the child's normal development. Implications for clinical practice and future research are discussed. PMID:23659816

  3. Serum response factor promotes resilience to chronic social stress through the induction of ΔFosB

    PubMed Central

    Vialou, Vincent; Maze, Ian; Renthal, William; LaPlant, Quincey C.; Watts, Emily L.; Mouzon, Ezekiell; Ghose, Subroto; Tamminga, Carol A.; Nestler, Eric J.

    2010-01-01

    The molecular mechanisms underlying stress- and drug-induced neuronal adaptations are incompletely understood. One molecule implicated in such adaptations is ΔFosB, a transcription factor that accumulates in the rodent nucleus accumbens (NAc), a key brain reward region, in response to either chronic stress or repeated exposure to drugs of abuse. The upstream transcriptional mechanisms controlling ΔFosB induction by these environmental stimuli remain elusive. Here, we identify the activity-dependent transcription factor, serum response factor (SRF), as a novel upstream mediator of stress-, but not cocaine-, induced ΔFosB. SRF is downregulated in NAc of both human depressed patients and in mice chronically exposed to social defeat stress. This downregulation of SRF is absent in resilient animals. Through the use of inducible mutagenesis, we show that stress-mediated induction of ΔFosB, which occurs predominantly in resilient mice, is dependent on SRF expression in this brain region. Furthermore, NAc-specific genetic deletion of SRF promotes a variety of pro-depressant- and anxiety-like phenotypes and renders animals more sensitive to the deleterious effects of chronic stress. In contrast, we demonstrate that SRF does not play a role in ΔFosB accumulation in NAc in response to chronic cocaine exposure. Furthermore, NAc-specific knockout of SRF has no effect on cocaine-induced behaviors, indicating that chronic social defeat stress and repeated cocaine exposure regulate ΔFosB accumulation and behavioral sensitivity through independent mechanisms. PMID:20980616

  4. Transcranial near-infrared laser therapy applied to promote clinical recovery in acute and chronic neurodegenerative diseases

    PubMed Central

    Lapchak, Paul A

    2012-01-01

    One of the most promising methods to treat neurodegeneration is noninvasive transcranial near-infrared laser therapy (NILT), which appears to promote acute neuroprotection by stimulating mitochondrial function, thereby increasing cellular energy production. NILT may also promote chronic neuronal function restoration via trophic factor-mediated plasticity changes or possibly neurogenesis. Clearly, NILT is a treatment that confers neuroprotection or neurorestoration using pleiotropic mechanisms. The most advanced application of NILT is for acute ischemic stroke based upon extensive preclinical and clinical studies. In laboratory settings, NILT is also being developed to treat traumatic brain injury, Alzheimer’s disease and Parkinson’s disease. There is some intriguing data in the literature that suggests that NILT may be a method to promote clinical improvement in neurodegenerative diseases where there is a common mechanistic component, mitochondrial dysfunction and energy impairment. This article will analyze and review data supporting the continued development of NILT to treat neurodegenerative diseases. PMID:22145842

  5. Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection.

    PubMed

    Jiang, Xinguo; Khan, Mohammad A; Tian, Wen; Beilke, Joshua; Natarajan, Ramesh; Kosek, Jon; Yoder, Mervin C; Semenza, Gregg L; Nicolls, Mark R

    2011-06-01

    Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2⁺ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpression induced via an adenoviral vector prolonged airway microvascular perfusion, preserved epithelial integrity, extended the time window for the graft to be rescued from chronic rejection, and attenuated airway fibrotic remodeling. HIF-1α overexpression induced the expression of proangiogenic factors such as Sdf1, Plgf, and Vegf, and promoted the recruitment of vasoreparative Tie2⁺ cells. This study demonstrates that a therapy that enhances vascular integrity during acute rejection may promote graft health and prevent chronic rejection. PMID:21606594

  6. The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients

    PubMed Central

    Yalçın, Serap; Mutlu, Pelin; Çetin, Türker; Sarper, Meral; Özgür, Gökhan; Avcu, Ferit

    2015-01-01

    Objective: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients. Materials and Methods: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. Results: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML. Conclusions: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings. PMID:26376814

  7. 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

  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. PMID:25474842

  9. Interleukin-22 Promotes Proliferation of Liver Stem/Progenitor Cells in Mice and Patients with Chronic HBV Infection

    PubMed Central

    Feng, Dechun; Kong, Xiaoni; Weng, Honglei; Park, Ogyi; Wang, Hua; Dooley, Steven; Gershwin, M. Eric; Gao, Bin

    2012-01-01

    Background & Aims Proliferation of liver stem/progenitor cells (LPCs), which can differentiate into hepatocytes or biliary epithelial cells, is often observed in chronically inflamed regions of liver in patients. We investigated how inflammation might promote proliferation of LPCs. Methods We examined the role of interleukin (IL)-22, a survival factor for hepatocytes, on proliferation of LPCs in patients with chronic hepatitis B virus (HBV) infection and in mice. Proliferation of LPCs in mice was induced by feeding a diet that contained 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Results Hepatic expression of IL-22 was increased in patients with HBV and correlated with the grade of inflammation and proliferation of LPCs. Mice on the DDC diet that overexpressed an IL-22 transgene specifically in liver (IL-22TG), or that were infected with an IL-22–expressing adenovirus, had increased proliferation of LPCs. Signal transducer and activator of transcription (STAT) 3, a component of the IL-22 signaling pathway, was activated in LPCs isolated from DDC-fed IL-22TG mice. Deletion of STAT3 from livers of IL-22TG mice reduced proliferation of LPCs. Moreover, the receptors IL-22R1 and IL-10R2 were detected on EpCAM+CD45– LPCs isolated from DDC-fed wild-type mice. Culture of these cells with IL-22 activated STAT3 and led to cell proliferation, but IL-22 had no effect on proliferation of STAT3-deficient EpCAM+CD45– LPCs. IL-22 also activated STAT3 and promoted proliferation of cultured BMOL cells (a mouse LPC line). Conclusion In livers of mice and patients with chronic HBV infection, inflammatory cells produce IL-22, which promotes proliferation of LPCs via STAT3. These findings link inflammation with proliferation of LPCs in patients with HBV infection. PMID:22484119

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

    PubMed

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

    2014-11-01

    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. PMID:25386050

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

    PubMed Central

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

    2014-01-01

    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. PMID:25386050

  12. 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

  13. 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

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

    PubMed

    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

  15. Mast cells can promote the development of multiple features of chronic asthma in mice

    PubMed Central

    Yu, Mang; Tsai, Mindy; Tam, See-Ying; Jones, Carol; Zehnder, James; Galli, Stephen J.

    2006-01-01

    Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell–deficient (KitW-sh/W-sh and/or KitW/W-v) mice engrafted with FcRγ+/+ or FcRγ–/– mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcRγ and therefore could not be activated by either antigen- and IgE-dependent aggregation of FcεRI or the binding of antigen-IgG1 immune complexes to FcγRIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both FcRγ-dependent and FcRγ-independent pathways of mast cell activation as important for the expression of key features of this asthma model. PMID:16710480

  16. 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…

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

    PubMed

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

    2016-07-01

    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

  18. 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. PMID:22167808

  19. Immunomodulatory Device Promotes a Shift of Circulating Monocytes to a Less Inflammatory Phenotype in Chronic Hemodialysis Patients.

    PubMed

    Szamosfalvi, Balazs; Westover, Angela; Buffington, Deborah; Yevzlin, Alexander; Humes, H David

    2016-01-01

    Patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD) suffer accelerated morbidity and mortality rates caused by cardiovascular disease and infections. Chronic inflammation plays a critical role in these poor outcomes. The activated monocyte (MO) has become a prime therapeutic target to modulate this inflammatory process. A selective cytopheretic device (SCD) was evaluated to assess its effects on the circulating MO pool. A pilot trial was undertaken in 15 ESRD patients on HD with C-reactive protein (CRP) levels greater than 5 mg/dl. An excellent safety profile was observed with no decline in leukocyte (LE) or platelet counts. The effect of SCD therapy on MO phenotypes in these patients was determined on peripheral blood MO utilizing flow cytometry. SCD therapy promoted a shift in MO phenotype from predominantly CD14 expressing MO at baseline/pre-SCD therapy to CD14 expressing MO post-SCD therapy. A significant shift in MO population phenotype afforded by a single SCD therapy session was observed (p < 0.013). In a subset of patients (n = 7) presenting with type 2 diabetes mellitus (T2D), this persistent decline in MO CD14 expression was sustained as long as 2 weeks posttherapy. These results demonstrate that the SCD therapy has the potential to modulate the chronic proinflammatory state in ESRD patients. PMID:27258222

  20. [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. PMID:24519350

  1. 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. PMID:20623537

  2. 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

  3. 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. PMID:25323240

  4. Hepatitis B Virus Core Promoter Mutations in Patients With Chronic Hepatitis B and Hepatocellular Carcinoma in Bucharest, Romania

    PubMed Central

    Constantinescu, Ileana; Dinu, Andrei-Antoniu; Boscaiu, Voicu; Niculescu, Marius

    2014-01-01

    Background: Accurate and personalized molecular virological diagnosis of hepatitis B virus (HBV) infection is crucial for individualized selection of patients for antiviral therapy in Romania. Objectives: We aimed to investigate HBV mutations in Romanian patients with chronic HBV infection, also to match HBV genotypes with HBV mutations identified and clinical outcomes. Patients and Methods: This was a cross-sectional study. A total of 484 Romanian patients with chronic HBV infection and hepatocellular carcinoma (HCC) were investigated. This was performed in Fundeni Clinical Institute, Bucharest, Romania during January 2005 to August 2010. HBsAg positive patients with chronic HBV infection admitted to Fundeni Clinical Institute were randomly enrolled in the study. Analysis was performed in the Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania. Indirect diagnosis was performed with enhanced chemiluminescence method using Architect i2000SR and HBV-DNA was quantified with COBAS TaqMan HBV PCR. Direct sequencing of the PCR-products was performed with the PCR-product sequencing kit. HBV genotyping was performed with INNO-LiPA DR Amplification and INNO-LiPA HBV precore-core. Results: We detected two HBV genotypes; A (8.1%) and D (60.5%), and a mixture of genotypes A and D (31.4%) (P < 0.001). Basal core promoter (BCP) A1762T/G1764A and precore (PC) G1896A mutations were detected in these Romanian patients with chronic HBV infection. HBV chronic carriers had mainly genotype D (54.4%) and HBV WT (64.0%). BCP A1762T, G1764A and PC G1896A were significantly associated with HCC-tissue HBV sequencing (75.3%) (P < 0.001). PC G1896A alone was detected in HCC-serum HBV sequencing group (66.7%). Conclusions: Genotype D was the main genotype detected in Romanian patients with chronic HBV infection. Genotype D presented both BCP and PC mutations more frequently. PMID:25477976

  5. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice

    PubMed Central

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-01-01

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  9. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice.

    PubMed

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-05-11

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  10. Promoting the treatment of chronic wounds: experience from Initiative Chronische Wunden of Germany.

    PubMed

    Münter, Karl-Christian

    2016-01-01

    The German wound healing society ICW (Initiative Chronische Wunden) started a training program for nurses in 2005. Certified by TÜV Rheinland the courses are regularly audited and the quality is ensured. More than 30,000 nurses attended these courses in Germany. In three Chinese hospitals the ICW courses have been adopted. A close collaboration between Chinese and German experts in wound healing let to their further development and improvement. The article reviews the need for education in the treatment of chronic wounds for medical personnel-nurses and doctors. Experiences and perspectives are discussed. PMID:27602234

  11. 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

  12. Polymorphisms of the ELANE Gene Promoter Region in End-Stage Chronic Kidney Disease Patients

    PubMed Central

    Fernandes, Rafael; Freitas, Bruno; Miranda, Vasco; Costa, Elísio; Santos-Silva, Alice; Bronze-da-Rocha, Elsa

    2016-01-01

    End-stage renal disease (ESRD) patients have a high mortality rate that exceeds that of non-ESRD population. The hemodialysis procedure induces neutrophil activation and elastase release, which might have a role in the inflammatory process and in the development of oxidative stress. The ELANE gene encodes the neutrophil elastase. We analyzed the effect of ELANE promoter region polymorphisms and its relation with the circulating levels of elastase, as well as several clinical, biochemical and inflammatory markers in 123 ESRD patients. We found two duplications in heterozygosity in the promoter region and a new polymorphism, the c.-801G>A. ESRD patients heterozygous for the c.-903T>G polymorphism had no changes in the circulating levels of elastase or other evaluated variables, and those homozygous for the c.-741G>A polymorphism showed significant effects on neutrophils count, as well as in neutrophils/lymphocytes ratio, which might be associated with an increased inflammatory process. PMID:27136588

  13. The B cell mutator AID promotes B lymphoid blast crisis and drug-resistance in chronic myeloid leukemia

    PubMed Central

    Klemm, Lars; Duy, Cihangir; Iacobucci, Ilaria; Kuchen, Stefan; von Levetzow, Gregor; Feldhahn, Niklas; Henke, Nadine; Li, Zhiyu; Hoffmann, Thomas K.; Kim, Yong-mi; Hofmann, Wolf-Karsten; Jumaa, Hassan; Groffen, John; Heisterkamp, Nora; Martinelli, Giovanni; Lieber, Michael R; Casellas, Rafael; Müschen, Markus

    2009-01-01

    Summary Chronic myeloid leukemia (CML) is induced by BCR-ABL1 and can be effectively treated for many years with Imatinib until leukemia cells acquire drug resistance through BCR-ABL1 mutations and progress into fatal B lymphoid blast crisis (LBC). Despite its clinical significance, the mechanism of progression into LBC is unknown. Here we show that LBC but not CML cells express the B cell-specific mutator enzyme AID. We demonstrate that AID expression in CML cells promotes overall genetic instability by hypermutation of tumor suppressor and DNA repair genes. Importantly, our data uncover a causative role of AID activity in the acquisition of BCR-ABL1 mutations leading to Imatinib-resistance, thus providing a rationale for the rapid development of drug resistance and blast crisis progression. PMID:19732723

  14. 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

  15. FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-like Receptor Signaling

    PubMed Central

    Bhattacharyya, Swati; Tamaki, Zenshiro; Wang, Wenxia; Hinchcliff, Monique; Hoover, Paul; Getsios, Spiro; White, Eric S.; Varga, John

    2015-01-01

    Scleroderma is a progressive autoimmune disease affecting multiple organs. Fibrosis, the hallmark of scleroderma, represents transformation of self-limited wound healing into a deregulated self-sustaining process. The factors responsible for maintaining persistent fibroblast activation in scleroderma and other conditions with chronic fibrosis are not well understood. Toll-like receptor 4 (TLR4) and its damage-associated endogenous ligands are implicated in immune and fibrotic responses. We now show that fibronectin extra domain A (FnEDA) is an endogenous TLR4 ligand markedly elevated in the circulation and lesional skin biopsies from patients with scleroderma, as well as in mice with experimentally induced cutaneous fibrosis. Synthesis of FnEDA was preferentially stimulated by transforming growth factor–β in normal fibroblasts and was constitutively up-regulated in scleroderma fibroblasts. Exogenous FnEDA was a potent stimulus for collagen production, myofibroblast differentiation, and wound healing in vitro and increased the mechanical stiffness of human organotypic skin equivalents. Each of these profibrotic FnEDA responses was abrogated by genetic, RNA interference, or pharmacological disruption of TLR4 signaling. Moreover, either genetic loss of FnEDA or TLR4 blockade using a small molecule mitigated experimentally induced cutaneous fibrosis in mice. These observations implicate the FnEDA-TLR4 axis in cutaneous fibrosis and suggest a paradigm in which aberrant FnEDA accumulation in the fibrotic milieu drives sustained fibroblast activation via TLR4. This model explains how a damage-associated endogenous TLR4 ligand might contribute to converting self-limited tissue repair responses into intractable fibrogenesis in chronic conditions such as scleroderma. Disrupting sustained TLR4 signaling therefore represents a potential strategy for the treatment of fibrosis in scleroderma. PMID:24739758

  16. 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. PMID:25224310

  17. Promoter hypomethylation and expression is conserved in mouse chronic lymphocytic leukemia induced by decreased or inactivated Dnmt3a

    PubMed Central

    Haney, Staci L.; Upchurch, G. Michael; Opavska, Jana; Klinkebiel, David; Hlady, Ryan A.; Suresh, Abhinav; Pirruccello, Samuel J.; Shukla, Vipul; Lu, Runqing; Costinean, Stefan; Rizzino, Angie; Karpf, Adam R.; Joshi, Shantaram; Swanson, Patrick; Opavsky, Rene

    2016-01-01

    SUMMARY DNA methyltransferase 3a (DNMT3A) catalyzes the formation of 5-methyl-cytosine in mammalian genomic DNA and it is frequently mutated in human hematologic malignancies. Bi-allelic loss of Dnmt3a in mice results in leukemia and lymphoma, including chronic lymphocytic leukemia (CLL). Here we investigate whether mono-allelic loss of Dnmt3a is sufficient to induce disease. We show that by 16 months of age, 65% of Dnmt3a+/− mice develop a CLL-like disease and 15% of mice develop non-malignant myeloproliferation. Genome-wide methylation analysis reveals that reduced Dnmt3a levels induce promoter hypomethylation at similar loci in Dnmt3a+/− and Dnmt3aΔ/Δ CLL, suggesting that promoters are particularly sensitive to Dnmt3a levels. Gene-expression analysis identified 26 hypomethylated and over-expressed genes common to both Dnmt3a+/− and Dnmt3aΔ/Δ CLL as putative oncogenic drivers. Our data provide evidence that Dnmt3a is a haplo-insufficient tumor suppressor in CLL and highlights the importance of deregulated molecular events in disease pathogenesis. PMID:27134162

  18. Promoter Hypomethylation and Expression Is Conserved in Mouse Chronic Lymphocytic Leukemia Induced by Decreased or Inactivated Dnmt3a.

    PubMed

    Haney, Staci L; Upchurch, G Michael; Opavska, Jana; Klinkebiel, David; Hlady, Ryan A; Suresh, Abhinav; Pirruccello, Samuel J; Shukla, Vipul; Lu, Runqing; Costinean, Stefan; Rizzino, Angie; Karpf, Adam R; Joshi, Shantaram; Swanson, Patrick; Opavsky, Rene

    2016-05-10

    DNA methyltransferase 3a (DNMT3A) catalyzes the formation of 5-methyl-cytosine in mammalian genomic DNA, and it is frequently mutated in human hematologic malignancies. Bi-allelic loss of Dnmt3a in mice results in leukemia and lymphoma, including chronic lymphocytic leukemia (CLL). Here, we investigate whether mono-allelic loss of Dnmt3a is sufficient to induce disease. We show that, by 16 months of age, 65% of Dnmt3a(+/-) mice develop a CLL-like disease, and 15% of mice develop non-malignant myeloproliferation. Genome-wide methylation analysis reveals that reduced Dnmt3a levels induce promoter hypomethylation at similar loci in Dnmt3a(+/-) and Dnmt3a(Δ/Δ) CLL, suggesting that promoters are particularly sensitive to Dnmt3a levels. Gene expression analysis identified 26 hypomethylated and overexpressed genes common to both Dnmt3a(+/-) and Dnmt3a(Δ/Δ) CLL as putative oncogenic drivers. Our data provide evidence that Dnmt3a is a haplo-insufficient tumor suppressor in CLL and highlights the importance of deregulated molecular events in disease pathogenesis. PMID:27134162

  19. ENDURANCE EXERCISE PROMOTES CARDIORESPIRATORY REHABILITATION WITHOUT NEURORESTORATION IN THE CHRONIC MOUSE MODEL OF PARKINSONISM WITH SEVERE NEURODEGENERATION

    PubMed Central

    Al-Jarrah, Muhammed; Pothakos, Konstantinos; Novikova, Lesya; Smirnova, Irina V.; Kurz, Max J.; Stehno-Bittel, Lisa; Lau, Yuen-Sum

    2007-01-01

    release-dependent locomotor activity was markedly inhibited in the sedentary Parkinsonian mice, and remained to be 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. PMID:17869432

  20. Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine in rats

    PubMed Central

    Zack, Martin; Featherstone, Robert E.; Mathewson, Sarah; Fletcher, Paul J.

    2014-01-01

    Addiction is considered to be a brain disease caused by chronic exposure to drugs. Sensitization of brain dopamine (DA) systems partly mediates this effect. Pathological gambling (PG) is considered to be a behavioral addiction. Therefore, PG may be caused by chronic exposure to gambling. Identifying a gambling-induced sensitization of DA systems would support this possibility. Gambling rewards evoke DA release. One episode of slot machine play shifts the DA response from reward delivery to onset of cues (spinning reels) for reward, in line with temporal difference learning principles. Thus, conditioned stimuli (CS) play a key role in DA responses to gambling. In primates, DA response to a CS is strongest when reward probability is 50%. Under this schedule the CS elicits an expectancy of reward but provides no information about whether it will occur on a given trial. During gambling, a 50% schedule should elicit maximal DA release. This closely matches reward frequency (46%) on a commercial slot machine. DA release can contribute to sensitization, especially for amphetamine. Chronic exposure to a CS that predicts reward 50% of the time could mimic this effect. We tested this hypothesis in three studies with rats. Animals received 15 × 45-min exposures to a CS that predicted reward with a probability of 0, 25, 50, 75, or 100%. The CS was a light; the reward was a 10% sucrose solution. After training, rats received a sensitizing regimen of five separate doses (1 mg/kg) of d-amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to a 90-min locomotor activity test. In all three studies the 50% group displayed greater activity than the other groups in response to both challenge doses. Effect sizes were modest but consistent, as reflected by a significant group × rank association (ϕ = 0.986, p = 0.025). Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine much like exposure to

  1. Insufficient autophagy promotes bronchial epithelial cell senescence in chronic obstructive pulmonary disease.

    PubMed

    Fujii, Satoko; Hara, Hiromichi; Araya, Jun; Takasaka, Naoki; Kojima, Jun; Ito, Saburo; Minagawa, Shunsuke; Yumino, Yoko; Ishikawa, Takeo; Numata, Takanori; Kawaishi, Makoto; Hirano, Jun; Odaka, Makoto; Morikawa, Toshiaki; Nishimura, Stephen; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

    2012-08-01

    Tobacco smoke-induced accelerated cell senescence has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cell senescence is accompanied by the accumulation of damaged cellular components suggesting that in COPD, inhibition of autophagy may contribute to cell senescence. Here we look at whether autophagy contributes to cigarette smoke extract (CSE) - induced cell senescence of primary human bronchial epithelial cells (HBEC), and further evaluate p62 and ubiquitinated protein levels in lung homogenates from COPD patients. We demonstrate that CSE transiently induces activation of autophagy in HBEC, followed by accelerated cell senescence and concomitant accumulation of p62 and ubiquitinated proteins. Autophagy inhibition further enhanced accumulations of p62 and ubiquitinated proteins, resulting in increased senescence and senescence-associated secretory phenotype (SASP) with interleukin (IL)-8 secretion. Conversely, autophagy activation by Torin1, a mammalian target of rapamycin (mTOR inhibitor), suppressed accumulations of p62 and ubiquitinated proteins and inhibits cell senescence. Despite increased baseline activity, autophagy induction in response to CSE was significantly decreased in HBEC from COPD patients. Increased accumulations of p62 and ubiquitinated proteins were detected in lung homogenates from COPD patients. Insufficient autophagic clearance of damaged proteins, including ubiquitinated proteins, is involved in accelerated cell senescence in COPD, suggesting a novel protective role for autophagy in the tobacco smoke-induced senescence-associated lung disease, COPD. PMID:22934255

  2. Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia.

    PubMed

    Jia, Li; Clear, Andrew; Liu, Feng-Ting; Matthews, Janet; Uddin, Nadiha; McCarthy, Aine; Hoxha, Elena; Durance, Catherine; Iqbal, Sameena; Gribben, John G

    2014-03-13

    Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B cells that are highly dependent on the microenvironment for maintenance and expansion. However, little is known regarding the mechanisms whereby CLL cells create their favorable microenvironment for survival. High-mobility group protein B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted by innate immune cells and passively released by injured or dying cells. We found significantly increased HMGB1 levels in the plasma of CLL patients compared with healthy controls, and HMGB1 concentration is associated with absolute lymphocyte count. We therefore sought to determine potential roles of HMGB1 in modulating the CLL microenvironment. CLL cells passively released HMGB1, and the timing and concentrations of HMGB1 in the medium were associated with differentiation of nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the markers for NLCs, was associated with shorter overall survival of CLL patients. HMGB1-mediated NLC differentiation involved internalization of both receptor for advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9). Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway. In conclusion, this study demonstrates for the first time that CLL cells might modulate their microenvironment by releasing HMGB1. PMID:24464016

  3. 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.

  4. 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. PMID:26162424

  5. Muscle RING Finger-1 Promotes a Maladaptive Phenotype in Chronic Hypoxia-Induced Right Ventricular Remodeling

    PubMed Central

    Campen, Matthew J.; Paffett, Michael L.; Colombo, E. Sage; Lucas, Selita N.; Anderson, Tamara; Nysus, Monique; Norenberg, Jeffrey P.; Gershman, Ben; Hesterman, Jacob; Hoppin, Jack; Willis, Monte

    2014-01-01

    Exposure to chronic hypoxia (CH) induces elevated pulmonary artery pressure/resistance, leading to an eventual maladaptive right ventricular hypertrophy (RVH). Muscle RING finger-1 (MuRF1) is a muscle-specific ubiquitin ligase that mediates myocyte atrophy and has been shown to play a role in left ventricular hypertrophy and altered cardiac bioenergetics in pressure overloaded hearts. However, little is known about the contribution of MuRF1 impacting RVH in the setting of CH. Therefore, we hypothesized that MuRF1 deletion would enhance RVH compared to their wild-type littermates, while cardiac-specific overexpression would reduce hypertrophy following CH-induced pulmonary hypertension. We assessed right ventricular systolic pressure (RVSP), right ventricle to left ventricle plus septal weight ratio (RV/LV+S) and hematocrit (Hct) following a 3-wk isobaric CH exposure. Additionally, we conducted dual-isotope SPECT/CT imaging with cardiac function agent 201Tl-chloride and cell death agent 99mTc-annexin V. Predictably, CH induced pulmonary hypertension, measured by increased RVSP, RV/LV+S and Hct in WT mice compared to normoxic WT mice. Normoxic WT and MuRF1-null mice exhibited no significant differences in RVSP, RV/LV+S or Hct. CH-induced increases in RVSP were also similar between WT and MuRF1-null mice; however, RV/LV+S and Hct were significantly elevated in CH-exposed MuRF1-null mice compared to WT. In cardiac-specific MuRF1 overexpressing mice, RV/LV+S increased significantly due to CH exposure, even greater than in WT mice. This remodeling appeared eccentric, maladaptive and led to reduced systemic perfusion. In conclusion, these results are consistent with an atrophic role for MuRF1 regulating the magnitude of right ventricular hypertrophy following CH-induction of pulmonary hypertension. PMID:24811453

  6. Muscle RING finger-1 promotes a maladaptive phenotype in chronic hypoxia-induced right ventricular remodeling.

    PubMed

    Campen, Matthew J; Paffett, Michael L; Colombo, E Sage; Lucas, Selita N; Anderson, Tamara; Nysus, Monique; Norenberg, Jeffrey P; Gershman, Ben; Hesterman, Jacob; Hoppin, Jack; Willis, Monte

    2014-01-01

    Exposure to chronic hypoxia (CH) induces elevated pulmonary artery pressure/resistance, leading to an eventual maladaptive right ventricular hypertrophy (RVH). Muscle RING finger-1 (MuRF1) is a muscle-specific ubiquitin ligase that mediates myocyte atrophy and has been shown to play a role in left ventricular hypertrophy and altered cardiac bioenergetics in pressure overloaded hearts. However, little is known about the contribution of MuRF1 impacting RVH in the setting of CH. Therefore, we hypothesized that MuRF1 deletion would enhance RVH compared to their wild-type littermates, while cardiac-specific overexpression would reduce hypertrophy following CH-induced pulmonary hypertension. We assessed right ventricular systolic pressure (RVSP), right ventricle to left ventricle plus septal weight ratio (RV/LV+S) and hematocrit (Hct) following a 3-wk isobaric CH exposure. Additionally, we conducted dual-isotope SPECT/CT imaging with cardiac function agent 201Tl-chloride and cell death agent 99mTc-annexin V. Predictably, CH induced pulmonary hypertension, measured by increased RVSP, RV/LV+S and Hct in WT mice compared to normoxic WT mice. Normoxic WT and MuRF1-null mice exhibited no significant differences in RVSP, RV/LV+S or Hct. CH-induced increases in RVSP were also similar between WT and MuRF1-null mice; however, RV/LV+S and Hct were significantly elevated in CH-exposed MuRF1-null mice compared to WT. In cardiac-specific MuRF1 overexpressing mice, RV/LV+S increased significantly due to CH exposure, even greater than in WT mice. This remodeling appeared eccentric, maladaptive and led to reduced systemic perfusion. In conclusion, these results are consistent with an atrophic role for MuRF1 regulating the magnitude of right ventricular hypertrophy following CH-induction of pulmonary hypertension. PMID:24811453

  7. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3

    PubMed Central

    Croker, Ben A; Kiu, Hiu; Pellegrini, Marc; Toe, Jesse; Preston, Simon; Metcalf, Donald; O’Donnell, Joanne A; Cengia, Louise H; McArthur, Kate; Nicola, Nicos A; Alexander, Warren S; Roberts, Andrew W

    2011-01-01

    The lack of expression of the Suppressor of Cytokine Signalling-3 (SOCS3) or inactivation of the negative regulatory capacity of SOCS3 has been well documented in rheumatoid arthritis, viral hepatitis and cancer. The specific qualitative and quantitative consequences of SOCS3-deficiency on IL-6-mediated pro- and anti-inflammatory responses remain controversial in vitro and unknown in vivo. Mice with a conditional deletion of SOCS3 in hematopoietic cells develop lethal inflammatory disease during adult life and develop gross histopathological changes during experimental arthritis, typified by elevated IL-6 levels. To clarify the nature of the IL-6 responses in vivo, we generated mice deficient in SOCS3 (SOCS3−/Δvav) or both SOCS3 and IL-6 (IL-6−/−/SOCS3−/Δ vav) and examined responses in models of acute and chronic inflammation. Acute responses to IL-1β were lethal to SOCS3−/Δ vav mice but not IL-6−/−/SOCS3−/Δ vav mice, indicating that IL-6 was required for the lethal inflammation induced by IL-1β. Administration of IL-1β to SOCS3−/Δ vav mice induced systemic apoptosis of lymphocytes in the thymus, spleen and lymph nodes that was dependent on the presence of IL-6. IL-6-deficiency prolonged survival of SOCS3−/Δ vav mice and ameliorated spontaneous inflammatory disease developing during adult life. Infection of SOCS3−/Δ vav mice with LCMV induced a lethal inflammatory response that was dependent on IL-6, despite SOCS3−/Δ vav mice controlling viral replication. We conclude that SOCS3 is required for survival during inflammatory responses and is a critical regulator of IL-6 in vivo. PMID:21519345

  8. 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…

  9. Promotion of Lung Health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

    PubMed Central

    Budinger, G. R. Scott; Escobar, Gabriel J.; Hansel, Nadia N.; Hanson, Corrine K.; Huffnagle, Gary B.; Buist, A. Sonia

    2014-01-01

    Lung-related research primarily focuses on the etiology and management of diseases. In recent years, interest in primary prevention has grown. However, primary prevention also includes “health promotion” (actions in a population that keep an individual healthy). We encourage more research on population-based (public health) strategies that could not only maximize lung health but also mitigate “normal” age-related declines—not only for spirometry but across multiple measures of lung health. In developing a successful strategy, a “life course” approach is important. Unfortunately, we are unable to achieve the full benefit of this approach until we have better measures of lung health and an improved understanding of the normal trajectory, both over an individual’s life span and possibly across generations. We discuss key questions in lung health promotion, with an emphasis on the upper (healthier) end of the distribution of lung functioning and resiliency and briefly summarize the few interventions that have been studied to date. We conclude with suggestions regarding the most promising future research for this important, but largely neglected, area of lung research. PMID:24754821

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. CCR2 Deficiency Promotes Exacerbated Chronic Erosive Neutrophil-Dominated Chikungunya Virus Arthritis

    PubMed Central

    Poo, Yee Suan; Nakaya, Helder; Gardner, Joy; Larcher, Thibaut; Schroder, Wayne A.; Le, Thuy T.; Major, Lee D.

    2014-01-01

    monocyte/macrophage-dominated inflammatory arthritic infiltrates seen after infection with arthritogenic alphaviruses such as chikungunya virus. Surprisingly, the viral arthritis caused by chikungunya virus in CCR2-deficient mice was more severe, prolonged, and erosive and was neutrophil dominated, with viral replication and persistence not being significantly affected. Monocytes/macrophages recruited by CCL2 thus also appear to be important for both preventing even worse pathology mediated by neutrophils and promoting resolution of inflammation. Caution might thus be warranted when considering the use of therapeutic agents that target CCR2/CCL2 or inflammatory monocytes/macrophages for the treatment of alphaviral (and perhaps other viral) arthritides. Individuals with diminished CCR2 responses (due to drug treatment or other reasons) may also be at risk of exacerbated arthritic disease following alphaviral infection. PMID:24696480

  16. 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. PMID:19378625

  17. 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

  18. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord.

    PubMed

    Karimi-Abdolrezaee, Soheila; Eftekharpour, Eftekhar; Wang, Jian; Schut, Desiree; Fehlings, Michael G

    2010-02-01

    The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for spinal cord injury (SCI). However, to date NPC transplantation has exhibited only limited success in the treatment of chronic SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial scar around the site of chronic SCI negatively influence the long-term survival and integration of transplanted NPCs and their therapeutic potential for promoting functional repair and plasticity. We targeted CSPGs in the chronically injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week later, the same rats were treated with transplants of NPCs and transient infusion of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs successfully integrate and extensively migrate within the host spinal cord and principally differentiate into oligodendrocytes. Furthermore, this combined strategy promoted the axonal integrity and plasticity of the corticospinal tract and enhanced the plasticity of descending serotonergic pathways. These neuroanatomical changes were also associated with significantly improved neurobehavioral recovery after chronic SCI. Importantly, this strategy did not enhance the aberrant synaptic connectivity of pain afferents, nor did it exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key biological and functional benefits for the combined use of ChABC, growth factors, and NPCs to repair the chronically injured spinal cord. These findings could potentially bring us closer to the application of NPCs for patients suffering from chronic SCI or other conditions characterized by the formation of a glial scar. PMID:20130176

  19. 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

  20. 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

  1. 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

  2. β-Arrestin1 promotes the progression of chronic myeloid leukaemia by regulating BCR/ABL H4 acetylation

    PubMed Central

    Qin, R; Li, K; Qi, X; Zhou, X; Wang, L; Zhang, P; Zou, L

    2014-01-01

    Background: β-Arrestins are scaffold proteins that interact with various cellular signals. Although β-arrestin2 mediates the initiation and progression of myeloid leukaemia, the critical role of β-arrestin1 in the chronic myeloid leukaemia (CML) is still unknown. The aim of this study is to investigate the essential function of β-arrestin1 in CML. Methods: The expressions of β-arrestin1 and BCR/ABL in CML patients, animal models and K562 cells were measured by RT–PCR, immunofluorescence and western blotting. The effect of β-arrestin1 on CML animal models and K562 cells by colony formation, MTT and survival analysis were assessed. BCR/ABL H4 acetylation was analysed through the use of Chromatin-immunoprecipitation (ChIP) -on-chip and confirmed by ChIP respectively. Co-immunoprecipitation and confocal were examined for the binding of β-arrestin1 with enhancer of zeste homologue 2 (EZH2). Results: The higher expression of β-arrestin1 is positively correlated with clinical phases of CML patients. Depletion of β-arrestin1 decelerates progression of K562 and primary cells, and increases survival of CML mice. Importantly, silenced β-arrestin1 results in the decrease of BCR/ABL H4 acetylation level in K562 cells. Further data illustrate that nuclear β-arrestin1 binds to EZH2 to mediate BCR/ABL acetylation and thus regulates cell progression in K562 cells and the survival of CML mice. Conclusions: Our findings reveal a novel function of β-arrestin1 binding to EZH2 to promote CML progression by regulating BCR/ABL H4 acetylation. PMID:24937675

  3. 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

  4. 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

  5. Immune-enhancing diet and cytokine expression during chronic sepsis: an immune-enhancing diet containing L-arginine, fish oil, and RNA fragments promotes intestinal cytokine expression during chronic sepsis in rats.

    PubMed

    Hurt, Ryan T; Matheson, Paul J; Mays, Michael P; Garrison, R Neal

    2006-01-01

    Chronic feeding with enteral immune-enhancing diets (IEDs) provides benefits based on composition of the diet, route of feeding, and timing of feeding in relation to timing of trauma or surgery. Our prior studies of acute feeding in naïve rats demonstrated that IED promotes blood flow and proinflammatory cytokines in the ileum. We hypothesized that chronic feeding with IED would shift gut immune status to an anti-inflammatory state during chronic sepsis, resulting in an altered state of cytokine expression in the gut. Five days prior to feeding, gauze was implanted subcutaneously in the backs of male Sprague-Dawley rats, which were fed for 3 days with either control diet (CD, Boost; Mead-Johnson, Evansville, IL) or IED (Impact; Novartis) and randomly assigned to one of four groups: saline control (NS) + control diet (CD), sepsis (EC) + CD, NS + IED, or EC + IED. EC rats were inoculated with 10(9) CFU Escherichia coli and 10(9) CFU Bacteroides fragilis in 2 ml normal saline into the back sponge while NS rats received 2 mL normal saline alone. After 3 days, animals were anesthetized and gut tissue samples were harvested and frozen at -80 degrees C. Tissue protein was extracted and ELISA was performed for interleukin (IL-1beta, IL-5, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. In saline controls, IED feeding decreased IL-1beta, IL-5, IL-6, TNF-alpha, and IFN-gamma and increased IL-10 compared with CD-fed animals. In septic animals, IED feeding increased IL-5 and IL-6, while decreasing IFN-gamma and IL-10 in the distal third of the small intestine compared with CD-fed septic rats, whereas IL-1beta and TNF-alpha levels were unchanged. Chronic IED feeding produced a anti-inflammatory state via decreased IFN-gamma and increased IL-5 and IL-6, which both promote gut IgA class switching, suggesting that the gut is shifted toward humoral immunity during chronic IED feeding in septic rats. PMID:16368490

  6. 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

  7. Neutrophils confer T cell resistance to myeloid-derived suppressor cell-mediated suppression to promote chronic inflammation.

    PubMed

    Ryan, Sean O; Johnson, Jenny L; Cobb, Brian A

    2013-05-15

    Low-grade chronic inflammation can persist in aging humans unnoticed for years or even decades, inflicting continuous damage that can culminate later in life as organ dysfunction, physical frailty, and some of the most prominent debilitating and deadly age-associated diseases, including rheumatoid arthritis, diabetes, heart disease, and cancer. Despite the near universal acceptance of these associations, the mechanisms underlying unresolved inflammation remain poorly understood. In this study, we describe a novel inducible method to examine systemic chronic inflammation using susceptible animal models. Induced inflammation results in unresolved innate cellular responses and persistence of the same serum proinflammatory molecules used as diagnostic biomarkers and therapeutic targets for chronic inflammation in humans. Surprisingly, we found long-term persistence of an inflammation-associated neutrophil cell population constitutively producing the proinflammatory IFN-γ cytokine, which until now has only been detected transiently in acute inflammatory responses. Interestingly, these cells appear to confer T cell resistance to the otherwise potent anti-inflammatory function of myeloid-derived suppressor cells, revealing a novel mechanism for the maintenance of chronic inflammatory responses over time. This discovery represents an attractive target to resolve inflammation and prevent the inflammation-induced pathologies that are of critical concern for the well-being of the aging population. PMID:23576679

  8. 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. PMID:25673578

  9. 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. PMID:25591610

  10. Eosinophils Reduce Chronic Inflammation in Adipose Tissue by Secreting Th2 Cytokines and Promoting M2 Macrophages Polarization

    PubMed Central

    Zhang, Yi; Yang, Peng; Cui, Ran; Zhang, Manna; Li, Hong; Qian, Chunhua; Sheng, Chunjun; Qu, Shen; Bu, Le

    2015-01-01

    Obesity is now recognized as a low-grade, chronic inflammatory disease that is linked to a myriad of disorders including cardiovascular diseases, type 2 diabetes, and liver diseases. Recently it is found that eosinophils accelerate alternative activation macrophage (AAM) polarization by secreting Th2 type cytokines such as interleukin-4 and interleukin-13, thereby reducing metainflammation in adipose tissue. In this review, we focused on the role of eosinophils in regulating metabolic homeostasis and obesity. PMID:26688684

  11. 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

  12. Task-related training combined with transcutaneous electrical nerve stimulation promotes upper limb functions in patients with chronic stroke.

    PubMed

    Kim, Tae Hoon; In, Tae Sung; Cho, Hwi-young

    2013-01-01

    Severe upper limb paresis is a major contributor to disability after stroke. This study investigated the efficacy of task-related training (TRT) with transcutaneous electrical nerve stimulation (TENS) on recovery of upper limb motor function in chronic-stroke survivors. Thirty patients with chronic stroke were randomly allocated two groups: the TRT+TENS group (n = 15) and the TRT+placebo (TRT+PLBO) group (n = 15). Patients in the TRT+TENS group received TENS stimulation (two to three times the sensory threshold), while subjects in the TRT+PLBO group received TENS without real electrical stimulation. TENS was applied to muscle belly of triceps and wrist extensors, while placebo (PLBO) stimulation was administrated without real electrical stimulation. Both interventions were given for 30 minutes per day, 5 days per week, for a period of 4 weeks. The primary outcomes were assessed with Fugl-Meyer assessment scores (FMA), Manual function test (MFT), Box and block test (BBT), and Modified Ashworth scale (MAS), each of which was performed one day before and one day after intervention. Both groups showed significant improvements in FMA, MFT, and BBT after intervention. When compared with the TRT+PLBO group, the TRT+TENS group showed significantly greater improvements in FMA (p = 0.034), MFT (p = 0.037), and BBT (p = 0.042). In MAS score, significant improvement was observed only in the TRT+TENS group (p = 0.011). Our findings indicate that TRT with TENS can reduce motor impairment and improve motor activity in stroke survivors with chronic upper limb paresis, highlighting the benefits of somatosensory stimulation from TENS. PMID:24097280

  13. Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors.

    PubMed

    Lemos, Dario R; Babaeijandaghi, Farshad; Low, Marcela; Chang, Chih-Kai; Lee, Sunny T; Fiore, Daniela; Zhang, Regan-Heng; Natarajan, Anuradha; Nedospasov, Sergei A; Rossi, Fabio M V

    2015-07-01

    Depending on the inflammatory milieu, injury can result either in a tissue's complete regeneration or in its degeneration and fibrosis, the latter of which could potentially lead to permanent organ failure. Yet how inflammatory cells regulate matrix-producing cells involved in the reparative process is unknown. Here we show that in acutely damaged skeletal muscle, sequential interactions between multipotent mesenchymal progenitors and infiltrating inflammatory cells determine the outcome of the reparative process. We found that infiltrating inflammatory macrophages, through their expression of tumor necrosis factor (TNF), directly induce apoptosis of fibro/adipogenic progenitors (FAPs). In states of chronic damage, however, such as those in mdx mice, macrophages express high levels of transforming growth factor β1 (TGF-β1), which prevents the apoptosis of FAPs and induces their differentiation into matrix-producing cells. Treatment with nilotinib, a kinase inhibitor with proposed anti-fibrotic activity, can block the effect of TGF-β1 and reduce muscle fibrosis in mdx mice. Our findings reveal an unexpected anti-fibrotic role of TNF and suggest that disruption of the precisely timed progression from a TNF-rich to a TGF-β-rich environment favors fibrotic degeneration of the muscle during chronic injury. PMID:26053624

  14. 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. PMID:27270564

  15. 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

  16. 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. PMID:25868067

  17. 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. PMID:27150465

  18. Chronic Morphine-Induced MicroRNA-124 Promotes Microglial Immunosuppression by Modulating P65 and TRAF6

    PubMed Central

    Qiu, Shuwei; Feng, Yimin; LeSage, Gene; Zhang, Ying; Stuart, Charles; He, Lei; Li, Yi; Caudle, Yi; Peng, Ying; Yin, Deling

    2014-01-01

    Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. Toll-like receptors (TLRs) and acetylcholine (ACh) are widely expressed in the immune and nervous systems and play critical roles in immune responses. Here we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages (BMM) through differential regulation of TLRs and acetylcholinesterase (AChE). Either morphine or inhibition of ACh significantly promoted up-regulation of microRNA-124 (miR-124) in microglia, BMM, and in the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-κB p65 and TNF receptor-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, while p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently up-regulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia. PMID:25539811

  19. IL17 Functions through the Novel REG3β-JAK2-STAT3 Inflammatory Pathway to Promote the Transition from Chronic Pancreatitis to Pancreatic Cancer.

    PubMed

    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

    2015-11-15

    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 IL17 pathway mediates this phenomenon and can be targeted with antibodies, but the downstream mechanisms by which IL17 functions during this transition are currently unclear. In this study, we demonstrate that IL17 induces the expression of REG3β, a well-known mediator of pancreatitis, during acinar-to-ductal metaplasia and in early pancreatic intraepithelial neoplasia (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 pathophysiologic role for REG3β during pancreatitis and PDAC initiation. PMID:26404002

  20. 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. PMID:26104856

  1. 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

  2. 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. PMID:26242598

  3. Adapted Physical Activity for the Promotion of Health and the Prevention of Multifactorial Chronic Diseases: the Erice Charter.

    PubMed

    Romano-Spica, Vincenzo; Macini, Pierluigi; Fara, Gaetano Maria; Giammanco, Giuseppe

    2015-01-01

    The Erice Charter was unanimously approved at the conclusion of the 47th Residential Course "Adapted Physical Activity in Sport, Wellness and Fitness: New Challenges for Prevention and Health Promotion", held on 20-24 April 2015 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health. After an intense discussion the participants identified the main points associated with the relevance of physical activity for Public Health, claiming the pivotal role of the Department of Prevention in coordinating and managing preventive actions. The participants underlined the importance of the physicians specialized in Hygiene, Preventive Medicine and Public Health. The contribution of other operators such as physicians specialized in Sport Medicine was stressed. Further, the holders of the new degree in Human Movement and Sport Sciences were considered fundamental contributors for the performance of physical activity and their presence was seen as a promising opportunity for the Departments of Prevention. Primary prevention based on recreational physical activities should become easily accessible for the population, avoiding obstacles such as certification steps or complex bureaucracy. The Sport Doctor is recognized as the principal referent for preliminary physical evaluation and clinical monitoring in secondary and tertiary prevention actions based on adapted physical activities. Developing research in the field is essential as well as implementing higher education on physical activity management in Schools of Public Health. PMID:26051140

  4. 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

  5. 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. PMID:25724866

  6. Deletion of Intestinal Epithelial Cell STAT3 Promotes T Lymphocyte STAT3 Activation and Chronic Colitis Following Acute Dextran Sodium Sulfate Injury in Mice

    PubMed Central

    Willson, Tara A.; Jurickova, Ingrid; Collins, Margaret; Denson, Lee A.

    2015-01-01

    BACKGROUND Intestinal epithelial cell (IEC) Stat3 is required for wound healing following acute Dextran Sodium Sulfate (DSS) injury. We hypothesized that loss of IEC STAT3 would promote the development of chronic colitis following acute DSS injury. METHODS Colitis was induced in IEC-specific Stat3 deficient mice (Stat3ΔIEC) and littermate controls (Stat3Flx/Flx) with 4%DSS for 7 days, followed by water consumption for 21 days. Epithelial and immune mediators and severity of colitis were determined. RESULTS Survival, colon length, and histologic injury were significantly worse at day 28 in Stat3ΔIEC mice. IEC proliferation and apoptosis did not vary by genotype at day 14 or day 28. The colonic lamina propria frequency of pSTAT3+ cells was increased at day 28 and correlated with histologic injury in Stat3ΔIEC mice. The frequency of colonic F480+pSTAT3+ macrophages and CD3+pSTAT3+ T-lymphocytes were increased in Stat3ΔIEC mice as compared to Stat3Flx/Flx controls. In Stat3ΔIEC mice, colonic expression of Stat3 target genes Reg3β and Reg3γ which mediate epithelial restitution were significantly decreased, while expression of IL-17a, IFNγ, CXCL2, CXCL10, and CCL2 were significantly increased and correlated with the increase in histologic severity at Day 28(p<.05). IL-17a expression also correlated with the increased lamina propria frequency of CD3+pSTAT3+ T-lymphocytes. CONCLUSIONS Loss of intestinal epithelial Stat3 leads to more severe chronic inflammation following acute injury which is not accounted for by a sustained defect in epithelial proliferation or apoptosis 7 or 21 days after one cycle of DSS but rather defective REG3 expression and expansion of pSTAT3+ lymphocytes and IL-17a expression. PMID:23429443

  7. 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. PMID:26922802

  8. 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. PMID:27350078

  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. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. 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. PMID:27450718

  14. 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. PMID:26617183

  15. 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. PMID:19800040

  16. 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. PMID:27314669

  17. Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

    PubMed

    Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

    2016-05-01

    Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as

  18. 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

  19. 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

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

    2015-07-30

    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

  20. Chronic Vitamin C Deficiency Promotes Redox Imbalance in the Brain but Does Not Alter Sodium-Dependent Vitamin C Transporter 2 Expression

    PubMed Central

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

    2014-01-01

    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. PMID:24787032

  1. A Promoter Polymorphism in the CD59 Complement Regulatory Protein Gene in Donor Lungs Correlates With a Higher Risk for Chronic Rejection After Lung Transplantation.

    PubMed

    Budding, K; van de Graaf, E A; Kardol-Hoefnagel, T; Broen, J C A; Kwakkel-van Erp, J M; Oudijk, E-J D; van Kessel, D A; Hack, C E; Otten, H G

    2016-03-01

    Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p = 0.016) and monocytes (p = 0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL-6 (p = 0.047) and fibroblast growth factor β (p = 0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody-mediated complement lysis (p < 0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long-term survival (p = 0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p = 0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation. PMID:26517734

  2. Two Novel Missense Mutations and a 5bp Deletion in the Erythroid-Specific Promoter of the PKLR Gene in Two Unrelated Patients With Pyruvate Kinase Deficient Transfusion-Dependent Chronic Nonspherocytic Hemolytic Anemia.

    PubMed

    Kager, Leo; Minkov, Milen; Zeitlhofer, Petra; Fahrner, Bernhard; Ratzinger, Franz; Boztug, Kaan; Dossenbach-Glaninger, Astrid; Haas, Oskar A

    2016-05-01

    We report two children with severe chronic hemolytic anemia, the cause of which was difficult to establish because of transfusion dependency. Reduced erythrocyte pyruvate kinase activity in their asymptomatic parents provided the diagnostic clues for mutation screening of the PKLR gene and revealed that one child was a compound heterozygote of a novel paternally derived 5-bp deletion in the promoter region (c.-88_-84delTCTCT) and a maternally derived missense mutation in exon nine (c.1174G>A; p.Ala392Thr). The second child was a compound heterozygote of two novel missense mutations, namely a paternally derived exon ten c.1381G>A (p.Glu461Lys) and a maternally derived exon seven c.907-908delCC (p.Pro303GlyfsX12) variant. PMID:26728349

  3. Chronic stress promoted the growth of ovarian carcinoma via increasing serum levels of norepinephrine and interleukin-10 and altering nm23 and NDRG1 expression in tumor tissues in nude mice.

    PubMed

    Gao, Guolan; Sun, Jianling; Gao, Jun; Xiong, Lijuan; Yu, Liqun; Gao, Yulian

    2013-02-01

    The current study aimed to examine the effects and underlying mechanisms of chronic psychological stress on the growth of ovarian carcinoma. Human ovarian carcinoma cells SKOV-3 were subcutaneously inoculated into nude mice to establish an ectopic mouse model. The animals were experimentally stressed 6 h daily for a total of 42 days with a physical restraint system. We examined the effects of stress on the growth of tumor cells that were inoculated 7 days after the initiation of stress. The growth of SKOV-3 xenografts in the stress group showed a more rapid trend than that in the control. The mean weight of tumors that were removed at the end of the experiment increased by 71.7% in the stress group as compared to the control. In order to explore the underlying mechanisms, we first determined the serum levels of norepinephrine (NE) and interleukin 10 (IL-10) in the mice using an enzyme-linked immunoabsorbent assay (ELISA) and then analyzed protein expression profiles of SKOV-3 xenografts using a proteomics-based approach combining two-dimensional electrophoresis with ultra performance liquid chromatography-electrospray tandem mass spectrometry (nanoUPLC-ESI-MS/MS). Results demonstrated that serum levels of NE and IL-10 were obviously increased in the mice receiving 6 h of immobilization daily for 42 days. In xenografts exposed to stress, a tumor promoting protein nm23 was significantly upregulated while a tumor suppressing protein NDRG1 was obviously downregulated, which were confirmed by subsequent Western blot analysis. Results obtained in the current study suggested that chronic stress promoted the growth of ovarian carcinoma in nude mice through increasing serum levels of NE and IL-10 and altering nm23 and NDRG1 expression in tumor tissues. PMID:23524894

  4. 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

  5. Sustained exposure to the DNA demethylating agent, 2'-deoxy-5-azacytidine, leads to apoptotic cell death in chronic myeloid leukemia by promoting differentiation, senescence, and autophagy.

    PubMed

    Schnekenburger, Michael; Grandjenette, Cindy; Ghelfi, Jenny; Karius, Tommy; Foliguet, Bernard; Dicato, Mario; Diederich, Marc

    2011-02-01

    In addition to its demethylating properties, 2'-deoxy-5-azacytidine (DAC) induces cell cycle arrest, differentiation, cell sensitization to chemotherapy, and cell death. However, the mechanisms by which DAC induces antiproliferation via these processes and how they are interconnected remain unclear. In this study, we found that a clinically relevant concentration of DAC triggered erythroid and megakaryocytic differentiation in the human chronic myeloid leukemia (CML) K-562 and MEG-01 cell lines, respectively. In addition, cells showed a marked increase in cell size in both cell lines and a more adhesive cell profile for MEG-01. Furthermore, DAC treatment induced cellular senescence and autophagy as shown by β-galactosidase staining and by autophagosome formation, respectively. After prolonged DAC treatment, phosphatidyl serine exposure, nuclear morphology analysis, and caspase cleavage revealed an activation of mitochondrial-dependent apoptosis in CML cells. This activation was accompanied by a decrease of anti-apoptotic proteins and an increase of calpain activity. Finally, we showed that combinatory treatment of relatively resistant CML with DAC and either conventional apoptotic inducers or with an histone deacetylase inhibitor increased synergistically apoptosis. We therefore conclude that induction of differentiation, senescence, and autophagy in CML are a key in cell sensitization and DAC-induced apoptosis. PMID:21044612

  6. 'Getting back to normal': the added value of an art-based programme in promoting 'recovery' for common but chronic mental health problems.

    PubMed

    Makin, Sally; Gask, Linda

    2012-03-01

    OBJECTIVES. The aim of this project was to explore the added value of participation in an Arts on Prescription (AoP) programme to aid the process of recovery in people with common but chronic mental health problems that have already undergone a psychological 'talking'-based therapy. METHODS. The study utilized qualitative in-depth interviews with 15 clients with persistent anxiety and depression who had attended an 'AoP' service and had previously received psychological therapy. RESULTS and discussion. Attending AoP aided the process of recovery, which was perceived by participants as 'returning to normality' through enjoying life again, returning to previous activities, setting goals and stopping dwelling on the past. Most were positive about the benefits they had previously gained from talking therapies. However, these alone were not perceived as having been sufficient to achieve recovery. The AoP offered some specific opportunities in this regard, mediated by the therapeutic and effect of absorption in an activity, the specific creative potential of art, and the social aspects of attending the programme. CONCLUSIONS. For some people who experience persistent or relapsing common mental health problems, participation in an arts-based programme provides 'added value' in aiding recovery in ways not facilitated by talking therapies alone. PMID:21985790

  7. 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

  8. RalA, a GTPase targeted by miR-181a, promotes transformation and progression by activating the Ras-related signaling pathway in chronic myelogenous leukemia

    PubMed Central

    Luo, Xiaochuang; Yang, Juhua; Li, Yumin; Li, Tianfu; Wang, Ruirui; Fei, Jia

    2016-01-01

    BCR/ABL is a well-known activator of multiple signaling pathways. RalA, a Ras downstream signaling molecule and a small GTPase, plays an important role in Bcr-Abl-induced leukemogenesis but the exact mechanism remains elusive. Here, we show that RalA GTPase activity is commonly high in chronic myelogenous leukemia (CML) cell lines and patient samples. Overexpression of RalA results in malignant transformation and progression, and induces resistance to imatinib (IM) in BaF3 and K562 cell lines. RalA reduced survival and led to IM resistance in a xenografted mouse model. Ablation of RalA by either siRNA or miR-181a, a RalA targeting microRNA, attenuated the malignant phenotypes in K562 cells. RBC8, a selective Ral inhibitor, enhanced the inhibitory effects of IM in K562, KCL22 and BaF3-P210 cells. Interestingly, the phospho-specific protein microarray assay revealed that multiple phosphorylation signal proteins were decreased by RalA inhibition, including SAPK, JNK, SRC, VEGFR2, P38 MAPK, c-Kit, JunB, and Keratin18. Among them, P38 MAPK and SAPK/JNK are Ras downstream signaling kinases. Taken together, RalA GTPase might be an important oncogene activating the Ras-related signaling pathway in CML. PMID:26967392

  9. 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

  10. 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.

  11. Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation.

    PubMed

    Zhang, Hengwei; Sun, Wen; Li, Xing; Wang, Mengmeng; Boyce, Brendan F; Hilton, Matthew J; Xing, Lianping

    2016-09-01

    Notch signaling plays a critical role in maintaining bone homeostasis partially by controlling the formation of osteoblasts from mesenchymal stem cells (MSCs). We reported that TNF activates Notch signaling in MSCs which inhibits osteoblast differentiation in TNF transgenic (TNF-Tg) mice, a mouse model of chronic inflammatory arthritis. In the current study, we used Hes1-GFP and Hes1-GFP/TNF-Tg mice to study the distribution and dynamic change of Notch active cells in normal and inflammatory bone loss and mechanisms mediating their enhanced proliferation. We found that Hes1-GFP+ cells are composed of cells expressing mesenchymal, hematopoietic and endothelial surface markers. CD45-/Hes1-GFP+ cells express high levels of mesenchymal markers and form CFU-F and CFU-ALP colonies. Expansion of CFU-F colonies is associated with a rapid increase in Hes1-GFP+ cell numbers and their GFP intensity. The GFP signal is lost when a CFU-F colony differentiates into an ALP+ osteoblast colony. TNF increases the numbers of CD45-/Hes1-GFP+ cells, which are stained negatively for osteoblast marker osteocalcin and localized adjacent to endosteal and trabecular bone surfaces. CD45-/Hes1-GFP+ cells in Hes1-GFP/TNF-Tg mice have increased BrdU incorporation and PDGFRβ levels. TNF increases the number of proliferating Hes1-GFP+ cells, which is prevented by a specific PDGFRβ inhibitor. Notch inhibition blocks TNF-mediated PDGFRβ expression and cell proliferation. Thus, TNF-induced MSC proliferation is mediated by PDGFRβ signal, which works at downstream of Notch. Hes1-GFP mice can be used to assess the activation status of Notch in bone cells. PMID:27269414

  12. Chronic cholecystitis

    MedlinePlus

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  13. Chronic Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Chronic bronchitis is one type ...

  14. Chronic Bronchitis

    MedlinePlus

    ... carry air to your lungs. It causes a cough that often brings up mucus. It can also cause shortness of breath, wheezing, a low fever, and chest tightness. There are two main types of bronchitis: acute and chronic. Chronic bronchitis is one type of COPD (chronic ...

  15. Chronic migraine.

    PubMed

    Schwedt, Todd J

    2014-01-01

    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. PMID:24662044

  16. 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 ...

  17. Chronic pancreatitis.

    PubMed

    Majumder, Shounak; Chari, Suresh T

    2016-05-01

    Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. PMID:26948434

  18. Chronic cholecystitis

    MedlinePlus

    ... foods may relieve symptoms in people. However, the benefit of a low-fat diet has not been proven. Alternative Names Cholecystitis - chronic Images Cholecystitis, CT scan Cholecystitis, cholangiogram Cholecystolithiasis Gallstones, cholangiogram Cholecystogram References Wang ...

  19. Chronic Pain

    MedlinePlus

    ... adults. Common chronic pain complaints include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (pain resulting ... Institute of Neurological Disorders and Stroke (NINDS). Low Back Pain Fact Sheet Back Pain information sheet compiled by ...

  20. Chronic Pain

    MedlinePlus

    ... your pain. Medicines used for chronic pain include pain relievers, antidepressants, and anticonvulsants. Different types of medicines help ... If your doctor recommends an over-the-counter pain reliever, read and follow the instructions on the box. ...

  1. Ear infection - chronic

    MedlinePlus

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... Chole RA. Chronic otitis media, mastoiditis, and petrositis. In: Flint PW, Haughey BH, Lund LJ, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  2. 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

  3. 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. PMID:26165783

  4. 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 ...

  5. Chronic Bronchitis

    MedlinePlus

    ... risk for emphysema or chronic obstructive pulmonary disease (COPD)? What medicines will help relieve my symptoms? What lifestyle changes should I make at home to help relieve my symptoms? Is it safe for me to exercise? What kind of exercise should I do? What ...

  6. 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

  7. Exercise therapy for chronic pain.

    PubMed

    Kroll, Heather R

    2015-05-01

    The benefit of exercise for pain control likely comes from the impact of exercise on the endogenous opioid system and on central pain modulatory systems. Patients with some chronic pain conditions seem to have a dysfunctional endogenous pain modulatory system, which should be considered when prescribing exercise. The prescription of exercise for chronic pain must address the biomechanical issues and the psychosocial factors that contribute to the patient's pain and disability. Patient education, coordination of care within the health care team, and selecting an exercise regimen that is meaningful to and achievable by the patient are all important components to promote a successful rehabilitation program. PMID:25952064

  8. Chronic pain - resources

    MedlinePlus

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- www.theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org ...

  9. 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 ...

  10. Low back pain - chronic

    MedlinePlus

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause ...

  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

    Burrall, B A; Halpern, G M; Huntley, A C

    1990-03-01

    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 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

  14. 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.

  15. 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.…

  16. Chronicity of orofacial pain.

    PubMed

    Gerschman, J A

    2000-10-01

    Acute and chronic orofacial pain continues to be poorly understood and managed. The National Health and Medical Research Council of Australia (NHMRC) 1999 report on acute pain management promotes the development of evidence based clinical practice guidelines aimed at improving both the quality of health care and health outcomes in medical and dental practice in Australia. Nerve signals arising from sites of tissue or nerve injury lead to long term changes in the central nervous system and the amplification and persistence of pain. These nociceptor activity-induced neuronal changes known as central sensitization, have important clinical implications in the development of new approaches to the management of persistent pain. These findings and implications are discussed in relationship to poorly managed and understood conditions such as oral dysaesthesia, burning mouth syndrome, atypical facial pain/atypical odontalgia, peripheral nerve injury, deafferentation and phantom tooth syndrome. PMID:11709938

  17. [Chronic constipation].

    PubMed

    Degen, L

    2007-04-01

    Complaints of chronic constipation may substantially impair the quality of life of a patient. The disease feeling is shaped not only by objective parameters but also by subjective perceptions. This is along-considered into the so-called Rome-III-criteria. In the majority of the patients no distinct pathology can be found. A smaller group of patients however exhibit isolated or in combination a slow colonic transit or a pelvic floor dysfunction. Secondary extraintestinal causes are to be looked for particularly during a first clinical evaluation. Apart from general clinical investigations if necessary combined with a colonscopy, specific function tests (transit measurements, defecography) may be applied. Different laxative agents are the primary cornerstone of treatment. In selected cases biofeedback training or even surgical intervention can be successfully adopted. PMID:17663207

  18. Fighting Chronic Pain

    MedlinePlus

    ... pain, bone pain from spread of cancer, fibromyalgia, chronic fatigue syndrome Neurologic: "Phantom limb" pain after amputation, nerve pain from diabetes Read More "Chronic Pain" Articles Easing Chronic Pain: Better Treatments and ...

  19. Chronic Pain Medicines

    MedlinePlus

    ... Treatment of chronic pain usually involves medicines and therapy. Medicines used for chronic pain include pain relievers, antidepressants and anticonvulsants. Different types of medicines help ...

  20. 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

  1. 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

  2. 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) made in the past year. Recent findings Tropical pancreatitis associates with SPINK1 and/or CFTR gene mutations in approximately 50% of patients, similar to the frequency in idiopathic CP. Corticosteroids increase secretin-stimulated pancreatic bicarbonate concentrations in AIP by restoring mislocalized CFTR protein to the apical ductal membrane. Most patients with asymptomatic hyperenzymemia have pancreatic lesions of unclear significance or no pancreatic lesions. Common pitfalls in the use of diagnostic tests for EPI confound interpretation of findings in IBS and severe renal insufficiency. Further study is needed to improve the accuracy of endoscopic ultrasonography (EUS) to diagnose CP. Celiac plexus block provides short term pain relief in a subset of patients. Summary Results of this year’s investigations further elucidated the genetic associations of tropical pancreatitis, a reversible mislocalization of ductal CFTR in AIP, the association of asymptomatic pancreatic hyperenzymemia with pancreatic disorders, limitations of diagnostic tests for EPI, diagnosis of CP by EUS and endoscopic pancreatic function testing and treatment of pain. PMID:21844753

  3. 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

  4. 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

  5. Chronic motor tic disorder

    MedlinePlus

    Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start at age 5 or 6 and get worse until age 12. They often improve during adulthood.

  6. Chronic subdural hematoma

    MedlinePlus

    Subdural hemorrhage - chronic; Subdural hematoma - chronic; Subdural hygroma ... Ling GSF. Traumatic brain injury and spinal cord injury. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; ...

  7. Chronic Venous Insufficiency

    MedlinePlus

    ... What is Chronic V enous I nsufficiency (CVI)? Varicose veins are hereditary most of the time and generally ... members of the same family. Much less commonly, varicose veins develop after Chronic venous insufficiency (CVI) is a ...

  8. Chronic lymphocytic leukemia (CLL)

    MedlinePlus

    CLL; Leukemia - chronic lymphocytic (CLL) ... Byrd JC, Flynn JM. Chronic lymphocytic leukemia. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier ...

  9. Chronic Kidney Diseases

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes 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 ...

  10. Chronic kidney disease

    MedlinePlus

    Chronic kidney disease is the slow loss of kidney function over time. The main job of the kidneys is to ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some time. ...

  11. Chronic granulomatous disease

    MedlinePlus

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... In chronic granulomatous disease (CGD), immune system cells called ... some types of bacteria and fungi. This disorder leads to long- ...

  12. Chronic obstructive pulmonary disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000091.htm Chronic obstructive pulmonary disease To use the sharing features on this page, please enable JavaScript. Chronic obstructive pulmonary disease (COPD) is a common lung disease. Having COPD ...

  13. 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 ...

  14. 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. PMID:24192597

  15. Mapping chronic illness in the age of globalization: reclaiming the good for the chronically ill.

    PubMed

    del Pilar Camargo Plazas, Maria

    2009-01-01

    Until recently, infectious diseases were the main cause of death worldwide. New medical discoveries and the evolution of public health improved life expectancy and the ability to survive acute threats, thus changing the course of diseases from acute to chronic. Today, chronic illness is the most important health concern worldwide. Chronic illness increases existing poverty and pushes other people into it. As nurses, members of the healthcare system and members of this world, we cannot forget that our response toward globalization and chronic disease has to be centered in leadership through reorienting local and national healthcare systems. All actions must be grounded in the ethical treatment of the ill; we cannot close our eyes in hospitals or communities to what is happening now worldwide because our responsibility is to promote health, prevent disease, and care for human beings. PMID:19461220

  16. 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

  17. Promoting regular physical activity in pulmonary rehabilitation.

    PubMed

    Garcia-Aymerich, Judith; Pitta, Fabio

    2014-06-01

    Patients with chronic respiratory diseases are usually physically inactive, which is an important negative prognostic factor. Therefore, promoting regular physical activity is of key importance in reducing morbidity and mortality and improving the quality of life in this population. A current challenge to pulmonary rehabilitation is the need to develop strategies that induce or facilitate the enhancement of daily levels of physical activity. Because exercise training alone, despite improving exercise capacity, does not consistently generate similar improvements in physical activity in daily life, there is also a need to develop behavioral interventions that help to promote activity. PMID:24874131

  18. [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. PMID:24371971

  19. Chronic silent otitis media.

    PubMed

    Paparella, Michael M; Schachern, Patricia A; Cureoglu, Sebahattin

    2002-01-01

    Otitis media occurs along a continuum. For example, otitis media with effusion characterized by fluid pathology can lead to chronic otitis media plus chronic mastoiditis, characterized by the presence of intractable tissue pathology such as cholesteatoma, cholesterol granuloma or granulation tissue. The literature defines chronic otitis media as having a tympanic membrane perforation and otorrhea. Amongst many other sequelae, which can result from the continuum, an important common one is chronic silent otitis media. This overlooked entity which includes pathology beneath an intact tympanic membrane is commonly seen in our human temporal bone laboratory and in patients. The clinical pathological correlates of this important disease are discussed herein. PMID:12021496

  20. Treatment of chronic urticaria.

    PubMed

    Jurakić Toncić, Ruzica; Lipozencić, Jasna; Marinović, Branka

    2009-01-01

    Urticaria is a disorder characterized by rapid onset of localized swelling of the skin or mucosa, called wheals or urtica. According to frequency and duration, urticaria can be divided into acute and chronic type. Chronic urticaria is any type of urticaria occurring every day or twice per week, lasting longer than 6 weeks. Chronic urticaria is a common disorder and estimated prevalence is 1% of the population. Also, it is not rare in childhood. The pathogenesis of chronic urticaria has not yet been completely understood. Chronic urticaria is a heterogeneous group of disorders, and according to the etiology and cause, several groups of chronic urticaria are distinguished, i.e. autoimmune, pseudoallergic, infection-related, physical urticaria, vasculitis urticaria and idiopathic urticaria. Treatment and management of chronic urticaria can be non-pharmacological and pharmacological, and sometimes it is not possible to control the disease with antihistamines only, which are considered to be the mainstay of treatment. In severe cases of chronic urticaria, especially if autoimmunity has been proven, several authors describe different modules of immunomodulation: cyclosporine, cyclophosphamide, mycophenolate-mofetil, omalizumab, plasmapheresis, systemic corticosteroids, and immunoglobulin therapy. This article primarily addresses the treatment of chronic idiopathic and autoimmune urticaria. PMID:20021986

  1. Molecular Mechanisms of Mouse Skin Tumor Promotion

    PubMed Central

    Rundhaug, Joyce E.; Fischer, Susan M.

    2010-01-01

    Multiple molecular mechanisms are involved in the promotion of skin carcinogenesis. Induction of sustained proliferation and epidermal hyperplasia by direct activation of mitotic signaling pathways or indirectly in response to chronic wounding and/or inflammation, or due to a block in terminal differentiation or resistance to apoptosis is necessary to allow clonal expansion of initiated cells with DNA mutations to form skin tumors. The mitotic pathways include activation of epidermal growth factor receptor and Ras/Raf/mitogen-activated protein kinase signaling. Chronic inflammation results in inflammatory cell secretion of growth factors and cytokines such as tumor necrosis factor-α and interleukins, as well as production of reactive oxygen species, all of which can stimulate proliferation. Persistent activation of these pathways leads to tumor promotion. PMID:21297902

  2. Promoting positive outcomes in obese patients.

    PubMed

    Troia, Cecilia

    2002-01-01

    Obese patients are seen in every practice setting. Obesity is a chronic disease that may lead to physical and emotional problems, which may have an impact on the social and psychological functioning of the patient. With appropriate preoperative, intraoperative, and postoperative precautions; monitoring; and restructuring the environment to promote care and safety, the incidence of poor surgical outcomes can be minimized. This paper will address the significance of obesity, related diseases, and proper care of the obese patient. PMID:12035338

  3. [Natural history of chronic hepatitis B].

    PubMed

    Fonseca, José Carlos Ferraz da

    2007-01-01

    An estimated 350 million people worldwide are chronically infected with hepatitis B virus (HBV). Three phases of chronic hepatitis B virus infection is are recognized: the immune tolerant phase (HBeAg-positive, high levels of serum HBV-DNA, normal ALT, and no evidence of active liver diseases), the immune clearance phase or chronic hepatitis phase (HBeAg-positive, high levels of serum HBV-DNA, elevated ALT, and active liver disease ), and the inactive carrier state or asymptomatic phase (HBsAg-positive in serum without HBeAg, HBV-DNA levels than < 10(5) copies/mL, and normal ALT levels). Chronic hepatitis B is classified into 2 major forms: HBeAg-positive disease (wild-type HBV) and HBeAg negative disease (pre-core/core promoter HBV variant). Both forms can lead to liver cirrhosis, hepatic decompensation and liver cancer. The purpose of this article is to review the principal aspects of natural history of chronic hepatitis B. PMID:18200423

  4. 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. PMID:16861848

  5. 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.

  6. Chronic daily headaches

    PubMed Central

    Ahmed, Fayyaz; Parthasarathy, Rajsrinivas; Khalil, Modar

    2012-01-01

    Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches. PMID:23024563

  7. Microglial Activation & Chronic Neurodegeneration

    PubMed Central

    Lull, Melinda E.; Block, Michelle L.

    2010-01-01

    Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including TNFα, NO, IL1-β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (ex. LPS or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss over time. While the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s Disease. Here, we review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype. PMID:20880500

  8. Chronic cough: an update.

    PubMed

    Iyer, Vivek N; Lim, Kaiser G

    2013-10-01

    Cough persisting beyond 8 weeks (ie, chronic cough) is one of the most common reasons for an outpatient visit. A protracted cough can negatively affect one's quality of life by causing anxiety, physical discomfort, social isolation, and personal embarrassment. Herein, the anatomy and physiology of the cough reflex are reviewed. Upper airway cough syndrome, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease account for most chronic cough after excluding smoking, angiotensin-converting enzyme inhibitor use, and chronic bronchitis. Many patients have more than one reason for chronic cough. Treating the underlying cause(s) resolves cough in most instances. There are some coughs that seem refractory despite an extensive work-up. The possibility of a hypersensitive cough reflex response has been proposed to explain these cases. Several clinical algorithms to evaluate chronic cough are presented. PMID:24079681

  9. Importance of exercise immunology in health promotion.

    PubMed

    Neto, J C Rosa; Lira, F S; de Mello, M T; Santos, Ronaldo Vagner T

    2011-11-01

    Chronic physical exercise with adequate intensity and volume associated with sufficient recovery promotes adaptations in several physiological systems. While intense and exhaustive exercise is considered an important immunosuppressor agent and increases the incidence of upper respiratory tract infections (URTI), moderate regular exercise has been associated with significant disease protection and is a complementary treatment of many chronic diseases. The effects of chronic exercise occur because physical training can induce several physiological, biochemical and psychological adaptations. More recently, the effect of acute exercise and training on the immunological system has been discussed, and many studies suggest the importance of the immune system in prevention and partial recovery in pathophysiological situations. Currently, there are two important hypotheses that may explain the effects of exercise and training on the immune system. These hypotheses including (1) the effect of exercise upon hormones and cytokines (2) because exercise can modulate glutamine concentration. In this review, we discuss the hypothesis that exercise may modulate immune functions and the importance of exercise immunology in respect to chronic illnesses, chronic heart failure, malnutrition and inflammation. PMID:20976509

  10. 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. PMID:25999227

  11. HIV: A Chronic Condition.

    PubMed

    Zimmerman, Daniel D

    2015-01-01

    By virtue of the success of anti-retroviral therapy (ART), human immunodeficiency virus (HIV) infection has evolved into a chronic disease in which the typical complications of acquired immune deficiency syndrome (AIDS) are no longer the dominant problem. Rather than dealing with acute and potentially life-threatening complications, clinicians are now confronted with managing a chronic disease that, in the absence of a cure, will persist for many decades. (1) This review will focus on the longer term sequelae and consequences of chronic HIV infection. PMID:27584920

  12. [Chronic lower back pain].

    PubMed

    Werber, A; Schiltenwolf, M

    2012-02-01

    Poor efficiency in terms of treatment of unspecific back pain and related chronic pain syndromes has led to the necessity of general care guidelines addressing evidence-based strategies for treatment of lower back pain (LBP). Systematically validated and reviewed algorithms have been established for all kinds of unspecific back pain, covering both acute and chronic syndromes. Concerning the impact of psychosocial risk factors in the development of chronic LBP, multimodal treatment is preferred to monomodal strategies. Self-responsible acting on the part of the patient should be supported while invasive methods in particular, i.e. operative treatment, should be avoided due to lacking evidence in outcome efficiency. PMID:22349772

  13. 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. PMID:19080038

  14. Chronic variable stress activates hematopoietic stem cells

    PubMed Central

    Courties, Gabriel; Dutta, Partha; Iwamoto, Yoshiko; Zaltsman, Alex; von zur Muhlen, Constantin; Bode, Christoph; Fricchione, Gregory L.; Denninger, John; Lin, Charles P.; Vinegoni, Claudio; Libby, Peter; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

    2014-01-01

    Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis1,2. While incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known crosstalk between the brain and immune system includes the hypothalamic–pituitary–adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic–adrenal–medullary axis, which controls stress–induced catecholamine release in support of the fight–or–flight reflex3,4. It remains unknown however if chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive progenitors, giving rise to higher levels of disease–promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Sympathetic nerve fibers release surplus noradrenaline, which uses the β3 adrenergic receptor to signal bone marrow niche cells to decrease CXCL12 levels. Consequently, elevated hematopoietic stem cell proliferation increases output of neutrophils and inflammatory monocytes. When atherosclerosis–prone ApoE−/− mice encounter chronic stress, accelerated hematopoiesis promotes plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans. PMID:24952646

  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. What Is Chronic Pain?

    MedlinePlus Videos and Cool Tools

    ... Contact Us Shop FAQs The Art of Pain Management Resources Going to the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs Resource Guide to Chronic Pain Treatments Pain ...

  17. Chronic appendicitis in children

    PubMed Central

    Kim, David; Butterworth, Sonia A.; Goldman, Ran D.

    2016-01-01

    Abstract Question 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? Answer 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. PMID:27303020

  18. Chronic thyroiditis (Hashimoto disease)

    MedlinePlus

    ... gland that often results in reduced thyroid function ( hypothyroidism ). Causes Chronic thyroiditis or Hashimoto disease is a ... TSH). This condition is also known as subclinical hypothyroidism. If there is no evidence of thyroid hormone ...

  19. Chronic fatigue syndrome

    MedlinePlus

    ... reduction techniques can help manage chronic (long-term) pain and fatigue. They are not used as the primary treatment for CFS. Relaxation techniques include: Biofeedback Deep breathing exercises Hypnosis Massage therapy Meditation Muscle relaxation techniques Yoga Newer ...

  20. 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 ...

  1. Chronic Pelvic Pain

    MedlinePlus

    ... found. How is chronic pelvic pain diagnosed? Your health care provider will ask about your medical history. You will have a physical exam, including a pelvic exam . Tests also may be done to find the cause. ...

  2. Chronic rhinosinusitis pathogenesis.

    PubMed

    Stevens, Whitney W; Lee, Robert J; Schleimer, Robert P; Cohen, Noam A

    2015-12-01

    There are a variety of medical conditions associated with chronic sinonasal inflammation, including chronic rhinosinusitis (CRS) and cystic fibrosis. In particular, CRS can be divided into 2 major subgroups based on whether nasal polyps are present or absent. 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 might 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 patients with cystic fibrosis, CRS without nasal polyps, or CRS with nasal polyps. PMID:26654193

  3. 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 ...

  4. Chronic inflammatory polyneuropathy

    MedlinePlus

    ... nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy means several nerves are involved. It usually ... demyelinating polyneuropathy (CIDP) is the most common chronic neuropathy caused by an abnormal immune response. CIDP occurs ...

  5. Sleep and Chronic Disease

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Sleep and Sleep Disorders Note: Javascript is disabled or is not supported ... CDC.gov . Sleep About Us About Sleep Key Sleep Disorders Sleep and Chronic Disease How Much Sleep Do ...

  6. American Chronic Pain Association

    MedlinePlus

    ... ACPA Contact Us Shop FAQs The Art of Pain Management Resources Going to the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs Resource Guide to Chronic Pain Treatments Pain ...

  7. Anemia of chronic disease

    MedlinePlus

    Anemia of inflammation; AOCD; ACD ... Anemia is a lower-than-normal number of red blood cells in the blood. Some conditions can lead to anemia of chronic disease include: Autoimmune disorders , such as ...

  8. Survey of bacterial diversity in chronic wounds using Pyrosequencing, DGGE, and full ribosome shotgun sequencing.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Chronic wound pathogenic biofilms are host-pathogen environments that colonize and exist as a cohabitation of many bacterial species that cooperate to promote their own survival and the chronic nature of the infection. Few studies have performed extensive surveys of the different populat...

  9. Chronic Obstructive Pulmonary Disease.

    PubMed

    Hattab, Yousef; Alhassan, Sulaiman; Balaan, Marvin; Lega, Mark; Singh, Anil C

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic smoking-related lung disease associated with significant mortality and morbidity. It carries an enormous economic burden on the health care system. This results in a significant social impact on affected patients and their families. In this article, we review COPD in general, critical care management of patients presenting with acute exacerbation of COPD, and methods of prevention. PMID:26919673

  10. Hypertension in Chronic Glomerulonephritis.

    PubMed

    Ihm, Chun-Gyoo

    2015-12-01

    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

  11. "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…

  12. Natural Selection Promotes Antigenic Evolvability

    PubMed Central

    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

  13. Early origins of chronic obstructive pulmonary disease.

    PubMed

    Narang, Indra; Bush, Andrew

    2012-04-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and a significant challenge for adult physicians. However, there is a misconception that COPD is a disease of only adult smokers. There is a growing body of evidence to support the hypothesis that chronic respiratory diseases such as COPD have their origins in early life. In particular, adverse maternal factors will interact with the environment in a susceptible host promoting altered lung growth and development antenatally and in early childhood. Subsequent lung injury and further gene-environment interactions may result in permanent lung injury manifest by airway obstruction predisposing to COPD. This review will discuss the currently available data regarding risk factors in early life and their role in determining the COPD phenotype. PMID:22265926

  14. 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

  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. 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,…

  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. PMID:2359571

  18. [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. PMID:22532241

  19. 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

  20. [Chronic exertional compartment syndrome].

    PubMed

    Rom, Eyal; Tenenbaum, Shay; Chechick, Ofir; Burstein, Gideon; Amit, Yehuda; Thein, Ran

    2013-10-01

    Chronic exertional compartment syndrome is an uncommon phenomenon first reported in the mid 50's. This condition is characterized by sharp pain during physical activity, causing reduction in activity frequency or intensity and even abstention. This syndrome is caused by elevation of the intra-compartmental pressure which leads to decreased tissue perfusion, thus ischemic damage to the tissue ensues. Chronic exertional syndrome is usually related to repetitive physical activity, usually in young people and athletes. The physical activity performed by the patient causes a rise in intra-compartmental pressure and thereby causes pain. The patient discontinues the activity and the pain subsides within minutes of rest. Chronic exertional syndrome is reported to occur in the thigh, shoulder, arm, hand, foot and gluteal region, but most commonly in the leg, especially the anterior compartment. The diagnosis of chronic exertional syndrome is primarily based on patients' medical history, supported by intramuscular pressure measurement of the specific compartment involved. Treatment of chronic exertional syndrome, especially the anterior and lateral compartment of the leg is mainly by surgery i.e. fasciotomy. If the patient is reluctant to undergo a surgical procedure, the conservative treatment is based on abstention from the offending activity, changing footwear or using arch support. However, the conservative approach is not as successful as surgical treatment. PMID:24450036

  1. [Chronic pain and rehabilitation].

    PubMed

    Berker, Ender; Dinçer, Nilay

    2005-04-01

    The perception and interpretation of pain is the end point of an interaction of cognitive, cultural, and environmental factors and this complex interaction effects the pain response and quality of life of each person which shows that pain perception and the verbal and behavioral response shows variations and is specific for each patient. Chronic pain can be due to Fibromyalgia Syndrome (FMS) and Neuropathic Pain (NP) where the underlying pathophysiologic mechanisms are being revealed or it can be chronic low back pain (CLBP) where pain persists in spite of healing of tissue and no underlying pathologic mechanism can be defected. Central sensitization, inhibition of descending pain inhibitory systems, functional changes in autonomic nervous system amd neurotransmitter as well as changes in stress response system are factors contributing to the initiation and maintenance of pain and cognitive, behavioral factors are also important contributors in chronic pain. Biopsychosocial and biomedical mechanisms should be assessed in the rehabilitation interventions. The aims of rehabilitation in chronic pain are to increase activity tolerance, functional capacity and to decrease socio-economic loads. The targets of activity should be physical, functional and social. Psychologic based programs as cognitive-behavioral techniques and operant conditioning are also valid procedures in rehabilitation of chronic pain patients. Rehabilitation should be multidisciplinary and of long-term targeted to valid out-come for success. PMID:15977088

  2. [Cycloferon therapy of chronic gastroduodenitis in children].

    PubMed

    Yermak, S Yu; Lialikov, S A; Zubritsky, M G; Borodavko, O N

    2014-01-01

    The efficiency of immunomodulating therapy with cycloferon in children aged from 10 to 16 years with verified chronic gastroduodenitis was estimated. It was shown that the cycloferon treatment provided reliable increase of T- and B-cellular populations in mucous membranes of the stomach and duodenum, normalization of the number of CD8-lymphocytes, higher titers of IgG antibodies to herpes viruses 1 and 2. It also promoted reduction of inflammation in the mucous membranes along with reduction of the disease clinical signs. PMID:25975104

  3. 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

  4. 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. PMID:25108498

  5. 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

  6. 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. PMID:18372870

  7. Chronic urticaria: recent advances.

    PubMed

    Greaves, Malcolm W; Tan, Kian Teo

    2007-10-01

    Chronic urticaria is an umbrella term, which encompasses physical urticarias, chronic "idiopathic" urticaria and urticarial vasculitis. It is important to recognize patients with physical urticarias as the investigation and treatment differs in important ways from patients with idiopathic chronic urticaria or urticarial vasculitis. Although relatively uncommon, urticarial vasculitis is an important diagnosis to make and requires histological confirmation by biopsy. Underlying systemic disease and systemic involvement, especially of the kidneys, should be sought. It is now recognized that chronic "idiopathic" urticaria includes a subset with an autoimmune basis caused by circulating autoantibodies against the high affinity IgE receptor (FceR1) and less commonly against IgE. Although the autologous serum skin test has been proven useful in prompting search for and characterization of circulating wheal-producing factors in chronic urticaria, its specificity as a screening test for presence of functional anti-FceR1 is low, and confirmation by demonstration of histamine-releasing activity in the patient's serum must be the benchmark test in establishing this diagnosis. Improved screening tests are being sought; for example, ability of the chronic urticaria patient's serum to evoke expression of CD 203c on donor human basophils is showing some promise. The strong association between autoimmune thyroid disease and autoimmune urticaria is also an area of ongoing research. Drug treatment continues to be centered on the H1 antihistamines, and the newer second-generation compounds appear to be safe and effective even in off-label dosage. Use of systemic steroids should be confined to special circumstances such as tapering regimens for acute flare-ups. Use of leukotriene antagonists is becoming popular, but the evidence for efficacy is conflicting. Cyclosporin is also effective and can be used in selected cases of autoimmune urticaria, and it is also effective in non

  8. 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…

  9. Health Knowledge Effects: An Integrated Community Health Promotion Platform.

    PubMed

    Chang, I-Chiu; Lin, Chih-Yu; Tseng, Hsiao-Ting; Ho, Wen-Yu

    2016-03-01

    The Taiwanese government subsidizes healthcare providers offering preventive medicine to patients to help reduce the threats of chronic sickness and halt skyrocketing medical expenditures. Usually, nurses are the primary workers who perform community health promotion; however, because of the chronic shortage of working nurses, many Taiwan hospitals have closed wards and deferred the responsibility of promoting primary prevention. With a community health promotion platform integrating interactive response features and Web sites for community patients and hospital staff, a case hospital efficiently sustained the community health services. The objective of this study was to assess the impact of the integrated community health promotion platform for conducting education. Fifty-four patients/residents were invited to join a quasi-experiment of health education, and a follow-up survey was conducted to assess the acceptance of the community health promotion platform from both the experimental group of learners/users and the hospital staff. The results showed that the community health promotion platform was effective in improving participant health awareness. The experimental group outperformed the control group, with higher posttest scores and longer knowledge retention. Furthermore, users indicated a high acceptance of the community health promotion platform. PMID:26657621

  10. Haemorheological consequences of chronic cigarette smoking.

    PubMed

    Ernst, E

    1995-10-01

    Smoking is a universally accepted major cardiovascular risk factor, but the mechanisms by which it promotes ischaemic vascular disease are not fully understood. The changes that chronic smoking exerts on the flow properties of blood might contribute to an explanation. It is well documented that smoking leads to a rise in haematocrit. It also alters the rheological behaviour of red blood cells and increases both plasma viscosity and fibrinogen levels. Finally, it increases the total white cell count and modifies leukocyte function. Together these changes cumulate in a significant deterioration of the flow properties of blood, as evidenced by a steep increase in whole blood viscosity. Alterations of blood rheology in turn can promote atherothrombogenesis in several ways. It seems possible, therefore, that one mechanism by which smoking increases the risk of vascular diseases operates through its complex effects on blood rheology. PMID:8749271