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Sample records for fatigue immune dysfunction

  1. Functional capacity evaluations of persons with chronic fatigue immune dysfunction syndrome.

    PubMed

    Barrows, D M

    1995-04-01

    Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) is estimated to affect 2 to 5 million people in the United States. Despite its high incidence, persons with CFIDS have been neglected by the medical community mainly because there is no singular confirming diagnostic test or proven effective treatment. The CFIDS population is incorrectly stereotyped as upper-middle-class, white, female hypochondriacs; consequently, symptoms often are belittled or ignored. In reality, CFIDS is a severe medical condition that affects women, men, and children of any race and often causes long-term or total disability. The results of a modified functional capacity evaluation developed by the author and completed on 86 persons with CFIDS between 1988 and 1990 confirm that this population has severe physical and cognitive disabilities that affect their professional, familial, and social lives. The results of these evaluations are used to present a profile of persons with CFIDS that can serve as a basis for understanding this population and for guiding intervention. PMID:7785715

  2. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    SciTech Connect

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. )

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  3. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

    PubMed Central

    Rutherford, Gina; Manning, Philip; Newton, Julia L.

    2016-01-01

    Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME. PMID:26998359

  4. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome.

    PubMed

    Rutherford, Gina; Manning, Philip; Newton, Julia L

    2016-01-01

    Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME. PMID:26998359

  5. Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature.

    PubMed

    Filler, Kristin; Lyon, Debra; Bennett, James; McCain, Nancy; Elswick, Ronald; Lukkahatai, Nada; Saligan, Leorey N

    2014-06-01

    Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1,220 articles. After application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature. PMID:25147756

  6. Association of mitochondrial dysfunction and fatigue: A review of the literature

    PubMed Central

    Filler, Kristin; Lyon, Debra; Bennett, James; McCain, Nancy; Elswick, Ronald; Lukkahatai, Nada; Saligan, Leorey N.

    2014-01-01

    Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1220 articles. After the application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature. PMID:25147756

  7. Effects of Nutritional Supplementation on Fatigue, and Autonomic and Immune Dysfunction in Patients with End-Stage Renal Disease: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

    PubMed Central

    Fukuda, Sanae; Koyama, Hidenori; Kondo, Kazuhiro; Fujii, Hisako; Hirayama, Yoshinobu; Tabata, Tsutomu; Okamura, Mikio; Yamakawa, Tomoyuki; Okada, Shigeki; Hirata, Sumio; Kiyama, Hiroshi; Kajimoto, Osami; Watanabe, Yasuyoshi; Inaba, Masaaki; Nishizawa, Yoshiki

    2015-01-01

    Background Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment. We hypothesized that multinutritional support would improve quality of life, fatigue symptoms, and potential quantitative measures including endocrine, immune and autonomic functions in patients with ESRD undergoing hemodialysis. Methods Two hundred and two hemodialysis patients were randomly assigned to receive active treatment (containing vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, carnitine, coenzyme Q10, naïve galacto-oligosaccharide, and zinc) or placebo after each dialysis session for 12 weeks. The patients and attending physicians were blinded to the treatment, and 172 patients (86 in each group) completed the study. Fatigue was evaluated via fatigue questionnaire at 0, 4, and 12 weeks. To assess human herpes virus (HHV) 6 and 7 reactivation, numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12. Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography. Results Clinical characteristics, changes in fatigue, quality of life score, endocrine functions, and laboratory data did not differ significantly between the two groups. Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo. Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers. Similarly, HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance. Conclusions Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis. PMID:25746727

  8. Immune surveillance for ERAAP dysfunction.

    PubMed

    Nagarajan, Niranjana A; Shastri, Nilabh

    2013-09-01

    The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1(b), a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1(b) complex were frequent in naïve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1(b) complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction. PMID:23433779

  9. Chronic fatigue syndrome and mitochondrial dysfunction

    PubMed Central

    Myhill, Sarah; Booth, Norman E.; McLaren-Howard, John

    2009-01-01

    This study aims to improve the health of patients suffering from chronic fatigue syndrome (CFS) by interventions based on the biochemistry of the illness, specifically the function of mitochondria in producing ATP (adenosine triphosphate), the energy currency for all body functions, and recycling ADP (adenosine diphosphate) to replenish the ATP supply as needed. Patients attending a private medical practice specializing in CFS were diagnosed using the Centers for Disease Control criteria. In consultation with each patient, an integer on the Bell Ability Scale was assigned, and a blood sample was taken for the “ATP profile” test, designed for CFS and other fatigue conditions. Each test produced 5 numerical factors which describe the availability of ATP in neutrophils, the fraction complexed with magnesium, the efficiency of oxidative phosphorylation, and the transfer efficiencies of ADP into the mitochondria and ATP into the cytosol where the energy is used. With the consent of each of 71 patients and 53 normal, healthy controls the 5 factors have been collated and compared with the Bell Ability Scale. The individual numerical factors show that patients have different combinations of biochemical lesions. When the factors are combined, a remarkable correlation is observed between the degree of mitochondrial dysfunction and the severity of illness (P<0.001). Only 1 of the 71 patients overlaps the normal region. The “ATP profile” test is a powerful diagnostic tool and can differentiate patients who have fatigue and other symptoms as a result of energy wastage by stress and psychological factors from those who have insufficient energy due to cellular respiration dysfunction. The individual factors indicate which remedial actions, in the form of dietary supplements, drugs and detoxification, are most likely to be of benefit, and what further tests should be carried out. PMID:19436827

  10. Tumor-induced immune dysfunction.

    PubMed

    Kiessling, R; Wasserman, K; Horiguchi, S; Kono, K; Sjöberg, J; Pisa, P; Petersson, M

    1999-10-01

    Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease. PMID:10501847

  11. Immune Dysfunction in Aged Horses.

    PubMed

    McFarlane, Dianne

    2016-08-01

    The aging process in people is associated with changes in adaptive and innate immune responses. Similar changes occur in aged horses. Age-related progressive impairment in the ability to respond to pathogen challenge and an increased inflammatory reactivity may predispose geriatric horses to many diseases of old age. Specific recommendations for immune modification of older horses, including an age-appropriate vaccination schedule, are not currently available. In addition, the effect of old age on risk of infectious disease is poorly documented. More work is needed to better understand the interactions of age on immunity, vaccine response, and disease risk in horses. PMID:27329495

  12. Immune dysfunction in Australian Aborigines.

    PubMed

    Roberts-Thomson, P J; Roberts-Thomson, R A; Nikoloutsopoulos, T; Gillis, D

    2005-12-01

    An examination of the prevalence and phenotype of immune disorders in different ethnic groups may provide important clues to the etiopathogenesis of these disorders. Whilst still conjectural the restricted and somewhat unique polymorphisms of the MHC (and other genetic loci involving host defences) of the Australian Aborigines may provide an explanation for their apparent heightened susceptibility to newly encountered infections and their resistance to many (auto) immune and allergic disorders. In comparison with non-Aboriginal Australians, Australian Aborigines have heightened frequencies of rheumatic fever, systemic lupus erythematosus, various infections and post-streptococcal glomerulonephritis. In contrast various autoimmune disorders (e.g. rheumatoid arthritis, multiple sclerosis, CREST, biliary cirrhosis, coeliac disease, pernicious anaemia, vitiligo), B27 related arthropathies, psoriasis, lymphoproliferative disorders and atopic disorders appear infrequent or absent. Similarly various autoantibodies occur with increased or diminished frequency. With continuing racial admixture, social deprivation and deleterious lifestyles of these people it is likely that further changes in both the frequencies and phenotype of these immune disorders will occur. It is only with a full understanding of the pathogenic mechanisms involved in these immune disorders that meaningful and clinical relevant interventions will be possible. PMID:16572744

  13. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    PubMed Central

    Brand, Rhonda M.; Stottlemyer, John Mark; Cline, Rachel A.; Donahue, Cara; Behari, Jaideep; Falo, Louis D.

    2015-01-01

    Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. PMID:26561838

  14. The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.

    PubMed

    Morris, Gerwyn; Berk, Michael; Galecki, Piotr; Walder, Ken; Maes, Michael

    2016-03-01

    Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways. PMID:25598355

  15. Immune Dysfunction in Uremia—An Update

    PubMed Central

    Cohen, Gerald; Hörl, Walter H.

    2012-01-01

    Kidney dysfunction leads to disturbed renal metabolic activities and to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body. Cardiovascular disease (CVD) and infections are the main causes for the increased occurrence of morbidity and mortality among patients with chronic kidney disease (CKD). Both complications are directly or indirectly linked to a compromised immune defense. The specific coordinated roles of polymorphonuclear leukocytes (PMNLs), monocytes/macrophages, lymphocytes and antigen-presenting cells (APCs) in maintaining an efficient immune response are affected. Their normal response can be impaired, giving rise to infectious diseases or pre-activated/primed, leading to inflammation and consequently to CVD. Whereas the coordinated removal via apoptosis of activated immune cells is crucial for the resolution of inflammation, inappropriately high apoptotic rates lead to a diminished immune response. In uremia, the balance between pro- and anti-inflammatory and between pro- and anti-apoptotic factors is disturbed. This review summarizes the interrelated parameters interfering with the immune response in uremia, with a special focus on the non-specific immune response and the role of uremic toxins. PMID:23202302

  16. Immune and hemorheological changes in Chronic Fatigue Syndrome

    PubMed Central

    2010-01-01

    Background Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. Methods Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ and CD56brightCD16-) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed. Results CFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56brightCD16- NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56dimCD16+ NK cells were similar between the two groups. Conclusion These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients. PMID:20064266

  17. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  18. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  19. Monitoring of the Immune Dysfunction in Cancer Patients.

    PubMed

    Santegoets, Saskia J A M; Welters, Marij J P; van der Burg, Sjoerd H

    2016-01-01

    Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system. PMID:27598210

  20. FSTL1 promotes bone metastasis by causing immune dysfunction.

    PubMed

    Kudo-Saito, Chie

    2013-11-01

    In spite of significant advances in our understanding of the metastatic process, the relationship between the dissemination of primary neoplasms to the bones and antitumor immunity remains poorly understood. We have recently identified follistatin-like 1 (FSTL1), a soluble protein secreted by snail family zinc finger 1 (SNAI1)-expressing cancer cells, as a key determinant of bone metastasis that operates by inducing a systemic state of immune dysfunction. PMID:24482748

  1. Epigenetic Dysfunction in Turner Syndrome Immune Cells.

    PubMed

    Thrasher, Bradly J; Hong, Lee Kyung; Whitmire, Jason K; Su, Maureen A

    2016-05-01

    Turner syndrome (TS) is a chromosomal condition associated with partial or complete absence of the X chromosome that involves characteristic findings in multiple organ systems. In addition to well-known clinical characteristics such as short stature and gonadal failure, TS is also associated with T cell immune alterations and chronic otitis media, suggestive of a possible immune deficiency. Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a downregulated gene in TS immune cells. Importantly, UTX is an X-linked gene that escapes X-chromosome inactivation and thus is haploinsufficient in TS. Mice with T cell-specific UTX deficiency have impaired clearance of chronic viral infection due to decreased frequencies of T follicular helper (Tfh) cells, which are critical for B cell antibody generation. In parallel, TS patients have decreased Tfh frequencies in peripheral blood. Together, these findings suggest that haploinsufficiency of the X-linked UTX gene in TS T cells underlies an immune deficit, which may manifest as increased predisposition to chronic otitis media. PMID:27039394

  2. A mechanism for trauma induced muscle wasting and immune dysfunction

    NASA Astrophysics Data System (ADS)

    Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

    A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

  3. Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

    PubMed Central

    Morris, Gerwyn; Maes, Michael

    2014-01-01

    Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease. PMID:24669210

  4. The effects of low-intensity laser irradiation on the fatigue induced by dysfunction of mitochondria

    NASA Astrophysics Data System (ADS)

    Xu, Xiao-Yang; Liu, Timon C.; Duan, Rui; Liu, Xiao-Guang

    2003-12-01

    Exercise-induced fatigue has long been an important field in sports medicine. The electron leak of mitochondrial respiratory chain during the ATP synthesis integrated with proton leak and O-.2 can decrease the efficiency of ATP synthesis in mitochondria. And the exercise-induced fatigue occur followed by the decrease of performance. If the dysfunction of mitochondria can be avoided, the fatigue during the exercise may be delayed and the performance may be enhanced. Indeed there are some kind of materials can partially prevent the decrease of ATP synthesis efficiency in mitochondria. But the side effects and safety of these materials is still needed to be studied. Low intensity laser can improve the mitochondria function. It is reasonable to consider that low intensity laser therapy may become the new and more effective way to delay or elimination the fatigue induced by dysfunction of mitochondria. Because the effect of laser irradiation may not be controlled exactly when study in vivo, we use electrical stimulation of C2C12 muscle cells in culture to define the effect of low intensity laser on the dysfunction of mitochondria, and to define the optimal laser intensity to prevent the decrease of ATP synthesis efficiency. Our study use the C2C12 muscle cells in culture to define some of the mechanisms involved in the contractile-induced changes of mitochondrial function firstly in sports medicine and may suggest a useful study way to other researchers. We also give a new way to delay or eliminating the fatigue induced by dysfunction of mitochondria without side effect.

  5. Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence.

    PubMed

    Cvejic, Erin; Birch, Rachael C; Vollmer-Conna, Uté

    2016-05-01

    Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities. Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments. PMID:27032787

  6. Multiple sclerosis and fatigue: A review on the contribution of inflammation and immune-mediated neurodegeneration.

    PubMed

    Patejdl, Robert; Penner, Iris K; Noack, Thomas K; Zettl, Uwe K

    2016-03-01

    Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics

  7. Mental Fatigue and Executive Dysfunction in Patients with Cushing's Syndrome in Remission

    PubMed Central

    Papakokkinou, Eleni; Johansson, Birgitta; Berglund, Peter; Ragnarsson, Oskar

    2015-01-01

    Patients with Cushing's syndrome (CS) in remission often suffer from impaired quality of life and cognitive dysfunction. The primary aim was to investigate the occurrence of mental fatigue, characterized by mental exhaustion and long recovery time following mentally strenuous tasks, in patients with CS in remission. The secondary aim was to examine whether the newly developed parts C and D of the trail making test (TMT) are more sensitive, compared to the conventional parts A and B, to evaluate attention and executive function. This was a cross-sectional study including 51 patients with CS in remission and 51 controls. All subjects completed the self-administrated mental fatigue scale (MFS) and performed all four parts of the TMT. The patients had worse outcome on all components of the MFS except for sensitivity to noise. After adjustment for mental fatigue, depression, and anxiety, the patients performed worse only on part D of the TMT (P < 0.05). Mental fatigue is common in patients with CS in remission and can be captured by using the MFS. The most demanding part of the TMT, part D, is more useful to capture cognitive deficits in patients with CS in remission compared to the conventional parts A and B. PMID:26221060

  8. Immune-Mediated Vascular Injury and Dysfunction in Transplant Arteriosclerosis

    PubMed Central

    von Rossum, Anna; Laher, Ismail; Choy, Jonathan C.

    2015-01-01

    Solid organ transplantation is the only treatment for end-stage organ failure but this life-saving procedure is limited by immune-mediated rejection of most grafts. Blood vessels within transplanted organs are targeted by the immune system and the resultant vascular damage is a main contributor to acute and chronic graft failure. The vasculature is a unique tissue with specific immunological properties. This review discusses the interactions of the immune system with blood vessels in transplanted organs and how these interactions lead to the development of transplant arteriosclerosis, a leading cause of heart transplant failure. PMID:25628623

  9. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?

    PubMed

    Castro-Marrero, Jesús; Cordero, Mario D; Sáez-Francas, Naia; Jimenez-Gutierrez, Conxita; Aguilar-Montilla, Francisco J; Aliste, Luisa; Alegre-Martin, José

    2013-11-20

    Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions. PMID:23600892

  10. Endothelial Dysfunction and Inflammation: Immunity in Rheumatoid Arthritis

    PubMed Central

    Yang, XueZhi; Chang, Yan; Wei, Wei

    2016-01-01

    Inflammation, as a feature of rheumatoid arthritis (RA), leads to the activation of endothelial cells (ECs). Activated ECs induce atherosclerosis through an increased expression of leukocyte adhesion molecules. Endothelial dysfunction (ED) is recognized as a failure of endothelial repair mechanisms. It is also an early preclinical marker of atherosclerosis and is commonly found in RA patients. RA is now established as an independent cardiovascular risk factor, while mechanistic determinants of ED in RA are still poorly understood. An expanding body of study has shown that EC at a site of RA is both active participant and regulator of inflammatory process. Over the last decade, a role for endothelial dysfunction in RA associated with cardiovascular disease (CVD) has been hypothesized. At the same time, several maintenance drugs targeting this phenomenon have been tested, which has promising results. Assessment of endothelial function may be a useful tool to identify and monitor RA patients. PMID:27122657

  11. Fatigue

    MedlinePlus

    ... sleep. Fatigue is a lack of energy and motivation. Drowsiness and apathy (a feeling of not caring ... fatigue symptoms, and your lifestyle, habits, and feelings. Tests that may be ordered include the following: Blood ...

  12. Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome.

    PubMed

    Rajeevan, Mangalathu S; Dimulescu, Irina; Murray, Janna; Falkenberg, Virginia R; Unger, Elizabeth R

    2015-08-01

    Recent evidence suggests immune and inflammatory alterations are important in chronic fatigue syndrome (CFS). This study was done to explore the association of functionally important genetic variants in inflammation and immune pathways with CFS. Peripheral blood DNA was isolated from 50 CFS and 121 non-fatigued (NF) control participants in a population-based study. Genotyping was performed with the Affymetrix Immune and Inflammation Chip that covers 11K single nucleotide polymorphisms (SNPs) following the manufacturer's protocol. Genotyping accuracy for specific genes was validated by pyrosequencing. Golden Helix SVS software was used for genetic analysis. SNP functional annotation was done using SPOT and GenomePipe programs. CFS was associated with 32 functionally important SNPs: 11 missense variants, 4 synonymous variants, 11 untranslated regulatory region (UTR) variants and 6 intronic variants. Some of these SNPs were in genes within pathways related to complement cascade (SERPINA5, CFB, CFH, MASP1 and C6), chemokines (CXCL16, CCR4, CCL27), cytokine signaling (IL18, IL17B, IL2RB), and toll-like receptor signaling (TIRAP, IRAK4). Of particular interest is association of CFS with two missense variants in genes of complement activation, rs4151667 (L9H) in CFB and rs1061170 (Y402H) in CFH. A 5' UTR polymorphism (rs11214105) in IL18 also associated with physical fatigue, body pain and score for CFS case defining symptoms. This study identified new associations of CFS with genetic variants in pathways including complement activation providing additional support for altered innate immune response in CFS. Additional studies are needed to validate the findings of this exploratory study. PMID:26116897

  13. Fatigue

    MedlinePlus

    ... chemotherapy and radiation Recovering from major surgery Anxiety, stress, or depression Staying up too late Drinking too much alcohol or too many caffeinated drinks Pregnancy One disorder that causes extreme fatigue is chronic ...

  14. Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review.

    PubMed

    Joshi, M N; Whitelaw, B C; Palomar, M T P; Wu, Y; Carroll, P V

    2016-09-01

    Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs' mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5-36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and 'high-dose' glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine-related consequences of this novel class of immunotherapies. PMID:26998595

  15. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination

    NASA Astrophysics Data System (ADS)

    de Santo, Carmela; Serafini, Paolo; Marigo, Ilaria; Dolcetti, Luigi; Bolla, Manlio; del Soldato, Piero; Melani, Cecilia; Guiducci, Cristiana; Colombo, Mario P.; Iezzi, Manuela; Musiani, Piero; Zanovello, Paola; Bronte, Vincenzo

    2005-03-01

    Active suppression of tumor-specific T lymphocytes can limit the immune-mediated destruction of cancer cells. Of the various strategies used by tumors to counteract immune attacks, myeloid suppressors recruited by growing cancers are particularly efficient, often resulting in the induction of systemic T lymphocyte dysfunction. We have previously shown that the mechanism by which myeloid cells from tumor-bearing hosts block immune defense strategies involves two enzymes that metabolize L-arginine: arginase and nitric oxide (NO) synthase. NO-releasing aspirin is a classic aspirin molecule covalently linked to a NO donor group. NO aspirin does not possess direct antitumor activity. However, by interfering with the inhibitory enzymatic activities of myeloid cells, orally administered NO aspirin normalized the immune status of tumor-bearing hosts, increased the number and function of tumor-antigen-specific T lymphocytes, and enhanced the preventive and therapeutic effectiveness of the antitumor immunity elicited by cancer vaccination. Because cancer vaccines and NO aspirin are currently being investigated in independent phase I/II clinical trials, these findings offer a rationale to combine these treatments in subjects with advanced neoplastic diseases. arginase | immunosuppression | myeloid cells | nitric oxide | immunotherapy

  16. Effector, Memory, and Dysfunctional CD8+ T Cell Fates in the Antitumor Immune Response

    PubMed Central

    2016-01-01

    The adaptive immune system plays a pivotal role in the host's ability to mount an effective, antigen-specific immune response against tumors. CD8+ tumor-infiltrating lymphocytes (TILs) mediate tumor rejection through recognition of tumor antigens and direct killing of transformed cells. In growing tumors, TILs are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment. These interactions and signals can lead to transcriptional, functional, and phenotypic changes in TILs that diminish the host's ability to eradicate the tumor. In addition to effector and memory CD8+ T cells, populations described as exhausted, anergic, senescent, and regulatory CD8+ T cells have been observed in clinical and basic studies of antitumor immune responses. In the context of antitumor immunity, these CD8+ T cell subsets remain poorly characterized in terms of fate-specific biomarkers and transcription factor profiles. Here we discuss the current characterization of CD8+ T cell fates in antitumor immune responses and discuss recent insights into how signals in the tumor microenvironment influence TIL transcriptional networks to promote CD8+ T cell dysfunction. PMID:27314056

  17. Fatigue

    MedlinePlus

    ... Fatigue can be a symptom of anemia, particularly iron-deficiency anemia . Your body needs iron to make hemoglobin, the substance in red blood ... tissues and to your baby. Your need for iron increases during pregnancy because of the needs of ...

  18. Colonic Immune Suppression, Barrier Dysfunction, and Dysbiosis by Gastrointestinal Bacillus anthracis Infection

    PubMed Central

    Sahay, Bikash; Zadeh, Mojgan; Cheng, Sam X.; Wang, Gary P.; Owen, Jennifer L.; Mohamadzadeh, Mansour

    2014-01-01

    Gastrointestinal (GI) anthrax results from the ingestion of Bacillus anthracis. Herein, we investigated the pathogenesis of GI anthrax in animals orally infected with toxigenic non-encapsulated B. anthracis Sterne strain (pXO1+ pXO2−) spores that resulted in rapid animal death. B. anthracis Sterne induced significant breakdown of intestinal barrier function and led to gut dysbiosis, resulting in systemic dissemination of not only B. anthracis, but also of commensals. Disease progression significantly correlated with the deterioration of innate and T cell functions. Our studies provide critical immunologic and physiologic insights into the pathogenesis of GI anthrax infection, whereupon cleavage of mitogen-activated protein kinases (MAPKs) in immune cells may play a central role in promoting dysfunctional immune responses against this deadly pathogen. PMID:24945934

  19. Lung involvement in childhood measles: severe immune dysfunction revealed by quantitative immunohistochemistry.

    PubMed

    Moussallem, Tálib Moysés; Guedes, Fernanda; Fernandes, Elaine Raniero; Pagliari, Carla; Lancellotti, Carmen Lucia Penteado; de Andrade, Heitor Franco; Duarte, Maria Irma Seixas

    2007-08-01

    Measles, accounting for nearly 1 million deaths each year, presents intense involvement of lymphoid organs and the lungs. The immune response in situ in the lungs was determined in blocks recovered from 42 necropsies of children who died from measles determined by immune cell phenotype (CD4, CD8, CD20, CD45RO, CD68, natural killer [NK], and antigen S-100 B [S100]) and cytokine production (interferon, tumor necrosis factor, interleukin [IL]-1, IL-2, IL-4, IL-10, and IL-12). Compared with the lungs of age-paired controls, patients with measles presented severe depletion of CD4+, CD20+, CD68+, NK+, and S100+ cells in alveolus- and bronchus-associated lymphoid tissue without depletion of CD8+ cells. Most of these features were similar in both forms of measles lung involvement, Hecht giant cell, or interstitial pneumonia, but S100+ cells were depleted in bronchus-associated lymphoid tissue from patients with Hecht pneumonia, which also occurs more frequently in malnourished children. IL-10- and IL-12-producing cells were depleted in patients with measles, whereas IL-1-, interferon-, and IL-4-producing cells were more frequently seen in the alveolus of patients with measles compared with controls. Quantitative in situ immune cell phenotype and function in the lung in measles demonstrated severe immune dysfunction, with loss of key cells, such as dendritic, CD4+, and NK+ cells, and deficient cytokine production, which allows for a better comprehension of local reactions in this process. PMID:17499339

  20. In vitro immune toxicity of polybrominated diphenyl ethers on murine peritoneal macrophages: apoptosis and immune cell dysfunction.

    PubMed

    Lv, Qi-Yan; Wan, Bin; Guo, Liang-Hong; Zhao, Lixia; Yang, Yu

    2015-02-01

    Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and are often detected in the environment, wildlife, and humans, presenting potential threats to ecosystem and human health. PBDEs can cause neurotoxicity, hepatotoxicity, and endocrine disruption. However, data on PBDE immunotoxicity are limited, and the toxicity mechanisms remain largely unknown. Both immune cell death and dysfunction can modulate the responses of the immune system. This study examined the toxic effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) on the immune system by using peritoneal macrophages as the model. The macrophages were exposed to PBDEs, and cell death was determined through flow cytometry and immunochemical blot. The results showed that after 24h of exposure, BDE-47 (>5 μM) and BDE-209 (>20 μM) induced cell apoptosis, increased intracellular reactive oxygen species (ROS) formation and depleted glutathione. BDE-47 was more potent than BDE-209; the cytotoxic concentrations for BDE-47 and BDE-209 were determined to be 5 μM and 20 μM, respectively, during 24h of exposure. However, pretreatment with n-acetyl-l-cysteine (ROS scavenger) partially reversed the cytotoxic effects. Further gene expression analyses on Caspase-3,-8,-9, TNFR1, and Bax revealed that both intrinsic and extrinsic apoptotic pathways were activated. More importantly, non-cytotoxic concentrations BDE-47 (<2 μM) and BDE-209 (<10 μM) could impair macrophage accessory cell function in a concentration-dependent manner, but no effects were observed on phagocytic responses. These revealed effects of PBDEs on macrophages may shed light on the toxicity mechanisms of PBDEs and suggest the necessity of evaluating cellular functionality during the risk assessment of PBDE immunotoxicity. PMID:25462306

  1. Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study

    PubMed Central

    van der Burg, Mirjam; la Bastide-van Gemert, Sacha; Hogendorf, Lianne A.; van Ravenswaaij-Arts, Conny M. A.; Schölvinck, Elisabeth H.

    2015-01-01

    CHARGE syndrome is a variable, multiple congenital malformation syndrome. Patients with CHARGE syndrome have frequent infections that are presumed to be due to anatomical anomalies of the craniofacial region and upper airway, and cranial nerve problems resulting in swallowing difficulties and aspiration. The possible contribution of immunological abnormalities to these infections has not been systematically studied even though immune deficiencies have been described in patients with 22q11.2 deletion syndrome, a condition which shares remarkable clinical overlap with CHARGE syndrome. We assessed the frequency and nature of immune dysfunction in 24 children with genetically proven CHARGE syndrome. All patients, or their parents, completed a questionnaire on infectious history. Their immune system was extensively assessed through full blood counts, immunoglobulin levels, lymphocyte subpopulations, peripheral B- and T-cell differentiation, T-receptor excision circle (TREC) analysis, T-cell function, and vaccination responses. All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions. Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients. Despite normal peripheral B-cell differentiation and immunoglobulin production in all patients, 83% of patients had insufficient antibody titers to one or more early childhood vaccinations. Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections. PMID:26544072

  2. Variable Neuroendocrine-Immune Dysfunction in Individuals with Unfavorable Outcome after Severe Traumatic Brain Injury

    PubMed Central

    Santarsieri, Martina; Kumar, Raj G.; Kochanek, Patrick M.; Berga, Sarah L.; Wagner, Amy K.

    2014-01-01

    Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0–6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale (GOS) scores at 6 months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas], soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome (indirect effect estimate= −0.253, 95% CI (−0.481, −0.025), p=0.03). Correlational analysis between mean cortisol levels and ILS were examined separately within each cortisol TRAJ group and by outcome. Within the low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a negative correlation between ILS and mean cortisol (r=−0.562, p=0.045). Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol (r=0.391, p=0.006). Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of

  3. Variable neuroendocrine-immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury.

    PubMed

    Santarsieri, M; Kumar, R G; Kochanek, P M; Berga, S; Wagner, A K

    2015-03-01

    Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0-6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale (GOS) scores at 6months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas], soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome (indirect effect estimate=-0.253, 95% CI (-0.481, -0.025), p=0.03). Correlational analysis between mean cortisol levels and ILS were examined separately within each cortisol TRAJ group and by outcome. Within the low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a negative correlation between ILS and mean cortisol (r=-0.562, p=0.045). Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol (r=0.391, p=0.006). Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of neuroendocrine-immune

  4. An approach to symptoms at the interface of medicine and psychiatry: pain, insomnia, weight loss and anorexia, fatigue and forgetfulness, and sexual dysfunction.

    PubMed

    Freudenreich, Oliver; Kontos, Nicholas; Nejad, Shamim H; Gross, Anne F

    2010-11-01

    Primary care physicians commonly deal with patients who present with a somatic complaint for which no clear organic etiology can be found. This article discusses how a psychiatrist thinks about somatic symptoms (eg, pain, insomnia, weight loss and loss of appetite, fatigue and forgetfulness, sexual dysfunction) in a patient who might have depression. The management of a patient in whom no satisfactory medical or psychiatric diagnosis can be made is also reviewed briefly. PMID:20951279

  5. TRESK channel as a potential target to treat T-cell mediated immune dysfunction

    SciTech Connect

    Han, Jaehee; Kang, Dawon

    2009-12-25

    In this review, we propose that TRESK background K{sup +} channel could serve as a potential therapeutic target for T-cell mediated immune dysfunction. TRESK has many immune function-related properties. TRESK is abundantly expressed in the thymus, the spleen, and human leukemic T-lymphocytes. TRESK is highly activated by Ca{sup 2+}, calcineurin, acetylcholine, and histamine which induce hypertrophy, whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and FK506. Cyclosporine A and FK506 target the binding site of nuclear factor of activated T-cells (NFAT) to inhibit calcineurin. Interestingly, TRESK possesses an NFAT-like docking site that is present at its intracellular loop. Calcineurin has been found to interact with TRESK via specific NFAT-like docking site. When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK. The activation of both TRESK and NFAT via Ca{sup 2+}-calcineurin-NFAT/TRESK pathway could modulate the transcription of new genes in addition to regulating several aspects of T-cell function.

  6. Metabolic Syndrome after Hematopoietic Cell Transplantation: At the Intersection of Treatment Toxicity and Immune Dysfunction.

    PubMed

    Turcotte, Lucie M; Yingst, Ashley; Verneris, Michael R

    2016-07-01

    Hematopoietic cell transplantation (HCT) survivors face a multitude of short- and long-term health complications in the years after treatment. One important health complication that is associated with significant morbidity is metabolic syndrome (MetSyn). This constellation of findings, which includes obesity, glucose and lipid dysmetabolism, and hypertension, places affected individuals at increased risk for type 2 diabetes mellitus, cardiovascular complications, and stroke. Previous studies have linked MetSyn in HCT survivors to prior treatment; however, few studies have addressed the potential roles of systemic inflammation and immune system dysfunction after HCT. Within this review, we address the recent advances in the understanding of adipose tissue biology, immune, and inflammatory mechanisms involved in MetSyn in non-HCT patients, and lastly, we discuss potential novel mechanisms that may play a role in MetSyn development after HCT, such as hematopoietic stem cell source, inflammatory status of the stem cell donor, and microbiome composition, all of which represent potential new directions for post-HCT MetSyn research. PMID:27013015

  7. Gut Epithelial Barrier Dysfunction and Innate Immune Activation Predict Mortality in Treated HIV Infection

    PubMed Central

    Hunt, Peter W.; Sinclair, Elizabeth; Rodriguez, Benigno; Shive, Carey; Clagett, Brian; Funderburg, Nicholas; Robinson, Janet; Huang, Yong; Epling, Lorrie; Martin, Jeffrey N.; Deeks, Steven G.; Meinert, Curtis L.; Van Natta, Mark L.; Jabs, Douglas A.; Lederman, Michael M.

    2014-01-01

    Background. While inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear. Methods. We assessed immunologic predictors of mortality in a case-control study within the Longitudinal Study of the Ocular Complications of AIDS (LSOCA), using conditional logistic regression. Sixty-four case patients who died within 12 months of treatment-mediated viral suppression were each matched to 2 control individuals (total number of controls, 128) by duration of antiretroviral therapy–mediated viral suppression, nadir CD4+ T-cell count, age, sex, and prior cytomegalovirus (CMV) retinitis. A similar secondary analysis was conducted in the SCOPE cohort, which had participants with less advanced immunodeficiency. Results. Plasma gut epithelial barrier integrity markers (intestinal fatty acid binding protein and zonulin-1 levels), soluble CD14 level, kynurenine/tryptophan ratio, soluble tumor necrosis factor receptor 1 level, high-sensitivity C-reactive protein level, and D-dimer level all strongly predicted mortality, even after adjustment for proximal CD4+ T-cell count (all P ≤ .001). A higher percentage of CD38+HLA-DR+ cells in the CD8+ T-cell population was a predictor of mortality before (P = .031) but not after (P = .10) adjustment for proximal CD4+ T-cell count. Frequencies of senescent (defined as CD28−CD57+ cells), exhausted (defined as PD1+ cells), naive, and CMV-specific T cells did not predict mortality. Conclusions. Gut epithelial barrier dysfunction, innate immune activation, inflammation, and coagulation—but not T-cell activation, senescence, and exhaustion—independently predict mortality in individuals with treated HIV infection with a history of AIDS and are viable targets for interventions. PMID:24755434

  8. Immunization Associated with Erectile Dysfunction Based on Cross-Sectional and Genetic Analyses

    PubMed Central

    Xu, Jianfeng; Gao, Yong; Tan, Aihua; Yang, Xiaobo; Qin, Xue; Hu, Yanling; Mo, Zengnan

    2014-01-01

    Erectile dysfunction (ED) is a global disease affecting a large number of people. Some studies have found a relationship between low-grade inflammation and ED. We hypothesized that the immune system might play a key role in the outcome of ED. Five immune agents (C3, C4, IgA, IgM, and IgG) were collected based on the Fangchenggang Area Male Health and Examination Survey (FAMHES), using methods of a traditional cross-sectional analysis. Our results repeated the significant association between ED and metabolic syndrome, obesity, and so forth. However, there seemed to be no positive relation between the tested indexes and ED risk in the baseline analysis (C3: P = 0.737; C4: P = 0.274; IgA: P = 0.943; IgG: P = 0.069; IgM: P = 0.985). Then, after adjusting for age and multivariate covariates, a potentially significant association between ED and IgG was discovered (P = 0.025 and P = 0.034, respectively). Meanwhile, in order to describe the development of ED on a gene level, SNP–set kernel-machine association test (SKAT) was applied with the known humoral immune genes involved. The outcomes suggested that PTAFR (binary P value: 0.0096; continuous P value: 0.00869), IL27 (0.0029; 0.1954), CD37 (0.0248; 0.5196), CD40 (0.7146; 0.0413), IL7R (0.1223; 0.0222), PSMB9 (0.1237; 0.0212), and CXCR3 (0.0849; 0.0478) might be key genes in ED, especially IL27, when we restricted the family-wise error rate (FWER) to 0.5. Our study shows that IgG and seven genes (PTAFR, CD37, CD40, IL7R, PSMB9, CXCR3, and especially IL27) might be key factors in the pathogenesis of ED, which could pave the way for future gene and immune therapies. PMID:25343742

  9. Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression.

    PubMed Central

    Lloyd, A; Hickie, I; Hickie, C; Dwyer, J; Wakefield, D

    1992-01-01

    The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS. PMID:1733640

  10. Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice

    PubMed Central

    Li, Ming; Guo, Kequan; Adachi, Yasushi; Ikehara, Susumu

    2016-01-01

    Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice. PMID:26840301

  11. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

    PubMed Central

    Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

    2015-01-01

    Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

  12. Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue

    PubMed Central

    Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo

    2015-01-01

    Objective: This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Methods: Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral “Pishu” once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Results: Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes and correct CD4+/CD8+ ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Conclusions: Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively. PMID:26770528

  13. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

    PubMed Central

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-01

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID:26819512

  14. Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection.

    PubMed

    Williamson, Lauren L; McKenney, Erin A; Holzknecht, Zoie E; Belliveau, Christine; Rawls, John F; Poulton, Susan; Parker, William; Bilbo, Staci D

    2016-01-01

    The incidence of autoimmune and inflammatory diseases has risen dramatically in post-industrial societies. "Biome depletion" - loss of commensal microbial and multicellular organisms such as helminths (intestinal worms) that profoundly modulate the immune system - may contribute to these increases. Hyperimmune-associated disorders also affect the brain, especially neurodevelopment, and increasing evidence links early-life infection to cognitive and neurodevelopmental disorders. We have demonstrated previously that rats infected with bacteria as newborns display life-long vulnerabilities to cognitive dysfunction, a vulnerability that is specifically linked to long-term hypersensitivity of microglial cell function, the resident immune cells of the brain. Here, we demonstrate that helminth colonization of pregnant dams attenuated the exaggerated brain cytokine response of their offspring to bacterial infection, and that combined with post-weaning colonization of offspring with helminths (consistent with their mothers treatment) completely prevented enduring microglial sensitization and cognitive dysfunction in adulthood. Importantly, helminths had no overt impact on adaptive immune cell subsets, whereas exaggerated innate inflammatory responses in splenic macrophages were prevented. Finally, helminths altered the effect of neonatal infection on the gut microbiome; neonatal infection with Escherichia coli caused a shift from genera within the Actinobacteria and Tenericutes phyla to genera in the Bacteroidetes phylum in rats not colonized with helminths, but helminths attenuated this effect. In sum, these data point toward an inter-relatedness of various components of the biome, and suggest potential mechanisms by which this helminth might exert therapeutic benefits in the treatment of neuroinflammatory and cognitive disorders. PMID:26162711

  15. PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells in zymosan-induced multiple organs dysfunction syndromes.

    PubMed

    Liu, Qian; Lv, Yi; Zhao, Min; Jin, Yiduo; Lu, Jiangyang

    2015-01-01

    This research is to investigate the role of tolerant spleen dendritic cells (DC) in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and MODS were induced by intraperotineal injection of zymosan. The immunity of DC was determined by examining interleukin (IL)-10, IL-12, IL-2, major histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture. The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum, spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after zymosan injection while the IL-12p40 and IL-10 were increased. The expression of MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were increased at early stage after zymosan injection. At 5 d and 12 d, the expression of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was increased, accompanied with decreased proliferation of T-cell and decrease of IL-2 in spleen and serum. Application of PD-L1 antibody improved the above changes. At late stage of MODS mice induced by zymosan, the expression of co-stimulators and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell activities by tolerant DCs and the immune inhibition. PMID:25973021

  16. PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells in zymosan-induced multiple organs dysfunction syndromes

    PubMed Central

    Liu, Qian; Lv, Yi; Zhao, Min; Jin, Yiduo; Lu, Jiangyang

    2015-01-01

    This research is to investigate the role of tolerant spleen dendritic cells (DC) in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and MODS were induced by intraperotineal injection of zymosan. The immunity of DC was determined by examining interleukin (IL)-10, IL-12, IL-2, major histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture. The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum, spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after zymosan injection while the IL-12p40 and IL-10 were increased. The expression of MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were increased at early stage after zymosan injection. At 5 d and 12 d, the expression of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was increased, accompanied with decreased proliferation of T-cell and decrease of IL-2 in spleen and serum. Application of PD-L1 antibody improved the above changes. At late stage of MODS mice induced by zymosan, the expression of co-stimulators and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell activities by tolerant DCs and the immune inhibition. PMID:25973021

  17. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

    PubMed

    Glavan, T W; Gaulke, C A; Santos Rocha, C; Sankaran-Walters, S; Hirao, L A; Raffatellu, M; Jiang, G; Bäumler, A J; Goulart, L R; Dandekar, S

    2016-05-01

    HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance. PMID:26376368

  18. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection

    PubMed Central

    Glavan, Tiffany W.; Gaulke, Christopher A; Rocha, Clarissa Santos; Sankaran-Walters, Sumathi; Hirao, Lauren A; Raffatellu, Manuela; Jiang, Guochun; Bäumler, Andreas J.; Goulart, Luiz R.; Dandekar, Satya

    2015-01-01

    HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRR) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRR and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of TLR4 and 8 was down modulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early anti-retroviral therapy led to viral suppression, but only partial maintenance of gut PRR and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes and ineffective viral clearance. PMID:26376368

  19. Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.

    PubMed

    Cleare, A J; Miell, J; Heap, E; Sookdeo, S; Young, L; Malhi, G S; O'Keane, V

    2001-08-01

    These neuroendocrine studies were part of a series of studies testing the hypotheses that 1) there may be reduced activity of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve the core symptoms. We measured ACTH and cortisol responses to human CRH, the insulin stress test, and D-fenfluramine in 37 medication-free patients with CDC-defined chronic fatigue syndrome but no comorbid psychiatric disorders and 28 healthy controls. We also measured 24-h urinary free cortisol in both groups. All patients (n = 37) had a pituitary challenge test (human CRH) and a hypothalamic challenge test [either the insulin stress test (n = 16) or D-fenfluramine (n = 21)]. Baseline cortisol concentrations were significantly raised in the chronic fatigue syndrome group for the human CRH test only. Baseline ACTH concentrations did not differ between groups for any test. ACTH responses to human CRH, the insulin stress test, and D- fenfluramine were similar for patient and control groups. Cortisol responses to the insulin stress test did not differ between groups, but there was a trend for cortisol responses both to human CRH and D-fenfluramine to be lower in the chronic fatigue syndrome group. These differences were significant when ACTH responses were controlled. Urinary free cortisol levels were lower in the chronic fatigue syndrome group compared with the healthy group. These results indicate that ACTH responses to pituitary and hypothalamic challenges are intact in chronic fatigue syndrome and do not support previous findings of reduced central responses in hypothalamic-pituitary-adrenal axis function or the hypothesis of abnormal CRH secretion in chronic fatigue syndrome. These data further suggest that the hypocortisolism found in chronic fatigue syndrome may be secondary to reduced adrenal gland output. Thirty-two patients were treated with a low-dose hydrocortisone regime in a double

  20. Shedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice.

    PubMed

    Strand, Mari E; Aronsen, Jan Magnus; Braathen, Bjørn; Sjaastad, Ivar; Kvaløy, Heidi; Tønnessen, Theis; Christensen, Geir; Lunde, Ida G

    2015-11-01

    response, promoting immune cell recruitment, extracellular matrix remodeling and mitigating cardiac dysfunction in response to LPS. PMID:26449522

  1. Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection.

    PubMed

    Li, Zhen; Jiao, Yanmei; Hu, Yu; Cui, Lianxian; Chen, Dexi; Wu, Hao; Zhang, Jianmin; He, Wei

    2015-09-01

    γδ T cells play important roles in innate immunity as the first-line of defense against infectious diseases. Human immunodeficiency virus (HIV) infection disrupts the balance between Vδ(1) T cells and Vδ(2) T cells and causes dysfunction among γδ T cells. However, the biological mechanisms and clinical consequences of this disruption require further investigation. In this study, we performed a comprehensive analysis of phenotype and function of memory γδ T cells in cohorts of Chinese individuals with HIV infection. We found a dynamic change in memory Vδ(2) γδ T cells, skewed toward an activated and terminally differentiated effector memory phenotype T(EMRA) Vδ(2) γδ T cell, which may account for the dysfunction of Vδ(2) γδ T cells in HIV disease. In addition, we found that IL-17-producing γδ T cells were significantly increased in HIV-infected patients with fast disease progression and positively correlated with HLA-DR(+) γδ T cells and CD38(+)HLA-DR(+) γδ T cells. This suggests the IL-17 signaling pathway is involved in γδ T-cell activation and HIV pathogenesis. Our findings provide novel insights into the role of Vδ(2) T cells during HIV pathogenesis and represent a sound basis on which to consider immune therapies with these cells. PMID:25220734

  2. Evidence for Immune Response, Axonal Dysfunction and Reduced Endocytosis in the Substantia Nigra in Early Stage Parkinson’s Disease

    PubMed Central

    Dijkstra, Anke A.; Ingrassia, Angela; de Menezes, Renee X.; van Kesteren, Ronald E.; Rozemuller, Annemieke J. M.; Heutink, Peter; van de Berg, Wilma D. J.

    2015-01-01

    Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of Parkinson’s disease (PD). To elucidate molecular mechanisms underlying neuronal dysfunction and alpha-synuclein pathology in the premotor phase of PD, we investigated the transcriptome of the substantia nigra (SN) of well-characterized iLBD, PD donors and age-matched controls with Braak alpha-synuclein stage ranging from 0–6. In Braak alpha-synuclein stages 1 and 2, we observed deregulation of pathways linked to axonal degeneration, immune response and endocytosis, including axonal guidance signaling, mTOR signaling, EIF2 signaling and clathrin-mediated endocytosis in the SN. In Braak stages 3 and 4, we observed deregulation of pathways involved in protein translation and cell survival, including mTOR and EIF2 signaling. In Braak stages 5 and 6, we observed deregulation of dopaminergic signaling, axonal guidance signaling and thrombin signaling. Throughout the progression of PD pathology, we observed a deregulation of mTOR, EIF2 and regulation of eIF4 and p70S6K signaling in the SN. Our results indicate that molecular mechanisms related to axonal dysfunction, endocytosis and immune response are an early event in PD pathology, whereas mTOR and EIF2 signaling are impaired throughout disease progression. These pathways may hold the key to altering the disease progression in PD. PMID:26087293

  3. Immune-Mediated Metabolic Kynurenine Pathways Are Involved in the Postoperative Cognitive Dysfunction after Cardiopulmonary Bypass.

    PubMed

    Yi, Shuang Qiang; Yang, Mi; Duan, Kai Ming

    2015-10-01

    Postoperative cognitive dysfunction (POCD) after cardiopulmonary bypass is a serious complication that can lead to personality changes, memory loss, reduction in the ability to learn, and other central nervous system dysfunctions. In recent years, there have been improvements in measures to protect the brain during surgery, although the incidence of cognitive dysfunction after cardiac surgery remains high (33 to 83% short-term and 20 to 60% long-term cognitive dysfunction). Despite the large amount of basic and clinical research on the incidence of POCD, its exact pathogenesis and complexity are not clear. Many studies have shown that the kynurenine pathway (KP) and cognitive function in humans are closely related. Some reports also show that the imbalance of some metabolites of the KP such as kynurenic acid and quinolinic acid (QUIN), which act in dynamic equilibrium under physiologic conditions, have effects on the central nervous system and can significantly affect cognitive function. Further studies have shown that inflammatory mediators may act on key enzymes of the KP causing KP-induced disorders. Severe inflammatory reaction occurs in patients undergoing cardiopulmonary bypass, which triggers metabolic pathways that are closely related to changes in cognitive function. In this review, we summarize that inflammation-induced metabolic kynurenine (KYN) pathway disorders are likely to have an important role in incidence of POCD after CPB surgery. PMID:25893921

  4. Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets.

    PubMed

    Craig, Courtney

    2015-11-01

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is an idiopathic illness characterized by debilitating fatigue and neuro-immune abnormalities. A growing body of evidence proposes mitochondrial dysfunction as a central perpetrator of the illness due to activation of immune-inflammatory pathways that burden the mitochondria. Under a model of mitochondrial dysfunction, this paper explores dietary strategies that are mitoprotective. Studied for decades, the cellular mechanisms of ketogenic diets, fasting, and caloric restriction now reveal mitochondria-specific mechanisms which could play a role in symptom reduction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Future research should examine the physiological effects of these dietary strategies in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. PMID:26315446

  5. Apathy/depression, but not subjective fatigue, is related with cognitive dysfunction in patients with multiple sclerosis

    PubMed Central

    2014-01-01

    Background Cognitive impairment could affect quality of life for patients with multiple sclerosis (MS), and cognitive function may be correlated with several factors such as depression and fatigue. This study aimed to evaluate cognitive function in Japanese patients with MS and the association between cognitive function and apathy, fatigue, and depression. Methods The Brief Repeatable Battery of Neuropsychological tests (BRB-N) was performed in 184 Japanese patients with MS and 163 healthy controls matched for age, gender, and education. The Apathy Scale (AS), Fatigue Questionnaire (FQ), and Beck Depression Inventory Second Edition (BDI-II) were used to evaluate apathy, fatigue, and depression, respectively. Student’s t-test was used to compare MS patients and healthy controls. Correlations between two factors were assessed using the Pearson correlation test, and multiple regression analysis was used to evaluate how much each factor affected the BRB-N score. Results In all BRB-N tests, patients with MS scored significantly lower than controls, and the effect size of symbol digit modalities test was the highest among the 9 tests of the BRB-N. Patients with MS had higher AS (p < 0.001), FQ (p < 0.0001), and BDI-II (p < 0.0001) scores than controls. In patients with MS, scores on most of the BRB-N tests correlated with scores on the AS and BDI-II; however, there was little correlation between scores on the BRB-N tests and those on the FQ. Conclusions Cognitive function was impaired, particularly information-processing speed, and decreased cognitive function was correlated with apathy and depression in Japanese patients with MS. Despite the association between cognitive variables and depression/apathy, cognitive function was impaired beyond the effect of depression and apathy. However, subjective fatigue is not related with cognitive impairment. Taken together, this suggests that different therapeutic approaches are needed to improve subjective fatigue

  6. Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay

    PubMed Central

    Verronèse, E.; Delgado, A.; Valladeau-Guilemond, J.; Garin, G.; Guillemaut, S.; Tredan, O.; Ray-Coquard, I.; Bachelot, T.; N'Kodia, A.; Bardin-Dit-Courageot, C.; Rigal, C.; Pérol, D.; Caux, C.; Ménétrier-Caux, C.

    2016-01-01

    ABSTRACT Monitoring functional competence of immune cell populations in clinical routine represents a major challenge. We developed a whole-blood assay to monitor functional competence of peripheral innate immune cells including NK cells, dendritic and monocyte cell subsets through their ability to produce specific cytokines after short-term stimulation, detected through intra-cytoplasmic staining and multi-parametric flow-cytometry. A PMA/ionomycin T cell activation assay complemented this analysis. Comparing cohorts of healthy women and breast cancer (BC) patients at different stages, we identified significant functional alteration of circulating immune cells during BC progression prior to initiation of treatment. Of upmost importance, as early as the localized primary tumor (PT) stage, we observed functional alterations in several innate immune populations and T cells i.e. (i) reduced TNFα production by BDCA-1+ DC and non-classical monocytes in response to Type-I IFN, (ii) a strong drop in IFNγ production by NK cells in response to either Type-I IFN or TLR7/8 ligand, and (iii) a coordinated impairment of cytokine (IL-2, IFNγ, IL-21) production by T cell subpopulations. Overall, these alterations are further accentuated according to the stage of the disease in first-line metastatic patients. Finally, whereas we did not detect functional modification of DC subsets in response to TLR7/8 ligand, we highlighted increased IL-12p40 production by monocytes specifically at first relapse (FR). Our results reinforce the importance of monitoring both innate and adaptive immunity to better evaluate dysfunctions in cancer patients and suggest that our whole-blood assay will be useful to monitor response to treatment, particularly for immunotherapeutic strategies. PMID:27141361

  7. Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

    PubMed Central

    Hardcastle, Sharni Lee; Brenu, Ekua Weba; Johnston, Samantha; Nguyen, Thao; Huth, Teilah; Ramos, Sandra; Staines, Donald; Marshall-Gradisnik, Sonya

    2015-01-01

    Immunological dysregulation is present in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), with recent studies also highlighting the importance of examining symptom severity. This research addressed this relationship between CFS/ME severity subgroups, assessing serum immunoglobulins and serum cytokines in severe and moderate CFS/ME patients. Participants included healthy controls (n= 22), moderately (n = 22) and severely (n=19) affected CFS/ME patients. The 1994 Fukuda Criteria defined CFS/ME and severity scales confirmed mobile and housebound CFS/ME patients as moderate and severe respectively. IL-1β was significantly reduced in severe compared with moderate CFS/ME patients. IL-6 was significantly decreased in moderate CFS/ME patients compared with healthy controls and severe CFS/ME patients. RANTES was significantly increased in moderate CFS/ME patients compared to severe CFS/ME patients. Serum IL-7 and IL-8 were significantly higher in the severe CFS/ME group compared with healthy controls and moderate CFS/ME patients. IFN-γ was significantly increased in severe CFS/ME patients compared with moderately affected patients. This was the first study to show cytokine variation in moderate and severe CFS/ME patients, with significant differences shown between CFS/ME symptom severity groups. This research suggests that distinguishing severity subgroups in CFS/ME research settings may allow for a more stringent analysis of the heterogeneous and otherwise inconsistent illness. PMID:26516304

  8. Gut inflammation in chronic fatigue syndrome.

    PubMed

    Lakhan, Shaheen E; Kirchgessner, Annette

    2010-01-01

    Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis.Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut.If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients. PMID:20939923

  9. IL-15 Prevents Apoptosis, Reverses Innate and Adaptive Immune Dysfunction, and Improves Survival in Sepsis

    PubMed Central

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G.; Muenzer, Jared T.; Ferguson, Thomas A.; Chang, Katherine; Osborne, Dale F.; Clark, Andrew T.; Coopersmith, Craig M.; McDunn, Jonathan E.; Hotchkiss, Richard S.

    2010-01-01

    L-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2×2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-γ, as well as the percentage of NK cells that produced IFN-γ. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder. PMID:20026737

  10. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

    PubMed

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G; Muenzer, Jared T; Ferguson, Thomas A; Chang, Katherine; Osborne, Dale F; Clark, Andrew T; Coopersmith, Craig M; McDunn, Jonathan E; Hotchkiss, Richard S

    2010-02-01

    IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder. PMID:20026737

  11. Innate Immune Dysfunctions in Aged Mice Facilitate the Systemic Dissemination of Methicillin-Resistant S. aureus

    PubMed Central

    Tseng, Ching Wen; Kyme, Pierre A.; Arruda, Andrea; Ramanujan, V. Krishnan; Tawackoli, Wafa; Liu, George Y.

    2012-01-01

    Elderly humans show increased susceptibility to invasive staphylococcal disease after skin and soft tissue infection. However, it is not understood how host immunity changes with aging, and how that predisposes to invasive disease. In a model of severe skin infection, we showed that aged mice (16- to 20-month-old) exhibit dramatic bacterial dissemination compared with young adult mice (2-month-old). Bacterial dissemination was associated with significant reductions of CXCL1 (KC), polymorphonuclear cells (PMNs), and extracellular DNA traps (NETs) at the infection site. PMNs and primary skin fibroblasts isolated from aged mice showed decreased secretion of CXCL2 (MIP-2) and KC in response to MRSA, and in vitro analyses of mitochondrial functions revealed that the mitochondrial electron transport chain complex I plays a significant role in induction of chemokines in the cells isolated from young but not old mice. Additionally, PMNs isolated from aged mice have reduced ability to form NETs and to kill MRSA. Expression of nuclease by S. aureus led to increased bacterial systemic dissemination in young but not old mice, suggesting that defective NETs formation in elderly mice permitted nuclease and non-nuclease expressing S. aureus to disseminate equally well. Overall, these findings suggest that gross impairment of both skin barrier function and innate immunity contributes to the propensity for MRSA to disseminate in aged mice. Furthermore, the study indicates that contribution of bacterial factors to pathogenicity may vary with host age. PMID:22844481

  12. Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction.

    PubMed

    Kudo-Saito, Chie; Fuwa, Takafumi; Murakami, Kouichi; Kawakami, Yutaka

    2013-10-15

    Bone metastasis greatly deteriorates the quality of life in patients with cancer. Although mechanisms have been widely investigated, the relationship between cancer bone metastasis and antitumor immunity in the host has been much less studied. Here, we report a novel mechanism of bone metastasis mediated by FSTL1, a follistatin-like glycoprotein secreted by Snail(+) tumor cells, which metastasize frequently to bone. We found that FSTL1 plays a dual role in bone metastasis-in one way by mediating tumor cell invasion and bone tropism but also in a second way by expanding a population of pluripotent mesenchymal stem-like CD45(-)ALCAM(+) cells derived from bone marrow. CD45(-)ALCAM(+) cells induced bone metastasis de novo, but they also generated CD8(low) T cells with weak CTL activity in the periphery, which also promoted bone metastasis in an indirect manner. RNA interference-mediated attenuation of FSTL1 in tumor cells prevented bone metastasis along with the parallel increase in ALCAM(+) cells and CD8(low) T cells. These effects were accompanied by heightened antitumor immune responses in vitro and in vivo. In clinical specimens of advanced breast cancer, ALCAM(+) cells increased with FSTL1 positivity in tumor tissues, but not in adjacent normal tissues, consistent with a causal connection between these molecules. Our findings define FSTL1 as an attractive candidate therapeutic target to prevent or treat bone metastasis, which remains a major challenge in patients with cancer. PMID:23966294

  13. Effect of Splenic Regulatory T-cell Apoptosis on the Postresuscitation Immune Dysfunction in a Porcine Model

    PubMed Central

    Gu, Wei; Zhang, Qian; Li, Chun-Sheng

    2016-01-01

    Background: Postresuscitation immune dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The purpose of this study was to investigate whether splenic regulatory T-cell (Treg) apoptosis was involved in the postresuscitation immune dysfunction. Methods: Thirty-eight pigs were randomly divided into sham-operated group (SHAM group, n = 8), 12 h post return of spontaneous circulation (ROSC) group, 24 h post-ROSC group, and 48 h post-ROSC group (n = 10 per group). A Wuzhishan miniature porcine model of 8-min ventricular fibrillation cardiac arrest (CA) was established. The apoptosis rates of Treg in the spleen were tested by flow cytometry; the expressions of forkhead/winged helix transcription factor (Foxp3) of Treg in the spleen were detected by real-time polymerase chain reaction; and the levels of interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-γ) of Treg in the spleen were detected by enzyme-linked immunosorbent assay. Results: The apoptosis rates of Treg in all post-ROSC groups were significantly lower than that of SHAM group (7.7% ± 1.9%, 7.1% ± 1.8%, 6.2% ± 0.4% vs. 13.1% ± 1.6%; P < 0.05); the expression levels of Foxp3 and IL-10 were also decreased with the increase of apoptosis rates of Treg. Helper T-cells CD4+ lymphocyte subsets were significantly lower in the post-ROSC groups compared with SHAM group (29.1% ± 2.2%, 24.3% ± 2.2%, 24.1% ± 2.5% vs. 43.8% ± 4.5%; P < 0.01) at 12, 24, and 48 h after ROSC. Compared with SHAM group, the levels of IFN-γ (161.0 ± 12.9, 167.7 ± 10.5, 191.2 ± 7.7 vs. 7.6 ± 0.9 ng/L) and IL-4 (27.7 ± 6.2, 35.9 ± 3.5, 50.6 ± 6.1 vs. 13.3 ± 2.3 ng/L) and the ratio of IFN-γ/IL-4 (8.6 ± 2.3, 4.9 ± 0.4, 4.5 ± 0.9 vs. 0.8 ± 0.2) were all greatly elevated in all post-ROSC groups (P < 0.05). Conclusions: Apoptosis rate of Treg was significantly decreased after CA, and thus the proportion of Treg was increased and the inhibitory effects were

  14. Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction

    PubMed Central

    Zhao, Sanhu; Yang, Yanyong; Liu, Wen; Xuan, Zhiqiang; Wu, Shouming; Yu, Shunfei; Mei, Ke; Huang, Yijuan; Zhang, Pei; Cai, Jianming; Ni, Jin; Zhao, Yaoxian

    2014-01-01

    Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H2 was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H2 could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H2 treatment. H2 also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H2. Finally, we found that H2 could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H2 as an effective radioprotective agent on immune system by scavenging reactive oxygen species. PMID:24618260

  15. Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.

    PubMed

    Wernstedt Asterholm, Ingrid; Kim-Muller, Ja Young; Rutkowski, Joseph M; Crewe, Clair; Tao, Caroline; Scherer, Philipp E

    2016-09-01

    Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. PMID:27397737

  16. Prominent Lymphatic Vessel Hyperplasia with Progressive Dysfunction and Distinct Immune Cell Infiltration in Lymphedema.

    PubMed

    Gousopoulos, Epameinondas; Proulx, Steven T; Scholl, Jeannette; Uecker, Maja; Detmar, Michael

    2016-08-01

    Lymphedema is a common complication that occurs after breast cancer treatment in up to 30% of the patients undergoing surgical lymph node excision. It is associated with tissue swelling, fibrosis, increased risk of infection, and impaired wound healing. Despite the pronounced clinical manifestations of the disease, little is known about the morphological and functional characteristics of the lymphatic vasculature during the course of lymphedema progression. We used an experimental murine tail lymphedema model where sustained fluid stasis was generated on disruption of lymphatic flow, resulting in chronic edema formation with fibrosis and adipose tissue deposition. Morphological analysis of the lymphatic vessels revealed a dramatic expansion during the course of the disease, with active proliferation of lymphatic endothelial cells at the early stages of lymphedema. The lymphatic capillaries exhibited progressively impaired tracer filling and retrograde flow near the surgery site, whereas the collecting lymphatic vessels showed a gradually decreasing contraction amplitude with unchanged contraction frequency, leading to lymphatic contraction arrest at the later stages of the disease. Lymphedema onset was associated with pronounced infiltration by immune cells, predominantly Ly6G(+) and CD4(+) cells, which have been linked to impaired lymphatic vessel function. PMID:27315777

  17. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit

    PubMed Central

    Myhill, Sarah; Booth, Norman E; McLaren-Howard, John

    2013-01-01

    We report on an audit of 138 ME/CFS patients who attended a private practice and took the ATP Profile biomedical test. The results revealed that all of these patients had measureable mitochondrial dysfunction. A basic treatment regime, based on 1) eating the evolutionary correct stone-age diet, 2) ensuring optimum hours of good quality sleep, 3) taking a standard package of nutritional supplements, and 4) getting the right balance between work and rest, was recommended for all patients. Additions to the basic regime were tailored for each patient according to the results of the ATP Profile and additional nutritional tests and clues from the clinical history. Mitochondrial function is typically impaired in two ways: substrate or co-factor deficiency, and inhibition by chemicals, exogenous or endogenous. For the former, additional nutrients are recommended where there is a deficiency, and for the latter, improvement of anti-oxidant status and selective chelation therapy or far-infrared saunas are appropriate. We show case histories of nine patients who have taken the ATP Profile on three or four occasions, and a before-and-after treatment summary of the 34 patients who have had at least two ATP Profile tests separated by some months. Finally, we summarize the results for the 30 patients who followed all aspects of the treatment regime and compare them with the 4 patients who were lax on two or more aspects of the treatment regime. All patients who followed the treatment regime improved in mitochondrial function by on average a factor of 4. PMID:23236553

  18. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit.

    PubMed

    Myhill, Sarah; Booth, Norman E; McLaren-Howard, John

    2013-01-01

    We report on an audit of 138 ME/CFS patients who attended a private practice and took the ATP Profile biomedical test. The results revealed that all of these patients had measureable mitochondrial dysfunction. A basic treatment regime, based on 1) eating the evolutionary correct stone-age diet, 2) ensuring optimum hours of good quality sleep, 3) taking a standard package of nutritional supplements, and 4) getting the right balance between work and rest, was recommended for all patients. Additions to the basic regime were tailored for each patient according to the results of the ATP Profile and additional nutritional tests and clues from the clinical history. Mitochondrial function is typically impaired in two ways: substrate or co-factor deficiency, and inhibition by chemicals, exogenous or endogenous. For the former, additional nutrients are recommended where there is a deficiency, and for the latter, improvement of anti-oxidant status and selective chelation therapy or far-infrared saunas are appropriate. We show case histories of nine patients who have taken the ATP Profile on three or four occasions, and a before-and-after treatment summary of the 34 patients who have had at least two ATP Profile tests separated by some months. Finally, we summarize the results for the 30 patients who followed all aspects of the treatment regime and compare them with the 4 patients who were lax on two or more aspects of the treatment regime. All patients who followed the treatment regime improved in mitochondrial function by on average a factor of 4. PMID:23236553

  19. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

    PubMed Central

    Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

    2016-01-01

    Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and

  20. [Endothelial dysfunction and nonspecific immune reactions in development and progression of osteoarthrosis in women engaged into manual work].

    PubMed

    Maliutina, N N; Nevzorova, M S

    2015-01-01

    The article considers mechanisms of development and progression of osteoarthrosis as an occupationally conditioned disease in women of manual work. Women working in physical overstrain conditions are under occupational risk with dysfunction of many body systems. The authors set a hypothesis on association of endothelial dysfunction markers dysbalance and structural remodelling of cartilage matrix as a proof of degenerative changes. PMID:26596115

  1. Chronic fatigue syndrome. 1: Etiology and pathogenesis.

    PubMed

    Farrar, D J; Locke, S E; Kantrowitz, F G

    1995-01-01

    Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by debilitating fatigue and other somatic and neuropsychiatric symptoms. A range of heterogeneous clinical and laboratory findings have been reported in patients with CFS. Various theories have been proposed to explain the underlying pathophysiologic processes but none has been proved. Research findings of immunologic dysfunction and neuroendocrine changes suggest the possible dysregulation of interactions between the nervous system and the immune system. Without a clear understanding of its etiopathogenesis, CFS has no definitive treatment. Management approaches have been necessarily speculative, and they have evolved separately in a number of medical and nonmedical disciplines. The results of several controlled treatment studies have been inconclusive. An accurate case definition identifying homogeneous subtypes of CFS is needed. The integration of medical and psychologic treatment modalities and the use of both biologic and psychologic markers to evaluate treatment response will enhance future treatment strategies. PMID:7579775

  2. Immunizations

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  3. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  4. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  5. Bone Components Downregulate Expression of Toll-Like Receptor 4 on the Surface of Human Monocytic U937 Cells: A Cell Model for Postfracture Immune Dysfunction

    PubMed Central

    Lin, Jui-An; Lin, Feng-Yen; Chen, Ta-Liang

    2015-01-01

    To mimic the immune status of monocyte in the localized fracture region, toll-like receptor 4 (TLR4) surface expression in human monocytic U937 cells was used as the main target to assess immune dysfunction following bone component exposure. We first identified the effects of bone components (including the marrow content) on TLR4 surface expression and then examined the mechanisms underlying the changes. The level of microRNA-146a expression, an indicator of endotoxin tolerance, was also assayed. Bone component exposure downregulated TLR4 surface expression at 24 h by flow cytometry analysis, compatible with the result obtained from the membranous portion of TLR4 by western blot analysis. The cytoplasmic portion of TLR4 paradoxically increased after bone component exposure. Impaired TLR4 trafficking from the cytoplasm to the membrane was related to gp96 downregulation, as observed by western blot analysis, and this was further evidenced by gp96-TLR4 colocalization under confocal microscopy. TaqMan analysis revealed that the expression of microRNA-146a was also upregulated. This cell model demonstrated that bone component exposure downregulated TLR4 surface expression in a gp96-related manner in human monocytic U937 cells, an indicator of immunosuppression at 24 h. Immune dysfunction was further evidenced by upregulation of microRNA-146a expression at the same time point. PMID:26273144

  6. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

    PubMed Central

    Lu, Wei; Mehraj, Vikram; Vyboh, Kishanda; Cao, Wei; Li, Taisheng; Routy, Jean-Pierre

    2015-01-01

    Introduction Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. Method We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Discussion Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. Conclusion The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials. PMID:26130226

  7. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures

    PubMed Central

    Rossignol, D A; Frye, R E

    2012-01-01

    Recent studies have implicated physiological and metabolic abnormalities in autism spectrum disorders (ASD) and other psychiatric disorders, particularly immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures (‘four major areas'). The aim of this study was to determine trends in the literature on these topics with respect to ASD. A comprehensive literature search from 1971 to 2010 was performed in these four major areas in ASD with three objectives. First, publications were divided by several criteria, including whether or not they implicated an association between the physiological abnormality and ASD. A large percentage of publications implicated an association between ASD and immune dysregulation/inflammation (416 out of 437 publications, 95%), oxidative stress (all 115), mitochondrial dysfunction (145 of 153, 95%) and toxicant exposures (170 of 190, 89%). Second, the strength of evidence for publications in each area was computed using a validated scale. The strongest evidence was for immune dysregulation/inflammation and oxidative stress, followed by toxicant exposures and mitochondrial dysfunction. In all areas, at least 45% of the publications were rated as providing strong evidence for an association between the physiological abnormalities and ASD. Third, the time trends in the four major areas were compared with trends in neuroimaging, neuropathology, theory of mind and genetics (‘four comparison areas'). The number of publications per 5-year block in all eight areas was calculated in order to identify significant changes in trends. Prior to 1986, only 12 publications were identified in the four major areas and 51 in the four comparison areas (42 for genetics). For each 5-year period, the total number of publications in the eight combined areas increased progressively. Most publications (552 of 895, 62%) in the four major areas were published in the last 5 years (2006–2010). Evaluation

  8. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction.

    PubMed

    Couette, Maryline; Boisse, Marie-Françoise; Maison, Patrick; Brugieres, Pierre; Cesaro, Pierre; Chevalier, Xavier; Gherardi, Romain K; Bachoud-Levi, Anne-Catherine; Authier, François-Jérôme

    2009-11-01

    Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression. PMID:19748679

  9. Anti-fatigue and vasoprotective effects of quercetin-3-O-gentiobiose on oxidative stress and vascular endothelial dysfunction induced by endurance swimming in rats.

    PubMed

    Lin, Yin; Liu, Hua-Liang; Fang, Jie; Yu, Chen-Huan; Xiong, Yao-Kang; Yuan, Ke

    2014-06-01

    Chronic fatigue accumulation increases the incidence of cardiovascular disease while the treatment of antioxidants could prevent this development. We have previously shown that quercetin-3-O-gentiobiose (QG), a flavonoid isolated from tonic herb Okra, possesses anti-oxidative properties. In the present study, the protective effects of QG were evaluated in a rat model of load-induced endurance swimming. Oral administration of QG at the doses of 25-75mg/kg could significantly improve the endurance capability of rats to fatigue along with decrease serum lactic acid and blood urea nitrogen levels were decreased. Moreover, QG could alleviate vascular impairments, enhance the activities of antioxidant enzymes and attenuate the levels of inflammatory cytokines (MCP-1, IL-6 and TNF-α). The results indicated that QG had anti-fatigue and vasoprotective effects and represented a potential agent for the treatment of aortic pathology involved with fatigue- and related syndrome. PMID:24685824

  10. Individual Differences in Self-Regulatory Failure and Menstrual Dysfunction Predict Upper Respiratory Infection Symptoms and Antibody Response to Flu Immunization

    PubMed Central

    Strauman, Timothy J.; Coe, Christopher L.; McCrudden, Megan C.; Vieth, Angela Z.; Kwapil, Lori

    2008-01-01

    Prior research indicates that cognitive priming manipulations that activate personal goals acutely increase or decrease natural killer cell cytotoxicity depending on whether individuals see themselves as making or failing to make progress toward their goals. Those findings in a laboratory setting revealed a psychobiological pathway whereby experiences of failure can influence health, but did not assess the impact of chronic perceived success/failure in goal pursuit on actual health outcomes. Three new studies investigated whether individual differences in perceived failure to attain personal goals influenced the self-reported symptoms of upper respiratory infections (URIs) as well as antibody response to flu immunization. Based on pilot data in young women, it also was hypothesized that the occurrence of menstrual dysfunction might interact with goal pursuit failure to more specifically predict cold and flu symptoms and optimal responses to vaccination. Perceived failure to attain goals did predict the reporting of URI symptoms as well as antibody levels post-immunization, both alone and in combination with menstrual dysfunction. PMID:18294813

  11. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures.

    PubMed

    Gunn, Shelly R; Gunn, G Gibson; Mueller, Francis W

    2016-01-01

    BACKGROUND Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. CASE REPORT A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient's water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient's symptoms resolved. He is off medications, back to work, and resuming normal exercise. CONCLUSIONS This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and may represent a treatable underlying disease etiology in a subset of genetically susceptible patients with RUC, CFS, and other immune disorders. PMID:27165859

  12. Integrated Immune

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

    2010-01-01

    This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  13. The role of immune activation in contributing to vascular dysfunction and the pathophysiology of hypertension during preeclampsia

    PubMed Central

    LaMarca, Babbette

    2012-01-01

    Summary Alterations in vascular function contributes to hypertension as well as multi-organ dysfunction in women with preeclampsia (1,4, 11–14). Preterm preeclampsia remains a leading cause of maternal death and perinatal morbidity and most recently it has been recognized that women whom endure preeclampsia are at a greater risk for cardiovascular disease later in life. The pathophysiologic processes that underlie preeclampsia has been proposed to occur in two stages: stage 1, reduced placental perfusion, and stage 2, the maternal clinical syndrome (1,4). Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors that have profound effects on blood flow and arterial pressure regulation (Figure 1) (1, 4, 10, 11). These factors include a host of molecules such as the soluble VEGF receptor-1 (sFlt-1), the angiotensin II type-1 receptor autoantibody (AT1-AA), and cytokines such as TNF-α and Interleukin 6 which in turn generate widespread dysfunction of the maternal vascular endothelium (1–11). This dysfunction results in formation of factors such as endothelin, reactive oxygen species (ROS), and augmented vascular sensitivity to angiotensin II (1–11). In addition, preeclampsia is also associated with decreased formation of vasodilators such as nitric oxide and prostacyclin (1–11). These alterations in vascular function not only lead to hypertension but multi-organ dysfunction, especially in women with early onset preeclampsia (1,4, 11–14). Therefore, identifying the connection between placental ischemia and maternal cardiovascular abnormalities is an important area of investigation (1,10,11,21). In addition, the quantitative importance of the various endothelial and humoral factors that mediate vascular dysfunction and hypertension during preeclampsia remains to be elucidated. PMID:20502423

  14. Immunizations.

    PubMed

    Sanford, Christopher A; Jong, Elaine C

    2016-03-01

    Vaccinations are a cornerstone of the pretravel consultation. The pretravel provider should assess a traveler's past medical history, planned itinerary, activities, mode of travel, and duration of stay and make appropriate vaccine recommendations. Given that domestic vaccine-preventable illnesses are more common in international travelers than are exotic or low-income nation-associated vaccine-preventable illnesses, clinicians should first ensure that travelers are current regarding routine immunizations. Additional immunizations may be indicated in some travelers. Familiarity with geographic distribution and seasonality of infectious diseases is essential. Clinicians should be cognizant of which vaccines are live, as there exist contraindications for live vaccines. PMID:26900111

  15. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  16. Fatigue in systemic lupus erythematosus.

    PubMed

    Ahn, Grace E; Ramsey-Goldman, Rosalind

    2012-04-01

    Systemic lupus erythematosus is a chronic inflammatory autoimmune disease often characterized by fatigue, with significant effects on physical functioning and wellbeing. The definition, prevalence and factors associated with fatigue, including physical activity, obesity, sleep, depression, anxiety, mood, cognitive dysfunction, vitamin D deficiency/insufficiency, pain, effects of medications and comorbidities, as well as potential therapeutic options of fatigue in the systemic lupus erythematosus population are reviewed. Due to variability in the reliability and validity of various fatigue measures used in clinical studies, clinical trial data have been challenging to interpret. Further investigation into the relationships between these risk factors and fatigue, and improved measures of fatigue, may lead to an improvement in the management of this chronic inflammatory disease. PMID:22737181

  17. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

    PubMed Central

    Shanely, R. Andrew; Nieman, David C.; Perkins-Veazie, Penelope; Henson, Dru A.; Meaney, Mary P.; Knab, Amy M.; Cialdell-Kam, Lynn

    2016-01-01

    Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID:27556488

  18. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity.

    PubMed

    Shanely, R Andrew; Nieman, David C; Perkins-Veazie, Penelope; Henson, Dru A; Meaney, Mary P; Knab, Amy M; Cialdell-Kam, Lynn

    2016-01-01

    Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID:27556488

  19. Overcoming Hypoxia-Mediated Tumor Progression: Combinatorial Approaches Targeting pH Regulation, Angiogenesis and Immune Dysfunction

    PubMed Central

    McDonald, Paul C.; Chafe, Shawn C.; Dedhar, Shoukat

    2016-01-01

    Hypoxia is an important contributor to the heterogeneity of the microenvironment of solid tumors and is a significant environmental stressor that drives adaptations which are essential for the survival and metastatic capabilities of tumor cells. Critical adaptive mechanisms include altered metabolism, pH regulation, epithelial-mesenchymal transition, angiogenesis, migration/invasion, diminished response to immune cells and resistance to chemotherapy and radiation therapy. In particular, pH regulation by hypoxic tumor cells, through the modulation of cell surface molecules such as extracellular carbonic anhydrases (CAIX and CAXII) and monocarboxylate transporters (MCT-1 and MCT-4) functions to increase cancer cell survival and enhance cell invasion while also contributing to immune evasion. Indeed, CAIX is a vital regulator of hypoxia mediated tumor progression, and targeted inhibition of its function results in reduced tumor growth, metastasis, and cancer stem cell function. However, the integrated contributions of the repertoire of hypoxia-induced effectors of pH regulation for tumor survival and invasion remain to be fully explored and exploited as therapeutic avenues. For example, the clinical use of anti-angiogenic agents has identified a conundrum whereby this treatment increases hypoxia and cancer stem cell components of tumors, and accelerates metastasis. Furthermore, hypoxia results in the infiltration of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg) and Tumor Associated Macrophages (TAMs), and also stimulates the expression of PD-L1 on tumor cells, which collectively suppress T-cell mediated tumor cell killing. Therefore, combinatorial targeting of angiogenesis, the immune system and pH regulation in the context of hypoxia may lead to more effective strategies for curbing tumor progression and therapeutic resistance, thereby increasing therapeutic efficacy and leading to more effective strategies for the treatment of patients with

  20. Irreversible loss of pDCs by apoptosis during early HIV infection may be a critical determinant of immune dysfunction.

    PubMed

    Meera, Singh; Madhuri, Thakar; Manisha, Ghate; Ramesh, Paranjape

    2010-06-01

    The dendritic cell subsets myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) play an important role in HIV pathogenesis. While pDCs play a major role in the innate immune response, mDCs are important for induction of the antigen-specific immune response. We studied pDCs and mDCs at different stages of HIV infection, and found that there were decreased percentages of pDCs and mDCs in the advanced stage of the disease (p < 0.0001), and that slow progressors did not show as great a decrease as more healthy individuals. Persons who had acquired infection within the last year showed a normal mDC percentage but a lower pDC percentage (p = 0.0092) than healthy individuals (0.16%). pDC percentages in those with late-stage disease did not revert to normal after successful antiretroviral therapy (ART), whereas mDC percentages reverted to levels comparable to those seen in the healthy population (0.08% pre-ART to 0.18% post-ART; p < 0.0001). The pDC population had high levels of apoptotic markers in those with recent (p = 0.0025) and advanced (p = 0.0012) HIV infection, with no difference in their migratory capacity from controls and slow progressors, indicating that apoptosis is the major mechanism of declining pDC numbers in the circulation. mDCs showed increased levels of apoptotic markers (p = 0.0012), as well as migration (p = 0.03), in those with advanced-stage disease compared to controls, suggesting that both migration and apoptosis contribute to the decline seen in mDCs in the circulation. The irreversible loss of pDCs due to apoptosis seen early in HIV infection may be responsible for an impaired innate anti-HIV immune response. However, the presence of functionally-competent pDCs in slow progressors implies that the loss of pDCs early in infection may be critical to control of HIV infection through innate immune mechanisms, and may influence the progression of disease. PMID:20565289

  1. Accumulation of hyporesponsive, calcium extruding memory T cells as a key feature of age-dependent immune dysfunction.

    PubMed

    Miller, R A

    1991-03-01

    In this review I propose a hypothesis with a number of testable predictions: that the age-dependent decline in T lymphocyte function is largely the result of the accumulation of memory T lymphocytes with over-active plasma membrane calcium pumps. This idea is consistent with much, though not all, of the currently available data. I will start by presenting the evidence that suggested and most clearly supports this idea, then discuss apparently contrary data (some of it still difficult to reconcile with the model), and lastly consider the implications of the model for our understanding of late life development of the T cell immune system. PMID:2001603

  2. Urinary Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Urinary Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... dysfunction is normal following initial therapy for localized prostate cancer. But it’s important to realize that not all ...

  3. Trypanosoma cruzi-induced host immune system dysfunction: a rationale for parasite immunosuppressive factor(s) encoding gene targeting

    PubMed Central

    2001-01-01

    An intense suppression of T cell proliferation to mitogens and to antigens is observed in a large number of parasitic infections. The impairment of T cell proliferation also occurred during the acute phase of Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi. A wealth of evidence has accumulated that illustrates the ability of T. cruzi released molecules to influence directly a variety of diverse immunological functions. In this paper, we review the data concerning the immunoregulatory effects of T. cruzi Tc24 (a B cell activator antigen) and Tc52 (an immunosuppressive protein) released molecules on the host immune system. The gene targeting approach developed to further explore the biological function(s) of Tc52 molecule, revealed interesting unexpected functional properties. Indeed, in addition to its immunusuppressive activity a direct or indirect involvement of Tc52 gene product alone or in combination with other cellular components in T. cruzi differentiation control mechanisms have been evidenced. Moreover, targeted Tc52 replacement allowed the obtention of parasite mutants exhibiting low virulence in vitro and in vivo. Thus, the generation of a complete deficiency state of virulence factors by gene targeting should provide a means to assess the importance of these factors in the pathophysiological processes and disease progression. It is hoped that such approaches might allow rational design of tools to control T. cruzi infections. PMID:12488621

  4. Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis.

    PubMed

    Huth, T K; Brenu, E W; Ramos, S; Nguyen, T; Broadley, S; Staines, D; Marshall-Gradisnik, S

    2016-01-01

    Patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and multiple sclerosis (MS) suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue-related symptoms suffered by patients with CFS/ME and MS, dysfunction of the immune system and, in particular, reduced natural killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS. The purpose of this pilot study was to compare NK cellular mechanisms in patients with CFS/ME and MS to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56(dim) CD16(+) and CD56(bright) CD16(+/-) NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins. All participants in this study were female and included 14 patients with CFS/ME, nine patients with MS and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune-enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56(bright) CD16(+/-) NK cells and expression of CD94 was significantly increased on CD56(dim) CD16(+) NK cells in comparison with the controls. Co-expression of CD57 and perforin was significantly increased on CD56(dim) CD16(+) NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. The results from this pilot study suggest that NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway. PMID:26381393

  5. Gene Expression of Mesothelioma in Vinylidene Chloride-Exposed F344/N Rats Reveals Immune Dysfunction, Tissue Damage, and Inflammation Pathways

    PubMed Central

    Blackshear, Pamela E.; Pandiri, Arun R.; Nagai, Hiroaki; Bhusari, Sachin; Hong, Lily; Ton, Thai-Vu T.; Clayton, Natasha P.; Wyde, Michael; Shockley, Keith R.; Peddada, Shyamal D.; Gerrish, Kevin E.; Sills, Robert C.; Hoenerhoff, Mark J.

    2014-01-01

    A majority (~80%) of human malignant mesotheliomas are asbestos-related. However, non-asbestos risk factors (radiation, chemicals, genetic factors) account for up to 30% of cases. A recent two-year National Toxicology Program carcinogenicity bioassay showed that male F344/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and vinylidene chloride-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from vinylidene chloride-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the NF-kB signaling pathway, IL-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and NK and DC signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, proinflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor and cell cycle regulation, resulting in an increased incidence of mesothelioma. PMID:24958746

  6. Bowel Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Bowel Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... rectal worse. Back to Side Effects Print | Understanding Prostate Cancer Research Faces of Prostate Cancer About PCF Take ...

  7. Traditional Chinese Medicine for Chronic Fatigue Syndrome

    PubMed Central

    Chen, Rui; Moriya, Junji; Yamakawa, Jun-ichi; Takahashi, Takashi

    2010-01-01

    More and more patients have been diagnosed as having chronic fatigue syndrome (CFS) in recent years. Western drug use for this syndrome is often associated with many side-effects and little clinical benefit. As an alternative medicine, traditional Chinese medicine (TCM) has provided some evidences based upon ancient texts and recent studies, not only to offer clinical benefit but also offer insights into their mechanisms of action. It has perceived advantages such as being natural, effective and safe to ameliorate symptoms of CFS such as fatigue, disordered sleep, cognitive handicaps and other complex complaints, although there are some limitations regarding the diagnostic standards and methodology in related clinical or experimental studies. Modern mechanisms of TCM on CFS mainly focus on adjusting immune dysfunction, regulating abnormal activity in the hypothalamic-pituitary-adrenal (HPA) axis and serving as an antioxidant. It is vitally important for the further development to establish standards for ‘zheng’ of CFS, i.e. the different types of CFS pathogenesis in TCM, to perform randomized and controlled trials of TCM on CFS and to make full use of the latest biological, biochemical, molecular and immunological approaches in the experimental design. PMID:18955323

  8. The neuroimmune basis of fatigue.

    PubMed

    Dantzer, Robert; Heijnen, Cobi Johanna; Kavelaars, Annemieke; Laye, Sophie; Capuron, Lucile

    2014-01-01

    The exact nature and pathophysiology of fatigue remain largely elusive despite its high prevalence in physically ill patients. Studies on the relationship between the immune system and the central nervous system provide a new perspective on the mechanisms of fatigue. Inflammatory mediators that are released by activated innate immune cells at the periphery and in the central nervous system alter the metabolism and activity of neurotransmitters, generate neurotoxic compounds, decrease neurotrophic factors, and profoundly disturb the neuronal environment. The resulting alterations in fronto-striatal networks together with the activation of insula by inflammatory interoceptive stimuli underlie the many dimensions of fatigue including reduced incentive motivation, decreased behavioral flexibility, uncertainty about usefulness of actions, and awareness of fatigue. PMID:24239063

  9. Influence of Pistachios on Performance and Exercise-Induced Inflammation, Oxidative Stress, Immune Dysfunction, and Metabolite Shifts in Cyclists: A Randomized, Crossover Trial

    PubMed Central

    Nieman, David C.; Scherr, Johannes; Luo, Beibei; Meaney, Mary Pat; Dréau, Didier; Sha, Wei; Dew, Dustin A.; Henson, Dru A.; Pappan, Kirk L.

    2014-01-01

    Objectives Pistachio nut ingestion (3 oz./d, two weeks) was tested for effects on exercise performance and 21-h post-exercise recovery from inflammation, oxidative stress, immune dysfunction, and metabolite shifts. Methods Using a randomized, crossover approach, cyclists (N = 19) engaged in two 75-km time trials after 2-weeks pistachio or no pistachio supplementation, with a 2-week washout period. Subjects came to the lab in an overnight fasted state, and ingested water only or 3 oz. pistachios with water before and during exercise. Blood samples were collected 45 min pre-exercise, and immediately post-, 1.5-h post-, and 21-h post-exercise, and analyzed for plasma cytokines, C-reactive protein (CRP), F2-isoprostanes (F2-IsoP), granulocyte phagocytosis (GPHAG) and oxidative burst activity (GOBA), and shifts in metabolites. Results Performance time for the 75-km time trial was 4.8% slower under pistachio conditions (2.84±0.11 and 2.71±0.07 h, respectively, P = 0.034). Significant time effects were shown for plasma cytokines, CRP, F2-IsoP, GPHAG, and GOBA, with few group differences. Metabolomics analysis revealed 423 detectable compounds of known identity, with significant interaction effects for 19 metabolites, especially raffinose, (12Z)-9,10-Dihydroxyoctadec-12-enoate (9,10-DiHOME), and sucrose. Dietary intake of raffinose was 2.19±0.15 and 0.35±0.08 mg/d during the pistachio and no pistachio periods, and metabolomics revealed that colon raffinose and sucrose translocated to the circulation during exercise due to increased gut permeability. The post-exercise increase in plasma raffinose correlated significantly with 9,10-DiHOME and other oxidative stress metabolites. Conclusions In summary, 2-weeks pistachio nut ingestion was associated with reduced 75-km cycling time trial performance and increased post-exercise plasma levels of raffinose, sucrose, and metabolites related to leukotoxic effects and oxidative stress. Trial Registration Clinical

  10. Immune System to Brain Signaling: Neuropsychopharmacological Implications

    PubMed Central

    Capuron, Lucile; Miller, Andrew H.

    2011-01-01

    There has been an explosion in our knowledge of the pathways and mechanisms by which the immune system can influence the brain and behavior. In the context of inflammation, pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its down stream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appear to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. The elucidation of the mechanisms by which the immune system influences behavior yields a host of targets for potential therapeutic development as well as informing strategies for the prevention of neuropsychiatric disease in at risk populations. PMID:21334376

  11. Pathogenic tracks in fatigue syndromes.

    PubMed

    Moutschen, M; Triffaux, J M; Demonty, J; Legros, J J; Lefèbvre, P J

    1994-01-01

    This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors. Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased. Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system. A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself. PMID:7871934

  12. Integrated Immune Experiment

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2009-01-01

    This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  13. Biobehavioral Factors Mediate Exercise Effects on Fatigue in Breast Cancer Survivors

    PubMed Central

    Rogers, Laura Q; Vicari, Sandra; Trammell, Rita; Hopkins-Price, Patricia; Fogleman, Amanda; Spenner, Allison; Rao, Krishna; Courneya, Kerry S; Hoelzer, Karen S; Robbs, Randall; Verhulst, Steven

    2015-01-01

    Purpose Examine mediators of fatigue response to an exercise intervention for breast cancer survivors (BCS) in a pilot randomized controlled trial. Methods Postmenopausal BCS (n=46; ≤ Stage II), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discussion group sessions provided behavioral support to improve adherence. Fatigue, serum cytokines, accelerometer physical activity, cardiorespiratory fitness, sleep dysfunction, and psychosocial factors were assessed at baseline and 3 months. Results Exercise intervention effect sizes for fatigue were: fatigue intensity d=0.30 (p=.34), interference d=−0.38 (p=.22), and general fatigue d=−0.49 (p=.13). Using Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin (IL)-6 (82%), IL-10 (94%), IL-6:IL-10 (49%), and tumor necrosis factor (TNF)-alpha:IL-10 (78%) with reduced sleep dysfunction increasing the relationship between intervention and fatigue intensity rather than mediating intervention effects (−88%). Decrease in fatigue interference was mediated by sleep dysfunction (35%) while IL-10 and pro:anti-inflammatory cytokine ratios increased the relationship between intervention and interference (−25% to −40%). The reduction in general fatigue was significantly mediated by minutes of physical activity (76%), sleep dysfunction (45%), and physical activity enjoyment (40%) with IL-10 (−40%) and IL-6:IL-10 (−11%) increasing the intervention-fatigue relationship. In the intervention group, higher baseline fatigue, anxiety, depression, and perceived exercise barriers interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention. Conclusions Biobehavioral factors mediated and enhanced

  14. Understanding and Treating Fatigue in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.

    PubMed

    Jopson, Laura; Dyson, Jessica K; Jones, David E J

    2016-02-01

    Fatigue is a significant problem for patients with primary biliary cirrhosis and although experienced less by patients with primary sclerosing cholangitis, a minority still report significant fatigue. Fatigue is the symptom with the greatest impact on quality of life, particularly when associated with social dysfunction. The pathogenesis of fatigue in cholestatic liver disease is complex, poorly understood, and probably has central and peripheral components. Managing fatigue in cholestatic liver disease presents a challenge for clinicians given the complexity and its numerous associations. This article presents a structured approach to managing fatigue in cholestatic liver disease to improve fatigue severity and quality of life. PMID:26593295

  15. 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 ...

  16. Nivolumab-induced thyroid dysfunction.

    PubMed

    Tanaka, Ryota; Fujisawa, Yasuhiro; Maruyama, Hiroshi; Nakamura, Yasuhiro; Yoshino, Koji; Ohtsuka, Mikio; Fujimoto, Manabu

    2016-06-01

    Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible. PMID:27012985

  17. Diastolic Dysfunction

    PubMed Central

    Jeong, Euy-Myoung; Dudley, Samuel C.

    2016-01-01

    Despite the growing number of patients affected, the understanding of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) is still poor. Clinical trials, largely based on successful treatments for systolic heart failure, have been disappointing, suggesting that HFpEF has a different pathology to that of systolic dysfunction. In this review, general concepts, epidemiology, diagnosis, and treatment of diastolic dysfunction are summarized, with an emphasis on new experiments suggesting that oxidative stress plays a crucial role in the pathogenesis of at least some forms of the disease. This observation has lead to potential new diagnostics and therapeutics for diastolic dysfunction and heart failure caused by diastolic dysfunction. PMID:25746522

  18. A Multi-Ingredient Containing Carbohydrate, Proteins L-Glutamine and L-Carnitine Attenuates Fatigue Perception with No Effect on Performance, Muscle Damage or Immunity in Soccer Players

    PubMed Central

    Naclerio, Fernando; Larumbe-Zabala, Eneko; Cooper, Robert; Allgrove, Judith; Earnest, Conrad P.

    2015-01-01

    We investigated the effects of ingesting a multi-ingredient (53g carbohydrate, 14.5g whey protein, 5g glutamine, 1.5g L-carnitine-L-tartrate) supplement, carbohydrate only, or placebo on intermittent performance, perception of fatigue, immunity, and functional and metabolic markers of recovery. Sixteen amateur soccer players ingested their respective treatments before, during and after performing a 90-min intermittent repeated sprint test. Primary outcomes included time for a 90-min intermittent repeated sprint test (IRS) followed by eleven 15 m sprints. Measurements included creatine kinase, myoglobin, interleukine-6, Neutrophil; Lymphocytes and Monocyte before (pre), immediately after (post), 1h and 24h after exercise testing period. Overall, time for the IRS and 15 m sprints was not different between treatments. However, the perception of fatigue was attenuated (P<0.001) for the multi-ingredient (15.9±1.4) vs. placebo (17.8±1.4) but not for the carbohydrate (17.0±1.9) condition. Several changes in immune/inflammatory indices were noted as creatine kinase peaked at 24h while Interleukin-6 and myoglobin increased both immediately after and at 1h compared with baseline (P<0.05) for all three conditions. However, Myoglobin (P<0.05) was lower 1h post-exercise for the multi-ingredient (241.8±142.6 ng·ml-1) and CHO (265.4±187.8 ng·ml-1) vs. placebo (518.6±255.2 ng·ml-1). Carbohydrate also elicited lower neutrophil concentrations vs. multi-ingredient (3.9±1.5 109/L vs. 4.9±1.8 109/L, P = 0.016) and a reduced (P<0.05) monocytes count (0.36±0.09 109/L) compared to both multi-ingredient (0.42±0.09 109/L) and placebo (0.42±0.12 109/L). In conclusion, multi-ingredient and carbohydrate supplements did not improve intermittent performance, inflammatory or immune function. However, both treatments did attenuate serum myoglobin, while only carbohydrate blunted post-exercise leukocytosis. PMID:25915424

  19. A multi-ingredient containing carbohydrate, proteins L-glutamine and L-carnitine attenuates fatigue perception with no effect on performance, muscle damage or immunity in soccer players.

    PubMed

    Naclerio, Fernando; Larumbe-Zabala, Eneko; Cooper, Robert; Allgrove, Judith; Earnest, Conrad P

    2015-01-01

    We investigated the effects of ingesting a multi-ingredient (53 g carbohydrate, 14.5 g whey protein, 5 g glutamine, 1.5 g L-carnitine-L-tartrate) supplement, carbohydrate only, or placebo on intermittent performance, perception of fatigue, immunity, and functional and metabolic markers of recovery. Sixteen amateur soccer players ingested their respective treatments before, during and after performing a 90-min intermittent repeated sprint test. Primary outcomes included time for a 90-min intermittent repeated sprint test (IRS) followed by eleven 15 m sprints. Measurements included creatine kinase, myoglobin, interleukine-6, Neutrophil; Lymphocytes and Monocyte before (pre), immediately after (post), 1 h and 24 h after exercise testing period. Overall, time for the IRS and 15 m sprints was not different between treatments. However, the perception of fatigue was attenuated (P<0.001) for the multi-ingredient (15.9±1.4) vs. placebo (17.8±1.4) but not for the carbohydrate (17.0±1.9) condition. Several changes in immune/inflammatory indices were noted as creatine kinase peaked at 24 h while Interleukin-6 and myoglobin increased both immediately after and at 1 h compared with baseline (P<0.05) for all three conditions. However, Myoglobin (P<0.05) was lower 1 h post-exercise for the multi-ingredient (241.8±142.6 ng·ml(-1)) and CHO (265.4±187.8 ng·ml(-1)) vs. placebo (518.6±255.2 ng·ml(-1)). Carbohydrate also elicited lower neutrophil concentrations vs. multi-ingredient (3.9±1.5 10(9)/L vs. 4.9±1.8 10(9)/L, P = 0.016) and a reduced (P<0.05) monocytes count (0.36±0.09 10(9)/L) compared to both multi-ingredient (0.42±0.09 10(9)/L) and placebo (0.42±0.12 10(9)/L). In conclusion, multi-ingredient and carbohydrate supplements did not improve intermittent performance, inflammatory or immune function. However, both treatments did attenuate serum myoglobin, while only carbohydrate blunted post-exercise leukocytosis. PMID:25915424

  20. Chronic fatigue syndrome following a toxic exposure.

    PubMed

    Racciatti, D; Vecchiet, J; Ceccomancini, A; Ricci, F; Pizzigallo, E

    2001-04-10

    Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS. PMID:11327394

  1. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

    PubMed

    Hornig, M; Gottschalk, G; Peterson, D L; Knox, K K; Schultz, A F; Eddy, M L; Che, X; Lipkin, W I

    2016-02-01

    Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β, suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity. PMID:25824300

  2. Preclinical Diastolic Dysfunction

    PubMed Central

    Wan, Siu-Hin; Vogel, Mark W.; Chen, Horng H

    2014-01-01

    Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed. PMID:24291270

  3. Erectile dysfunction.

    PubMed

    Yafi, Faysal A; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P; Hellstrom, Wayne J G

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man's quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner's sexual experience and the couple's quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  4. High dose thiamine improves fatigue in multiple sclerosis

    PubMed Central

    Costantini, Antonio; Nappo, Agostino; Pala, Maria Immacolata; Zappone, Antonietta

    2013-01-01

    The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23861280

  5. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock.

    PubMed

    Zhang, Yong; Zhang, Jinxiang; Korff, Sebastian; Ayoob, Faez; Vodovotz, Yoram; Billiar, Timothy R

    2014-09-01

    An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin 6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse IL-6 monoclonal antibody immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower-extremity injury. Interleukin 6 levels and signaling were transiently suppressed following administrations of anti-IL-6 monoclonal antibody following hemorrhagic shock and lower-extremity injury. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and macrophage inhibitory protein 1α at both 6 and 24 h. Furthermore, the shift to TH2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of postinjury care could be used to guide IL-6-based interventions. PMID:24978887

  6. Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease

    PubMed Central

    2016-01-01

    Chronic kidney disease (CKD) is an increasing and global health problem with a great economic burden for healthcare system. Therefore to slow down the progression of this condition is a main objective in nephrology. It has been extensively reported that microinflammation, immune system deregulation, and oxidative stress contribute to CKD progression. Additionally, dialysis worsens this clinical condition because of the contact of blood with bioincompatible dialytic devices. Numerous studies have shown the close link between immune system impairment and CKD but most have been performed using classical biomolecular strategies. These methodologies are limited in their ability to discover new elements and enable measuring the simultaneous influence of multiple factors. The “omics” techniques could overcome these gaps. For example, transcriptomics has revealed that mitochondria and inflammasome have a role in pathogenesis of CKD and are pivotal elements in the cellular alterations leading to systemic complications. We believe that a larger employment of this technique, together with other “omics” methodologies, could help clinicians to obtain new pathogenetic insights, novel diagnostic biomarkers, and therapeutic targets. Finally, transcriptomics could allow clinicians to personalize therapeutic strategies according to individual genetic background (nutrigenomic and pharmacogenomic). In this review, we analyzed the available transcriptomic studies involving CKD patients. PMID:27419142

  7. Gonadotropin-releasing hormone agonist prevents l-arginine induced immune dysfunction independent of gonadal steroids: Relates with a decline in elevated thymus and brain nitric oxide levels.

    PubMed

    Ullewar, Meenal P; Umathe, Sudhir N

    2016-07-01

    The present study was carried out to find out the effect of leuprolide, a gonadotropin-releasing hormone (GnRH) receptor agonist, on l-arginine induced immunosuppression, and relates with brain and thymus levels of nitric oxide (NO). Further, the effect of leuprolide was studied in sham operated, ovariectomized and castrated mice to understand the role of sex steroids in l-arginine induced immunosuppression. Treatment with l-arginine (250, 500, 1000 mg/kg/i.p. for 7 days) increased brain and thymus levels of NO; measured by using 'NO Measuring Instrument' (Innovative Instruments Inc., USA) in dose dependent manner. It also decreased cellularity, relative weight of thymus, DNA fragmentation, humoral, and cell mediated immunity response to sheep RBC. Prior treatment of leuprolide (100μg/mouse, s.c. for 7 days) prevented l-arginine induced rise in brain and thymus tissue levels of NO as well as the changes in immunological parameters. The protective effect of leuprolide against l-arginine induced immunosuppression and rise in brain and tissue nitric oxide levels was even evident in ovariectomized and castrated mice, suggesting that the observed effect of leuprolide is independent of sex steroids, and correlated with its ability to prevent l-arginine induced rise in CNS and peripheral immune tissue levels of NO. PMID:27130798

  8. Gustatory dysfunction

    PubMed Central

    Maheswaran, T.; Abikshyeet, P.; Sitra, G.; Gokulanathan, S.; Vaithiyanadane, V.; Jeelani, S.

    2014-01-01

    Tastes in humans provide a vital tool for screening soluble chemicals for food evaluation, selection, and avoidance of potentially toxic substances. Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition, and reduced quality of life. Dental practitioners are often the first clinicians to be presented with complaints about taste dysfunction. This brief review provides a summary of the common causes of taste disorders, problems associated with assessing taste function in a clinical setting and management options available to the dental practitioner. PMID:25210380

  9. A Pathway Proteomic Profile of Ischemic Stroke Survivors Reveals Innate Immune Dysfunction in Association with Mild Symptoms of Depression – A Pilot Study

    PubMed Central

    Nguyen, Vinh A.; Carey, Leeanne M.; Giummarra, Loretta; Faou, Pierre; Cooke, Ira; Howells, David W.; Tse, Tamara; Macaulay, S. Lance; Ma, Henry; Davis, Stephen M.; Donnan, Geoffrey A.; Crewther, Sheila G.

    2016-01-01

    Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery–Åsberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI–MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro-inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the

  10. Sexual dysfunction in uremia.

    PubMed

    Palmer, B F

    1999-06-01

    In summary, sexual dysfunction is a common finding in both men and women with chronic renal failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently accompany the chronic renal failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamicpituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first-line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic renal failure. PMID:10361878

  11. Ejaculatory dysfunction.

    PubMed

    Phillips, Elizabeth; Carpenter, Christina; Oates, Robert D

    2014-02-01

    Ejaculatory dysfunction may occur after many different disorders ranging from traumatic spinal cord injury to diabetes mellitus. With an understanding of the many facets and nuances of the ejaculatory apparatus, both anatomic and neurologic, the well-versed clinician can proceed along a safe, efficient, and appropriate treatment algorithm to help affected men and their partners achieve parenthood. PMID:24286771

  12. Erectile Dysfunction

    MedlinePlus

    ... or vascular problems, will have a more difficult time returning to pre-treatment function. Management of Erectile Dysfunction When a man is sexually aroused, the erectile nerves running alongside the penis stimulate the ... blood to rush in. At the same time, tiny valves at the base of the penis ...

  13. Memory dysfunction.

    PubMed

    Amici, Serena

    2012-01-01

    Memory is the cognitive ability that allows to acquire, store and recall information; its dysfunction is called amnesia and can be a presentation of unilateral ischemic stroke in the territory of the posterior cerebral and anterior choroidal artery as well as subarachnoid hemorrhage. PMID:22377863

  14. Sensory Dysfunction

    MedlinePlus

    ... to Web version Sensory Dysfunction Overview Why are smell and taste important? Your senses of smell and taste let you fully enjoy the scents ... bitter and sour. Flavor involves both taste and smell. For example, because a person is able to ...

  15. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Chronic fatigue syndrome. 4.88a Section 4.88a Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88a Chronic fatigue syndrome....

  16. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Chronic fatigue syndrome. 4.88a Section 4.88a Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88a Chronic fatigue syndrome....

  17. Fatigue in psoriasis: a phenomenon to be explored.

    PubMed

    Skoie, I M; Ternowitz, T; Jonsson, G; Norheim, K; Omdal, R

    2015-01-01

    Fatigue is a prevalent and substantial phenomenon in many patients with chronic inflammatory diseases, often rated by patients as the most troublesome symptom and aspect of their disease. It frequently interferes with physical and social functions and may lead to social withdrawal, long-standing sick leave and disability. Although psychological and somatic factors such as depression, sleep disorders, pain and anaemia influence fatigue, the underlying pathophysiological mechanisms by which fatigue is generated and regulated are largely unknown. Increasing evidence points towards a genetic and molecular basis for fatigue as part of the innate immune system and cellular stress responses. Few studies have focused on fatigue in dermatological diseases. Most of these studies describe fatigue as a phenomenon related to psoriatic arthritis and describe the beneficial effects of biological agents on fatigue observed in clinical studies. It is therefore possible that this problem has been underestimated and deserves more attention in the dermatological community. In this review, we provide a definition and explanation for chronic fatigue, describe some commonly used instruments for measuring fatigue, and present hypothetical biological mechanisms with an emphasis on activation of the innate immune system and oxidative stress. An overview of relevant clinical studies covering the theme 'psoriasis and fatigue' is given. PMID:25557165

  18. Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

    PubMed Central

    Jason, L. A.; Porter, N.; Herrington, J.; Sorenson, M.; Kubow, S.

    2010-01-01

    Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) is one of the more complex illnesses involving multiple systems within the body. Onset of ME/CFS frequently occurs quickly, and many patients report a prior exposure to a viral infection. This debilitating illness can affect the immune, neuroendocrine, autonomic, and neurologic systems. Abnormal biological findings among some patients have included aberrant ion transport and ion channel activity, cortisol deficiency, sympathetic nervous system hyperactivity, EEG spike waves, left ventricular dysfunction in the heart, low natural killer cell cytotoxicity, and a shift from Th1 to Th2 cytokines. We propose that the kindling and oxidative stress theories provide a heuristic template for better understanding the at times conflicting findings regarding the etiology and pathophysiology of this illness. PMID:21253446

  19. Dysfunctional voiding.

    PubMed

    Chiozza, M L

    2002-01-01

    Wetting may be considered the Cinderella of paediatric medicine. Before discussing dysfunctional voiding, the milestones of the normal development of continence in the child and the definitions used to describe this topic are presented. Bladder storage requires (1): accommodation of increasing volumes of urine at low intravesical pressure and with appropriate sensation; (2): a bladder outlet that is closed and not modified during increase in intra-abdominal pressure; (3): absence of involuntary bladder contractions. Development of continence in the child involves three independent factors maturing concomitantly: (1) development of normal bladder capacity; (2) maturation of urethral sphincter function; (3) development of neural control over bladder-sphincter function. All these processes are discussed. Abnormalities of any of these maturational sequences, which run parallel and overlapping, may result in clinically evident abnormalities of bladder sphincter control. Although dysfunctional voiding (DV) in children is very common its prevalence has not been well studied and, to date, and its origin is not well known. In a correct evaluation of functional voiding we must take into account different elements: the bladder capacity (that increases during the first 8 years of life roughly 30 ml per year), the micturition frequency, post-void residual volumes, bladder dynamics, urinary flow rates. Thus the correct assessment of children with lower urinary tract dysfunction should include a detailed history. Signs of DV range from urge syndrome to complex incontinence patterns during the day and the night. In addition to incontinence problems, children may have frequency, urgency, straining to void, weak or interrupted urinary stream, urinary tract infections (UTIs) and chronic constipation with or without encopresis. DV are also referred in enuretic children who wet the bed more than one time per night and have a functional bladder capacity lower than attended for age

  20. Exercise, inflammation, and fatigue in cancer survivors

    PubMed Central

    LaVoy, Emily C.P.; Fagundes, Christopher P.; Dantzer, Robert

    2016-01-01

    Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal function and result in the symptom of cancer-related fatigue. Exercise training interventions have been shown to be some of the more successful treatment options to address cancer-related fatigue. In this review, we discuss the literature regarding the causes of persistent fatigue in cancer survivors and the mechanisms by which exercise may relieve this symptom. There is still much work to be done until the prescription of exercise becomes standard practice for cancer survivors. With improvements in the quality of studies, evidenced-based exercise interventions will allow exercise scientists and oncologists to work together to treat cancer-related fatigue. PMID:26853557

  1. Immune response

    MedlinePlus

    Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense system ...

  2. Nursing Fatigue: An Evidence-Based Practice Review for Oncology Nurses
.

    PubMed

    Ferris, Jordan

    2015-12-01

    Nursing fatigue is a current and well-researched topic. Many negative outcomes and consequences exist for patients and nurses that have been linked to nursing fatigue. Medical errors are one such consequence, and these errors have become one of the top three preventable deaths in the United States. Oncology nurses are not immune to fatigue, and the consequences of their fatigue can be much more harmful to patients. PMID:26583629

  3. Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes.

    PubMed

    MacKinnon, L T

    2000-10-01

    Overtraining is a process of excessive exercise training in high-performance athletes that may lead to overtraining syndrome. Overtraining syndrome is a neuroendocrine disorder characterized by poor performance in competition, inability to maintain training loads, persistent fatigue, reduced catecholamine excretion, frequent illness, disturbed sleep and alterations in mood state. Although high-performance athletes are generally not clinically immune deficient, there is evidence that several immune parameters are suppressed during prolonged periods of intense exercise training. These include decreases in neutrophil function, serum and salivary immunoglobulin concentrations and natural killer cell number and possibly cytotoxic activity in peripheral blood. Moreover, the incidence of symptoms of upper respiratory tract infection increases during periods of endurance training. However, all of these changes appear to result from prolonged periods of intense exercise training, rather than from the effects of overtraining syndrome itself. At present, there is no single objective marker to identify overtraining syndrome. It is best identified by a combination of markers, such as decreases in urinary norepinephrine output, maximal heart rate and blood lactate levels, impaired sport performance and work output at 110% of individual anaerobic threshold, and daily self-analysis by the athlete (e.g. high fatigue and stress ratings). The mechanisms underlying overtraining syndrome have not been clearly identified, but are likely to involve autonomic dysfunction and possibly increased cytokine production resulting from the physical stress of intense daily training with inadequate recovery. PMID:11050533

  4. A Role for Homeostatic Drive in the Perpetuation of Complex Chronic Illness: Gulf War Illness and Chronic Fatigue Syndrome

    PubMed Central

    Craddock, Travis J. A.; Fritsch, Paul; Rice, Mark A.; del Rosario, Ryan M.; Miller, Diane B.; Fletcher, Mary Ann; Klimas, Nancy G.; Broderick, Gordon

    2014-01-01

    A key component in the body's stress response, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates changes across a broad range of major biological systems. Its dysfunction has been associated with numerous chronic diseases including Gulf War Illness (GWI) and chronic fatigue syndrome (CFS). Though tightly coupled with other components of endocrine and immune function, few models of HPA function account for these interactions. Here we extend conventional models of HPA function by including feed-forward and feedback interaction with sex hormone regulation and immune response. We use this multi-axis model to explore the role of homeostatic regulation in perpetuating chronic conditions, specifically GWI and CFS. An important obstacle in building these models across regulatory systems remains the scarcity of detailed human in vivo kinetic data as its collection can present significant health risks to subjects. We circumvented this using a discrete logic representation based solely on literature of physiological and biochemical connectivity to provide a qualitative description of system behavior. This connectivity model linked molecular variables across the HPA axis, hypothalamic-pituitary-gonadal (HPG) axis in men and women, as well as a simple immune network. Inclusion of these interactions produced multiple alternate homeostatic states and sexually dimorphic responses. Experimental data for endocrine-immune markers measured in male GWI subjects showed the greatest alignment with predictions of a naturally occurring alternate steady state presenting with hypercortisolism, low testosterone and a shift towards a Th1 immune response. In female CFS subjects, expression of these markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation. These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent interaction with the

  5. Community Immunity (Herd Immunity)

    MedlinePlus

    ... Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" Immunity) Vaccines can prevent outbreaks of disease and save ... disease is contained. This is known as "community immunity." In the illustration below, the top box depicts ...

  6. Low cycle fatigue

    NASA Technical Reports Server (NTRS)

    Solomon, H. D. (Editor); Kaisand, L. R. (Editor); Halford, G. R. (Editor); Leis, B. N. (Editor)

    1988-01-01

    The papers contained in this volume focus on various aspects of low cycle fatigue, including cyclic deformation, crack propagation, high-temperature low cycle fatigue, microstructural defects, multiaxial and variable amplitude loading, and life prediction. Papers are presented on the low cycle fatigue of some aluminum alloys, prediction of crack growth under creep-fatigue loading conditions, high-temperature low cycle fatigue behavior and lifetime prediction of a nickel-base ODS alloy, and an integrated approach to creep-fatigue life prediction. Other topics discussed include thermal fatigue testing of coated monocrystalline superalloys, low cycle fatigue of Al-Mg-Si alloys, and the effect of superimposed stresses at high frequency on low cycle fatigue.

  7. Cancer-related fatigue. Clinical practice guidelines in oncology.

    PubMed

    2003-07-01

    These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with their daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for current disease and treatment status, a review of body systems, and an in-depth fatigue evaluation. In addition, the patient is assessed for the presence of seven treatable factors known to contribute to fatigue: pain, emotional distress, sleep disturbance, anemia, alterations in nutrition, deconditioning, and comorbidities. If any of these conditions are present, they should be treated according to practice guidelines, with referral to other care professionals as appropriate, and the patient's fatigue should be reevaluated regularly. If none of the seven factors are present or the fatigue is unresolved, selection of appropriate fatigue management and treatment strategies is considered within the context of the patient's clinical status: receiving active cancer treatment, receiving disease-free long-term follow-up, or receiving care at the end of life. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, psychosocial programs to manage stress and

  8. Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

    PubMed Central

    Staines, Donald R.

    2006-01-01

    Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity. Adenylate cyclase-activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their receptors are potentially immunogenic. VNs are widely distributed in the body particularly in the central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells, reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-respiratory function, thermoregulation, memory, concentration and executive functions such as emotional responses including social cues and appropriate behaviour. They are co-transmitters for a number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system against toxic assault as well as being important in the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of certain fatigue-related syndromes based on loss of immunological tolerance to these VNs or their receptors following infection, other events or de novo resulting in significant

  9. Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

    PubMed Central

    Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

    2015-01-01

    Background/Aims This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Methods Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. Results The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. Conclusions There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability. PMID:25717051

  10. The first report of cabergoline-induced immune hemolytic anemia in an adolescent with prolactinoma.

    PubMed

    Gürbüz, Fatih; Yağcı-Küpeli, Begül; Kör, Yılmaz; Yüksel, Bilgin; Zorludemir, Suzan; Gürbüz, Berrak Bilginer; Küpeli, Serhan

    2014-01-01

    Prolactinomas are common pituitary tumors that can cause gonadal dysfunction and infertility related to hyperprolactinemia. Dopamine agonists are the first-line treatment in these patients. Cabergoline leads to significant reduction in serum prolactin levels and tumor size in patients with prolactinoma. Dopamine agonists have been associated with adverse effects such as nausea, vomiting and psychosis. We report here a case with cabergoline-induced immune hemolytic anemia. The patient had cabergoline treatment history for prolactinoma and presented with weakness, fatigue, nausea, and paleness. Laboratory findings revealed severe anemia-related immune hemolysis. There were no causes identified to explain hemolytic anemia except cabergoline. Therefore, cabergoline therapy was stopped and subsequently hemolytic anemia resolved and did not occur again. This is the first reported pediatric case with prolactinoma and cabergoline-induced hemolytic anemia. Clinicians should be watchful for this rare side effect induced by cabergoline. PMID:23945126

  11. HIV and neurocognitive dysfunction.

    PubMed

    Spudich, Serena

    2013-09-01

    The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists despite ART remains a challenge to the community of patients, providers and investigators aiming to optimize quality of life for those living with HIV. Cognitive dysfunction in treated HIV may reflect early irreversible CNS injury accrued before ART is typically initiated, ongoing low-level CNS infection and progressive injury in the setting of ART, or comborbidities including effects of treatment which may confound the beneficial reduction in viral replication and immune activation effected by ART. PMID:23860944

  12. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease.

    PubMed

    Underhill, R A

    2015-12-01

    The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors. Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen. ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases. Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients' genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks. The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients' immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen. Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins

  13. Neuromuscular dysfunction in nonbacterial prostatitis.

    PubMed

    Hellstrom, W J; Schmidt, R A; Lue, T F; Tanagho, E A

    1987-08-01

    Although chronic nonbacterial prostatitis is common, the condition remains poorly understood and refractory to treatment. Another approach, i.e., a urodynamic explanation, seems warranted. The underlying cause of the symptoms may be an inappropriate spasm of of the distal urethra/external sphincteric unit, leading to increased pressure in the prostatic urethra with a resultant reflux of urine into the prostatic ducts. The presence of urine (sterile or infected) could induce ductal and periductal inflammation, which could further aggravate spasm of the involved pelvic musculature, exacerbating the voiding dysfunction. We present 3 patients in whom this sequence of events was documented radiographically and urodynamically. Consequently, treatment involved modulation of the dysfunction of the distal urethra/external sphincteric unit: (1) reeducation by reassurance and biofeedback was the initial line of therapy; (2) pharmacologic manipulation using alpha-blockers (to affect smooth and striated muscle irritability) and striated muscle relaxants was next tried; (3) finally, in unremitting symptoms, we used selective sacral-root electro-stimulation, successfully fatiguing the involved muscles and relieving the voiding dysfunction. PMID:3497475

  14. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  15. [Fatigue in neuromuscular disease].

    PubMed

    Van Engelen, B G M; Kalkman, J S; Schillings, M L; Van Der Werf, S P; Bleijenberg, G; Zwarts, M J

    2004-07-01

    Chronic fatigue is a symptom of diseases such as cancer, multiple sclerosis, Parkinson's and cerebrovascular disease. Fatigue can also be present in people with no demonstrable somatic disease. If certain criteria are met, chronic-fatigue syndrome may be diagnosed in these cases. Fatigue is a multi-dimensional concept with physiological and psychological dimensions. The 'Short Fatigue Questionnaire' consisting of 4 questions is a tool to measure fatigue with a high degree of reliability and validity. Within the group of neuromuscular disorders, fatigue has been reported by patients with post-polio syndrome, myasthenia gravis, and Guillain-Barré syndrome. The percentage of neuromuscular patients suffering from severe fatigue (64%) is comparable with that of patients with multiple sclerosis, a disease in which fatigue is an acknowledged symptom. Now that reliable psychological and clinical neurophysiological techniques are available, a multidisciplinary approach to fatigue in patients with well-defined neuromuscular disorders may contribute towards the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal being to develop methods of treatment for fatigue in neuromuscular patients. PMID:15283024

  16. Fatigue of composites

    NASA Technical Reports Server (NTRS)

    Salkind, M. J.

    1972-01-01

    The failure mechanisms in the fatigue of composite materials are analyzed in terms of the requirements for designing fatigue-critical composite structures. Fiber reinforced polymers, fiber reinforced metals, fatigue of composite structures, and composite design considerations are discussed. It is concluded that composite materials offer the engineer the opportunity for tailoring stiffness in different directions for designing dynamic components.

  17. Bulk silicon is susceptible to fatigue

    NASA Astrophysics Data System (ADS)

    Bhowmick, Sanjit; Meléndez-Martínez, Juan José; Lawn, Brian R.

    2007-11-01

    It has long been held that bulk silicon is immune from fatigue. We present contrary evidence demonstrating severe fatigue in macroscale cracks produced in cyclic loading of single-crystal silicon with a sphere indenter. The key ingredient is a component of shear stress acting on the cracks during contraction and expansion of the contact circle. This gives rise to frictional sliding at the crack walls, dislodging and ejecting slabs of material and debris onto the silicon surface. The damage expands with continued cycling, leading to progressive degradation of the surface. The results have implications concerning the function of silicon-based devices.

  18. Heat shock proteins and chronic fatigue in primary Sjögren's syndrome.

    PubMed

    Bårdsen, Kjetil; Nilsen, Mari Mæland; Kvaløy, Jan Terje; Norheim, Katrine Brække; Jonsson, Grete; Omdal, Roald

    2016-04-01

    Fatigue occurs frequently in patients with cancer, neurological diseases and chronic inflammatory diseases, but the biological mechanisms that lead to and regulate fatigue are largely unknown. When the innate immune system is activated, heat shock proteins (HSPs) are produced to protect cells. Some extracellular HSPs appear to recognize cellular targets in the brain, and we hypothesize that fatigue may be generated by specific HSPs signalling through neuronal or glial cells in the central nervous system. From a cohort of patients with primary Sjögren's syndrome, 20 patients with high and 20 patients with low fatigue were selected. Fatigue was evaluated with a fatigue visual analogue scale. Plasma concentrations of HSP32, HSP60, HSP72 and HSP90α were measured and analysed to determine if there were associations with the level of fatigue. Plasma concentrations of HSP90α were significantly higher in patients with high fatigue compared with those with low fatigue, and there was a tendency to higher concentrations of HSP72 in patients with high fatigue compared with patients with low fatigue. There were no differences in concentrations of HSP32 and HSP60 between the high- and low-fatigue groups. Thus, extracellular HSPs, particularly HSP90α, may signal fatigue in chronic inflammation. This supports the hypothesis that fatigue is generated by cellular defence mechanisms. PMID:26921255

  19. Heat shock proteins and chronic fatigue in primary Sjögren’s syndrome

    PubMed Central

    Bårdsen, Kjetil; Nilsen, Mari Mæland; Kvaløy, Jan Terje; Norheim, Katrine Brække; Jonsson, Grete

    2016-01-01

    Fatigue occurs frequently in patients with cancer, neurological diseases and chronic inflammatory diseases, but the biological mechanisms that lead to and regulate fatigue are largely unknown. When the innate immune system is activated, heat shock proteins (HSPs) are produced to protect cells. Some extracellular HSPs appear to recognize cellular targets in the brain, and we hypothesize that fatigue may be generated by specific HSPs signalling through neuronal or glial cells in the central nervous system. From a cohort of patients with primary Sjögren’s syndrome, 20 patients with high and 20 patients with low fatigue were selected. Fatigue was evaluated with a fatigue visual analogue scale. Plasma concentrations of HSP32, HSP60, HSP72 and HSP90α were measured and analysed to determine if there were associations with the level of fatigue. Plasma concentrations of HSP90α were significantly higher in patients with high fatigue compared with those with low fatigue, and there was a tendency to higher concentrations of HSP72 in patients with high fatigue compared with patients with low fatigue. There were no differences in concentrations of HSP32 and HSP60 between the high- and low-fatigue groups. Thus, extracellular HSPs, particularly HSP90α, may signal fatigue in chronic inflammation. This supports the hypothesis that fatigue is generated by cellular defence mechanisms. PMID:26921255

  20. Cognitive and Physical Fatigue Tasks Enhance Pain, Cognitive Fatigue and Physical Fatigue in People with Fibromyalgia

    PubMed Central

    Dailey, Dana L; Keffala, Valerie J; Sluka, Kathleen A

    2014-01-01

    Objective Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue. The primary objective of this study was to determine if pain, perceived cognitive fatigue, and perceived physical fatigue were enhanced in participants with fibromyalgia compared to healthy controls during a cognitive fatigue task, a physical fatigue task and a dual fatigue task. Methods Twenty four people with fibromyalgia and 33 healthy controls completed pain, fatigue and function measures. A cognitive fatigue task (Controlled Oral Word Association Test) and physical fatigue task (Valpar peg test) were done individually and combined for a dual fatigue task. Resting pain, perceived cognitive fatigue and perceived physical fatigue were assessed during each task using visual analogue scales. Function was assessed with shoulder range of motion and grip. Results People with fibromyalgia had significantly higher increases in pain, cognitive fatigue and physical fatigue when compared to healthy controls after completion of a cognitive fatigue task, a physical fatigue task, or a dual fatigue task (p<0.01). People with fibromyalgia performed equivalently on measures of physical performance and cognitive performance on the physical and cognitive fatigue tasks, respectively. Conclusions These data show that people with fibromyalgia show larger increases in pain, perceived cognitive fatigue and perceived physical fatigue to both cognitive and physical fatigue tasks compared to healthy controls. The increases in pain and fatigue during cognitive and physical fatigue tasks could influence subject participation in daily activities and rehabilitation. PMID:25074583

  1. Thyroid dysfunction from antineoplastic agents.

    PubMed

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  2. Fatigue handbook: Offshore steel structures

    SciTech Connect

    Almarnaess, A.

    1985-01-01

    The contents of this book are: Overview of Offshore Steel Structures; Loads on Ocean Structures; Fracture Mechanics As a Tool in Fatigue Analysis; Basic Fatigue Properties of Welded Joints; Significance of Defects; Improving the Fatigue Strength of Welded Joints; Effects of Marine Environment and Cathodic Protection on Fatigue of Structural Steels Fatigue of Tubular Joints; Unstable Fracture; Fatigue Life Calculations; and Fatigue in Building Codes Background and Applications.

  3. Altered resting brain connectivity in persistent cancer related fatigue.

    PubMed

    Hampson, Johnson P; Zick, Suzanna M; Khabir, Tohfa; Wright, Benjamin D; Harris, Richard E

    2015-01-01

    There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = -0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As

  4. Multiaxial fatigue low cycle fatigue testing

    NASA Technical Reports Server (NTRS)

    Zamrik, S. Y.

    1985-01-01

    Multiaxial testing methods are reviewed. Advantages and disadvantages of each type test is discussed. Significant multiaxial data available in the literature is analyzed. The yield theories are compared for multiaxial fatigue analysis.

  5. A biopsychosocial model of fatigue and depression following stroke.

    PubMed

    Ormstad, Heidi; Eilertsen, Grethe

    2015-12-01

    Poststroke fatigue (PSF) and poststroke depression (PSD) are both common and difficult sequelae following acute ischemic stroke (AIS). Two main perspectives to explain these sequelae are the biomedical perspective and the psychosocial perspective. Research has shown that PSF and PSD are undoubtedly associated with each other, although each can occur in the absence of the other. However, the nature of the relationship is unclear. For example, do stroke patients become fatigued because of being depressed, or do they become depressed because they are fatigued? Alternatively, is there a bidirectional relationship between these two sequelae, with each influencing the other? We propose a biopsychosocial model of PSF and PSD that supports the AIS-induced immune response and kynurenine pathway activation being related to fatigue but not (directly) to depression. We hypothesize that the risk of developing depression may be reduced if the experience of fatigue is acknowledged, and then addressed accordingly. PMID:26459975

  6. The Environment-Immune Route to Chronic Disease

    EPA Science Inventory

    Specific environmental factors including chemicals, drugs, microbes and both physical and psychological factors can affect the immune system producing dysfunction and, ultimately, an increased risk ofchronic disease. Several different types of immune alterations can result from e...

  7. Subrupture Tendon Fatigue Damage

    PubMed Central

    Laudier, Damien M.; Shine, Jean H.; Basta-Pljakic, Jelena; Jepsen, Karl J.; Schaffler, Mitchell B.; Flatow, Evan L.

    2016-01-01

    The mechanical and microstructural bases of tendon fatigue, by which damage accumulates and contributes to degradation, are poorly understood. To investigate the tendon fatigue process, rat flexor digitorum longus tendons were cyclically loaded (1–16 N) until reaching one of three levels of fatigue damage, defined as peak clamp-to-clamp strain magnitudes representing key intervals in the fatigue life: i) Low (6.0%–7.0%); ii) Moderate (8.5%–9.5%); and iii) High (11.0%–12.0%). Stiffness, hysteresis, and clamp-to-clamp strain were assessed diagnostically (by cyclic loading at 1–8 N) before and after fatigue loading and following an unloaded recovery period to identify mechanical parameters as measures of damage. Results showed that tendon clamp-to-clamp strain increased from pre- to post-fatigue loading significantly and progressively with the fatigue damage level (p≤0.010). In contrast, changes in both stiffness and hysteresis were significant only at the High fatigue level (p≤0.043). Correlative microstructural analyses showed that Low level of fatigue was characterized by isolated, transverse patterns of kinked fiber deformations. At higher fatigue levels, tendons exhibited fiber dissociation and localized ruptures of the fibers. Histomorphometric analysis showed that damage area fraction increased significantly with fatigue level (p≤0.048). The current findings characterized the sequential, microstructural events that underlie the tendon fatigue process and indicate that tendon deformation can be used to accurately assess the progression of damage accumulation in tendons. PMID:18683881

  8. Compassion fatigue in nurses.

    PubMed

    Yoder, Elizabeth A

    2010-11-01

    Compassion fatigue, trigger situations, and coping strategies were investigated in hospital and home care nurses. The Professional Quality of Life Scale measured compassion fatigue, compassion satisfaction, and burnout. Narrative questions elicited trigger situations and coping strategies. Compassion fatigue scores were significantly different between nurses who worked 8- or 12-hour shifts. Fifteen percent of the participants had scores indicating risk of the compassion fatigue. There were significant differences in compassion satisfaction, depending on the unit worked and time as a nurse. The most common category of trigger situations was caring for the patient. Work-related and personal coping strategies were identified. PMID:21035028

  9. The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups

    PubMed Central

    Twisk, Frank N. M.

    2014-01-01

    Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are used interchangeably, the diagnostic criteria define two distinct clinical entities. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after a minor exertion, are distinctive symptoms of ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic fatigue (syndrome), other disorders and deconditioning. The introduction of the label, but more importantly the diagnostic criteria for CFS have generated much confusion, mostly because chronic fatigue is a subjective and ambiguous notion. CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and unrefreshing sleep. Most of the research into ME and/or CFS in the last decades was based upon the multivalent CFS criteria, which define a heterogeneous patient group. Due to the fact that fatigue and other symptoms are non-discriminative, subjective experiences, research has been hampered. Various authors have questioned the physiological nature of the symptoms and qualified ME/CFS as somatization. However, various typical symptoms can be assessed objectively using standardized methods. Despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively, e.g., immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction. However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms

  10. Diaphragmatic dysfunction in Collagen VI myopathies.

    PubMed

    Quijano-Roy, S; Khirani, S; Colella, M; Ramirez, A; Aloui, S; Wehbi, S; de Becdelievre, A; Carlier, R Y; Allamand, V; Richard, P; Azzi, V; Estournet, B; Fauroux, B

    2014-02-01

    Collagen VI-related myopathies are hereditary disorders causing progressive restrictive respiratory insufficiency. Specific diaphragm involvement has been suggested by a drop in supine volumes. This pilot study aimed at characterizing the respiratory muscle phenotype in patients with COL6A1-3 genes mutations. Lung function, blood gases, muscle strength and respiratory mechanics were measured in 7 patients between 2002 and 2012. Patients were classified as Early-Severe (n = 3), Moderate-Progressive (n = 2) and Mild (n = 2) according to clinical disease presentation. Seven patients (aged 6-28) were evaluated. Forced vital capacity distinguished the Mild group (>60% predicted) from the two other groups (<50% predicted). This distinction was also possible using the motor function measure scale. Diaphragmatic dysfunction at rest was observed in all the Early-Severe and Moderate-Progressive patients. During a voluntary sniff maneuver diaphragmatic dysfunction was observed in all patients, as assessed by a negative gastric pressure. All patients had diaphragmatic fatigue assessed by a tension-time index over the threshold of 0.15. Diaphragmatic dysfunction during a maximal voluntary maneuver and diaphragmatic fatigue are constant features in Collagen VI myopathies. These observations can assist the diagnosis and should be taken in account for the clinical management, with the early detection of sleep-disordered breathing. PMID:24314752

  11. Parkinson's Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to α-Synuclein Oligomer

    PubMed Central

    Zuo, Li-Jun; Yu, Shu-Yang; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Du, Yang; Lian, Teng-Hong; Wang, Rui-Dan; Yu, Qiu-Jin; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yongjun

    2016-01-01

    Background and Purpose The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson's disease (PD) patients who experience fatigue. Methods PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins—α-synuclein oligomer, β-amyloid (Aβ)1-42, and tau—were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. Results The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ1-42 was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. Conclusions PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF. PMID:26869370

  12. Sexual Dysfunction and Infertility

    MedlinePlus

    ... American Society for Reproductive Medicine Sexual dysfunction and infertility What is sexual dysfunction and how common is ... and 40% of women. For couples dealing with infertility, it is even more common. Often, people ignore ...

  13. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  14. Elevated temperature biaxial fatigue

    NASA Technical Reports Server (NTRS)

    Jordan, E. H.

    1984-01-01

    A three year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for non-proportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved undertanding were through several critical non-proportional loading experiments. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C.

  15. [Thyroid dysfunction in primary care medicine].

    PubMed

    Wuerzner, Kaisa; Pasche, Olivier; Rodondi, Nicolas; Portmann, Luc

    2010-12-01

    Thyroid function tests include the measuring of the thyroid stimulating hormone (TSH) and free thyroxine (T4) in the case of abnormal TSH. These tests are frequently performed in primary care medicine since many clinical situations can be suggestive of dysthyroidism, as for example fatigue, depressive states or cardiac arthmia. In the case of subclinical thyroid dysfunction, the indications for treatment are controversial there being a lack of significant randomised studies. For primary care physicians faced with abnormal thyroid function tests we propose a diagnostic approach, clinical recommendations, and indications for referral to the specialist. PMID:21207724

  16. Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation.

    PubMed

    Askren, Mary K; Jung, Misook; Berman, Marc G; Zhang, Min; Therrien, Barbara; Peltier, Scott; Ossher, Lynn; Hayes, Daniel F; Reuter-Lorenz, Patricia A; Cimprich, Bernadine

    2014-09-01

    The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction. PMID:25138546

  17. Identifying Clinically Meaningful Fatigue with the Fatigue Symptom Inventory

    PubMed Central

    Donovan, Kristine A.; Jacobsen, Paul B.; Small, Brent J.; Munster, Pamela N.; Andrykowski, Michael A.

    2008-01-01

    The Fatigue Symptom Inventory (FSI) has been used extensively to assess and measure fatigue in a number of clinical populations. The purpose of the present study was to further establish its utility by examining its operating characteristics and determining the optimal cutoff score for identifying clinically meaningful fatigue. The SF-36 Vitality scale, a measure widely used to identify individuals with significant fatigue-related disability, was used to determine the sensitivity and specificity of the FSI. Results indicate that a score of 3 or greater on those items assessing fatigue in the past week is the optimal cutoff score for identifying clinically meaningful fatigue. Individuals who scored at or above the cutoff also reported significantly greater fatigue interference, more days of fatigue on average, and fatigue a greater proportion of each day in the past week. Findings suggest that the FSI can be used to discriminate effectively between individuals with and without clinically meaningful fatigue. PMID:18495413

  18. Vascular endothelial dysfunction and pharmacological treatment

    PubMed Central

    Su, Jin Bo

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  19. Vascular endothelial dysfunction and pharmacological treatment.

    PubMed

    Su, Jin Bo

    2015-11-26

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  20. Elevated temperature biaxial fatigue

    NASA Technical Reports Server (NTRS)

    Jordan, E. H.

    1985-01-01

    A 3 year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for nonproportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved understanding were through several critical nonproportional loading experiments. The direction of cracking observed on failed specimens was also recorded and used to guide the development of the theory. Cyclic deformation responses were permanently recorded digitally during each test. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C. In contrast to some other metals, loading path in nonproportional loading had little effect on fatigue lives. Strain rate had a small effect on fatigue lives at 649 C. Of the various correlating parameters the modified plastic work and octahedral shear stress were the most successful.

  1. Silent Burdens in Disease: Fatigue and Depression in SLE

    PubMed Central

    Fonseca, R.; Bernardes, M.; Terroso, G.; de Sousa, M.; Figueiredo-Braga, M.

    2014-01-01

    At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE. PMID:24592329

  2. Portable Immune-Assessment System

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.; Stowe, Raymond P.; Mishra, Saroj K.

    1995-01-01

    Portable immune-assessment system developed for use in rapidly identifying infections or contaminated environment. System combines few specific fluorescent reagents for identifying immune-cell dysfunction, toxic substances, buildup of microbial antigens or microbial growth, and potential identification of pathogenic microorganisms using fluorescent microplate reader linked to laptop computer. By using few specific dyes for cell metabolism, DNA/RNA conjugation, specific enzyme activity, or cell constituents, one makes immediate, onsite determination of person's health or of contamination of environment.

  3. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Chronic fatigue syndrome. 4.88a Section 4.88a Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and...

  4. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Chronic fatigue syndrome. 4.88a Section 4.88a Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and...

  5. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Chronic fatigue syndrome. 4.88a Section 4.88a Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and...

  6. Brain Tumors and Fatigue

    MedlinePlus

    ... tiredness. You may experience a profound lack of energy that can come on suddenly and bring dramatic ... to manage the severity. Respect the Fatigue The energy you’re accustomed to having has been transferred ...

  7. 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 ...

  8. Fatigue and Multiple Sclerosis

    MedlinePlus

    Fatigue - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area ... help* daily life for: positive-mom* The National MS Society is Here to Help Need More Information? ...

  9. Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome?

    PubMed Central

    Cordero, Mario D.; Segundo, María José; Sáez-Francàs, Naia; Calvo, Natalia; Román-Malo, Lourdes; Aliste, Luisa; Fernández de Sevilla, Tomás; Alegre, José

    2015-01-01

    Abstract Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS. We conducted an 8-week, randomized, double-blind placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. This study was registered in ClinicalTrials.gov (NCT02063126). A significant improvement of fatigue showing a reduction in fatigue impact scale total score (p<0.05) was reported in treated group versus placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH (p<0.001), CoQ10 (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher, and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confer potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings. Antioxid. Redox Signal. 22, 679–685. PMID:25386668

  10. Fatigue of restorative materials.

    PubMed

    Baran, G; Boberick, K; McCool, J

    2001-01-01

    Failure due to fatigue manifests itself in dental prostheses and restorations as wear, fractured margins, delaminated coatings, and bulk fracture. Mechanisms responsible for fatigue-induced failure depend on material ductility: Brittle materials are susceptible to catastrophic failure, while ductile materials utilize their plasticity to reduce stress concentrations at the crack tip. Because of the expense associated with the replacement of failed restorations, there is a strong desire on the part of basic scientists and clinicians to evaluate the resistance of materials to fatigue in laboratory tests. Test variables include fatigue-loading mode and test environment, such as soaking in water. The outcome variable is typically fracture strength, and these data typically fit the Weibull distribution. Analysis of fatigue data permits predictive inferences to be made concerning the survival of structures fabricated from restorative materials under specified loading conditions. Although many dental-restorative materials are routinely evaluated, only limited use has been made of fatigue data collected in vitro: Wear of materials and the survival of porcelain restorations has been modeled by both fracture mechanics and probabilistic approaches. A need still exists for a clinical failure database and for the development of valid test methods for the evaluation of composite materials. PMID:11603506

  11. Fatigue loading of tendon

    PubMed Central

    Shepherd, Jennifer H; Screen, Hazel R C

    2013-01-01

    Tendon injuries, often called tendinopathies, are debilitating and painful conditions, generally considered to develop as a result of tendon overuse. The aetiology of tendinopathy remains poorly understood, and whilst tendon biopsies have provided some information concerning tendon appearance in late-stage disease, there is still little information concerning the mechanical and cellular events associated with disease initiation and progression. Investigating this in situ is challenging, and numerous models have been developed to investigate how overuse may generate tendon fatigue damage and how this may relate to tendinopathy conditions. This article aims to review these models and our current understanding of tendon fatigue damage. We review the strengths and limitations of different methodologies for characterizing tendon fatigue, considering in vitro methods that adopt both viable and non-viable samples, as well as the range of different in vivo approaches. By comparing data across model systems, we review the current understanding of fatigue damage development. Additionally, we compare these findings with data from tendinopathic tissue biopsies to provide some insights into how these models may relate to the aetiology of tendinopathy. Fatigue-induced damage consistently highlights the same microstructural, biological and mechanical changes to the tendon across all model systems and also correlates well with the findings from tendinopathic biopsy tissue. The multiple testing routes support matrix damage as an important contributor to tendinopathic conditions, but cellular responses to fatigue appear complex and often contradictory. PMID:23837793

  12. Powering the Immune System: Mitochondria in Immune Function and Deficiency

    PubMed Central

    Walker, Melissa A.; Sims, Katherine B.; Walter, Jolan E.; Traggiai, Elisabetta

    2014-01-01

    Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings. PMID:25309931

  13. [Immune-mediated neuropathies].

    PubMed

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits. PMID:27474733

  14. Immune System and Schizophrenia

    PubMed Central

    Müller, Norbert; Schwarz, Markus J.

    2010-01-01

    Although an immune dysfunction and the involvement of infectious agents in the pathophysiology of schizophrenia are discussed since decades, the field never came into the mainstream of research. In schizophrenia a blunted type-1 immune response seems to be associated with a dysbalance in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan - kynurenine metabolism resulting in increased production of kynurenic acid in schizophrenia. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an NMDA antagonism in schizophrenia. The immunological effects of antipsychotics rebalance partly the immune imbalance and the overweight of the production of the kynurenic acid. This immunological imbalance results in an inflammatory state combined with increased prostaglandin E2 (PGE2) production and increased cyclo-oxygenase-2 (COX-2) expression. COX-2 inhibitors have been tested in clinical trials, pointing to favourable effects in schizophrenia. PMID:21057585

  15. Fatigue in frail elderly people.

    PubMed

    Toye, Christine; White, Kate; Rooksby, Karen

    2006-05-01

    Many frail older people are likely to suffer from fatigue, but tools to measure fatigue in this population are lacking. Stage one of this study explored and described the experiences of fatigue of 12 older people from Australian residential aged care facilities. Themes identified were pacing yourself, battling on, hitting rock bottom, feeling safe, and moving on. Findings indicated that, with support, frail elders may be able to manage fatigue effects themselves. A measure of fatigue was developed from stage one findings, with reference to the literature. In stage two of the study, the Frail Elder Fatigue Assessment Tool was subjected to panel review, piloting, and refinement. The refined tool comprises 20 items in three subscales: fatigue effects; fatigue resources; and adaptation to fatigue. Further work is required to establish the tool's psychometric properties, but it should then be useful for both research and clinical assessment purposes. PMID:16835559

  16. Immune Restoration

    MedlinePlus

    ... marrow cells immune to HIV infection. Letting the immune system repair itself: CD4 counts have increased for many ... have taken ART. Some scientists believe that the immune system might be able to heal and repair itself ...

  17. Immune response

    MedlinePlus Videos and Cool Tools

    ... cells. T cells are responsible for cell-mediated immunity. This type of immunity becomes deficient in persons with HIV, the virus ... blood. B lymphocytes provide the body with humoral immunity as they circulate in the fluids in search ...

  18. Fatigue During Head-And-Neck Radiotherapy: Prospective Study on 117 Consecutive Patients

    SciTech Connect

    Jereczek-Fossa, Barbara Alicja . E-mail: barbara.fossa@ieo.it; Santoro, Luigi; Alterio, Daniela; Franchi, Benedetta; Fiore, Maria Rosaria; Fossati, Piero; Kowalczyk, Anna; Canino, Paola; Ansarin, Mohssen; Orecchia, Roberto

    2007-06-01

    Purpose: Fatigue is an underevaluated cancer-related and treatment-related symptom. We analyzed fatigue in head and neck cancer patients undergoing radiotherapy (RT). Methods and Materials: A total of 117 patients were enrolled (mean age, 58 years). Radiation therapy (median dose, 66 Gy) was given with either exclusive or postoperative intent in 52 and 65 patients, respectively. Chemotherapy (CT) was added before and/or during RT in 61 patients. The patients completed a 20-item questionnaire (Multidimensional Fatigue Inventory [MFI-20]) before, during (weekly), and after RT. The impact of patient-, tumor-, and treatment-related factors on fatigue was evaluated with unifactorial and multifactorial tests. Results: Fatigue level increased during RT reaching a maximum at Week 6 and then slowly decreased. In multivariate stepwise regression analysis age (inversely related, p < 0.05), psychologic disorders (p < 0.005), and previous head-and-neck surgery (inversely related, p < 0.005) were correlated with higher pre-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p = 0.035), need of cortisone during RT (p = 0.005), and thyroid disorders (p = 0.032) were correlated with higher during-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p < 0.001), and need of cortisone during RT (p < 0.005) were correlated with higher post-RT fatigue level. No impact of gender, performance status, comorbidities other than psychologic and thyroid, tumor stage/site, RT intent, dose, volume, duration, or toxicity was observed. Conclusion: Fatigue affects all patients undergoing RT for head-and-neck cancer, reaches maximum score at the 6th week of RT, and slowly decreases thereafter. Age, thyroid dysfunction, psychologic disorders, pre-RT fatigue score, CT, and cortisone use are correlated with RT-related fatigue levels.

  19. Mechanics of fatigue crack closure

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr. (Editor); Elber, Wolf (Editor)

    1988-01-01

    Papers are presented on plasticity induced crack closure, crack closure in fatigue crack growth, the dependence of crack closure on fatigue loading variables, and a procedure for standardizing crack closure levels. Also considered are a statistical approach to crack closure determination, the crack closure behavior of surface cracks under pure bending, closure measurements on short fatigue cracks, and crack closure under plane strain conditions. Other topics include fatigue crack closure behavior at high stress ratios, the use of acoustic waves for the characterization of closed fatigue cracks, and the influence of fatigue crack wake length and state of stress on crack closure.

  20. Probabilistic Fatigue: Computational Simulation

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    2002-01-01

    Fatigue is a primary consideration in the design of aerospace structures for long term durability and reliability. There are several types of fatigue that must be considered in the design. These include low cycle, high cycle, combined for different cyclic loading conditions - for example, mechanical, thermal, erosion, etc. The traditional approach to evaluate fatigue has been to conduct many tests in the various service-environment conditions that the component will be subjected to in a specific design. This approach is reasonable and robust for that specific design. However, it is time consuming, costly and needs to be repeated for designs in different operating conditions in general. Recent research has demonstrated that fatigue of structural components/structures can be evaluated by computational simulation based on a novel paradigm. Main features in this novel paradigm are progressive telescoping scale mechanics, progressive scale substructuring and progressive structural fracture, encompassed with probabilistic simulation. These generic features of this approach are to probabilistically telescope scale local material point damage all the way up to the structural component and to probabilistically scale decompose structural loads and boundary conditions all the way down to material point. Additional features include a multifactor interaction model that probabilistically describes material properties evolution, any changes due to various cyclic load and other mutually interacting effects. The objective of the proposed paper is to describe this novel paradigm of computational simulation and present typical fatigue results for structural components. Additionally, advantages, versatility and inclusiveness of computational simulation versus testing are discussed. Guidelines for complementing simulated results with strategic testing are outlined. Typical results are shown for computational simulation of fatigue in metallic composite structures to demonstrate the

  1. [Neurogenic erectile dysfunction].

    PubMed

    Ramos, Antonio Sánchez; Durán, Juan Antonio Godino; Oliviero, Antonio

    2010-10-01

    Neurogenic erectile dysfunction is a consequence of alterations in neural pathways, autonomic, somatic, the combination of both or brain components that induce erection. This review aims to explain the physiopathological mechanisms of the most frequent neurological alterations causing erectile dysfunction and sexual disorders. PMID:20978292

  2. Probing the Diversity of T Cell Dysfunction in Cancer.

    PubMed

    Sowell, Ryan T; Kaech, Susan M

    2016-09-01

    T cell dysfunction in cancer comes in many forms, with two new varieties reported in this issue. Daley et al. find that T cells expressing γδ T cell receptors (TCR) promote pancreatic tumor growth by inhibiting activation of T cells with conventional TCRs. Singer et al. characterize dysfunctional tumor infiltrating lymphocytes to reveal a role for zinc homeostasis in anti-tumor immunity. PMID:27610560

  3. Sleep Dysfunction and Gastrointestinal Diseases

    PubMed Central

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A.; Borum, Marie L.

    2015-01-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  4. Sleep Dysfunction and Gastrointestinal Diseases.

    PubMed

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  5. [Pharmacotherapy of erectile dysfunction].

    PubMed

    Kovalev, V A; Koroleva, S V; Kamalov, A A

    2000-01-01

    Among the drugs used to treat erectile dysfunction most common are prostaglandins El, viagra, iochimbin, vasodilators and desaggregants, vitamins, biogenic stimulators, etc. The comparative analysis of their efficacy was made in 360 patients with erectile dysfunction, primarily at subcompensated stage, aged 17-83 years. Organic and psychogenic erectile dysfunctions were diagnosed in 69 and 31% of the patients, respectively. Intracavernous injections of prostaglandin El (Caverject) were effective in 74%, transurethral alprostadil (MUSE) when adjusting the dose--in 38.7% of the patients. Iochimbin in patients with organic and psychogenic forms of erectile dysfunctions was effective in 25 and 40% of patients, respectively. In 26.3 and 19% of such patients the response was obtained after use of the combination including xantinol, nicotinate, trental, biogenic stimulators and adaptogens. Viagra was effective in 60 and 77.3% of patients with psychogenic and organic erectile dysfunctions, respectively. PMID:16856460

  6. Fatigue Is Associated with Poor Sleep in People with Multiple Sclerosis and Cognitive Impairment

    PubMed Central

    Cameron, Michelle H.; Peterson, Vanessa; Boudreau, Eilis A.; Downs, Ashley; Lovera, Jesus; Kim, Edward; McMillan, Garnett P.; Turner, Aaron P.; Haselkorn, Jodie K.; Bourdette, Dennis

    2014-01-01

    Background. Fatigue is the most common symptom in people with multiple sclerosis (MS). Poor sleep also occurs in this population. Objective. The objective of this study was to determine the relationship between fatigue and sleep quality in people with MS and cognitive impairment. Method. This cross-sectional study assessed relationships among fatigue, assessed with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), sleep quality assessed with the Pittsburg Sleep Quality Index (PSQI), and demographics in 121 people with MS and cognitive impairment. Results. Fatigue was significantly correlated with poor sleep quality (MFIS: F = 15.60, P < 0.01; FSS: F = 12.09, P < 0.01). FSS scores were also significantly correlated with the PSQI subscore for daytime dysfunction and MFIS scores were significantly correlated with disability, age, and the PSQI subscores for sleep quality, sleep duration, and daytime dysfunction. Conclusions. This study demonstrates a relationship between fatigue and sleep quality in individuals with MS and cognitive impairment. PMID:24734182

  7. Fatigue is associated with poor sleep in people with multiple sclerosis and cognitive impairment.

    PubMed

    Cameron, Michelle H; Peterson, Vanessa; Boudreau, Eilis A; Downs, Ashley; Lovera, Jesus; Kim, Edward; McMillan, Garnett P; Turner, Aaron P; Haselkorn, Jodie K; Bourdette, Dennis

    2014-01-01

    Background. Fatigue is the most common symptom in people with multiple sclerosis (MS). Poor sleep also occurs in this population. Objective. The objective of this study was to determine the relationship between fatigue and sleep quality in people with MS and cognitive impairment. Method. This cross-sectional study assessed relationships among fatigue, assessed with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), sleep quality assessed with the Pittsburg Sleep Quality Index (PSQI), and demographics in 121 people with MS and cognitive impairment. Results. Fatigue was significantly correlated with poor sleep quality (MFIS: F = 15.60, P < 0.01; FSS: F = 12.09, P < 0.01). FSS scores were also significantly correlated with the PSQI subscore for daytime dysfunction and MFIS scores were significantly correlated with disability, age, and the PSQI subscores for sleep quality, sleep duration, and daytime dysfunction. Conclusions. This study demonstrates a relationship between fatigue and sleep quality in individuals with MS and cognitive impairment. PMID:24734182

  8. Fatigue of advanced materials

    SciTech Connect

    Dauskardt, R.H.; Ritchie, R.O. . Center for Advanced Materials); Cox, B.N. )

    1993-08-01

    The development of toughened ceramics over the past 10 to 15 years is arguably one of the most important materials breakthroughs of this century. Monolithic and composite ceramic materials having fracture toughnesses up to an order of magnitude higher than those available 20 years ago have been produced using technologies based on scientific understanding and micromechanical models for in situ phase transformation, fiber bridging, ductile-particle toughening, and other toughening mechanisms. The irony of this, however, is that although ceramics can now be seriously considered for many structural applications, they can also, contrary to popular belief, be susceptible to degradation under cyclic fatigue loading. This is true even when the loading is fully compressive. As a result, a great deal of attention is now being paid to ceramic fatigue, largely because of the importance of cyclic loading in many of the potential applications for ceramics, such as gas-turbine and reciprocating engines. However, because the field is in its infancy, only limited fatigue property data have been documented, understanding of salient fatigue mechanisms has not been achieved, and the design of ceramic microstructures for optimum fatigue resistance has yet to be attempted.

  9. Fatigue: an overview.

    PubMed

    Rosenthal, Thomas C; Majeroni, Barbara A; Pretorius, Richard; Malik, Khalid

    2008-11-15

    Fatigue, a common presenting symptom in primary care, negatively impacts work performance, family life, and social relationships. The differential diagnosis of fatigue includes lifestyle issues, physical conditions, mental disorders, and treatment side effects. Fatigue can be classified as secondary to other medical conditions, physiologic, or chronic. The history and physical examination should focus on identifying common secondary causes (e.g., medications, anemia, pregnancy) and life-threatening problems, such as cancer. Results of laboratory studies affect management in only 5 percent of patients, and if initial results are normal, repeat testing is generally not indicated. Treatment of all types of fatigue should include a structured plan for regular physical activity that consists of stretching and aerobic exercise, such as walking. Caffeine and modafinil may be useful for episodic situations requiring alertness. Short naps are proven performance enhancers. Selective serotonin reuptake inhibitors, such as fluoxetine, paroxetine, or sertraline, may improve energy in patients with depression. Patients with chronic fatigue may respond to cognitive behavior therapy. Scheduling regular follow-up visits, rather than sporadic urgent appointments, is recommended for effective long-term management. PMID:19035066

  10. Thermal fatigue of beryllium

    SciTech Connect

    Deksnis, E.; Ciric, D.; Falter, H.

    1995-09-01

    Thermal fatigue life of S65c beryllium castellated to a geometry 6 x 6 x (8-10)mm deep has been tested for steady heat fluxes of 3 MW/m{sup 2} to 5 MW/m{sup 2} and under pulsed heat fluxes (10-20 MW/m{sup 2}) for which the time averaged heat flux is 5 MW/m{sup 2}. These tests were carried out in the JET neutral beam test facility A test sequence with peak surface temperatures {le} 600{degrees}C produced no visible fatigue cracks. In the second series of tests, with T{sub max} {le} 750{degrees}C evidence for fatigue appeared after a minimum of 1350 stress cycles. These fatigue data are discussed in view of the observed lack of thermal fatigue in JET plasma operations with beryllium PFC. JET experience with S65b and S65c is reviewed; recent operations with {Phi} = 25 MW/m{sup 2} and sustained melting/resolidification are also presented. The need for a failure criterion for finite element analyses of Be PFC lifetimes is discussed.

  11. Genetics Home Reference: surfactant dysfunction

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions surfactant dysfunction surfactant dysfunction Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Surfactant dysfunction is a lung disorder that causes breathing ...

  12. [Chronic fatigue syndrome with special focus on systemic lupus erythematosus].

    PubMed

    Urbańska-Krawiec, Dagmara; Hrycek, Antoni

    2010-11-01

    Chronic fatigue is an ailment frequently reported in the course of several pathologies. When fatigue clearly predominates over other symptoms, it is referred to as chronic fatigue syndrome (CFS). Initial CFS definition and diagnostic criteria were published in 1988, and have been several times modified since that time. In 1994, Fukuda et al. presented precise guidelines for the evaluation and study of CFS. The etiopathogenic mechanisms of CFS have not yet been satisfactorily clarified although immune and hormonal responses as well as a decline in neurotransmitter concentrations have been implicated in the development of the disorder. Systemic lupus erythematosus (SLE) is an autoimmune disease, with chronic fatigue as a very common symptom observed in as many as 80% of the patients. Owing to its obscure pathogenesis, therapy for CFS remains a difficult and complex issue consisting mostly of the treatment of the underlying disease. Appropriate lifestyle and physical activity should be emphasized. Medications include antidepressants and glucocorticosteroids. Psychological counseling has also been recommended. Complex etiopathogenesis and the involvement of the immune and neurohormonal systems suggest that CFS might be a primary and not secondary disorder. Hence a significant role of medical professionals in the diagnosis and treatment of chronic fatigue syndrome. PMID:21268918

  13. Exercise, nutrition and immune function.

    PubMed

    Gleeson, Michael; Nieman, David C; Pedersen, Bente K

    2004-01-01

    Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function. Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune function and have other adverse effects on health. Immune system depression has also been associated with an excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. Conversely, consuming 30-60 g carbohydrate x h(-1) during sustained intensive exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence that so-called 'immune-boosting' supplements, including high doses of antioxidant vitamins, glutamine, zinc, probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking. PMID:14971437

  14. Low-cycle thermal fatigue

    NASA Technical Reports Server (NTRS)

    Halford, G. R.

    1986-01-01

    A state-of-the-art review is presented of the field of thermal fatigue. Following a brief historical review, the concept is developed that thermal fatigue can be viewed as processes of unbalanced deformation and cracking. The unbalances refer to dissimilar mechanisms occurring in opposing halves of thermal fatigue loading and unloading cycles. Extensive data summaries are presented and results are interpreted in terms of the unbalanced processes involved. Both crack initiation and crack propagation results are summarized. Testing techniques are reviewed, and considerable discussion is given to a technique for thermal fatigue simulation, known as the bithermal fatigue test. Attention is given to the use of isothermal life prediction methods for the prediction of thermal fatigue lives. Shortcomings of isothermally-based life prediction methods are pointed out. Several examples of analyses and thermal fatigue life predictions of high technology structural components are presented. Finally, numerous dos and don'ts relative to design against thermal fatigue are presented.

  15. Fatigue and Sleep during Cancer and Chemotherapy: Translational Rodent Models

    PubMed Central

    Ray, Maria; Rogers, Laura Q; Trammell, Rita A; Toth, Linda A

    2008-01-01

    The frequent occurrence of fatigue and disturbed sleep in cancer survivors and the negative effect of these symptoms on quality of life and clinical outcome underscore the need to identify mechanisms that cause cancer-related fatigue, with a view toward developing more effective treatments for this problem. Human studies of fatigue and disturbed sleep are limited by high inter-individual genetic and environmental variability, difficulties with behavioral or reporting compliance, and the subjective nature of the problems. Although animal models also must overcome the barrier of assessing fatigue and sleep disturbance in the absence of obvious objective clinical markers, animal studies are easier to control and standardize than are studies of people. Moreover, animal models are crucial to the identification and understanding of underlying disease mechanisms. This review describes the need for, the feasibility of, and several possible approaches to measuring fatigue in animal models of cancer and to relating such measures to disturbed sleep, immune function, and other potential mechanisms. Developing and using animal models to better understand fatigue and disturbed sleep related to cancer and its treatment has an enormous potential to expand the knowledge base and foster hypotheses necessary for the future development and testing of interventions. PMID:18589865

  16. A subsized fatigue specimen

    NASA Technical Reports Server (NTRS)

    Jeelani, S.; Natarajan, R.; Reddy, G. R.

    1986-01-01

    A subsized fatigue specimen has been designed to overcome the difficulty of machining a full-sized specimen from cast superalloy components. A finite element analysis confirmed that the stress was maximum at the gauge section for any given set of clamping and tensile loads, and that the stresses developed due to clamping forces were negligible compared with those due to tensile or compressive loads. Fatigue data generated using subsized specimens of AISI 4130 steel, 2024-T4 aluminum alloy and 6Al-4V titanium alloy compared well with those available in the literature for full-sized specimens.

  17. Hydraulic Fatigue-Testing Machine

    NASA Technical Reports Server (NTRS)

    Hodo, James D.; Moore, Dennis R.; Morris, Thomas F.; Tiller, Newton G.

    1987-01-01

    Fatigue-testing machine applies fluctuating tension to number of specimens at same time. When sample breaks, machine continues to test remaining specimens. Series of tensile tests needed to determine fatigue properties of materials performed more rapidly than in conventional fatigue-testing machine.

  18. Managing fatigue: clinical correlates, assessment procedures and therapeutic strategies.

    PubMed

    Penner, Ik; Calabrese, P

    2010-01-01

    The majority of patients with Multiple Sclerosis (MS) experience fatigue and for many susabjects concerned it is the most disabling symptom. Fatigue is most prominent in the afternoon and may be aggravated by heat. It has a tremendous negative impact on quality of life and is often one of the major reasons for early retirement and unemployment. Against further assumptions, fatigue can occur at all stages and is often present at the onset of the disease. Reliable assessment however, is difficult as it is a subjectively perceived lack of physical and/or mental energy interfering with intended activities and has to be differentiated from depression, consequences of sleep disorders, cognitive decline, and side-effects of medication. Moreover, fatigue is not directly related to overall disease evolution, to disability levels or localized lesions, although an association with dysfunction of fronto-thalamo-basal-ganglia circuits seems likely. Several therapeutic approaches including pharmacological as well as non-pharmacological strategies are available but an evidence-based specific gold-standard for the treatment of fatigue is still missing. PMID:20663419

  19. Fatigue and thermal fatigue of Pb-Sn solder joints

    SciTech Connect

    Frear, D.; Grivas, D.; McCormack, M.; Tribula, D.; Morris, J.W. Jr.

    1987-01-01

    This paper presents a fundamental investigation of the fatigue and thermal fatigue characteristics, with an emphasis on the microstructural development during fatigue, of Sn-Pb solder joints. Fatigue tests were performed in simple shear on both 60Sn-40Pb and 5Sn-95Pb solder joints. Isothermal fatigue tests show increasing fatigue life of 60Sn-40Pb solder joints with decreasing strain and temperature. In contrast, such behavior was not observed in the isothermal fatigue of 5Sn-95Pb solder joints. Thermal fatigue results on 60Sn-40Pb solder cycled between -55/sup 0/C and 125/sup 0/C show that a coarsened region develops in the center of the joint. Both Pb-rich and Sn-rich phases coarsen, and cracks form within these coarsened regions. The failure mode 60Sn-40Pb solder joints in thermal and isothermal fatigue is similar: cracks form intergranularly through the Sn-rich phase or along Sn/Pb interphase boundaries. Extensive cracking is found throughout the 5Sn-95Pb joint for both thermal and isothermal fatigue. In thermal fatigue the 5Sn-95Pb solder joints failed after fewer cycles than 60Sn-40Pb.

  20. Radial nerve dysfunction (image)

    MedlinePlus

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  1. 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

  2. Eustachian Tube Dysfunction

    MedlinePlus

    ... flying (because of altitude changes). Riding in elevators, driving through mountains or diving may also make your symptoms worse. Causes & Risk Factors What causes eustachian tube dysfunction? The most common ...

  3. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  4. Temporomandibular Joint Dysfunction

    MedlinePlus

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to ... For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that ...

  5. Sexual Dysfunction in Women

    PubMed Central

    Brown, Pamela

    1989-01-01

    Sexual dysfunction takes place in the context of women's lives and affects their sexuality and self-esteem. Awareness of these influences are vital to the management of the dysfunction and the promotion of positive sexuality. The family physician's contribution to both the prevention and management of sexual concerns includes an awareness of societal influences and facilitation of a woman's sense of her own power and control over her life. PMID:21248971

  6. Cellular dysfunction in sepsis.

    PubMed

    Singer, Mervyn

    2008-12-01

    Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors. PMID:18954700

  7. Marathon training and immune function.

    PubMed

    Nieman, David C

    2007-01-01

    Many components of the immune system exhibit adverse change after marathon-type exertion. These immune changes occur in several compartments of the immune system and body (e.g. the skin, upper respiratory tract mucosal tissue, lung, peritoneal cavity, blood and muscle). Of all immune cells, natural killer (NK) cells, neutrophils and macrophages (of the innate immune system) exhibit the greatest changes in response to marathon competition, both in terms of numbers and function. Many mechanisms appear to be involved, including exercise-induced changes in stress hormone and cytokine concentrations, body temperature changes, increases in blood flow and dehydration. During this 'open window' of immune dysfunction (which may last between 3 and 72 hours, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. Of the various nutritional and pharmacological countermeasures to marathon-induced immune perturbations that have been evaluated thus far, ingestion of carbohydrate beverages during intense and prolonged exercise has emerged as the most effective. However, carbohydrate ingestion during a marathon attenuates increases in plasma cytokines and stress hormones, but is largely ineffective against changes in other immune components including suppression of NK and T-cell function, and salivary IgA output. Other countermeasures, such as glutamine, antioxidant supplements and ibuprofen, have had disappointing results and thus the search for companion agents to carbohydrate continues. PMID:17465622

  8. Muscle Deoxygenation Causes Muscle Fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

    1999-01-01

    Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

  9. FATIGUE OF DENTAL CERAMICS

    PubMed Central

    Zhang, Yu; Sailer, Irena; Lawn, Brian R

    2013-01-01

    Objectives Clinical data on survival rates reveal that all-ceramic dental prostheses are susceptible to fracture from repetitive occlusal loading. The objective of this review is to examine the underlying mechanisms of fatigue in current and future dental ceramics. Data/sources The nature of various fatigue modes is elucidated using fracture test data on ceramic layer specimens from the dental and biomechanics literature. Conclusions Failure modes can change over a lifetime, depending on restoration geometry, loading conditions and material properties. Modes that operate in single-cycle loading may be dominated by alternative modes in multi-cycle loading. While post-mortem examination of failed prostheses can determine the sources of certain fractures, the evolution of these fractures en route to failure remains poorly understood. Whereas it is commonly held that loss of load-bearing capacity of dental ceramics in repetitive loading is attributable to chemically-assisted 'slow crack growth' in the presence of water, we demonstrate the existence of more deleterious fatigue mechanisms, mechanical rather than chemical in nature. Neglecting to account for mechanical fatigue can lead to gross overestimates in predicted survival rates. Clinical significance Strategies for prolonging the clinical lifetimes of ceramic restorations are proposed based on a crack-containment philosophy. PMID:24135295

  10. Cumulative fatigue damage models

    NASA Technical Reports Server (NTRS)

    Mcgaw, Michael A.

    1988-01-01

    The problem of calculating expected component life under fatigue loading conditions is complicated by the fact that component loading histories contain, in many cases, cyclic loads of widely varying amplitudes. In such a case a cumulative damage model is required, in addition to a fatigue damage criterion, or life relationship, in order to compute the expected fatigue life. The traditional cumulative damage model used in design is the linear damage rule. This model, while being simple to use, can yield grossly unconservative results under certain loading conditions. Research at the NASA Lewis Research Center has led to the development of a nonlinear cumulative damage model, named the double damage curve approach (DDCA), that has greatly improved predictive capability. This model, which considers the life (or loading) level dependence of damage evolution, was applied successfully to two polycrystalline materials, 316 stainless steel and Haynes 188. The cumulative fatigue behavior of the PWA 1480 single-crystal material is currently being measured to determine the applicability of the DDCA for this material.

  11. Fatigue resistance of duralumin

    NASA Technical Reports Server (NTRS)

    1922-01-01

    Where, in the following report, mention is made of fatigue, it always refers to the weakening of the material produced by rapidly changing stresses below the point of elasticity. The alternating stress was obtained by a test bar which was held at one end and subjected to rotation. Most of the tests were conducted on connecting rods.

  12. Fatigue of insect cuticle.

    PubMed

    Dirks, Jan-Henning; Parle, Eoin; Taylor, David

    2013-05-15

    Many parts of the insect exoskeleton experience repeated cyclic loading. Although the cuticle of insects and other arthropods is the second most common natural composite material in the world, so far nothing is known about its fatigue properties, despite the fact that fatigue undoubtedly limits the durability of body parts in vivo. For the first time, we here present experimental fatigue data of insect cuticle. Using force-controlled cyclic loading, we determined the number of cycles to failure for hind legs (tibiae) and hind wings of the locust Schistocerca gregaria, as a function of the applied cyclic stress. Our results show that, although both are made from cuticle, these two body parts behave very differently. Wing samples showed a large fatigue range, failing after 100,000 cycles when we applied 46% of the stress needed for instantaneous failure [the ultimate tensile strength (UTS)]. Legs, in contrast, were able to sustain a stress of 76% of the UTS for the same number of cycles to failure. This can be explained by the difference in the composition and structure of the material, two factors that, amongst others, also affect the well-known behaviour of engineering composites. Final failure of the tibiae occurred via one of two different failure modes--propagation in tension or buckling in compression--indicating that the tibia is 'optimized' by evolution to resist both failure modes equally. These results are further discussed in relation to the evolution and normal use of these two body parts. PMID:23393276

  13. Incompatibility and Mental Fatigue

    ERIC Educational Resources Information Center

    Herzog, Thomas R.; Hayes, Lauren J.; Applin, Rebecca C.; Weatherly, Anna M.

    2011-01-01

    A straightforward prediction from attention restoration theory is that the level of incompatibility in a person's life should be positively correlated with that person's level of mental (or directed attention) fatigue. The authors tested this prediction by developing a new self-report measure of incompatibility in which they attempted to isolate…

  14. Fatigue in Composite Materials

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The deformation and failure behavior of graphite/epoxy tubes under biaxial loading was investigated. The increase of basic understanding of and provide design information for the bi-axial response of graphite/epoxy composites to fatigue loads are considered.

  15. Four Pathways Involving Innate Immunity in the Pathogenesis of Preeclampsia

    PubMed Central

    Bounds, Kelsey R.; Newell-Rogers, M. Karen; Mitchell, Brett M.

    2015-01-01

    The maternal innate immune system plays an important role both in normal pregnancy as well as hypertensive disorders of pregnancy including preeclampsia (PE). We propose four pathways that involve excessive innate immunity that lead to most forms of PE. Pre-existing endothelial dysfunction plus pregnancy leads to an excessive innate immune response resulting in widespread inflammation, placental and renal dysfunction, vasoconstriction, and PE. Placental dysfunction due to shallow trophoblast invasion, inadequate spiral artery remodeling, and/or low placental perfusion initiates an innate immune response leading to excessive inflammation, endothelial and renal dysfunction, and PE. A heightened innate immune system due to pre-existing or acquired infections plus the presence of a paternally derived placenta and semi-allogeneic fetus cause an excessive innate immune response which manifests as PE. Lastly, an abnormal and excessive maternal immune response to pregnancy leads to widespread inflammation, organ dysfunction, and PE. We discuss the potential role of innate immunity in each of these scenarios, as well as the overlap, and how targeting the innate immune system might lead to therapies for the treatment of PE. PMID:26664892

  16. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

    PubMed Central

    2013-01-01

    Background Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity. Methods Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days. Results Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy. Conclusions Our results support the role of cytokines in the pathophysiology of CFS. PMID:23570606

  17. Genitourinary dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Yamanishi, Tomonori; Kishi, Masahiko

    2010-01-15

    Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:20077468

  18. Different types of fatigue in patients with facioscapulohumeral dystrophy, myotonic dystrophy and HMSN-I. Experienced fatigue and physiological fatigue.

    PubMed

    Kalkman, Joke S; Zwarts, Machiel J; Schillings, Maartje L; van Engelen, Baziel G M; Bleijenberg, Gijs

    2008-09-01

    Although fatigue is a common symptom in neuromuscular disorders, little is known about different types of fatigue. Sixty-five FSHD, 79 adult-onset MD and 73 HMSN type I patients were studied. Experienced fatigue was assessed with the CIS-fatigue subscale. Physiological fatigue was measured during a 2-min sustained maximal voluntary contraction of the biceps brachii muscle using the twitch interpolation technique to assess central activation failure (CAF) and peripheral fatigue. Experienced fatigue, CAF and peripheral fatigue appeared to be predominantly separate types of fatigue. PMID:18690504

  19. Immunizations - diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  20. Childhood Immunization

    MedlinePlus

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  1. Influence of catechol-o-methyltransferase genotype (Val158Met) on endocrine, sympathetic nervous and mucosal immune systems in breast cancer survivors.

    PubMed

    Fernández-de-Las-Peñas, César; Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Ambite-Quesada, Silvia; Díaz-Rodríguez, Lourdes; Rivas-Martínez, Inés; del Moral-Avila, Rosario; Arroyo-Morales, Manuel

    2012-04-01

    Stress can play an important role in development of cancer-related fatigue (CRF) by activating the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and altering the immune system. This study examined the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on salivary markers of HPA axis (cortisol), SNS (α-amylase) and immune (IgA) systems, as well as on CRF in breast cancer survivors (BCS). One-hundred BCS participated. After amplifying Val158Met COMT polymorphisms by polymerase chain reaction, three COMT genotypes were considered: Val/Val, Val/Met, Met/Met. Salivary cortisol, α-amylase activity, salivary flow rate, and IgA concentration were collected from non-stimulated saliva. CRF was assessed with the fatigue subscale of the Profile of Mood State (POMS) questionnaire. We found that BCS carrying Met/Met genotype reported higher cortisol concentration, α-amylase activity and greater CRF than those with Val/Met (P < 0.05) and Val/Val (P < 0.001) genotypes. No differences in salivary flow rate or IgA concentration (P > 0.20) were found. The results suggest that BCS carrying Met/Met genotype exhibit greater dysfunction of the HPA axis and SNS system associated with severe CRF. This study is important because it strives to understand biological factors that predispose some BCS to higher levels of CRF. PMID:21974969

  2. Probabilistic Mesomechanical Fatigue Model

    NASA Technical Reports Server (NTRS)

    Tryon, Robert G.

    1997-01-01

    A probabilistic mesomechanical fatigue life model is proposed to link the microstructural material heterogeneities to the statistical scatter in the macrostructural response. The macrostructure is modeled as an ensemble of microelements. Cracks nucleation within the microelements and grow from the microelements to final fracture. Variations of the microelement properties are defined using statistical parameters. A micromechanical slip band decohesion model is used to determine the crack nucleation life and size. A crack tip opening displacement model is used to determine the small crack growth life and size. Paris law is used to determine the long crack growth life. The models are combined in a Monte Carlo simulation to determine the statistical distribution of total fatigue life for the macrostructure. The modeled response is compared to trends in experimental observations from the literature.

  3. [Chronic fatigue syndrome].

    PubMed

    Henningsen, P; Martin, A

    2013-01-01

    Enduring and disabling fatigue that cannot be explained by a known disease is the main characteristic of chronic fatigue syndrome. Several definitions do exist, and classification approaches vary regarding supplementary symptoms, time course, and by implicit concepts of aetiology. CFS can be considered as a functional somatic syndrome, e. g. supported by the high rates of comorbid bodily complaints and syndromes that lack clear medical explanation. Accordingly the diagnostic process should not be limited to the thorough physical examination, but also address additional somatic complaints, psychosocial factors (specifically subjective illness beliefs), and impairments. Recently German medical and psychological societies provided treatment guidelines for functional somatic syndromes. Cognitive behavioural therapy and graded activity are evidence based treatment methods for CFS. PMID:23250694

  4. Chronic Fatigue Syndrome

    PubMed Central

    Leyton, Edward; Pross, Hugh

    1992-01-01

    To determine the effect of certain herbal and homeopathic preparations on symptoms, lymphocyte markers, and cytotoxic function of the lymphocytes in patients with chronic fatigue syndrome, we studied six outpatients diagnosed with the disease by their family physicians. Patients were given herbal and homeopathic preparations after a 3-week symptom-recording period. After treatment, symptoms were again recorded. Blood samples were taken before and after treatment. None of the values showed any significant change after treatment. PMID:21221272

  5. Echinoderm immunity.

    PubMed

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  6. Dysfunctional Uterine Bleeding

    PubMed Central

    Casper, Robert F.

    1983-01-01

    Dysfunctional uterine bleeding is most commonly associated with chronic anovulation. Early diagnosis of anovulation is important; the induction of regular withdrawal periods using a progestin such as Provera prevents the development of endometrial hyperplasia with the subsequent inevitable occurrence of a heavy, frightening vaginal bleed. The etiology of dysfunctional uterine bleeding occurring during ovulatory cycles is unknown and all medical therapies at present are necessarily experimental. Hysterectomy is probably the treatment of choice for women who have finished their childbearing career and in whom persisting menorrhagia during ovulatory cycles results in anemia. PMID:21283453

  7. Compassion fatigue: a nurse's primer.

    PubMed

    Lombardo, Barbara; Eyre, Caryl

    2011-01-01

    Most nurses enter the field of nursing with the intent to help others and provide empathetic care for patients with critical physical, mental, emotional, and spiritual needs. Empathic and caring nurses, however, can become victims of the continuing stress of meeting the often overwhelming needs of patients and their families, resulting in compassion fatigue. Compassion fatigue affects not only the nurse in terms of job satisfaction and emotional and physical health, but also the workplace environment by decreasing productivity and increasing turnover. We begin this article with a case study of a reactive nurse who did not seek help for her continuing stress. This is followed by a review of Watson's theoretical perspective related to compassion fatigue. Next we delineate symptoms of, and describe interventions for addressing compassion fatigue. We conclude by presenting a case study of a proactive nurse who avoided developing compassion fatigue and a discussion of future research needed to better prevent and ameliorate compassion fatigue. PMID:21800934

  8. Fatigue of fiberglass beam substructures

    SciTech Connect

    Mandell, J.F.; Combs, D.W.; Samborsky, D.D.

    1995-09-01

    Composite material beams representative of wind turbine blade substructure have been designed, fabricated, and tested under constant amplitude flexural fatigue loading. Beam stiffness, strength, and fatigue life are predicted based on detailed finite element analysis and the materials fatigue database developed using standard test coupons and special high frequency minicoupons.Beam results are in good agreement with predictions when premature adhesive and delamination failures are avoided in the load transfer areas. The results show that fiberglass substructures can be designed and fabricated to withstand maximum strain levels on the order of 8,000 microstrain for about 10{sup 6} cycles with proper structural detail design and the use of fatigue resistant laminate constructions. The study also demonstrates that the materials fatigue database and accurate analysis can be used to predict the fatigue life of composite substructures typical of blades.

  9. Probabilistic Fatigue Damage Program (FATIG)

    NASA Technical Reports Server (NTRS)

    Michalopoulos, Constantine

    2012-01-01

    FATIG computes fatigue damage/fatigue life using the stress rms (root mean square) value, the total number of cycles, and S-N curve parameters. The damage is computed by the following methods: (a) traditional method using Miner s rule with stress cycles determined from a Rayleigh distribution up to 3*sigma; and (b) classical fatigue damage formula involving the Gamma function, which is derived from the integral version of Miner's rule. The integration is carried out over all stress amplitudes. This software solves the problem of probabilistic fatigue damage using the integral form of the Palmgren-Miner rule. The software computes fatigue life using an approach involving all stress amplitudes, up to N*sigma, as specified by the user. It can be used in the design of structural components subjected to random dynamic loading, or by any stress analyst with minimal training for fatigue life estimates of structural components.

  10. Creep-Fatigue Interaction Testing

    NASA Technical Reports Server (NTRS)

    Halford, Gary R.

    2001-01-01

    Fatigue fives in metals are nominally time independent below 0.5 T(sub Melt). At higher temperatures, fatigue lives are altered due to time-dependent, thermally activated creep. Conversely, creep rates are altered by super. imposed fatigue loading. Creep and fatigue generally interact synergistically to reduce material lifetime. Their interaction, therefore, is of importance to structural durability of high-temperature structures such as nuclear reactors, reusable rocket engines, gas turbine engines, terrestrial steam turbines, pressure vessel and piping components, casting dies, molds for plastics, and pollution control devices. Safety and lifecycle costs force designers to quantify these interactions. Analytical and experimental approaches to creep-fatigue began in the era following World War II. In this article experimental and life prediction approaches are reviewed for assessing creep-fatigue interactions of metallic materials. Mechanistic models are also discussed briefly.