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Sample records for alters immune endocrine

  1. Altered time structure of neuro-endocrine-immune system function in lung cancer patients

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    Carughi Stefano

    2010-06-01

    TcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. Conclusion The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system

  2. Human disturbance alters endocrine and immune responses in the Galapagos marine iguana (Amblyrhynchus cristatus)

    Science.gov (United States)

    French, Susannah S; DeNardo, Dale F.; Greives, Timothy J.; Strand, Christine R.; Demas, Gregory E.

    2010-01-01

    Anthropogenic disturbance is a relevant and widespread facilitator of environmental change and there is clear evidence that it impacts natural populations. While population-level responses to major anthropogenic changes have been well studied, individual physiological responses to mild disturbance can be equally critical to the long-term survival of a species, yet they remain largely unexamined. The current study investigated the impact of seemingly low-level anthropogenic disturbance (ecotourism) on stress responsiveness and specific fitness-related immune measures in different breeding stages of the marine iguana (Amblyrhynchus cristatus). Specifically, we found stress-induced elevations in plasma corticosterone among tourist-exposed populations relative to undisturbed populations. We also found changes in multiple immunological responses associated with stress-related effects of human disturbance, including bacterial killing ability, cutaneous wound healing, and hemolytic complement activity, and the responses varied according to reproductive state. By identifying health-related consequences of human disturbance, this study provides critical insight into the conservation of a well-known species that has a very distinct ecology. The study also broadens the foundation of knowledge needed to understand the global significance of various levels of human disturbance. PMID:20708010

  3. Human disturbance alters endocrine and immune responses in the Galapagos marine iguana (Amblyrhynchus cristatus).

    Science.gov (United States)

    French, Susannah S; DeNardo, Dale F; Greives, Timothy J; Strand, Christine R; Demas, Gregory E

    2010-11-01

    Anthropogenic disturbance is a relevant and widespread facilitator of environmental change and there is clear evidence that it impacts natural populations. While population-level responses to major anthropogenic changes have been well studied, individual physiological responses to mild disturbance can be equally critical to the long-term survival of a species, yet they remain largely unexamined. The current study investigated the impact of seemingly low-level anthropogenic disturbance (ecotourism) on stress responsiveness and specific fitness-related immune measures in different breeding stages of the marine iguana (Amblyrhynchus cristatus). Specifically, we found stress-induced elevations in plasma corticosterone among tourist-exposed populations relative to undisturbed populations. We also found changes in multiple immunological responses associated with stress-related effects of human disturbance, including bacterial killing ability, cutaneous wound healing, and hemolytic complement activity, and the responses varied according to reproductive state. By identifying health-related consequences of human disturbance, this study provides critical insight into the conservation of a well-known species that has a very distinct ecology. The study also broadens the foundation of knowledge needed to understand the global significance of various levels of human disturbance. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Immunization alters body odor.

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    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  5. Alterations in polyadenylation and its implications for endocrine disease

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    Anders eRehfeld

    2013-05-01

    Full Text Available IntroductionPolyadenylation is the process in which the pre-mRNA is cleaved at the poly(A site and a poly(A tail is added - a process necessary for normal mRNA formation. Genes with multiple poly(A sites can undergo alternative polyadenylation, producing distinct mRNA isoforms with different 3’ untranslated regions (3’ UTRs and in some cases different coding regions. Two thirds of all human genes undergo alternative polyadenylation. The efficiency of the polyadenylation process regulates gene expression and alternative polyadenylation plays an important part in post-transcriptional regulation, as the 3’ UTR contains various cis-elements associated with post-transcriptional regulation, such as target sites for microRNAs and RNA-binding proteins.Implications of alterations in polyadenylation for endocrine diseaseAlterations in polyadenylation have been found to be causative of neonatal diabetes and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked and to be associated with type I and II diabetes, pre-eclampsia, fragile X-associated premature ovarian insufficiency, ectopic Cushing syndrome and many cancer diseases, including several types of endocrine tumor diseases.PerspectivesRecent developments in high-throughput sequencing have made it possible to characterize polyadenylation genome-wide. Antisense elements inhibiting or enhancing specific poly(A site usage can induce desired alterations in polyadenylation, and thus hold the promise of new therapeutic approaches. SummaryThis review gives a detailed description of alterations in polyadenylation in endocrine disease, an overview of the current literature on polyadenylation and summarizes the clinical implications of the current state of research in this field.

  6. Endocrine alterations in HIV-infected patients

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    Sujit Kumar Tripathy

    2015-01-01

    Full Text Available Aims and objectives: To study the frequency of thyroid, adrenal and gonadal dysfunction in newly diagnosed HIV-infected patients and to correlate them at different levels of CD4 cell counts. Materials and Methods: Forty-three HIV-positive cases were included in the study group. Cases were divided into three groups on the basis of CD4 cell count. Serum free T3, free T4, TSH, Cortisol, FSH, LH, testosterone and estradiol were estimated by the radioimmunoassay method. Hormone levels between cases were compared and their correlation with CD4 count was analyzed. Results: Prevalence of gonadal dysfunction (88.3% was the most common endocrine dysfunction followed by thyroid (60.4% and adrenal dysfunction (27.9%. Secondary hypogonadism (68.4% was more common than primary (31.6%. Low T3 syndrome, that is, isolated low free T3, was the most common (25.6% thyroid dysfunction followed by secondary hypothyroidism (16.2% and subclinical hypothyroidism (11.6%. Adrenal excess (16.3% was more common than adrenal insufficiency (11.6%. The difference in hormonal dysfunction between male and female was statistically insignificant (P > 0.05. 27.9% of patients had multiple hormone deficiency. There was negligible or no correlation between CD4 count and serum hormone level. Conclusion: In our study, endocrine dysfunction was quite common among HIV-infected patients but there was no correlation between hormone levels and CD4 count. Endocrine dysfunctions and role of hormone replacement therapy in HIV-infected patient needs to be substantiated by large longitudinal study, so that it will help to reduce morbidity, improve quality of life.

  7. Rare endocrine cancers have novel genetic alterations

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    A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

  8. Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

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    Oriana del Rocío Cruz Guzmán

    2012-01-01

    Full Text Available Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

  9. Phytochemicals for taming agitated immune-endocrine-neural axis.

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    Patel, Seema

    2017-07-01

    Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome.

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    Buckley, Maria M; O'Mahony, Siobhain M; O'Malley, Dervla

    2014-07-21

    Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.

  11. Altered Cellular Metabolism Drives Trained Immunity.

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    Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

    2018-04-04

    Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. An exploratory study into the effect of exhausting bicycle exercise on endocrine and immune responses in post-menopausal women : Relationships between vigour and plasma cortisol concentrations and lymphocyte proliferation following exercise

    NARCIS (Netherlands)

    van der Pompe, G; Bernards, N; Kavelaars, A; Heijnen, C

    It is well-established that bicycle exercise alters the endocrine and immune responses in men, but little information is available for women, especially middle-aged, post-menopausal women. The purpose of our study was to document the endocrine and immune reactivity to exhausting bicycle exercise in

  13. Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

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    Ahmed, R G

    2016-09-01

    Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Construction and application of a bovine immune-endocrine cDNA microarray.

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    Tao, Wenjing; Mallard, Bonnie; Karrow, Niel; Bridle, Byram

    2004-09-01

    A variety of commercial DNA arrays specific for humans and rodents are widely available; however, microarrays containing well-characterized genes to study pathway-specific gene expression are not as accessible for domestic animals, such as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine immune-endocrine cDNA array was developed to evaluate genetic pathways involved in the immune-endocrine axis of cattle during periods of altered homeostasis provoked by physiological or environmental stressors, such as infection, vaccination or disease. For this purpose, 167 cDNA sequences corresponding to immune, endocrine and inflammatory response genes were collected and categorized. Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19, beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a partial sequence of the plasmid pACYC177. In addition, RNA extracted from un-stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S. aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific primers. The endocrine-associated genes were amplified from cDNA derived from un-stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The array was constructed in 4 repeating grids of 180 duplicated spots by coupling the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass slides. The bovine immune-endocrine arrays were standardized and preliminary gene expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate arrays/cow) in a time course study. Mononuclear cell-derived cytokine and chemokine (IL-2, IL-1alpha

  15. An overview of estrogen-associated endocrine disruption in fishes: evidence of effects on reproductive and immune physiology

    Science.gov (United States)

    Iwanowicz, L.R.; Blazer, V.S.

    2011-01-01

    Simply and perhaps intuitively defined, endocrine disruption is the abnormal modulation of normal hormonal physiology by exogenous chemicals. In fish, endocrine disruption of the reproductive system has been observed worldwide in numerous species and is known to affect both males and females. Observations of biologically relevant endocrine disruption most commonly occurs near waste water treatment plant outfalls, pulp and paper mills, and areas of high organic loading sometimes associated with agricultural practices. Estrogenic endocrine disrupting chemicals (EEDCs) have received an overwhelmingly disproportionate amount of scientific attention compared to other EDCs in recent years. In male fishes, exposure to EEDCs can lead to the induction of testicular oocytes (intersex), measurable plasma vitellogenin protein, altered sex steroid profiles, abnormal spawning behavior, skewed population sex ratios, and lessened reproductive success. Interestingly, contemporary research purports that EDCs modulate aspects of non-reproductive physiology including immune function. Here we present an overview of endocrine disruption in fishes associated with estrogenic compounds, implications of this phenomenon, and examples of EDC related research findings by our group in the Potomac River Watershed, USA.

  16. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-01-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...... cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might...

  17. Altered Immune Regulation in Type 1 Diabetes

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    Zóka, András; Műzes, Györgyi; Somogyi, Anikó; Varga, Tímea; Szémán, Barbara; Al-Aissa, Zahra; Hadarits, Orsolya; Firneisz, Gábor

    2013-01-01

    Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development. PMID:24285974

  18. Altered Immune Regulation in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    András Zóka

    2013-01-01

    Full Text Available Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.

  19. Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

    During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment. Copyright © 2012 S. Karger AG, Basel.

  20. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity.

    Science.gov (United States)

    Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J

    2017-03-31

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues.

  1. Corticosteroids and interleukin-1, messengers for communication between the endocrine and immune system in carp

    NARCIS (Netherlands)

    Weyts, F.A.A.

    1998-01-01

    Summary

    Stress-induced inummosuppression is a well known phenomenon and mostly attributed to actions of steroid hormones released upon activation of the hypothalamus-pituitary-adrenal (HPA)-axis. In mammals, this endocrine-immune interaction is part of a

  2. Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health.

    Science.gov (United States)

    Bansal, Amita; Henao-Mejia, Jorge; Simmons, Rebecca A

    2018-01-01

    The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity. Copyright © 2018 Endocrine Society.

  3. Radio immune analysis of endocrine system state at exposure to different physical factors

    International Nuclear Information System (INIS)

    Rozdyil's'ka, O.M.; Rozdtil's'kij, S.Yi.; Bratchuk, O.M.; Yakimova, T.P.

    1999-01-01

    Radio immune analysis allows to define more exactly the mechanisms of physical factors action and may be used for validation of new therapeutic techniques. The ultra-high frequency magneto therapy, sinusoid modulated current and direct current influence the state of the endocrine system differently but within the physiological norm. The most prominent action of the physical factor is observed at trans cerebral mode

  4. The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, α-zearalanol, and genistein): Effects on interferon-γ

    International Nuclear Information System (INIS)

    Calemine, Jillian; Zalenka, Julie; Karpuzoglu-Sahin, Ebru; Ward, Daniel L.; Lengi, Andrea; Ahmed, S. Ansar

    2003-01-01

    The immune system is a potential target for estrogenic endocrine disrupters. To date, there is limited information on whether estrogenic endocrine disruptors modulate the immune system of aged individuals. To address this issue, groups of 74-week-old mice were given nine oral doses of selected estrogenic endocrine disrupters: diethylstilbestrol (DES, 3 μg/100 g bw), α-zearalanol (0.5 mg/100 g bw), or genistein (0.15 mg/100 g bw) in corn oil, or corn oil alone, over 2.5 weeks. Both developmental (thymus) and mature (spleen) lymphoid organs were affected, although specific effects varied with the chemical. DES significantly decreased thymocyte numbers. However, relative percentages of thymocyte subsets were not altered. While splenic cellularity and percentages of T and B cells were unchanged, splenocytes from DES-exposed mice had significantly decreased ability to proliferate in response to Concanavalin-A (Con-A). Con-A-activated splenocytes from mice treated with genistein or α-zearalanol had decreased levels of interferon-γ (IFNγ) protein in their culture supernatants compared to similar cultures from oil-treated mice. RT-PCR analysis of Con-A-activated splenocytes revealed that the expression of IFNγ gene is altered by DES or genistein treatment. Together, these results suggest that estrogenic endocrine disruptors modulate the immune system of aged mice

  5. Endocrine-reproductive-immune interactions in female and male Galápagos marine iguanas.

    Science.gov (United States)

    Neuman-Lee, Lorin A; French, Susannah S

    2017-02-01

    Endocrine-immune interactions are variable across species and contexts making it difficult to discern consistent patterns. There is a paucity of data in non-model systems making these relationships even more nebulous, particularly in reptiles. In the present study, we have completed a more comprehensive test of the relationship among steroid hormones and ecologically relevant immune measures. We tested the relationship between baseline and stress-induced levels of sex and adrenal steroid hormones and standard ecoimmunological metrics in both female and male Galápagos marine iguanas (Amblyrhynchus cristatus). We found significant associations between adrenal activity and immunity, whereby females that mounted greater corticosterone responses to stress had lower basal and stress-induced immunity (i.e., bactericidal ability). Males showed the opposite relationship, suggesting sex-specific immunomodulatory actions of corticosterone. In both sexes, we observed a stress-induced increase in corticosterone, and in females a stress-induced increase in bactericidal ability. Consistent with other taxa, we also found that baseline corticosterone and testosterone in males was inversely related to baseline bactericidal ability. However, in females, we found a positive relationship between both testosterone and progesterone and bactericidal ability. Multivariate analysis did not discern any further endocrine-immune relationships, suggesting that interactions between adrenal, sex steroid hormones, and the immune system may not be direct and instead may be responding to other common stimuli, (i.e., reproductive status, energy). Taken together, these data illustrate significant endocrine-immune interactions that are highly dependent on sex and the stress state of the animal. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

    International Nuclear Information System (INIS)

    Martin-Skilton, Rebeca; Lavado, Ramon; Thibaut, Remi; Minier, Christophe; Porte, Cinta

    2006-01-01

    Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17β-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period

  7. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Skilton, Rebeca [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Lavado, Ramon [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Thibaut, Remi [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Minier, Christophe [Laboratoire d' Ecotoxicologie, Universite du Havre, 25 rue Philippe Lebon, B.P. 540, F-76058 Le Havre (France); Porte, Cinta [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)]. E-mail: cpvqam@cid.csic.es

    2006-05-15

    Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17{beta}-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period.

  8. Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes.

    Science.gov (United States)

    Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T

    2015-01-01

    Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

  9. The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus.

    Directory of Open Access Journals (Sweden)

    Patricia A Fair

    Full Text Available Immune and endocrine responses play a critical role in allowing animals to adjust to environmental perturbations. We measured immune and endocrine related markers in multiple samples from individuals from two managed-care care dolphin groups (n = 82 samples from 17 dolphins and single samples collected from two wild dolphin populations: Indian River Lagoon, (IRL FL (n = 26; and Charleston, (CHS SC (n = 19. The immune systems of wild dolphins were more upregulated than those of managed-care-dolphins as shown by higher concentrations of IgG and increases in lysozyme, NK cell function, pathogen antibody titers and leukocyte cytokine transcript levels. Collectively, managed-care care dolphins had significantly lower levels of transcripts encoding pro-inflammatory cytokine TNF, anti-viral MX1 and INFα and regulatory IL-10. IL-2Rα and CD69, markers of lymphocyte activation, were both lower in managed-care care dolphins. IL-4, a cytokine associated with TH2 activity, was lower in managed-care care dolphins compared to the free-ranging dolphins. Differences in immune parameters appear to reflect the environmental conditions under which these four dolphin populations live which vary widely in temperature, nutrition, veterinary care, pathogen/contaminant exposures, etc. Many of the differences found were consistent with reduced pathogenic antigenic stimulation in managed-care care dolphins compared to wild dolphins. Managed-care care dolphins had relatively low TH2 lymphocyte activity and fewer circulating eosinophils compared to wild dolphins. Both of these immunologic parameters are associated with exposure to helminth parasites which is uncommon in managed-care care dolphins. Less consistent trends were observed in a suite of hormones but significant differences were found for cortisol, ACTH, total T4, free T3, and epinephrine. While the underlying mechanisms are likely multiple and complex, the marked differences observed in the immune and endocrine

  10. Endocrine and Local IGF-I in the Bony Fish Immune System.

    Science.gov (United States)

    Franz, Anne-Constance; Faass, Oliver; Köllner, Bernd; Shved, Natallia; Link, Karl; Casanova, Ayako; Wenger, Michael; D'Cotta, Helena; Baroiller, Jean-François; Ullrich, Oliver; Reinecke, Manfred; Eppler, Elisabeth

    2016-01-26

    A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  11. Endocrine and Local IGF-I in the Bony Fish Immune System

    Directory of Open Access Journals (Sweden)

    Anne-Constance Franz

    2016-01-01

    Full Text Available A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived, which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  12. Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

    Science.gov (United States)

    Dreau, Didier; Morton, Darla S.; Foster, Mareva; Swiggett, Jeanene P.; Sonnenfeld, Gerald

    1995-01-01

    Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

  13. Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

    Science.gov (United States)

    David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

    2017-07-01

    Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

  14. Immune and endocrine responses of adult spring Chinook salmon during freshwater migration and sexual maturation

    Science.gov (United States)

    Maule, A.G.; Schrock, R.M.; Slater, C.; Fitzpatrick, M.S.; Schreck, C. B.

    1996-01-01

    The immuneendocrine responses in spring chinook salmon (Oncorhynchus tshawytscha) were examined during their freshwater migration and final maturation. In 1990, migrating fish had high plasma cortisol titres (means 200 ng ml−1) and generated relatively few antibody-producing cells (APC) from peripheral blood leukocytes (PBL) (100 –200 per culture). After three weeks acclimation in constant environmental conditions, plasma cortisol was reduced and APC increased. There were no changes in number or affinity of glucocorticoid receptors. Concentrations of several sex steroids correlated with APC in females, but there were no such correlations in males. In 1993, fish in a hatchery had significantly greater cortisol concentrations in primary circulation than in secondary circulation, but sex steroid concentrations did not differ between circulations. Mean lysozyme activity in the primary and secondary circulation did not differ in June. In August, activity in the primary circulation was significantly less than that of the secondary, perhaps the result of acute stress associated with sampling. While some sex steroids correlated with lysozyme activity, the fact that in both years all endocrine and immune variables that correlated with each other also correlated with the date of sample, raises the question as to whether or not these are cause-and-effect relations.

  15. Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

    Science.gov (United States)

    Marcu, Oana; Lera, Matthew P.; Sanchez, Max E.; Levic, Edina; Higgins, Laura A.; Shmygelska, Alena; Fahlen, Thomas F.; Nichol, Helen; Bhattacharya, Sharmila

    2011-01-01

    Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways. PMID:21264297

  16. Innate immune responses of Drosophila melanogaster are altered by spaceflight.

    Directory of Open Access Journals (Sweden)

    Oana Marcu

    2011-01-01

    Full Text Available Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways.

  17. Differential metamorphosis alters the endocrine response in anuran larvae exposed to T3 and atrazine

    International Nuclear Information System (INIS)

    Freeman, Jennifer L.; Beccue, Nathan; Rayburn, A. Lane

    2005-01-01

    Pesticide chemical contamination is one of the suspected contributors of the amphibian population decline. The herbicide atrazine is one of the major surface water contaminants in the U.S. A previous study has shown that atrazine at concentrations as low as 100 parts per billion (ppb) increased the time to metamorphosis in Xenopus laevis tadpoles. However, questions remain as to the applicability of a study of a non-native species to a native organism. The possible effects of atrazine on developing Bufo americanus were explored. Atrazine at potentially (albeit high) environmental concentrations was found not to delay the metamorphosis of developing B. americanus tadpoles as observed in X. laevis. Several studies have indicated that atrazine affects thyroid hormones. Since thyroid hormones are critical in amphibian metamorphosis, B. americanus and X. laevis tadpoles were exposed to exogenous 3,5,3'-triiodothyronine (T 3 ). X. laevis were found to be more responsive to the effects of exogenous T 3 compared to B. americanus, indicating that X. laevis may be more sensitive to endocrine active chemicals than B. americanus. In X. laevis, nuclear heterogeneity has been associated with metamorphosis. Flow cytometric analysis of the nuclei of normal metamorphing B. americanus indicates a decrease in the amount of thyroid mediated chromatin alterations relative to the nuclei of metamorphing X. laevis. Indications are that the differential response to endocrine disruption is due to the differential role of chromatin associated gene expression during metamorphosis of B. americanus versus X. laevis. A second native species, Hyla versicolor, was observed to have the X. laevis nuclear pattern with respect to metamorphosis. As such, sensitivity to endocrine disruption is hypothesized not to be limited to laboratory non-native species

  18. Detoxification, endocrine, and immune responses of tree swallow nestlings naturally exposed to air contaminants from the Alberta oil sands.

    Science.gov (United States)

    Cruz-Martinez, Luis; Fernie, Kim J; Soos, Catherine; Harner, Tom; Getachew, Fitsum; Smits, Judit E G

    2015-01-01

    Changes in environmental and wildlife health from contaminants in tailings water on the Canadian oil sands have been well-studied; however, effects of air contaminants on wildlife health have not. A field study was conducted to assess biological costs of natural exposure to oil sands-related air emissions on birds. Nest boxes for tree swallows (Tachycineta bicolor) were erected at two sites; within 5 km of active oil sands mining and extraction, and ≥ 60 km south, at one reference site. Passive air monitors were deployed at the nest boxes to measure nitrogen dioxide, sulfur dioxide, ozone, volatile organic compounds, and polycyclic aromatic hydrocarbons (PAHs). Nestlings were examined at day 9 post hatching to assess T cell function and morphometry. At day 14 post hatching, a subset of nestlings was euthanized to measure detoxification enzymes, endocrine changes, and histological alterations of immune organs. Except for ozone, all air contaminants were higher at the two oil sands sites than the reference site (up to 5-fold). Adult birds had similar reproductive performance among sites (p>0.05). Nestlings from industrial sites showed higher hepatic ethoxyresorufin O-dealkylase (EROD) induction (pfeather corticosterone (p>0.6), and no histological alterations in the spleen or bursa of Fabricius (p>0.05). This is the first report examining toxicological responses in wild birds exposed to air contaminants from industrial activity in the oil sands. It is also the first time that small, individual air contaminant monitors have been used to determine local contaminant levels in ambient air around nest boxes of wild birds. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Dietary selenium and nutritional plane alter specific aspects of maternal endocrine status during pregnancy and lactation.

    Science.gov (United States)

    Lemley, C O; Meyer, A M; Neville, T L; Hallford, D M; Camacho, L E; Maddock-Carlin, K R; Wilmoth, T A; Wilson, M E; Perry, G A; Redmer, D A; Reynolds, L P; Caton, J S; Vonnahme, K A

    2014-01-01

    Objectives were to examine effects of selenium (Se) supply and maternal nutritional plane during gestation on placental size at term and maternal endocrine profiles throughout gestation and early lactation. Ewe lambs (n = 84) were allocated to treatments that included Se supply of adequate Se (ASe; 11.5 μg/kg BW) or high Se (HSe; 77 μg/kg BW) initiated at breeding and nutritional plane of 60% (RES), 100% (CON), or 140% (EXC) of requirements beginning on day 40 of gestation. At parturition, lambs were removed from their dams, and ewes were transitioned to a common diet that met requirements of lactation. Blood samples were taken from a subset of ewes (n = 42) throughout gestation, during parturition, and throughout lactation to determine hormone concentrations. Cotyledon number was reduced (P = 0.03) in RES and EXC ewes compared with CON ewes. Placental delivery time tended (P = 0.08) to be shorter in HSe ewes than in ASe ewes, whereas placental delivery time was longer (P = 0.02) in RES ewes than in CON and EXC ewes. During gestation, maternal progesterone, estradiol-17β, and GH were increased (P nutritional plane. During the parturient process, HSe ewes tended to have greater (P = 0.06) concentrations of estradiol-17β than ASe ewes. Three hours after parturition a surge of GH was observed in ASe-RES ewes that was muted in HSe-RES ewes and not apparent in other ewes. Growth hormone area under the curve during the parturient process was increased (P < 0.05) in ASe-RES vs HSe-RES ewes. Ewes that were overfed during gestation had reduced (P < 0.05) estradiol-17β but greater IGF-I, triiodothyronine, and thyroxine (P < 0.05) compared with RES ewes. Even though ewes were transitioned to a common diet after parturition, endocrine status continued to be affected into lactation. Moreover, it appears that gestational diet may partially affect lactational performance through altered endocrine status. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

    Science.gov (United States)

    Bridges, Robert S.

    2015-01-01

    The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

  1. Alterations in adaptive immunity persist during long-duration spaceflight

    Science.gov (United States)

    Crucian, Brian; Stowe, Raymond P; Mehta, Satish; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

    2015-01-01

    Background: It is currently unknown whether immune system alterations persist during long-duration spaceflight. In this study various adaptive immune parameters were assessed in astronauts at three intervals during 6-month spaceflight on board the International Space Station (ISS). AIMS: To assess phenotypic and functional immune system alterations in astronauts participating in 6-month orbital spaceflight. Methods: Blood was collected before, during, and after flight from 23 astronauts participating in 6-month ISS expeditions. In-flight samples were returned to Earth within 48 h of collection for immediate analysis. Assays included peripheral leukocyte distribution, T-cell function, virus-specific immunity, and mitogen-stimulated cytokine production profiles. Results: Redistribution of leukocyte subsets occurred during flight, including an elevated white blood cell (WBC) count and alterations in CD8+ T-cell maturation. A reduction in general T-cell function (both CD4+ and CD8+) persisted for the duration of the 6-month spaceflights, with differential responses between mitogens suggesting an activation threshold shift. The percentage of CD4+ T cells capable of producing IL-2 was depressed after landing. Significant reductions in mitogen-stimulated production of IFNγ, IL-10, IL-5, TNFα, and IL-6 persisted during spaceflight. Following lipopolysaccharide (LPS) stimulation, production of IL-10 was reduced, whereas IL-8 production was increased during flight. Conclusions: The data indicated that immune alterations persist during long-duration spaceflight. This phenomenon, in the absence of appropriate countermeasures, has the potential to increase specific clinical risks for crewmembers during exploration-class deep space missions. PMID:28725716

  2. MONITORING TRAINING LOADS, STRESS, IMMUNE-ENDOCRINE RESPONSES AND PERFORMANCE IN TENNIS PLAYERS

    Directory of Open Access Journals (Sweden)

    Rodrigo Vitasovic Gomes

    2013-06-01

    Full Text Available The study aim was to investigate the effect of a periodised pre-season training plan on internal training load and subsequent stress tolerance, immune-endocrine responses and physical performance in tennis players. Well-trained young tennis players (n = 10 were monitored across the pre-season period, which was divided into 4 weeks of progressive overloading training and a 1-week tapering period. Weekly measures of internal training load, training monotony and stress tolerance (sources and symptoms of stress were taken, along with salivary testosterone, cortisol and immunoglobulin A. One repetition maximum strength, running endurance, jump height and agility were assessed before and after training. The periodised training plan led to significant weekly changes in training loads (i.e. increasing in weeks 3 and 4, decreasing in week 5 and post-training improvements in strength, endurance and agility (P < 0.05. Cortisol concentration and the symptoms of stress also increased in weeks 3 and/or 4, before returning to baseline in week 5 (P < 0.05. Conversely, the testosterone to cortisol ratio decreased in weeks 3 and 4, before returning to baseline in week 5 (P < 0.05. In conclusion, the training plan evoked adaptive changes in stress tolerance and hormonal responses, which may have mediated the improvements in physical performance.

  3. The influence of surgical stress on the psychoneuro-endocrine-immune axis.

    Directory of Open Access Journals (Sweden)

    Dahanukar S

    1996-01-01

    Full Text Available Stress is known to depress the immune system severely. This study was done to evaluate whether surgical stress influenced polymorphonuclear (PMN and monocyte functions in association with serum cortisol and the anxiety score as measured on the HARS Rating Scale. We found that surgery (irrespective of whether it was major or minor significantly depressed PMN and monocyte functions and increased serum cortisol levels. PMN phagocytosis correlated significantly (p < 0.05 with the rise in serum cortisol. In spite of these changes, postoperative clinical recovery was uneventful. No major alterations in the HARS scores were noted pre and post operatively. This study demonstrates that surgical stress depresses the immune system with a concomitant rise in cortisol.

  4. Alterations of Cellular Immune Reactions in Crew Members Overwintering in the Antarctic Research Station Concordia

    Science.gov (United States)

    Crucian, Brian; Feuerecker, Matthias; Moreels, Marjan; Crucian, Brian; Kaufmann, Ines; Salam, Alex Paddy; Rybka, Alex; Ulrike, Thieme; Quintens, Roel; Sams, Clarence F.; hide

    2012-01-01

    Background: Concordia Station is located inside Antarctica about 1000km from the coast at an altitude of 3200m (Dome C). Hence, individuals living in this harsh environment are exposed to two major conditions: 1.) hypobaric hypoxia and 2.) confinement and extreme isolation. Both hypoxia and confinement can affect human immunity and health, and are likely to be present during exploration class space missions. This study focused on immune alterations measured by a new global immunity test assay, similar to the phased out delayed type hypersensitivity (DTH) skin test. Methods: After informed written consent 14 healthy male subjects were included to the CHOICE-study (Consequences-of-longterm-Confinement-and-Hypobaric-HypOxia-on-Immunity-in-the Antarctic-Concordia-Environment). Data collection occurred during two winter-over periods lasting each one year. During the first campaign 6 healthy male were enrolled followed by a second campaign with 8 healthy males. Blood was drawn monthly and incubated for 48h with various bacterial, viral and fungal antigens followed by an analysis of plasma cytokine levels (TNF-alpha, IL2, IFN-gamma, IL10). As a control, blood was incubated without stimulation ("resting condition"). Goals: The scope of this study was to assess the consequences of hypoxia and confinement on cellular immunity as assessed by a new in vitro DTH-like test. Results: Initial results indicate that under resting conditions the in vitro DTH-like test showed low cytokine levels which remained almost unchanged during the entire observation period. However, cytokine responses to viral, bacterial and fungal antigens were remarkably reduced at the first month after arrival at Concordia when compared to levels measured in Europe prior to departure for Antarctica. With incrementing months of confinement this depressed DTH-like response tended to reverse, and in fact to show an "overshooting" immune reaction after stimulation. Conclusion: The reduced in vitro DTH-like test

  5. Altered immunity in crowded locust reduced fungal (Metarhizium anisopliae pathogenesis.

    Directory of Open Access Journals (Sweden)

    Yundan Wang

    2013-01-01

    Full Text Available The stress of living conditions, similar to infections, alters animal immunity. High population density is empirically considered to induce prophylactic immunity to reduce the infection risk, which was challenged by a model of low connectivity between infectious and susceptible individuals in crowded animals. The migratory locust, which exhibits polyphenism through gregarious and solitary phases in response to population density and displays different resistance to fungal biopesticide (Metarhizium anisopliae, was used to observe the prophylactic immunity of crowded animals. We applied an RNA-sequencing assay to investigate differential expression in fat body samples of gregarious and solitary locusts before and after infection. Solitary locusts devoted at least twice the number of genes for combating M. anisopliae infection than gregarious locusts. The transcription of immune molecules such as pattern recognition proteins, protease inhibitors, and anti-oxidation proteins, was increased in prophylactic immunity of gregarious locusts. The differentially expressed transcripts reducing gregarious locust susceptibility to M. anisopliae were confirmed at the transcriptional and translational level. Further investigation revealed that locust GNBP3 was susceptible to proteolysis while GNBP1, induced by M. anisopliae infection, resisted proteolysis. Silencing of gnbp3 by RNAi significantly shortened the life span of gregarious locusts but not solitary locusts. By contrast, gnbp1 silencing did not affect the life span of both gregarious and solitary locusts after M. anisopliae infection. Thus, the GNBP3-dependent immune responses were involved in the phenotypic resistance of gregarious locusts to fungal infection, but were redundant in solitary locusts. Our results indicated that gregarious locusts prophylactically activated upstream modulators of immune cascades rather than downstream effectors, preferring to quarantine rather than eliminate pathogens to

  6. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

    OpenAIRE

    Ciss?, Yasmine M.; Russart, Kathryn L.G.; Nelson, Randy J.

    2017-01-01

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to eit...

  7. The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

    Energy Technology Data Exchange (ETDEWEB)

    Buoso, Erica; Galasso, Marilisa; Ronfani, Melania [Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia (Italy); Papale, Angela; Galbiati, Valentina [Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano (Italy); Eberini, Ivano [Laboratorio di Biochimica e Biofisica Computazionale, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan (Italy); Marinovich, Marina [Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano (Italy); Racchi, Marco [Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia (Italy); Corsini, Emanuela, E-mail: emanuela.corsini@unimi.it [Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano (Italy)

    2017-06-15

    We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity and protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.

  8. Alterations in Gut Microbiota and Immunity by Dietary Fat.

    Science.gov (United States)

    Yang, Bo Gie; Hur, Kyu Yeon; Lee, Myung Shik

    2017-11-01

    Gut microbiota play critical physiological roles in energy extraction from the intestine and in the control of systemic immunity, as well as local intestinal immunity. Disturbance of gut microbiota leads to the development of several diseases, such as colitis, inflammatory bowel diseases, metabolic disorders, cancer, etc. From a metabolic point of view, the gut is a large metabolic organ and one of the first to come into contact with dietary fats. Interestingly, excessive dietary fat has been incriminated as a primary culprit of metabolic syndrome and obesity. After intake of high-fat diet or Western diet, extensive changes in gut microbiota have been observed, which may be an underlying cause of alterations in whole body metabolism and nutrient homeostasis. Here, we summarize recent data on changes in the gut microbiota and immunity associated with dietary fat, as well as their relationships with the pathogenesis of metabolic syndrome. These findings may provide insight into the understanding of the complex pathophysiology related to the development of metabolic diseases and offer an opportunity to develop novel candidates for therapeutic agents. © Copyright: Yonsei University College of Medicine 2017.

  9. Altered steroid metabolism in several teleost species exposed to endocrine disrupting substances in refuse dump leachate

    NARCIS (Netherlands)

    Noaksson, E.; Linderoth, M.; Bosveld, A.T.C.; Balk, L.

    2003-01-01

    Endocrine disruption associated with reproductive failure has been reported previously in female perch (Perca fluviatilis) and roach (Rutilus rutilus) from Lake Molnbyggen in Sweden and in female brook trout (Salvelinus fontinalis) from Vadbäcken, a stream emptying into Molnbyggen. Both Molnbyggen

  10. The endocrine system controlling sexual reproduction in animals: Part of the evolutionary ancient but well conserved immune system?

    Science.gov (United States)

    De Loof, Arnold; Schoofs, Liliane; Huybrechts, Roger

    2016-01-15

    Drastic changes in hormone titers, in particular of steroid hormones, are intuitively interpreted as necessary and beneficial for optimal functioning of animals. Peaks in progesterone- and estradiol titers that accompany the estrus cycle in female vertebrates as well as in ecdysteroids at each molt and during metamorphosis of holometabolous insects are prominent examples. A recent analysis of insect metamorphosis yielded the view that, in general, a sharp rise in sex steroid hormone titer signals that somewhere in the body some tissue(s) is undergoing programmed cell death/apoptosis. Increased steroid production is part of this process. Typical examples are ovarian follicle cells in female vertebrates and invertebrates and the prothoracic gland cells, the main production site of ecdysteroids in larval insects. A duality emerges: programmed cell death-apoptosis is deleterious at the cellular level, but it may yield beneficial effects at the organismal level. Reconciling both opposites requires reevaluating the probable evolutionary origin and role of peptidic brain hormones that direct steroid hormone synthesis. Do e.g. Luteinizing Hormone in vertebrates and Prothoracicotropic Hormone (PTTH: acting through the Torso receptor) in insects still retain an ancient role as toxins in the early immune system? Does the functional link of some neuropeptides with Ca(2+)-induced apoptosis make sense in endocrine archeology? The endocrine system as a remnant of the ancient immune system is undoubtedly counterintuitive. Yet, we will argue that such paradigm enables the logical framing of many aspects, the endocrine one inclusive of both male and female reproductive physiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Endocrine and metabolic disorders associated with human immune deficiency virus infection.

    Science.gov (United States)

    Unachukwu, C N; Uchenna, D I; Young, E E

    2009-01-01

    Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

  12. Differential metamorphosis alters the endocrine response in anuran larvae exposed to T{sub 3} and atrazine

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Jennifer L. [University of Illinois, Department of Crop Sciences, 1201 W. Gregory Drive, 320 ERML, Urbana, IL 61801 (United States); Beccue, Nathan [University of Illinois, Department of Crop Sciences, 1201 W. Gregory Drive, 320 ERML, Urbana, IL 61801 (United States); Rayburn, A. Lane [University of Illinois, Department of Crop Sciences, 1201 W. Gregory Drive, 320 ERML, Urbana, IL 61801 (United States)]. E-mail: arayburn@uiuc.edu

    2005-11-10

    Pesticide chemical contamination is one of the suspected contributors of the amphibian population decline. The herbicide atrazine is one of the major surface water contaminants in the U.S. A previous study has shown that atrazine at concentrations as low as 100 parts per billion (ppb) increased the time to metamorphosis in Xenopus laevis tadpoles. However, questions remain as to the applicability of a study of a non-native species to a native organism. The possible effects of atrazine on developing Bufo americanus were explored. Atrazine at potentially (albeit high) environmental concentrations was found not to delay the metamorphosis of developing B. americanus tadpoles as observed in X. laevis. Several studies have indicated that atrazine affects thyroid hormones. Since thyroid hormones are critical in amphibian metamorphosis, B. americanus and X. laevis tadpoles were exposed to exogenous 3,5,3'-triiodothyronine (T{sub 3}). X. laevis were found to be more responsive to the effects of exogenous T{sub 3} compared to B. americanus, indicating that X. laevis may be more sensitive to endocrine active chemicals than B. americanus. In X. laevis, nuclear heterogeneity has been associated with metamorphosis. Flow cytometric analysis of the nuclei of normal metamorphing B. americanus indicates a decrease in the amount of thyroid mediated chromatin alterations relative to the nuclei of metamorphing X. laevis. Indications are that the differential response to endocrine disruption is due to the differential role of chromatin associated gene expression during metamorphosis of B. americanus versus X. laevis. A second native species, Hyla versicolor, was observed to have the X. laevis nuclear pattern with respect to metamorphosis. As such, sensitivity to endocrine disruption is hypothesized not to be limited to laboratory non-native species.

  13. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

    Science.gov (United States)

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

    2015-10-01

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. Published by Elsevier Ltd.

  14. Food, stress, and reproduction: short-term fasting alters endocrine physiology and reproductive behavior in the zebra finch.

    Science.gov (United States)

    Lynn, Sharon E; Stamplis, Teresa B; Barrington, William T; Weida, Nicholas; Hudak, Casey A

    2010-07-01

    Stress is thought to be a potent suppressor of reproduction. However, the vast majority of studies focus on the relationship between chronic stress and reproductive suppression, despite the fact that chronic stress is rare in the wild. We investigated the role of fasting in altering acute stress physiology, reproductive physiology, and reproductive behavior of male zebra finches (Taeniopygia guttata) with several goals in mind. First, we wanted to determine if acute fasting could stimulate an increase in plasma corticosterone and a decrease in corticosteroid binding globulin (CBG) and testosterone. We then investigated whether fasting could alter expression of undirected song and courtship behavior. After subjecting males to fasting periods ranging from 1 to 10h, we collected plasma to measure corticosterone, CBG, and testosterone. We found that plasma corticosterone was elevated, and testosterone was decreased after 4, 6, and 10h of fasting periods compared with samples collected from the same males during nonfasted (control) periods. CBG was lower than control levels only after 10h of fasting. We also found that, coincident with these endocrine changes, males sang less and courted females less vigorously following short-term fasting relative to control conditions. Our data demonstrate that acute fasting resulted in rapid changes in endocrine physiology consistent with hypothalamo-pituitary-adrenal axis activation and hypothalamo-pituitary-gonadal axis deactivation. Fasting also inhibited reproductive behavior. We suggest that zebra finches exhibit physiological and behavioral flexibility that makes them an excellent model system for studying interactions of acute stress and reproduction. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Depresión y neuroplasticidad: Interacción de los sistemas nervioso, endocrino e inmune Depression and neuroplasticity: Interaction of nervous, endocrine and immune systems

    Directory of Open Access Journals (Sweden)

    Paola Cassano

    2010-04-01

    Full Text Available La depresión clínica es una enfermedad física y psíquica que presenta bases neuropatológicas, sin embargo aún no se tiene un conocimiento exacto del origen o causas de esta enfermedad. Se conoce que existe un componente genético, aunque el componente ambiental en el desarrollo de la depresión es innegable. El estrés juega un rol esencial en el desencadenamiento de la depresión. La interacción y respuesta del sistema endocrino, inmune y nervioso se encuentran afectadas en este desorden. La observación de los efectos de los antidepresivos sobre la neurotransmisión monoaminérgica ha llevado hace muchos años a la hipótesis de las monoaminas de la depresión. Sin embargo, esta hipótesis ya no puede explicar muchos de los efectos de las drogas antidepresivas. La nueva hipótesis para explicar los efectos de los antidepresivos es la de neuroplasticidad neuronal. Esta hipótesis propone que los cambios que esas drogas producen sobre diversos sistemas, entre ellos el sistema nervioso, el inmune y el endocrino, son capaces de inducir cambios neuroadaptativos en el cerebro. La neuroplasticidad ha sido definida como la habilidad del cerebro para reorganizarse a sí mismo y formar nuevas conexiones neuronales a lo largo de la vida. Se propone que el mecanismo por el cual los antidepresivos logran sus efectos es mediante la neuroplasticidad.Clinical depression is a physical and psychic disease that has neuropathological basis, although the clear understanding of its ethiopathology is still missing. There is evidence of a genetic component in depression, however, the participation of environment is crucial. Stress plays an essential role in the onset of depression. The interaction and the response of the endocrine system with the immune and nervous system are altered in depression. The observation of the effect of antidepressants on monoaminergic transmitters leads to the hypothesis of monoamines. However this hypothesis cannot explain many of

  16. Modulatory effects of defense and coping on stress-induced changes in endocrine and immune parameters

    NARCIS (Netherlands)

    Olff, M.; Brosschot, J. F.; Godaert, G.; Benschop, R. J.; Ballieux, R. E.; Heijnen, C. J.; de Smet, M. B.; Ursin, H.

    1995-01-01

    We examined whether habitual defense and coping affect the response of hormones (ACTH. cortisol, prolactin. endorphins, and noradrenaline) and immune parameters (numbers of T cells. B cells. natural killer [NK] cells, and proliferative responses to mitogens or antigens) to an acute laboratory

  17. Does Exercise Alter Immune Function and Respiratory Infections?

    Science.gov (United States)

    Nieman, David C.

    2001-01-01

    This paper examines whether physical activity influences immune function as a consequence risk of infection from the common cold and other upper respiratory tract infections (URTI) and whether the immune system responds differently to moderate versus intense physical exertion. Research indicates that people who participate in regular moderate…

  18. Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction.

    Science.gov (United States)

    Ahmed, R G

    2013-12-01

    Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the endocrine system. In the present study, early-weaned male rats were administered a single dose of 2,3,6-2',5'-pentachlorinated biphenyl (PCB 95; 32 mg/kg per day, by i.p. injection) for two consecutive days (postnatal days (PNDs) 15 and 16) and killed 24 and 48 h after the administration of the last dose. Compared with the control group, administration of PCB 95 induced a reduction (Pcolloidal contents at PND 18. The dyshormonogenesis and thyroid dysgenesis may be attributed to the elevation of DNA fragmentation at PNDs 17 and 18. Furthermore, this hypothyroid state revealed higher (Pinsulin at both PNDs compared with the control group. Interestingly, the body weight of the neonates in the PCB 95 group exhibited severe decreases throughout the experimental period in relation to that of the control group. These results imply that PCB 95 may act as a disruptor of the developmental hypothalamic-pituitary-thyroid axis. Hypothyroidism caused by PCB 95 may impair the adipokine axis, fat metabolism, and in general postnatal development. Thus, further studies need to be carried out to understand this concept.

  19. The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

    Directory of Open Access Journals (Sweden)

    Natale Valéria

    2006-08-01

    Full Text Available Abstract Background a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. Results elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. Conclusion highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.

  20. Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

    Science.gov (United States)

    Crucian, Brian; Sams, Clarence F.

    2013-01-01

    The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in- and post-flight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deep-space exploration missions.

  1. The endocrine-immune network during taeniosis by Taenia solium: The role of the pituitary gland.

    Science.gov (United States)

    Quintanar-Stephano, Andrés; Hernández-Cervantes, Rosalía; Moreno-Mendoza, Norma; Escobedo, Galileo; Carrero, Julio Cesar; Nava-Castro, Karen E; Morales-Montor, Jorge

    2015-12-01

    It is well known that sex hormones play an important role during Taenia solium infection; however, to our knowledge no studies exist concerning the immune response following complete or lobe-specific removal of the pituitary gland during T. solium infection. Thus, the aim of this work was to analyze in hamsters, the effects of lack of pituitary hormones on the duodenal immune response, and their impact on T. solium establishment and development. Thus, in order to achieve this goal, we perform anterior pituitary lobectomy (AL, n = 9), neurointermediate pituitary lobectomy (NIL, n = 9) and total hypophysectomy (HYPOX, n = 8), and related to the gut establishment and growth of T. solium, hematoxylin-eosin staining of duodenal tissue and immunofluorescence of duodenal cytokine expression and compared these results to the control intact (n = 8) and control infected group (n = 8). Our results indicate that 15 days post-infection, HYPOX reduces the number and size of intestinally recovered T. solium adults. Using semiquantitative immunofluorescent laser confocal microscopy, we observed that the mean intensity of duodenal IFN-γ and IL-12 Th1 cytokines was mildly expressed in the infected controls, in contrast with the high level of expression of these cytokines in the NIL infected hamsters. Likewise, the duodenum of HYPOX animals showed an increase in the expression of Th2 cytokines IL-5 and IL-6, when compared to control hamsters. Histological analysis of duodenal mucosa from HYPOX hamsters revealed an exacerbated inflammatory infiltrate located along the lamina propria and related to the presence of the parasite. We conclude that lobe-specific pituitary hormones affect differentially the T. solium development and the gut immune response. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Cupping regulates local immunomodulation to activate neural-endocrine-immune worknet.

    Science.gov (United States)

    Guo, Yang; Chen, Bo; Wang, Dong-Qiang; Li, Ming-Yue; Lim, Calista Hui-Min; Guo, Yi; Chen, Zelin

    2017-08-01

    Research on cupping therapy is lacking at home and abroad. However, cupping and acupuncture therapy are both surface stimulation therapies. This paper suggests the mechanism of cupping therapy and proposes that the same mechanism underlies both cupping and acupuncture therapy. The microenvironment is changed when stimulating the surface of the skin, and physical signals transform into biological signals, which also interact with each other in the body. These signalling cascades activate the neuroendocrine-immune system, which produces the therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome

    OpenAIRE

    Buckley, Maria M; O’Mahony, Siobhain M; O’Malley, Dervla

    2014-01-01

    Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked w...

  4. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    Science.gov (United States)

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  5. Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.).

    Science.gov (United States)

    Bado-Nilles, A; Techer, R; Porcher, J M; Geffard, A; Gagnaire, B; Betoulle, S; Sanchez, W

    2014-09-01

    Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Vitamin D endocrine system and the immune response in rheumatic diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Plebani, M; Shoenfeld, Yehuda; Adorini, Luciano; Tincani, Angela

    2011-01-01

    Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors (VDRs) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immunomodulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Serum levels of vitamin D have been found to be significantly lower in patients with systemic lupus erythematosus, undifferentiated connective tissue disease, and type-1 diabetes mellitus than in the healthy population. In addition, it was also found that lower levels of vitamin D were associated with higher disease activity in rheumatoid arthritis. Promising clinical results together with evidence for the regulation of multiple immunomodulatory mechanisms by VDR agonists represent a sound basis for further exploration of their potential in the treatment of rheumatic autoimmune disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals

    International Nuclear Information System (INIS)

    Wens, B.; De Boever, P.; Verbeke, M.; Hollanders, K.; Schoeters, G.

    2013-01-01

    Endocrine disrupting chemicals (EDCs) have the potential to interfere with the hormonal system and may negatively influence human health. Microarray analysis was used in this study to investigate differential gene expression in human peripheral blood cells (PBMCs) after in vitro exposure to EDCs. PBMCs, isolated from blood samples of four male and four female healthy individuals, were exposed in vitro for 18 h to either a dioxin-like polychlorinated biphenyl (PCB126, 1 μM), a non-dioxin-like polychlorinated biphenyl (PCB153, 10 μM), a brominated flame retardant (BDE47, 10 μM), a perfluorinated alkyl acid (PFOA, 10 μM) or bisphenol (BPA, 10 μM). ANOVA analysis revealed a significant change in the expression of 862 genes as a result of EDC exposure. The gender of the donors did not affect gene expression. Hierarchical cluster analysis created three groups and clustered: (1) PCB126-exposed samples, (2) PCB153 and BDE47, (3) PFOA and BPA. The number of differentially expressed genes varied per compound and ranged from 60 to 192 when using fold change and multiplicity corrected p-value as filtering criteria. Exposure to PCB126 induced the AhR signaling pathway. BDE47 and PCB153 are known to disrupt thyroid metabolism and exposure influenced the expression of the nuclear receptors PPARγ and ESR2, respectively. BPA and PFOA did not induce significant changes in the expression of known nuclear receptors. Overall, each compound produced a unique gene expression signature affecting pathways and GO processes linked to metabolism and inflammation. Twenty-nine genes were significantly altered in expression under all experimental conditions. Six of these genes (HSD11B2, MMP11, ADIPOQ, CEL, DUSP9 and TUB) could be associated with obesity and metabolic syndrome. In conclusion, microarray analysis identified that PBMCs altered their gene expression response in vitro when challenged with EDCs. Our screening approach has identified a number of gene candidates that warrant

  8. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti

  9. Prenatal cadmium exposure alters postnatal immune cell development and function

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B., E-mail: jbarnett@hsc.wvu.edu

    2012-06-01

    Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can

  10. Alterations in immune responses in prenatally irradiated dogs

    International Nuclear Information System (INIS)

    Nold, J.B.; Benjamin, S.A.; Miller, G.K.

    1988-01-01

    Immunologic responses were studied in beagle dogs following prenatal (35 days gestation) irradiation to evaluate the effects of ionizing radiation on the developing immune system. Each dog received 1.5 Gy 60 Co gamma irradiation or sham irradiation. Prenatally irradiated dogs exhibited a significant reduction in primary humoral antibody responses to inoculated sheep red blood cells, a T-dependent antigen, and a concurrent decrease in T-helper lymphocyte subpopulations in the peripheral blood at 3 to 4 months of age. Similarly, irradiated fetuses have been shown to have defects in epitheliostromal development of the thymus. It is suggested that the postnatal immunologic deficits may relate to the prenatal thymic injury

  11. Integrated analysis of HPV-mediated immune alterations in cervical cancer.

    Science.gov (United States)

    Chen, Long; Luan, Shaohong; Xia, Baoguo; Liu, Yansheng; Gao, Yuan; Yu, Hongyan; Mu, Qingling; Zhang, Ping; Zhang, Weina; Zhang, Shengmiao; Wei, Guopeng; Yang, Min; Li, Ke

    2018-05-01

    Human papillomavirus (HPV) infection is the primary cause of cervical cancer. HPV-mediated immune alterations are known to play crucial roles in determining viral persistence and host cell transformation. We sought to thoroughly understand HPV-directed immune alterations in cervical cancer by exploring publically available datasets. 130 HPV positive and 7 HPV negative cervical cancer cases from The Cancer Genome Atlas were compared for differences in gene expression levels and functional enrichment. Analyses for copy number variation (CNV) and genetic mutation were conducted for differentially expressed immune genes. Kaplan-Meier analysis was performed to assess survival and relapse differences across cases with or without alterations of the identified immune signature genes. Genes up-regulated in HPV positive cervical cancer were enriched for various gene ontology terms of immune processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially expressed immune genes identified 9 genes that displayed either CNV, genetic mutation and/or gene expression changes in at least 10% of the cases of HPV positive cervical cancer. Genomic amplification may cause elevated levels of these genes in some HPV positive cases. Finally, patients with alterations in at least one of the nine signature genes overall had earlier relapse compared to those without any alterations. The altered expression of either TFRC or MMP13 may indicate poor survival for a subset of cervical cancer patients (P=1.07E-07). We identified a novel immune gene signature for HPV positive cervical cancer that is potentially associated with early relapse of cervical cancer. Copyright © 2018. Published by Elsevier Inc.

  12. INTEGRATED QUANTITATIVE ASSESSMENT OF CHANGES IN NEURO-ENDOCRINE-IMMUNE COMPLEX AND METABOLISM IN RATS EXPOSED TO ACUTE COLD-IMMOBILIZATION STRESS

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    Sydoruk O Sydoruk

    2016-09-01

        Abstracts Background. It is known that the reaction of the neuroendocrine-immune complex to acute and chronic stress are different. It is also known about sex differences in stress reactions. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress at male rats. The purpose of this study - to carry out integrated quantitative estimation of neuroendocrine, immune and metabolic responses to acute stress at male and female rats. Material and research methods. The experiment is at 58 (28 male and 30 female white rats Wistar line weighing 170-280 g (Mean=220 g; SD=28 g. The day after acute (water immersion restraint stress determined HRV, endocrine, immune and metabolic parameters as well as gastric mucosa injuries and comparing them with parameters of intact animals. Results. Acute cold-immobilization stress caused moderate injuries the stomach mucosa as erosions and ulcers. Among the metabolic parameters revealed increased activity Acid Phosphatase, Asparagine and Alanine Aminotranspherase as well as Creatinephosphokinase. It was also found to reduce plasma Testosterone as well as serum Potassium and Phosphate probably due to increased Parathyrine and Mineralocorticoid activity and Sympathotonic shift of sympatho-vagal balance. Integrated quantitative measure manifestations of Acute Stress as mean of modules of Z-Scores makes for 10 metabolic parameters 0,75±0,10 σ and for 8 neuro-endocrine parameters 0,40±0,07 σ. Among immune parameters some proved resistant to acute stress factors, while 10 significant suppressed and 12 activated. Integrated quantitative measure poststressory changes makes 0,73±0,08 σ. Found significant differences integrated status intact males and females, whereas after stress differences are insignificant. Conclusion. The approach to integrated quantitative assessment of neuroendocrine-immune complex and metabolism may be useful for testing the

  13. Alteration of cellular immune responses in the seastar Asterias rubens following dietary exposure to cadmium

    International Nuclear Information System (INIS)

    Coteur, G.; Gillan, D.; Pernet, Ph.; Dubois, Ph.

    2005-01-01

    Several parameters of cellular immunity in seastars fed Cd-contaminated mussels were analyzed. The accumulation of cadmium in the seastars did not alter the concentration of amoebocytes in the coelomic fluid. On the contrary, the immune cells showed a reduced phagocytic activity and an increased production of reactive oxygen species. These effects may lead to an inability of the seastars to cope with bacterial infections and to oxidative damages to self tissue that could threaten the survival of the animals

  14. Immune system handling time may alter the outcome of competition between pathogens and the immune system.

    Science.gov (United States)

    Greenspoon, Philip B; Banton, Sydney; Mideo, Nicole

    2018-06-14

    Predators may be limited in their ability to kill prey (i.e., have type II or III functional responses), an insight that has had far-reaching consequences in the ecological literature. With few exceptions, however, this possibility has not been extended to the behaviour of immune cells, which kill pathogens much as predators kill their prey. Rather, models of the within-host environment have tended to tacitly assume that immune cells have an unlimited ability to target and kill pathogens (i.e., a type I functional response). Here we explore the effects of changing this assumption on infection outcomes (i.e., pathogen loads). We incorporate immune cell handling time into an ecological model of the within-host environment that considers both the predatory nature of the pathogen-immune cell interaction as well as competition between immune cells and pathogens for host resources. Unless pathogens can preempt immune cells for host resources, adding an immune cell handling time increases equilibrium pathogen load. We find that the shape of the relationship between energy intake and pathogen load can change: with a type I functional response, pathogen load is maximised at intermediate inputs, while for a type II or III functional response, pathogen load is solely increasing. With a type II functional response, pathogen load can fluctuate rather than settling to an equilibrium, a phenomenon unobserved with type I or III functional responses. Our work adds to a growing literature highlighting the role of resource availability in host-parasite interactions. Implications of our results for adaptive anorexia are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Endocrine system and obesity.

    Science.gov (United States)

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients. Copyright © 2010. Published by Elsevier Inc.

  16. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine.

    Science.gov (United States)

    Guan, Xi-ting; Shao, Feng; Xie, Xi; Chen, Lin; Wang, Weiwen

    2014-09-01

    Aspirin (ASP) is the most commonly used non-steroidal anti-inflammatory drug in the world. Recent clinical and preclinical evidence suggests that ASP may also exert psychoactive effects. It remains unclear whether ASP has antidepressant-like activity, and any molecular mechanisms underlying such activity have yet to be elucidated. Using the forced swimming test (FST), a well-established animal model of depression widely used to screen potential antidepressants in rodents, we investigated the effects of subacute treatment with ASP (0, 6, 12, 25, and 50mg/kg, i.p.) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in rats, in comparison to the clinical antidepressants imipramine (IMI) and fluoxetine (FLU). Serum levels of corticosterone, pro-inflammatory cytokine interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. ASP dose-dependently decreased immobility in the FST, without altering the locomotor activity in the open-field test. The inhibitory effects of higher doses (25 and 50mg/kg) of ASP on immobility were similar to that of FLU and IMI at a dose of 10mg/kg. In addition, the levels of corticosterone, IL-6, and TNF-α in peripheral blood were significantly increased after the FST exposure. IMI, but not FLU and ASP at any dose tested, significantly attenuated corticosterone responses in the FST. Both FLU and IMI treatment reduced the increase of IL-6 and TNF-α levels following the FST exposure. ASP dose-dependently decreased FST-induced increase of cytokine levels, as manifested by significantly stronger effects on IL-6 and TNF-α levels at higher doses (25 and 50mg/kg) than the lowest dose of ASP (6 mg/kg). In all, these results indicate that ASP treatment dose-dependently decreased the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of ASP might be involved in the antidepressant-like effect

  17. Risk of Crew Adverse Health Event Due to Altered Immune Response

    Science.gov (United States)

    Crucian, Brian; Kunz, Hawley; Sams, Clarence F.

    2015-01-01

    Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture

  18. The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis

    NARCIS (Netherlands)

    López-Casas, Pedro P.; Mizrak, Sefika C.; López-Fernández, Luis A.; Paz, María; de Rooij, Dirk G.; del Mazo, Jesús

    2012-01-01

    Environmental contaminants considered endocrine disruptors have been shown to affect testis development and function but the mechanisms of action are not clear. We now have analyzed the effects on the transcriptome in testes of mice exposed to mono-(2-ethylhexyl)-phthalate (9.2; 46.3 or 92.7

  19. The utilization of the climatic chamber to evaluate the influence of ambient conditions on endocrine, nervous and immune systems of rats.

    Directory of Open Access Journals (Sweden)

    Grazyna Wójcik

    2008-12-01

    Full Text Available The adaptation of an organism to a change in environmental conditions is a complex and in some aspects a poorly understood physiological process. The activating influence of stress on the sympathetic nervous system, the hypothalamic - pituitary - adrenal axis and the suppression of TSH, LH, FSH release is well known. The interplay of communication between the endocrine and immune systems plays an essential role in modulating the response to stress related mediators. The basis of many contradictory and incoherent results of experiments is due to the various methodologies of creating changes in environmental conditions, the way of collecting blood samples which influence stress mediators, the case of assessing the influence of many factors on reproductive functions and the performance of experiments without synchronization with the reproductive cycle. The review will focus on the presentation of simple and repeatable methods of development of an adaptation stress to changed environmental conditions (temperature, oxygenation, humidity and the technique of blood collection during hour-long estimation of interactions between the endocrine, nervous and immune systems. We would like to place emphasis on appropriate ways of performing experiments on female rats, with regards to the choice of a suitable phase of the reproductive cycle. Also on ways of anaesthesia and microsurgical techniques of vein catheterisation for repeated blood sampling. The performance of all phases of the experiment allow us to estimate only the influence of environmental conditions and eliminate interfering factors during the process of preparing animal for the experiment.

  20. The utilization of the climatic chamber to evaluate the influence of ambient conditions on endocrine, nervous and immune systems of rats.

    Science.gov (United States)

    Baran, Arkadiusz; Jakiel, Grzegorz; Wójcik, Grazyna

    2008-01-01

    The adaptation of an organism to a change in environmental conditions is a complex and in some aspects a poorly understood physiological process. The activating influence of stress on the sympathetic nervous system, the hypothalamic - pituitary - adrenal axis and the suppression of TSH, LH, FSH release is well known. The interplay of communication between the endocrine and immune systems plays an essential role in modulating the response to stress related mediators. The basis of many contradictory and incoherent results of experiments is due to the various methodologies of creating changes in environmental conditions, the way of collecting blood samples which influence stress mediators, the case of assessing the influence of many factors on reproductive functions and the performance of experiments without synchronization with the reproductive cycle. The review will focus on the presentation of simple and repeatable methods of development of an adaptation stress to changed environmental conditions (temperature, oxygenation, humidity) and the technique of blood collection during hour-long estimation of interactions between the endocrine, nervous and immune systems. We would like to place emphasis on appropriate ways of performing experiments on female rats, with regards to the choice of a suitable phase of the reproductive cycle. Also on ways of anaesthesia and microsurgical techniques of vein catheterisation for repeated blood sampling. The performance of all phases of the experiment allow us to estimate only the influence of environmental conditions and eliminate interfering factors during the process of preparing animal for the experiment.

  1. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  2. Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity.

    Directory of Open Access Journals (Sweden)

    Manikandan Subramanian

    Full Text Available Obesity-induced inflammation in visceral adipose tissue (VAT is a major contributor to insulin resistance and type 2 diabetes. Whereas innate immune cells, notably macrophages, contribute to visceral adipose tissue (VAT inflammation and insulin resistance, the role of adaptive immunity is less well defined. To address this critical gap, we used a model in which endogenous activation of T cells was suppressed in obese mice by blocking MyD88-mediated maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T cells in vitro, and VAT T and B cell activation was markedly reduced in Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice, thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting blood glucose, plasma insulin, and the glucose response to glucose and insulin were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus, CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this process does not have a discernible effect on macrophage-mediated VAT inflammation or systemic glucose homeostasis.

  3. Changes of serum endocrine hormone levels in patients with cancerrelated fatigue and their correlation with anti-tumor immune response and tumor load

    Directory of Open Access Journals (Sweden)

    Lu Yang

    2017-08-01

    Full Text Available Objective: To study the changes of serum endocrine hormone levels in patients with cancerrelated fatigue (CRF and their correlation with anti-tumor immune response and tumor load. Methods: A total of 137 patients who were diagnosed with primary lung cancer in West China Hospital, Sichuan University between June 2014 and November 2016 were selected and then divided into CRF group and control group according to their self-reported symptoms, serum was collected to determine the levels of endocrine hormones and tumor markers, and peripheral blood was collected to detect the levels of immune cells. Results: Serum ACTH and TSH levels of CRF group were significantly higher than those of control group while Cor, FT3 and FT4 levels were significantly lower than those of control group; peripheral blood CD11b+ CD15 - CD33+ CD14+ M-MDSC, CD11b+ CD15-CD33+ CD14- G-MDSC, CD4+ CD25+ CD127lowTreg and CD19+ CD5+ CD1d+ Breg levels as well as serum CEA, Cyfra21-1, SCC-Ag, HE4, GDF- 15 and PCNA levels of CRF group were significantly higher than those of control group, positively correlated with serum ACTH and TSH levels, and negatively correlated with Cor, FT3 and FT4 levels. Conclusion: The changes of thyroid hormone and adrenal cortical hormone levels in patients with cancer-related fatigue are closely related to the inhibited antitumor immune response and increased tumor load.

  4. Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin.

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2015-05-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. © 2013 Wiley Periodicals, Inc.

  5. Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

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    Luis Sarmiento

    2017-01-01

    Full Text Available Human enteroviruses (HEV, especially coxsackievirus serotype B (CVB and echovirus (E, have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1, 2'-5'-oligoadenylate synthetase 1 (OAS1, interferon-β (IFN-β, chemokine (C–X–C motif ligand 10 (CXCL10 and chemokine (C–C motif ligand 5 (CCL5. Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV.

  6. Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

    Science.gov (United States)

    Swaminathan, Ashwin; Lucas, Robyn M; Harley, David; McMichael, Anthony J

    2014-11-11

    The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations-particularly for children-to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

  7. Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

    Directory of Open Access Journals (Sweden)

    Ashwin Swaminathan

    2014-11-01

    Full Text Available The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations—particularly for children—to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

  8. High-Altitude-Induced alterations in Gut-Immune Axis: A review.

    Science.gov (United States)

    Khanna, Kunjan; Mishra, K P; Ganju, Lilly; Kumar, Bhuvnesh; Singh, Shashi Bala

    2018-03-04

    High-altitude sojourn above 8000 ft is increasing day by day either for pilgrimage, mountaineering, holidaying or for strategic reasons. In India, soldiers are deployed to these high mountains for their duty or pilgrims visit to the holy places, which are located at very high altitude. A large population also resides permanently in high altitude regions. Every year thousands of pilgrims visit Holy cave of Shri Amarnath ji, which is above 15 000 ft. The poor acclimatization to high altitude may cause alteration in immunity. The low oxygen partial pressure may cause alterations in gut microbiota, which may cause changes in gut immunity. Effect of high altitude on gut-associated mucosal system is new area of research. Many studies have been carried out to understand the physiology and immunology behind the high-altitude-induced gut problems. Few interventions have also been discovered to circumvent the problems caused due to high-altitude conditions. In this review, we have discussed the effects of high-altitude-induced changes in gut immunity particularly peyer's patches, NK cells and inflammatory cytokines, secretary immunoglobulins and gut microbiota. The published articles from PubMed and Google scholar from year 1975 to 2017 on high-altitude hypoxia and gut immunity are cited in this review.

  9. Endocrine Disrupting Chemicals and Disease Susceptibility

    Science.gov (United States)

    Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

    2011-01-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

  10. Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption.

    Science.gov (United States)

    Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

    2013-12-01

    Exposure to environmental chemicals known as endocrine disruptors (EDs) is in many cases associated with an unpredictable hazard for wildlife and human health. The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable ED assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17α-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Arterial and venous thrombosis in endocrine diseases

    NARCIS (Netherlands)

    van Zaane, Bregje; Stuijver, Danka J. F.; Squizzato, Alessandro; Gerdes, Victor E. A.

    2013-01-01

    Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency,

  12. Rim Pathway-Mediated Alterations in the Fungal Cell Wall Influence Immune Recognition and Inflammation.

    Science.gov (United States)

    Ost, Kyla S; Esher, Shannon K; Leopold Wager, Chrissy M; Walker, Louise; Wagener, Jeanette; Munro, Carol; Wormley, Floyd L; Alspaugh, J Andrew

    2017-01-31

    Compared to other fungal pathogens, Cryptococcus neoformans is particularly adept at avoiding detection by innate immune cells. To explore fungal cellular features involved in immune avoidance, we characterized cell surface changes of the C. neoformans rim101Δ mutant, a strain that fails to organize and shield immunogenic epitopes from host detection. These cell surface changes are associated with an exaggerated, detrimental inflammatory response in mouse models of infection. We determined that the disorganized strain rim101Δ cell wall increases macrophage detection in a contact-dependent manner. Using biochemical and microscopy methods, we demonstrated that the rim101Δ strain shows a modest increase in the levels of both cell wall chitin and chitosan but that it shows a more dramatic increase in chito-oligomer exposure, as measured by wheat germ agglutinin staining. We also created a series of mutants with various levels of cell wall wheat germ agglutinin staining, and we demonstrated that the staining intensity correlates with the degree of macrophage activation in response to each strain. To explore the host receptors responsible for recognizing the rim101Δ mutant, we determined that both the MyD88 and CARD9 innate immune signaling proteins are involved. Finally, we characterized the immune response to the rim101Δ mutant in vivo, documenting a dramatic and sustained increase in Th1 and Th17 cytokine responses. These results suggest that the Rim101 transcription factor actively regulates the C. neoformans cell wall to prevent the exposure of immune stimulatory molecules within the host. These studies further explored the ways in which immune cells detect C. neoformans and other fungal pathogens by mechanisms that include sensing N-acetylglucosamine-containing structures, such as chitin and chitosan. Infectious microorganisms have developed many ways to avoid recognition by the host immune system. For example, pathogenic fungi alter their cell surfaces to

  13. Chemical modulators of the innate immune response alter gypsy moth larval susceptibility to Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    Broderick Nichole A

    2010-04-01

    Full Text Available Abstract Background The gut comprises an essential barrier that protects both invertebrate and vertebrate animals from invasion by microorganisms. Disruption of the balanced relationship between indigenous gut microbiota and their host can result in gut bacteria eliciting host responses similar to those caused by invasive pathogens. For example, ingestion of Bacillus thuringiensis by larvae of some species of susceptible Lepidoptera can result in normally benign enteric bacteria exerting pathogenic effects. Results We explored the potential role of the insect immune response in mortality caused by B. thuringiensis in conjunction with gut bacteria. Two lines of evidence support such a role. First, ingestion of B. thuringiensis by gypsy moth larvae led to the depletion of their hemocytes. Second, pharmacological agents that are known to modulate innate immune responses of invertebrates and vertebrates altered larval mortality induced by B. thuringiensis. Specifically, Gram-negative peptidoglycan pre-treated with lysozyme accelerated B. thuringiensis-induced killing of larvae previously made less susceptible due to treatment with antibiotics. Conversely, several inhibitors of the innate immune response (eicosanoid inhibitors and antioxidants increased the host's survival time following ingestion of B. thuringiensis. Conclusions This study demonstrates that B. thuringiensis infection provokes changes in the cellular immune response of gypsy moth larvae. The effects of chemicals known to modulate the innate immune response of many invertebrates and vertebrates, including Lepidoptera, also indicate a role of this response in B. thuringiensis killing. Interactions among B. thuringiensis toxin, enteric bacteria, and aspects of the gypsy moth immune response may provide a novel model to decipher mechanisms of sepsis associated with bacteria of gut origin.

  14. Altered Immune Cytokine Expression Associated with KoRV B Infection and Season in Captive Koalas

    Science.gov (United States)

    Higgins, Damien P.

    2016-01-01

    Koala (Phascolarctos cinereus) populations are increasingly vulnerable and one of the main threats is chlamydial infection. Koala retrovirus (KoRV) has been proposed as an underlying cause of the koala’s susceptibility to infection with Chlamydia and high rates of lymphoid neoplasia; however, the regionally ubiquitous, endogenous nature of this virus suggests that KoRV A infection is not sufficient for immune suppression to occur. A recently discovered exogenous variant of KoRV, KoRV B, has several structural elements that cause increased pathogenicity in related retroviruses and was associated with lymphoid neoplasia in one study. The present study assesses whether KoRV B infection is associated with alterations in immune function. Cytokine gene expression by mitogen stimulated lymphocytes of KoRV B positive (n = 5–6) and negative (n = 6–7) captive koalas was evaluated by qPCR four times (April 2014-February 2015) to control for seasonal variation. Key immune genes in the Th1 pathway (IFNγ, TNFα), Th2 pathway (IL 10, IL4, IL6) and Th17 pathway (IL17A), along with CD4:CD8 ratio, were assessed. KoRV B positive koalas showed significantly increased up-regulation of IL17A and IL10 in three out of four sampling periods and IFNγ, IL6, IL4 and TNFα in two out of four. IL17A is an immune marker for chlamydial pathogenesis in the koala; increased expression of IL17A in KoRV B positive koalas, and concurrent immune dysregulation, may explain the differences in susceptibility to chlamydial infection and severity of disease seen between individuals and populations. There was also marked seasonal variation in up-regulation for most of the cytokines and the CD4:CD8 ratio. The up-regulation in both Th1 and Th2 cytokines mirrors changes associated with immune dysregulation in humans and felids as a result of retroviral infections. This is the first report of altered immune expression in koalas infected by an exogenous variant of KoRV and also the first report of

  15. Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

    Directory of Open Access Journals (Sweden)

    Michael A Pazos

    Full Text Available Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

  16. Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

    Science.gov (United States)

    Pazos, Michael A; Kraus, Thomas A; Muñoz-Fontela, César; Moran, Thomas M

    2012-01-01

    Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

  17. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    International Nuclear Information System (INIS)

    Bourguignon, M.; Perez, M.; Dubner, D.; Michelin, S.; Carosella, E.

    2006-01-01

    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  18. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Perez, M.; Dubner, D.; Michelin, S. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Carosella, E. [CEA, Service de Recherches en Hemato -Immunologie, 75 - Paris (France)

    2006-07-01

    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  19. Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

    Science.gov (United States)

    Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

    2018-01-01

    Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions

  20. PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    M. V. Osikov

    2016-01-01

    Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

  1. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys

    Science.gov (United States)

    Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol; insulin; adiponectin) responsiveness to acute stress (AS) were assessed in a ...

  2. Modulating effects of bioactive water Naftussya from layers Truskavets’ and Pomyarky on some metabolic and biophysic parameters at humans with dysfunction of neuro-endocrine-immune complex

    Directory of Open Access Journals (Sweden)

    Anatoliy I Gozhenko

    2016-12-01

    Full Text Available Background. Previously we have been carry out comparative investigation immediate effects of Bioactive Water Naftussya from layers Truskavets’, Pomyarky and Skhidnyts’a on neuro-endocrine-immune complex at men with its dysfunction. The aim of this study is the influence of the use of the course of Bioactive Water Naftussya from layers Truskavets’ and Pomyarky on some metabolic and biophysical parameters at similar patients. Materials and methods. The object of observation were 20 volunteers: ten women and ten men aged 33-76 years without clinical diagnose but with dysfunction of neuro-endocrine-immune complex and metabolism. In daily urine and venous blood we determined the content of electrolytes, nitrogenous metabolites and lipids, recorded conductivity of acupuncture points, rate of electronegative nuclei of buccal epithelium as well as parameters of gas discharge vizualisation (GDV. After examination volunteers within 7 days used bioactive water Naftussya (250 mL three times a day from Truskavets’ or Pomyarky layer, then repeated the tests listed. Results. Weekly use of Bioactive Water Naftussya increases in the normal level of plasma chloride and sodium, normalizes low level of bicarbonate and decreases within the normal levels of potassium and phosphate. Urinary excretion of sodium and chloride increases while excretion and concentration of uric acid decreases, as the urine concentration of phosphates. The index lithogenicity urine decreased from 112% to 103% norm standard. Initially reduced level of plasma triacylglycerides increases, while decreases in the normal level of cholesterol in low-density lipoprotein composition. Among the biophysical parameters detected increase in the normal conductivity acupuncture points Pg (ND at right side, which represent the nervous system, and left shift the ratio between the conductivity of acupuncture points MC (AVL, which represents the immune system. Increases electrokinetic index of

  3. Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

    Science.gov (United States)

    Markowitz, Geoffrey J; Michelotti, Gregory A; Diehl, Anna Mae; Wang, Xiao-Fan

    2015-04-01

    Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard to immune cell prevalence and presence of mediators of immune function. To better understand the consequences of liver disease on tumor growth and the interplay with its microenvironment, we utilized two standard methods of fibrosis induction and orthotopic implantation of tumors into the inflamed and fibrotic liver to mimic the liver condition in human HCC patients. Compared to non-diseased controls, tumor growth was significantly enhanced under fibrotic conditions. The immune cells that infiltrated the tumors were also drastically different, with decreased numbers of natural killer cells but greatly increased numbers of immune-suppressive CD11b + Gr1 hi myeloid cells in both models of fibrosis. In addition, there were model-specific differences: Increased numbers of CD11b + myeloid cells and CD4 + CD25 + T cells were found in tumors in the bile duct ligation model but not in the carbon tetrachloride model. Induction of fibrosis altered the cytokine production of implanted tumor cells, which could have farreaching consequences on the immune infiltrate and its functionality. Taken together, this work demonstrates that the combination of fibrosis induction with orthotopic tumor implantation results in a markedly different tumor microenvironment and tumor growth kinetics, emphasizing the necessity for more accurate modeling of HCC progression in mice, which takes into account the drastic changes in the tissue caused by chronic liver disease.

  4. Immunosenescence Is Associated With Altered Gene Expression And Epigenetic Regulation In Primary And Secondary Immune Organs

    Directory of Open Access Journals (Sweden)

    Corinne eSidler

    2013-10-01

    Full Text Available Deterioration of the immune system (immunosenescence with age is associated with an increased susceptibility to infection, autoimmune disease and cancer, and reduced responsiveness to vaccination. Immunosenescence entails a reduced supply of naïve T cells from the thymus and increased specialization of peripheral T cell clones. Both thymic involution and peripheral T cell homeostasis are thought to involve cellular senescence. In order to analyze this at the molecular level, we studied gene expression profiles, epigenetic status and genome stability in the thymus and spleen of 1-month, 4-month and 18-month-old Long Evans rats. In the thymus, altered gene expression, DNA and histone hypomethylation, increased genome instability and apoptosis were observed in 18-month-old animals compared to 1- and 4-month-old animals. In the spleen, alterations in gene expression and epigenetic regulation occurred already by the age of 4 months compared to 1 month and persisted in 18-month-old compared to 1-month-old rats. In both organs, these changes were accompanied by the altered composition of resident T cell populations. Our study suggests that both senescence and apoptosis may be involved in altered organ function.

  5. Early endocrine alterations reflect prolonged stress and relate to one year functional outcome in patients with severe brain injury

    DEFF Research Database (Denmark)

    Marina, Djordje; Klose, Marianne; Nordenbo, Annette

    2015-01-01

    OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...

  6. Tributyltin alters secretion of interleukin 1 beta from human immune cells.

    Science.gov (United States)

    Brown, Shyretha; Whalen, Margaret

    2015-08-01

    Tributyltin (TBT) has been used as a biocide in industrial applications such as wood preservation, antifouling paint and antifungal agents. Owing to its many uses, it contaminates the environment and has been found in human blood samples. Interleukin-1 beta (IL-1β) is a pro-inflammatory cytokine that promotes cell growth, tissue repair and immune response regulation. Produced predominately by both monocytes and macrophages, IL-1β appears to increase the invasiveness of certain tumors. This study shows that TBT modifies the secretion of IL-1β from increasingly reconstituted preparations of human immune cells. IL-1β secretion was examined after 24-, 48-h or 6-day exposures to TBT in highly enriched human natural killer (NK) cells, monocyte-depleted peripheral blood mononuclear cells (MD-PBMCs), PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes (PBMCs+granulocytes). TBT altered IL-1β secretion from all of the cell preparations. The 200 nM concentration of TBT normally blocked the secretion of IL-1β, whereas lower concentrations (usually 5-50 nM) elevated secretion of IL-1β. Examination of the signaling pathway(s) responsible for the elevated secretion of IL-1β was carried out in MD-PBMCs. Pathways examined were IL-1β processing (Caspase-1), mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NFκB). Results indicated that MAPK pathways (p44/42 and p38) appear to be the targets of TBT that lead to increased IL-1β secretion from immune cells. These results from human immune cells show IL-1β dysregulation by TBT is occurring ex vivo. Thus, the potential for in vivo effects on pro-inflammatory cytokine levels may possibly be a consequence of TBT exposures. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

    Science.gov (United States)

    Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

    2015-06-01

    Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

  8. The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy.

    Science.gov (United States)

    Akyol, Murat; Alacacioglu, Ahmet; Demir, Leyla; Kucukzeybek, Yuksel; Yildiz, Yasar; Gumus, Zehra; Kara, Mete; Salman, Tarik; Varol, Umut; Taskaynatan, Halil; Oflazoglu, Utku; Bayoglu, Vedat; Tarhan, Mustafa Oktay

    2017-01-01

    In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, pbody water (pbody composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.

  9. Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway.

    Science.gov (United States)

    Garfinkel, Benjamin P; Arad, Shiri; Le, Phuong T; Bustin, Michael; Rosen, Clifford J; Gabet, Yankel; Orly, Joseph

    2015-12-01

    Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.

  10. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...

  11. Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

    Directory of Open Access Journals (Sweden)

    Juan Marcos Mucci

    2015-01-01

    Full Text Available Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

  12. Endocrine modulation, inhibition of ovarian development and hepatic alterations in rainbow trout exposed to polluted river water

    Energy Technology Data Exchange (ETDEWEB)

    Vigano, Luigi, E-mail: vigano@irsa.cnr.i [Water Research Institute, National Council of Research, Brugherio, Milan (Italy); Benfenati, Emilio [Mario Negri Institute, Laboratory of Environmental Chemistry and Toxicology, Milan (Italy); Bottero, Sergio; Cevasco, Alessandra; Monteverde, Martino; Mandich, Alberta [Department of Environmental, Experimental and Applied Biology, University of Genoa, Genoa (Italy)

    2010-12-15

    Under laboratory conditions, female rainbow trout were exposed to graded concentrations of water from the River Lambro, a polluted tributary of the River Po, and to the effluent of a large wastewater treatment plant which flows into the River Lambro. In field exposures, trout were held in cages in the River Po upstream and downstream from the confluence of the River Lambro. After 10-day (laboratory) and 30-day (laboratory and field) exposures, trout were examined for several chemical, biochemical and histological endpoints. The results indicated that exposure to complex mixtures of chemicals, including estrogen receptor agonists, aryl-hydrocarbon receptor agonists, and probably antiandrogens, had occurred. Exposure altered the plasma levels of 17{beta}-estradiol and testosterone, and some treatments also enhanced the activity of hepatic ethoxyresorufin O-deethylase. Gonadal histology showed varying levels of degenerative processes characterised by oocyte atresia, haemorrhages, melano-macrophage centres (MMCs), and oogonia proliferation. Liver histology showed less severe effects. - This study examined the progression of hormonal and gonadal alterations in female trout exposed to river water from an area known to affect resident fish species.

  13. Endocrine modulation, inhibition of ovarian development and hepatic alterations in rainbow trout exposed to polluted river water

    International Nuclear Information System (INIS)

    Vigano, Luigi; Benfenati, Emilio; Bottero, Sergio; Cevasco, Alessandra; Monteverde, Martino; Mandich, Alberta

    2010-01-01

    Under laboratory conditions, female rainbow trout were exposed to graded concentrations of water from the River Lambro, a polluted tributary of the River Po, and to the effluent of a large wastewater treatment plant which flows into the River Lambro. In field exposures, trout were held in cages in the River Po upstream and downstream from the confluence of the River Lambro. After 10-day (laboratory) and 30-day (laboratory and field) exposures, trout were examined for several chemical, biochemical and histological endpoints. The results indicated that exposure to complex mixtures of chemicals, including estrogen receptor agonists, aryl-hydrocarbon receptor agonists, and probably antiandrogens, had occurred. Exposure altered the plasma levels of 17β-estradiol and testosterone, and some treatments also enhanced the activity of hepatic ethoxyresorufin O-deethylase. Gonadal histology showed varying levels of degenerative processes characterised by oocyte atresia, haemorrhages, melano-macrophage centres (MMCs), and oogonia proliferation. Liver histology showed less severe effects. - This study examined the progression of hormonal and gonadal alterations in female trout exposed to river water from an area known to affect resident fish species.

  14. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    Directory of Open Access Journals (Sweden)

    Renata eToth

    2015-10-01

    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  15. Heat and immunity: an experimental heat wave alters immune functions in three-spined sticklebacks (Gasterosteus aculeatus).

    Science.gov (United States)

    Dittmar, Janine; Janssen, Hannah; Kuske, Andra; Kurtz, Joachim; Scharsack, Jörn P

    2014-07-01

    Global climate change is predicted to lead to increased temperatures and more extreme climatic events. This may influence host-parasite interactions, immunity and therefore the impact of infectious diseases on ecosystems. However, little is known about the effects of rising temperatures on immune defence, in particular in ectothermic animals, where the immune system is directly exposed to external temperature change. Fish are ideal models for studying the effect of temperature on immunity, because they are poikilothermic, but possess a complete vertebrate immune system with both innate and adaptive immunity. We used three-spined sticklebacks ( Gasterosteus aculeatus) originating from a stream and a pond, whereby the latter supposedly were adapted to higher temperature variation. We studied the effect of increasing and decreasing temperatures and a simulated heat wave with subsequent recovery on body condition and immune parameters. We hypothesized that the immune system might be less active at low temperatures, but will be even more suppressed at temperatures towards the upper tolerable temperature range. Contrary to our expectation, we found innate and adaptive immune activity to be highest at a temperature as low as 13 °C. Exposure to a simulated heat wave induced long-lasting immune disorders, in particular in a stickleback population that might be less adapted to temperature variation in its natural environment. The results show that the activity of the immune system of an ectothermic animal species is temperature dependent and suggest that heat waves associated with global warming may immunocompromise host species, thereby potentially facilitating the spread of infectious diseases. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  16. Alterations of Innate Immunity Reactants in Transition Dairy Cows before Clinical Signs of Lameness

    Science.gov (United States)

    Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Deng, Qilan; Goldansaz, Seyed A.; Dunn, Suzanna M.; Ametaj, Burim N.

    2015-01-01

    Simple Summary Lameness is prevalent in dairy cows and early diagnosis and timely treatment of the disease can lower animal suffering, improve recovery rate, increase longevity, and minimize cow loss. However, there are no indications of disease until it appears clinically, and presently the only approach to deal with the sick cow is intensive treatment or culling. The results suggest that lameness affected serum concentrations of the several parameters related to innate immunity and carbohydrate metabolism that might be used to monitor health status of transition dairy cows in the near future. Abstract The objectives of this study were to evaluate metabolic and innate immunity alterations in the blood of transition dairy cows before, during, and after diagnosis of lameness during periparturient period. Blood samples were collected from the coccygeal vain once per week before morning feeding from 100 multiparous Holstein dairy cows during −8, −4, disease diagnosis, and +4 weeks (wks) relative to parturition. Six healthy cows (CON) and six cows that showed clinical signs of lameness were selected for intensive serum analyses. Concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), haptoglobin (Hp), serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), lactate, non-esterified fatty acids (NEFA), and β-hydroxybutyrate (BHBA) were measured in serum by ELISA or colorimetric methods. Health status, DMI, rectal temperature, milk yield, and milk composition also were monitored for each cow during the whole experimental period. Results showed that cows affected by lameness had greater concentrations of lactate, IL-6, and SAA in the serum vs. CON cows. Concentrations of TNF tended to be greater in cows with lameness compared with CON. In addition, there was a health status (Hs) by time (week) interaction for IL-1, TNF, and Hp in lameness cows vs. CON ones. Enhanced serum concentrations of lactate, IL-6, and SAA at −8 and

  17. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I.

    Science.gov (United States)

    Burgess, W; Liu, Q; Zhou, J; Tang, Q; Ozawa, A; VanHoy, R; Arkins, S; Dantzer, R; Kelley, K W

    1999-01-01

    Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3'-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular beta chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the alpha and gammac subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of

  18. Endocrine Disrupting Chemicals (EDCs)

    Science.gov (United States)

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

  19. Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics

    Directory of Open Access Journals (Sweden)

    Frank Euteneuer

    2017-11-01

    Full Text Available Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions with plasma levels of C-reactive protein (CRP, interleukin (IL-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

  20. Effects of resistance training periodization on performance and salivary immune-endocrine responses of elite female basketball players.

    Science.gov (United States)

    Nunes, J A; Crewther, B T; Viveiros, L; De Rose, D; Aoki, M S

    2011-12-01

    The aim of this paper was to examine the effects of resistance training periodization on the performance and salivary hormone-immune responses of elite female basketball players. Twelve female athletes were monitored across a 50 day period of resistance training that emphasized strength, endurance and power. One repetition maximum (1RM) strength, maximal repetitions at 50% 1RM and vertical jump performance was assessed pre- and post-training. Saliva samples were also collected at 0700, 0930, 1100 and 1730 hours and analyzed for testosterone (T), cortisol (C) and immunoglobulin A (IgA). Improvements in 1RM strength, maximal repetitions and vertical jump performance were identified post-training (PTraining had no effect on salivary T and C concentrations, but the T:C ratio increased at 0730 hours (Ptraining) in strength and T concentrations were positively correlated at 0730 hours (Ptraining increased muscle performance in elite female basketball players, but only minor changes in the salivary T:C ratio and IgA were noted. Correlational analysis identified a possible role for early morning changes in T as a regulator of individual strength changes.

  1. Fatty acid intake alters growth and immunity in milk-fed calves.

    Science.gov (United States)

    Hill, T M; Vandehaar, M J; Sordillo, L M; Catherman, D R; Bateman, H G; Schlotterbeck, R L

    2011-08-01

    The aim of the present study was to determine the effect of supplementing milk replacer (MR) with NeoTec4 (Provimi North America, Brookville, OH), a commercially available blend of butyric acid, coconut oil, and flax oil, on calf growth, efficiency, and indices of immune function. In trial 1a, 48 male Holstein calves were fed either a control MR that contained only animal fat or the same MR with NeoTec4 (treatment) along with free-choice starter. The MR (28.7% crude protein, 15.6% fat) was fed at an average of 1 kg of dry matter (DM)/d. In trial 1b, weaned calves from trial 1a were all fed dry starter for 28 d without NeoTec4 (phase 1), and then half the calves were fed NeoTec4 for 28 d (phase 2). In trial 2, 40 male Holstein calves were fed a control MR with lard, coconut oil, and soy lecithin or the same MR supplemented with NeoTec4 (treatment). The MR (22.8% crude protein, 18.9% fat) was fed at an average of 1 kg of DM/d; no starter was fed. In trial 1a, NeoTec4 improved average daily gain, feed intake, and feed efficiency, reduced the number of days that calves experienced scours, and reduced the medical treatments for clostridium sickness. In trials 1a and 2, NeoTec4 altered the inflammatory response to vaccination with Pasteurella at 5 wk of age and to challenge with Salmonella toxin at less than 2 wk of age (fed NeoTec4 for 6 d), as observed by reduced hyperthermia and hypophagia, and altered the tumor necrosis factor-α response. In addition, NeoTec4 enhanced the response in IL-4 and globular protein estimates postchallenge and enhanced titers for bovine viral diarrhea and respiratory parainfluenza-3. Postchallenge serum concentrations of albumin were lower and urea nitrogen concentrations were greater in control calves than in calves fed NeoTec4. In trial 1b, performance did not differ during the first 28 d when no calves received NeoTec4, but calves receiving NeoTec4 in the second 28 d had greater average daily gain and feed efficiency. We conclude that

  2. Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

    Science.gov (United States)

    Doyle, S L; Mongan, A M; Donohoe, C L; Pidgeon, G P; Sherlock, M; Reynolds, J V; Lysaght, J

    2017-06-01

    Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-β, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For

  3. Endocrine Diseases

    Science.gov (United States)

    ... Syndrome (PCOS) Pregnancy and Thyroid Disease Primary Hyperparathyroidism Prolactinoma Thyroid Tests Turner Syndrome Contact Us The National ... Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...

  4. Monitoring training load, recovery-stress state, immune-endocrine responses, and physical performance in elite female basketball players during a periodized training program.

    Science.gov (United States)

    Nunes, João A; Moreira, Alexandre; Crewther, Blair T; Nosaka, Ken; Viveiros, Luis; Aoki, Marcelo S

    2014-10-01

    This study investigated the effect of a periodized training program on internal training load (ITL), recovery-stress state, immune-endocrine responses, and physical performance in 19 elite female basketball players. The participants were monitored across a 12-week period before an international championship, which included 2 overloading and tapering phases. The first overloading phase (fourth to sixth week) was followed by a 1-week tapering, and the second overloading phase (eighth to 10th week) was followed by a 2-week tapering. ITL (session rating of perceived exertion method) and recovery-stress state (RESTQ-76 Sport questionnaire) were assessed weekly and bi-weekly, respectively. Pretraining and posttraining assessments included measures of salivary IgA, testosterone and cortisol concentrations, strength, jumping power, running endurance, and agility. Internal training load increased across all weeks from 2 to 11 (p ≤ 0.05). After the first tapering period (week 7), a further increase in ITL was observed during the second overloading phase (p ≤ 0.05). After the second tapering period, a decrease in ITL was detected (p ≤ 0.05). A disturbance in athlete stress-recovery state was noted during the second overloading period (p ≤ 0.05), before returning to baseline level in end of the second tapering period. The training program led to significant improvements in the physical performance parameters evaluated. The salivary measures did not change despite the fluctuations in ITL. In conclusion, a periodized training program evoked changes in ITL in elite female basketball players, which appeared to influence their recovery-stress state. The training plan was effective in preparing participants for competition, as indicated by improvements in recovery-stress state and physical performance after tapering.

  5. [Dementia due to Endocrine Diseases].

    Science.gov (United States)

    Matsunaga, Akiko; Yoneda, Makoto

    2016-04-01

    Endocrine diseases affecting various organs, such as the pituitary gland, the thyroid, the parathyroid, the adrenal glands and the pancreas, occasionally cause dementia. While Alzheimer's disease (AD) is the main cause of dementia in the elderly and is untreatable, dementia caused by endocrine diseases is treatable in most cases. However, patients with dementia associated with endocrine diseases show memory impairments similar to those found in AD, often leading to misdiagnoses. Patients with endocrine diseases often present with other characteristic systemic and neuropsychiatric symptoms caused by altered hormone levels. Such neuropsychiatric symptoms include involuntary movements, depression, seizures, and muscle weakness. In these cases, abnormalities in imaging and blood or urine tests are helpful in making a differential diagnosis. As delays in the diagnosis and treatment of these patients may cause irreversible brain damage, it is imperative for clinicians to carefully exclude the possibility of latent endocrine diseases when treating patients with dementia.

  6. Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

    Science.gov (United States)

    Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

    2015-10-01

    Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

  7. Maternal HIV infection alters the immune balance in the mother and fetus; implications for pregnancy outcome and infant health.

    Science.gov (United States)

    Pfeifer, Caroline; Bunders, Madeleine J

    2016-03-01

    With the rapid roll-out of combination antiretroviral therapy to prevent mother-to-child transmission of HIV, there is an annual increase in the number of uninfected infants born to HIV-infected women. Although the introduction of combination antiretroviral therapy has vastly improved pregnancy outcome and the health of infants born to HIV-infected women, concerns remain regarding the impact the maternal HIV infection on the pregnancy outcome and the health of HIV-exposed uninfected infants. Maternal HIV infection is associated with negative pregnancy outcomes such as low birth weight. In addition, an increased susceptibility to infections is reported in HIV-exposed uninfected infants compared with infants born to uninfected women. Studies have shown that HIV-exposure affects the maternal/fetal unit, with increase of proinflammatory cytokine produced by placental cells, as well as altered infant immune responses. These changes could provide the underlying conditions for negative pregnancy outcomes and facilitate mother-to-child transmission of HIV in the infant. Further studies are required to understand the underlying mechanisms and investigate whether these altered infant immune responses persist and have clinical consequences beyond childhood. HIV infection in pregnant women is associated with altered immune responses in HIV-infected women and their offspring with clinical consequences for pregnancy outcome and the HIV-exposed uninfected infant. Further studies are required to address the origin and long-term consequences of prenatal HIV-exposure and subsequent immune activation for infant health.

  8. Immunization

    Science.gov (United States)

    ... 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. ...

  9. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...... during gestation. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, and for parturition. As pregnancy advances, the relative number of trophoblasts increase...

  10. Abnormal Savda syndrome: long-term consequences of emotional and physical stress on endocrine and immune activities in an animal model.

    Science.gov (United States)

    Ablimit, Adiljan; Kühnel, Harald; Strasser, Alois; Upur, Halmurat

    2013-08-01

    To investigate the relationship between emotional status, cold-dry environment and long-term immune responses to the stressors, and the potential pathological mechanisms between causative factors of abnormal Savda syndrome (ASS) and the susceptibility to disease; thus to clarify the ASS, and secondly to identify the optimal ASS animal model for further studies on traditional Uighur therapeutical formulations. Sixty mice were randomly and equally divided into 4 groups: control and 3 stress groups. The cold-dry environment was applied by keeping the mice in a climatic chamber. The emotional stress was induced by the application of the repeated electric foot-shocks in the electric foot-shock apparatus. The mice of the combined stress group underwent the repeated electric foot-shock treatment before being housed in the climatic chamber. The experimental routine was repeated for 21 days. In order to look into endocrine and immune stress responses, ELISA was used to determine the serum levels of the hormones corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), Beta-endorphin (β-END) and corticosterone (CORT), of the cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), interferon-gamma (INF-γ) and tumor necrosis factor-alpha (TNF-α), and of the immunoglobulins immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG). Lymphocyte subsets were analyzed in duplicate in order to determine differences in the T cell ratio. In the cold-dry environment group, the serum levels of CRH, ACTH and CORT were significantly higher than those of the control group, whereas serum β-END was not found significantly different. In both the repeated electric foot-shock group as well as in the combined stress group the serum levels of CRH, ACTH, β-END and CORT were significantly higher. Compared to the control animals, the serum concentration of INF-γ was significantly lower in all three different stress groups. The serum level of IL-2 was decreased in

  11. The BPA-substitute bisphenol S alters the transcription of genes related to endocrine, stress response and biotransformation pathways in the aquatic midge Chironomus riparius (Diptera, Chironomidae.

    Directory of Open Access Journals (Sweden)

    Óscar Herrero

    Full Text Available Bisphenol S (BPS is an industrial alternative to the endocrine disruptor bisphenol A (BPA, and can be found in many products labeled "BPA-free". Its use has grown in recent years, and presently it is considered a ubiquitous emerging pollutant. To date there is a lack of information on the effects of BPS on invertebrates, although they represent more than 95% of known species in the animal kingdom and are crucial for the structure and proper function of ecosystems. In this study, real-time RT-PCR was used to determine the early detrimental effects of BPS on the transcriptional rate of genes in the model species Chironomus riparius, specifically those related to the ecdysone pathway (EcR, ERR, E74, Vtg, cyp18a1 crucial for insect development and metamorphosis, stress and biotransformation mechanisms (hsp70, hsp40, cyp4g, GPx, GSTd3 that regulate adaptive responses and determine survival, and ribosome biogenesis (its2, rpL4, rpL13 which is essential for protein synthesis and homeostasis. While 24-hour exposure to 0.5, 5, 50, and 500 μg/L BPS had no effect on larval survival, almost all the studied genes were upregulated following a non-monotonic dose-response curve. Genes with the greatest increases in transcriptional activity (fold change relative to control were EcR (3.8, ERR (2, E74 (2.4, cyp18a1 (2.5, hsp70 (1.7, hsp40 (2.5, cyp4g (6.4, GPx (1.8, and GST (2.1, while others including Vtg, GAPDH, and selected ribosomal genes remained stable. We also measured the transcriptional activity of these genes 24 hours after BPS withdrawal and a general downregulation compared to controls was observed, though not significant in most cases. Our findings showed that BPS exposure altered the transcriptional profile of these genes, which may have consequences for the hormone system and several metabolic pathways. Although further research is needed to elucidate its mode of action, these results raise new concerns about the safety of BPA alternatives.

  12. The BPA-substitute bisphenol S alters the transcription of genes related to endocrine, stress response and biotransformation pathways in the aquatic midge Chironomus riparius (Diptera, Chironomidae).

    Science.gov (United States)

    Herrero, Óscar; Aquilino, Mónica; Sánchez-Argüello, Paloma; Planelló, Rosario

    2018-01-01

    Bisphenol S (BPS) is an industrial alternative to the endocrine disruptor bisphenol A (BPA), and can be found in many products labeled "BPA-free". Its use has grown in recent years, and presently it is considered a ubiquitous emerging pollutant. To date there is a lack of information on the effects of BPS on invertebrates, although they represent more than 95% of known species in the animal kingdom and are crucial for the structure and proper function of ecosystems. In this study, real-time RT-PCR was used to determine the early detrimental effects of BPS on the transcriptional rate of genes in the model species Chironomus riparius, specifically those related to the ecdysone pathway (EcR, ERR, E74, Vtg, cyp18a1) crucial for insect development and metamorphosis, stress and biotransformation mechanisms (hsp70, hsp40, cyp4g, GPx, GSTd3) that regulate adaptive responses and determine survival, and ribosome biogenesis (its2, rpL4, rpL13) which is essential for protein synthesis and homeostasis. While 24-hour exposure to 0.5, 5, 50, and 500 μg/L BPS had no effect on larval survival, almost all the studied genes were upregulated following a non-monotonic dose-response curve. Genes with the greatest increases in transcriptional activity (fold change relative to control) were EcR (3.8), ERR (2), E74 (2.4), cyp18a1 (2.5), hsp70 (1.7), hsp40 (2.5), cyp4g (6.4), GPx (1.8), and GST (2.1), while others including Vtg, GAPDH, and selected ribosomal genes remained stable. We also measured the transcriptional activity of these genes 24 hours after BPS withdrawal and a general downregulation compared to controls was observed, though not significant in most cases. Our findings showed that BPS exposure altered the transcriptional profile of these genes, which may have consequences for the hormone system and several metabolic pathways. Although further research is needed to elucidate its mode of action, these results raise new concerns about the safety of BPA alternatives.

  13. Immune interactions in endometriosis

    Science.gov (United States)

    Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G

    2011-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease. PMID:21895474

  14. Secretion of Interferon gamma (IFNγ) from Human Immune Cells is Altered by Exposure to Tributyltin (TBT) and Dibutyltin (DBT)

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2013-01-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and also alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h and 6 day exposures to TBT (200- 2.5 nM) and DBT (5- 0.05 μM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from NK cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. PMID:24357260

  15. Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

    Science.gov (United States)

    Osada, Takuya; Morse, Michael A; Hobeika, Amy; Diniz, Marcio A; Gwin, William R; Hartman, Zachary; Wei, Junping; Guo, Hongtao; Yang, Xiao-Yi; Liu, Cong-Xiao; Kaneko, Kensuke; Broadwater, Gloria; Lyerly, H Kim

    2017-01-01

    Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions. Both preventative and therapeutic Ad-HER3-FL immunization delayed tumor growth but were associated with both intratumoral PD-1 expressing CD8 + T cells and regulatory CD4 + T cell infiltrates. Immune checkpoint inhibition with either anti-PD-1 or anti-PD-L1 antibodies increased intratumoral CD8 + T cell infiltration and eliminated tumor following preventive vaccination with Ad-HER3-FL vaccine. The combination of dual PD-1/PD-L1 and CTLA4 blockade slowed the growth of tumor in response to Ad-HER3-FL in the therapeutic model. We conclude that HER3-targeting vaccines activate HER3-specific T cells and induce anti-HER3 specific antibodies, which alters the intratumoral T cell infiltrate and responses to immune checkpoint inhibition.

  16. μ-opioid Receptor-Mediated Alterations of Allergen-Induced Immune Responses of Bronchial Lymph Node Cells in a Murine Model of Stress Asthma

    Directory of Open Access Journals (Sweden)

    Kaori Okuyama

    2012-01-01

    Conclusions: Restraint stress aggravated allergic airway inflammation in association with alterations in local immunity characterized by greater Th2-associated cytokine production and a reduced development of regulatory T cells, mediated by MORs.

  17. Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

    Science.gov (United States)

    Muyanja, Enoch; Ssemaganda, Aloysius; Ngauv, Pearline; Cubas, Rafael; Perrin, Helene; Srinivasan, Divya; Canderan, Glenda; Lawson, Benton; Kopycinski, Jakub; Graham, Amanda S; Rowe, Dawne K; Smith, Michaela J; Isern, Sharon; Michael, Scott; Silvestri, Guido; Vanderford, Thomas H; Castro, Erika; Pantaleo, Giuseppe; Singer, Joel; Gillmour, Jill; Kiwanuka, Noah; Nanvubya, Annet; Schmidt, Claudia; Birungi, Josephine; Cox, Josephine; Haddad, Elias K; Kaleebu, Pontiano; Fast, Patricia; Sekaly, Rafick-Pierre; Trautmann, Lydie; Gaucher, Denis

    2014-07-01

    Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Registration is not required for observational studies. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases

  18. Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples.

    Science.gov (United States)

    Wilson, Randall M; Marshall, Nicole E; Jeske, Daniel R; Purnell, Jonathan Q; Thornburg, Kent; Messaoudi, Ilhem

    2015-06-01

    Maternal obesity is one of the several key factors thought to modulate neonatal immune system development. Data from murine studies demonstrate worse outcomes in models of infection, autoimmunity, and allergic sensitization in offspring of obese dams. In humans, children born to obese mothers are at increased risk for asthma. These findings suggest a dysregulation of immune function in the children of obese mothers; however, the underlying mechanisms remain poorly understood. The aim of this study was to examine the relationship between maternal body weight and the human neonatal immune system. Umbilical cord blood samples were collected from infants born to lean, overweight, and obese mothers. Frequency and function of major innate and adaptive immune cell populations were quantified using flow cytometry and multiplex analysis of circulating factors. Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood. These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Altered tumor growth in vivo after immunization of mice with antitumor antibodies

    International Nuclear Information System (INIS)

    Gorczynski, R.M.; Kennedy, M.; Polidoulis, I.; Price, G.B.

    1984-01-01

    A comparison has been made between the growth patterns of two spontaneously appearing mammary adenocarcinomas in murine bone marrow radiation chimeras and in mice preimmunized with monoclonal antibodies (MAb) detecting embryo-associated antigenic determinants. A correlation was seen between the ability of the embryo-immunized chimeras to produce cytotoxic antibody to the tumors, as assessed by an antibody-dependent cellular cytotoxic assay, and the permissiveness of the mice for growth of a tumor transplant. In addition, mice deliberately preimmunized with cytotoxic MAb (antibody-dependent cellular cytotoxic assay) allowed more rapid growth specifically of that tumor earlier found to be most sensitive to the MAb used for immunization. By comparing the changing antigenic phenotype of tumor cells serially passaged through different immunized, nonimmunized mice, evidence was found suggesting that immunization could cause either antigen modulation of transferred tumor cells or a (transient) selective advantage to antigenically discrete subpopulations within the heterogeneous tumor population. Finally, a study has been made of the growth pattern of tumor cells transplanted into mice immunized with rabbit antibodies directed against the murine MAb. In this case, tumor growth was slowed preferentially for the tumor reactive with the specific MAb, and again, predictable changes in the antigenic spectrum of tumor cells harvested from these animals were observed. Our overall findings are interpreted in terms of the involvement of networks of antibodies reacting with embryo-associated antigens in the regulation of growth of the murine mammary adenocarcinomas studied

  20. Effect of Endocrine Disruptor Pesticides: A Review

    Directory of Open Access Journals (Sweden)

    Benoit Roig

    2011-06-01

    Full Text Available Endocrine disrupting chemicals (EDC are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air. For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  1. Immunologic Endocrine Disorders

    Science.gov (United States)

    Michels, Aaron W.; Eisenbarth, George S.

    2010-01-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

  2. Does Cancer Start in the Womb? Altered Mammary Gland Development and Predisposition to Breast Cancer due to in Utero Exposure to Endocrine Disruptors

    OpenAIRE

    Soto, Ana M.; Brisken, Cathrin; Schaeberle, Cheryl; Sonnenschein, Carlos

    2013-01-01

    We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary ...

  3. Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance.

    Science.gov (United States)

    Gibson, D L; Gill, S K; Brown, K; Tasnim, N; Ghosh, S; Innis, S; Jacobson, K

    2015-01-01

    Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

  4. In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Bosco, Anthony; McKenna, Katherine L.; Carter, Kim W.; Elliot, John G.; Berry, Luke J.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2012-01-01

    Background: Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood. Objectives: We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity. Methods: Pregnant BALB/c, C57BL/6, and C3H/HeARC mice were exposed to 0 (control) or 100 ?g/L...

  5. Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

    Science.gov (United States)

    Endocrine disrupting chemicals (EDCs) are exogenous substances that alter endocrine system function(s) and consequently cause adverse health effects in intact organisms or its progeny. The endocrine system is important for a wide range of biological processes, from normal cell si...

  6. System chemical biology studies of endocrine disruptors

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    Endocrine disrupting chemicals (EDCs) alter hormonal balance and other physiological systems through inappropriate developmental or adult exposure, perturbing the reproductive function of further generations. While disruption of key receptors (e.g., estrogen, androgen, and thyroid) at the ligand...

  7. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion.

    Directory of Open Access Journals (Sweden)

    John J Worthington

    2013-01-01

    Full Text Available Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.

  8. Exogenous administration of lipids to steers alters aspects of the innate immune response to endotoxin challenge

    Science.gov (United States)

    Limitations in energy availability are known to impede the efficiency of the immune response to endotoxemia. Therefore, this study examined the effects of increasing energy availability on the pro-inflammatory response to LPS in Holstein steers. Steers were randomly assigned to 1 of 3 groups (n = 7 ...

  9. STRESS AND DIFFERENTIAL ALTERATIONS IN IMMUNE-SYSTEM FUNCTIONS - CONCLUSIONS FROM SOCIAL STRESS STUDIES IN ANIMALS

    NARCIS (Netherlands)

    BOHUS, B; KOOLHAAS, JM; DERUITER, AJH; HEIJNEN, CJ

    1991-01-01

    Psychosocial factors are implicated in the development, in the course of, and in the recovery from disease. The immune system may be a mediator of the disease. Studies with animal models using social interactions in rodents suggest that short- and long-term social stress does not invariably suppress

  10. B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of Rhesus macaques

    Science.gov (United States)

    Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models. Their elicitation by immunization is thus highly desirable. The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutr...

  11. Altered neurological function in mice immunized with early endosome antigen 1

    Directory of Open Access Journals (Sweden)

    Fritzler Marvin J

    2004-01-01

    Full Text Available Abstract Background Autoantibodies directed against the 160 kDa endosome protein early endosome antigen 1 (EEA1 are seen in patients with neurological diseases. To determine if antibodies to EEA1 have a neuropathological effect, mice from three major histocompatability haplotype backgrounds (H2q, H2b and H2d were immunized with EEA1 (amino acids 82–1411 that was previously shown to contain the target EEA1 epitopes. The mice were then subjected to five neuro-behavioural tests: grid walking, forelimb strength, open field, reaching and rotarod. Results The immunized SWR/J mice with sustained anti-EEA1 antibodies had significantly reduced forelimb strength than the control non-immune mice of the same strain, and BALB/CJ immune mice demonstrated significantly more forelimb errors on the grid walk test than the control group. Conclusions Antibodies to recombinant EEA1 in mice may mediate neurological deficits that are consistent with clinical features of some humans that spontaneously develop anti-EEA1 autoantibodies.

  12. Iodinated contrast media alter immune responses in pro-inflammatory states.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

  13. Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function

    DEFF Research Database (Denmark)

    Yang, Jason H.; Bhargava, Prerna; McCloskey, Douglas

    2017-01-01

    Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect eithe...

  14. [The immuno-endocrine system. A new endocrine theory: the problem of the packed transport].

    Science.gov (United States)

    Csaba, György

    2011-05-15

    Since the eighties of the last century hormone content was justified in immune cells (lymphocytes, granulocytes, monocytes, macrophages and mast cells), which produce, store and secrete these hormones. Although the amount of these materials in immune cells is relatively small, the mass of the producers (immune cells) is so large, that the phenomenon must be considered from endocrinological point of view, underlying the important differences between the "classical" and immuno-endocrine systems. Cells of the classic (built-in) endocrine system are mono-producers, while immune cells can synthesize many types of hormones (polyproducers). In addition, these cells can transport the whole hormone-producing machinery to the site of need, producing a local effect. This can be observed, for example, in the case of endorphin producing immune cells during inflammation and during early pregnancy around the chorionic villi. Hormone producing immune cells also have receptors for many hormones, so that they are poly-receivers. Via hormone producing and receiving capacity there is a bidirectional connection between the neuro-endocrine and immuno-endocrine systems. In addition, there is a network inside the immuno-endocrine system. The packed transport theory attempts to explain the mechanism and importance of the immuno-endocrine system.

  15. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  16. Effects of Antibiotic Use on the Microbiota of the Gut and Associated Alterations of Immunity and Metabolism

    Directory of Open Access Journals (Sweden)

    M. Pilar Francino

    2013-11-01

    Full Text Available The excessively widespread use of antibiotics has created many threats. A well-known problem is the increasing bacterial resistance to antibiotics, which has clearly become a worldwide challenge to the effective control of infections by many pathogens. But, beyond affecting the pathogenic agents for which it is intended, antibiotic treatment also affects the mutualistic communities of microbes that inhabit the human body. As they inhibit susceptible organisms and select for resistant ones, antibiotics can have strong immediate effects on the composition of these communities, such as the proliferation of resistant opportunists that can cause accute disease. Furthermore, antibiotic-induced microbiota alterations are also likely to have more insidious effects on long-term health. In the case of the gut microbiota, this community interacts with many crucial aspects of human biology, including the regulation of immune and metabolic homeostasis, in the gut and beyond. It follows that antibiotic treatments bear the risk of altering these basic equilibria. Here, we review the growing literature on the effects of antibiotic use on gut microbiota composition and function, and their consequences for immunity, metabolism, and health.

  17. The Pseudomonas syringae type III effector HopG1 targets mitochondria, alters plant development, and suppresses plant innate immunity

    Science.gov (United States)

    Block, Anna; Guo, Ming; Li, Guangyong; Elowsky, Christian; Clemente, Thomas E.; Alfano, James R.

    2009-01-01

    Summary The bacterial plant pathogen Pseudomonas syringae uses a type III protein secretion system to inject type III effectors into plant cells. Primary targets of these effectors appear to be effector-triggered immunity (ETI) and pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). The type III effector HopG1 is a suppressor of ETI that is broadly conserved in bacterial plant pathogens. Here we show that HopG1 from P. syringae pv. tomato DC3000 also suppresses PTI. Interestingly, HopG1 localizes to plant mitochondria, suggesting that its suppression of innate immunity may be linked to a perturbation of mitochondrial function. While HopG1 possesses no obvious mitochondrial signal peptide, its N-terminal two-thirds was sufficient for mitochondrial localization. A HopG1-GFP fusion lacking HopG1’s N-terminal 13 amino acids was not localized to the mitochondria reflecting the importance of the N-terminus for targeting. Constitutive expression of HopG1 in Arabidopsis thaliana, Nicotiana tabacum (tobacco) and Lycopersicon esculentum (tomato) dramatically alters plant development resulting in dwarfism, increased branching and infertility. Constitutive expression of HopG1 in planta leads to reduced respiration rates and an increased basal level of reactive oxygen species. These findings suggest that HopG1’s target is mitochondrial and that effector/target interaction promotes disease by disrupting mitochondrial functions. PMID:19863557

  18. The innate immune response of equine bronchial epithelial cells is altered by training.

    Science.gov (United States)

    Frellstedt, Linda; Gosset, Philippe; Kervoaze, Gwenola; Hans, Aymeric; Desmet, Christophe; Pirottin, Dimitri; Bureau, Fabrice; Lekeux, Pierre; Art, Tatiana

    2015-01-17

    Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immune responses in trained horses. Bronchial epithelial biopsies were taken from 6 adult horses during lower airway endoscopy. EBEC were grown in vitro by an explant method. The innate immune response of EBEC was evaluated in vitro by treatment with TLR ligands. TLR3 is the most strongly expressed TLR at the mRNA level in EBEC and stimulation of EBEC with Poly(I:C), an analog of viral dsRNA, triggers a strong secretion of IFN-β, TNF-α, IL-6 and CXCL8. We further evaluated the EBEC innate immune response in horses that underwent a 4-month-training program. While training had no effect on TLR mRNA expression in EBEC as well as in bronchial biopsies, it increased the production of IFN-β after stimulation with a TLR3 ligand and decreased the secretion of TNF-α and IL-6 after stimulation with a TLR2 and TLR3 ligand. These findings may be implicated in the increased risk for viral and bacterial infections observed in sport horses. Altogether, we report a successful model for the culture of EBEC that can be applied to the investigation of pathophysiologic conditions in longitudinal studies.

  19. Celiac disease and endocrine autoimmunity.

    Science.gov (United States)

    Kahaly, George J; Schuppan, Detlef

    2015-01-01

    Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

  20. Horses experimentally infected with Sarcocystis neurona develop altered immune responses in vitro.

    Science.gov (United States)

    Witonsky, Sharon G; Ellison, Siobhan; Yang, Jibing; Gogal, Robert M; Lawler, Heather; Suzuki, Yasuhiro; Sriranganathan, Namalwar; Andrews, Frank; Ward, Daniel; Lindsay, David S

    2008-10-01

    Equine protozoal myeloencephalitis (EPM) due to Sarcocystis neurona infection is 1 of the most common neurologic diseases in horses in the United States. The mechanisms by which most horses resist disease, as well as the possible mechanisms by which the immune system may be suppressed in horses that develop EPM, are not known. Therefore, the objectives of this study were to determine whether horses experimentally infected with S. neurona developed suppressed immune responses. Thirteen horses that were negative for S. neurona antibodies in serum and cerebrospinal fluid (CSF) were randomly assigned to control (n = 5) or infected (n = 8) treatment groups. Neurologic exams and cerebrospinal fluid analyses were performed prior to, and following, S. neurona infection. Prior to, and at multiple time points following infection, immune parameters were determined. All 8 S. neurona-infected horses developed clinical signs consistent with EPM, and had S. neurona antibodies in the serum and CSF. Both infected and control horses had increased percentages (P < 0.05) of B cells at 28 days postinfection. Infected horses had significantly decreased (P < 0.05) proliferation responses as measured by thymidine incorporation to nonspecific mitogens phorbol myristate acetate (PMA) and ionomycin (I) as soon as 2 days postinfection.

  1. Past Life and Future Effects—How Heterologous Infections Alter Immunity to Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Aisha Souquette

    2018-05-01

    Full Text Available Influenza virus frequently mutates due to its error-prone polymerase. This feature contributes to influenza virus’s ability to evade pre-existing immunity, leading to annual epidemics and periodic pandemics. T cell memory plays a key protective role in the face of an antigenically distinct influenza virus strain because T cell targets are often derived from conserved internal proteins, whereas humoral immunity targets are often sites of increased mutation rates that are tolerated by the virus. Most studies of influenza T cell memory are conducted in naive, specific pathogen free mice and do not account for repetitive influenza infection throughout a lifetime, sequential acute heterologous infections between influenza infections, or heterologous chronic co-infections. By contrast to these mouse models, humans often experience numerous influenza infections, encounter heterologous acute infections between influenza infections, and are infected with at least one chronic virus. In this review, we discuss recent advances in understanding the effects of heterologous infections on the establishment and maintenance of CD8+ T cell immunological memory. Understanding the various factors that affect immune memory can provide insights into the development of more effective vaccines and increase reproducibility of translational studies between animal models and clinical results.

  2. Plasma immune protein analysis in the orange-spotted grouper Epinephelus coioides: Evidence for altered expressions of immune factors associated with a choline-supplemented diet.

    Science.gov (United States)

    Shiu, Ya-Li; Chiu, Kuo-Hsun; Huynh, Truong-Giang; Liu, Ping-Chung; Liu, Chun-Hung

    2017-06-01

    This study aimed to unravel the regulatory roles of choline in activating immune responses and disease resistance of the orange-spotted grouper Epinephelus coioides. Fish were fed a choline-supplemented diet at 1 g kg -1 of feed for 30 days. Fish fed a fish meal basal diet without choline-supplement served as controls. At the end of the feeding trial, fish were challenged with Vibrio alginolyticus. Meanwhile, plasma proteomics of fish in each group were also evaluated by two-dimensional gel electrophoresis (2-DE), and differentially expressed proteins were identified by tandem mass spectrophotometry (MS/MS), then a Western blot analysis or real-time polymerase chain reaction was used to confirm differential expressions of immune-enhancing proteins. Results showed that choline significantly increased survival of E. coioides 48 days after being injected with V. alginolyticus. From maps of plasma proteins, a comparative analysis between the control and choline groups revealed that 111 spots matched, with 26 altered expression spots in the choline group. Of these 26 spots, 16 were upregulated and 10 downregulated. After protein identification by reverse-phase nano-high-performance liquid chromatography-electrospray ionization MS/MS analysis, eight of 26 proteins were found to be immune-related proteins, all of which were upregulated, including complement 3 (C3), alpha-2-macroglobulin-P-like isoform (A2M), fibrinogen beta chain precursor (FBG), and immunoglobulin heavy constant mu (Ighm) proteins. Expression of the A2M protein and A2M enzyme activity in plasma of fish fed choline significantly increased compared to the control group. Additionally, A2M messenger (m)RNA transcripts were also upregulated in the liver and kidneys. Significantly higher C3 expressions at both the mRNA and protein levels were detected in the liver of fish in the choline group. Moreover, FBG gene expressions in the liver and kidneys significantly increased, while Ighm increased in the

  3. The clandestine organs of the endocrine system.

    Science.gov (United States)

    Garcia-Reyero, Natàlia

    2018-02-01

    This review analyzes what could be regarded as the "clandestine organs" of the endocrine system: the gut microbiome, the immune system, and the stress system. The immune system is very closely related to the endocrine system, with many intertwined processes and signals. Many researchers now consider the microbiome as an 'organ' that affects the organism at many different levels. While stress is certainly not an organ, it affects so many processes, including endocrine-related processes, that the stress response system deserved a special section in this review. Understanding the connections, effects, and feedback mechanisms between the different "clandestine organs" and the endocrine system will provide us with a better understanding of how an organism functions, as well as reinforce the idea that there are no independent organs or systems, but a complex, interacting network of molecules, cells, tissues, signaling pathways, and mechanisms that constitute an individual. Published by Elsevier Inc.

  4. Acute brief heat stress in late gestation alters neonatal calf innate immune functions.

    Science.gov (United States)

    Strong, R A; Silva, E B; Cheng, H W; Eicher, S D

    2015-11-01

    Heat stress, as one of the environmental stressors affecting the dairy industry, compromises the cow milk production, immune function, and reproductive system. However, few studies have looked at how prenatal heat stress (HS) affects the offspring. The objective of this study was to evaluate the effect of HS during late gestation on calf immunity. Calves were born to cows exposed to evaporative cooling (CT) or HS (cyclic 23-35°C) for 1 wk at 3 wk before calving. Both bull and heifer calves (CT, n=10; HS, n=10) were housed in similar environmental temperatures after birth. Both CT and HS calves received 3.78 L of pooled colostrum within 12 h after birth and were fed the same diet throughout the study. In addition to tumor necrosis factor α, IL-1β, IL-1 receptor antagonist (IL-1RA), and toll-like receptor (TLR)2, and TLR4 mRNA expression, the expression of CD14(+) and CD18(+) cells, and DEC205(+) dendritic cells were determined in whole blood samples at d 0, 3, 7, 14, 21, and 28. The neutrophil to lymphocyte ratio, differential cell counts, and the hematocrit were also determined. During late gestation, the HS cows had greater respiration rates, rectal temperatures, and tended to spend more time standing compared with the CT cows. The HS calves had less expression of tumor necrosis factor-α and TLR2 and greater levels of IL-1β, IL-1RA, and TLR4 compared with CT calves. The HS calves also had a greater percentage of CD18(+) cells compared with the CT calves. Additionally, a greater percentage of neutrophils and lesser percentage of lymphocytes were in the HS calves compared with the CT calves. The results indicate that biomarkers of calves' immunity are affected in the first several weeks after birth by HS in the dam during late gestation. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

    Science.gov (United States)

    Degnim, Amy C; Hoskin, Tanya L; Arshad, Muhammad; Frost, Marlene H; Winham, Stacey J; Brahmbhatt, Rushin A; Pena, Alvaro; Carter, Jodi M; Stallings-Mann, Melody L; Murphy, Linda M; Miller, Erin E; Denison, Lori A; Vachon, Celine M; Knutson, Keith L; Radisky, Derek C; Visscher, Daniel W

    2017-07-15

    Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD). Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm 2 for CD4 + T cells, CD8 + T cells, CD20 + B cells, and CD68 + macrophages and quantification of positive pixel measure for CD11c (dendritic cells). Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8 + T cells, CD11c + dendritic cells, CD20 + B cells, and CD68 + macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20 + cell density ( P = 0.04). Nearly 42% of BBD cases had no CD20 + B cells in evaluated lobules compared with 28% of BBD controls ( P = 0.02). The absence of CD20 + cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk. Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

    Science.gov (United States)

    D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

    2015-07-29

    Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how

  7. Altered biomarkers of mucosal immunity and reduced vaginal Lactobacillus concentrations in sexually active female adolescents.

    Directory of Open Access Journals (Sweden)

    Rebecca Pellett Madan

    Full Text Available Genital secretions collected from adult women exhibit in vitro activity against herpes simplex virus (HSV and Escherichia coli (E. coli, but prior studies have not investigated this endogenous antimicrobial activity or its mediators in adolescent females.Anti-HSV and anti-E.coli activity were quantified from cervicovaginal lavage (CVL specimens collected from 20 sexually active adolescent females (15-18 years. Soluble immune mediators that may influence this activity were measured in CVL, and concentrations of Lactobacillus jensenii and crispatus were quantified by PCR from vaginal swabs. Results for adolescents were compared to those obtained from 54 healthy, premenopausal adult women. Relative to specimens collected from adults, CVL collected from adolescent subjects had significantly reduced activity against E. coli and diminished concentrations of protein, IgG, and IgA but significantly increased anti-HSV activity and concentrations of interleukin (IL-1α, IL-6 and IL-1 receptor antagonist. Vaginal swabs collected from adolescent subjects had comparable concentrations of L. crispatus but significantly reduced concentrations of L. jensenii, relative to adult swabs.Biomarkers of genital mucosal innate immunity may differ substantially between sexually active adolescents and adult women. These findings warrant further study and may have significant implications for prevention of sexually transmitted infections in adolescent females.

  8. Altered levels of soluble CD18 may associate immune mechanisms with outcome in sepsis

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Juul-Madsen, Kristian; Hill Christiansen, Stig

    2017-01-01

    and phagocytosis through complement opsonisation, both processes relevant to the immune response during sepsis. Here, we investigate the role of soluble (s)CD18 in sepsis with emphasis on sCD18 as a mechanistic biomarker of immune reactions and outcome of sepsis. sCD18 levels were measured in fifteen septic....../CD18, also known as Mac-1 or complement receptor 3. Serum sCD18 levels in sepsis non-survivors displayed two distinct peaks permitting a partitioning into two groups, namely sCD18 “high” and sCD18 “low” with median levels of sCD18 at 2158 mU/ml (IQR 2093-2811 mU/ml) and 488 mU/ml (IQR 360-617 m......U/ml), respectively, at the day of ICU admission. Serum sCD18 levels partitioned sepsis non-survivors into one group of “high” sCD18 and low CRP and another group with “low” sCD18 and high CRP. Together with the mechanistic data generated in vitro, we suggest the partitioning in sCD18 to reflect a compensatory anti...

  9. Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

    Science.gov (United States)

    Spann, Redin A; Lawson, William J; Bidwell, Gene L; Zamarripa, C Austin; Maranon, Rodrigo O; Bandyopadhyay, Sibali; Taylor, Erin R; Reckelhoff, Jane F; Garrett, Michael R; Grayson, Bernadette E

    2018-01-31

    Bariatric surgery is increasingly employed to improve fertility and reduce obesity-related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism, and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnormalities that may be responsible for fetal demise during pregnancy. VSG dams studied on gestational day (G) 19 had reduced circulating T-cell (CD3 + and CD8 + ) populations compared with lean or obese controls. Further, local interleukin (IL) 1β and IL 1 receptor antagonist ( il1rn ) cmRNA were increased in placenta of VSG dams. Placental barrier function was also affected, with increased transplacental permeability to small molecules, increased matrix metalloproteinase 9 expression, and increased apoptosis in VSG. Furthermore, we identified increased placental mTOR signaling that may contribute to preserving the body weight of the fetuses during gestation. These changes occurred in the absence of a macronutrient deficit or gestational hypertension in the VSG dams. In summary, previous VSG in dams may contribute to fetal demise by affecting maternal immune system activity and compromise placental integrity. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  10. Children after Chernobyl: immune cells adaptive changes and stable alterations under low-dose irradiation

    International Nuclear Information System (INIS)

    Bazyka, D.A.; Chumak, A.A.; Bebeshko, V.G.; Beliaeva, N.V.

    1997-01-01

    Early changes of immune parameters in children evacuated from 30-km zone were characterized by E-rossette forming cells decrease and E-receptor non-stability in theophylline assay, surface Ig changes. Immunological follow-up of children inhabitants of territories contaminated with radionuclides after Chernobyl accident revealed TCR/CD3, CD4 and MHC CD3+, CD4+, CD57+ subsets, RIL-2, TrT expression and calcium channel activity. PMNC percentage with cortical thymocyte phenotype (CD1+, CD4+8+) was elevated during the first years after the accident and seemed to be of a compensatory origin. Combination of heterogenic activation and suppression subset reactions and changes in fine subset (Th1/Th2) organization were suggested. Adaptive and compensatory reactions were supposed and delayed hypersensitivity reactions increase as well. (author)

  11. Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

    DEFF Research Database (Denmark)

    Genster, Ninette; Østrup, Olga; Schjalm, Camilla

    2017-01-01

    . Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.......Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested...

  12. Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum

    Directory of Open Access Journals (Sweden)

    Jochen Hinkelbein

    2017-08-01

    Full Text Available Hypobaric hypoxia (HH during airline travel induces several (patho- physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF. Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software. In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades “regulation of haemostasis” (four proteins, “metabolism” (five proteins, and “leukocyte mediated immune response” (five proteins. Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight, analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis

  13. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    Science.gov (United States)

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. The molecular classification of hereditary endocrine diseases.

    Science.gov (United States)

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  15. Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

    Directory of Open Access Journals (Sweden)

    Fumiaki Obata

    2014-05-01

    Full Text Available Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM levels due to glycine N-methyltransferase (Gnmt upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.

  16. Altered immune parameters correlate with infection-related hospitalizations in children with Down syndrome.

    Science.gov (United States)

    Martínez, Elizabeth; Castañeda, Diana; Jaramillo, Sonia; Iregui, Alejandro; Quiñonez, Tatiana; Rodríguez, Jairo A; Herrera, Eddy; Gómez, Ana Milena; Rondón, Martin A; Prieto, Juan Carlos; Angel, Juana; Franco, Manuel A; Mesa, Martha C

    2016-07-01

    In addition to previously studied immunological variables, the relative expression of IFNGR2, IFNAR1, CD18, and CD275 (all encoded in chromosome 21) on circulating leucocytes and multifunctional T cells (evaluated by an intracellular cytokine/proliferation assay) were compared between children with Down syndrome (DS) and healthy controls (HC). As previously reported, numbers of lymphocytes, CD4(+) T cells, Treg cells, B cells, and levels of serum IgM were decreased, and levels of IgG and IgA were increased in children with DS. Moreover, the relative expression of CD18 on T and B cells (previously and not previously reported, respectively) were elevated in DS children (p⩽0.01). Age and numbers of B and Treg cells moderately correlated with retrospectively identified infection related hospitalizations (rho: 0.300-0.460, p⩽0.003). Age and the numbers of Treg cells also correlated with prospectively identified infection related hospitalizations. Future studies are necessary to clarify the role of these parameters in the immunity of DS patients. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  17. MicroRNA-29b mediates altered innate immune development in acute leukemia

    Science.gov (United States)

    Mundy-Bosse, Bethany L.; Scoville, Steven D.; Chen, Li; McConnell, Kathleen; Mao, Hsiaoyin C.; Ahmed, Elshafa H.; Zorko, Nicholas; Harvey, Sophia; Cole, Jordan; Zhang, Xiaoli; Costinean, Stefan; Croce, Carlo M.; Larkin, Karilyn; Byrd, John C.; Vasu, Sumithira; Blum, William; Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A.

    2016-01-01

    Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell–depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients. This absence was not due to elimination by cell death or selective reduction in proliferation, but rather to the result of a block in NK cell differentiation. Indeed, NK cells from leukemic mice and humans with AML showed lower levels of TBET and EOMES, transcription factors that are critical for terminal NK cell differentiation. Further, the microRNA miR-29b, a regulator of T-bet and EOMES, was elevated in leukemic NK cells. Finally, deletion of miR-29b in NK cells reversed the depletion of this NK cell subset in leukemic mice. These results indicate that leukemic evasion of NK cell surveillance occurs through miR-mediated dysregulation of lymphocyte development, representing an additional mechanism of immune escape in cancer. PMID:27775550

  18. Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

    Directory of Open Access Journals (Sweden)

    Francesca S. M. Tang

    2015-01-01

    Full Text Available Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood and suboptimal (ASubopt asthma symptom control. Methods. Peripheral blood neutrophils from AGood (ACQ 0.75, n=7, and healthy controls (HC (n=9 were stimulated with bacterial (LPS (1 μg/mL, fMLF (100 nM, and viral (imiquimod (3 μg/mL, R848 (1.5 μg/mL, and poly I:C (10 μg/mL surrogates or live rhinovirus (RV 16 (MOI1. Cell-free supernatant was collected after 1 h for neutrophil elastase (NE and matrix metalloproteinase- (MMP- 9 measurements or after 24 h for CXCL8 release. Results. Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.

  19. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria.

    Science.gov (United States)

    Hwang, John H; Lyes, Matthew; Sladewski, Katherine; Enany, Shymaa; McEachern, Elisa; Mathew, Denzil P; Das, Soumita; Moshensky, Alexander; Bapat, Sagar; Pride, David T; Ongkeko, Weg M; Crotty Alexander, Laura E

    2016-06-01

    Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25-44 now using these drug delivery devices. E-cigarette users expose their airways, cells of host defense, and colonizing bacteria to e-cigarette vapor (EV). Here, we report that exposure of human epithelial cells at the air-liquid interface to fresh EV (vaped from an e-cigarette device) resulted in dose-dependent cell death. After exposure to EV, cells of host defense-epithelial cells, alveolar macrophages, and neutrophils-had reduced antimicrobial activity against Staphylococcus aureus (SA). Mouse inhalation of EV for 1 h daily for 4 weeks led to alterations in inflammatory markers within the airways and elevation of an acute phase reactant in serum. Upon exposure to e-cigarette vapor extract (EVE), airway colonizer SA had increased biofilm formation, adherence and invasion of epithelial cells, resistance to human antimicrobial peptide LL-37, and up-regulation of virulence genes. EVE-exposed SA were more virulent in a mouse model of pneumonia. These data suggest that e-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria. Acute exposure to e-cigarette vapor (EV) is cytotoxic to airway cells in vitro. Acute exposure to EV decreases macrophage and neutrophil antimicrobial function. Inhalation of EV alters immunomodulating cytokines in the airways of mice. Inhalation of EV leads to increased markers of inflammation in BAL and serum. Staphylococcus aureus become more virulent when exposed to EV.

  20. Effects of alcohol on the endocrine system.

    Science.gov (United States)

    Rachdaoui, Nadia; Sarkar, Dipak K

    2013-09-01

    Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine, and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiologic and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease, and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Are endocrine and reproductive biomarkers altered in contaminant-exposed wild male Largemouth Bass (Micropterus salmoides) of Lake Mead, Nevada/Arizona, USA?

    Science.gov (United States)

    Goodbred, Steven L.; Patino, Reynaldo; Torres, Leticia; Echols, Kathy R.; Jenkins, Jill A.; Rosen, Michael R.; Orsak, Erik

    2015-01-01

    Male Largemouth Bass were sampled from two locations in Lake Mead (USA), a site influenced by treated municipal wastewater effluent and urban runoff (Las Vegas Bay), and a reference site (Overton Arm). Samples were collected in summer (July '07) and spring (March '08) to assess general health, endocrine and reproductive biomarkers, and compare contaminant body burdens by analyzing 252 organic chemicals. Sperm count and motility were measured in spring. Contaminants were detected at much higher frequencies and concentrations in fish from Las Vegas Bay than Overton Arm. Those with the highest concentrations included PCBs, DDTs, PBDEs, galaxolide, and methyl triclosan. Fish from Las Vegas Bay also had higher Fulton condition factor, hepatosomatic index, and hematocrit, and lower plasma 11-ketotestosterone concentration (KT). Gonadosomatic index (GSI) and sperm motility did not differ between sites, but sperm count was lower by nearly 50% in fish from Las Vegas Bay. A positive association between KT and GSI was identified, but this association was nonlinear. On average, maximal GSI was reached at sub-maximal KT concentrations. In conclusion, the higher concentration of contaminant body burdens coupled with reduced levels of KT and sperm count in fish from Las Vegas Bay suggest that male reproductive condition was influenced by contaminant exposures. Also, the nonlinear KT-GSI association provided a framework to understand why GSI was similar between male bass from both sites despite their large difference in KT, and also suggested the existence of post-gonadal growth functions of KT at high concentrations.

  2. Are endocrine and reproductive biomarkers altered in contaminant-exposed wild male Largemouth Bass (Micropterus salmoides) of Lake Mead, Nevada/Arizona, USA?

    Science.gov (United States)

    Goodbred, Steven L; Patiño, Reynaldo; Torres, Leticia; Echols, Kathy R; Jenkins, Jill A; Rosen, Michael R; Orsak, Erik

    2015-08-01

    Male Largemouth Bass were sampled from two locations in Lake Mead (USA), a site influenced by treated municipal wastewater effluent and urban runoff (Las Vegas Bay), and a reference site (Overton Arm). Samples were collected in summer (July '07) and spring (March '08) to assess general health, endocrine and reproductive biomarkers, and compare contaminant body burdens by analyzing 252 organic chemicals. Sperm count and motility were measured in spring. Contaminants were detected at much higher frequencies and concentrations in fish from Las Vegas Bay than Overton Arm. Those with the highest concentrations included PCBs, DDTs, PBDEs, galaxolide, and methyl triclosan. Fish from Las Vegas Bay also had higher Fulton condition factor, hepatosomatic index, and hematocrit, and lower plasma 11-ketotestosterone concentration (KT). Gonadosomatic index (GSI) and sperm motility did not differ between sites, but sperm count was lower by nearly 50% in fish from Las Vegas Bay. A positive association between KT and GSI was identified, but this association was nonlinear. On average, maximal GSI was reached at sub-maximal KT concentrations. In conclusion, the higher concentration of contaminant body burdens coupled with reduced levels of KT and sperm count in fish from Las Vegas Bay suggest that male reproductive condition was influenced by contaminant exposures. Also, the nonlinear KT-GSI association provided a framework to understand why GSI was similar between male bass from both sites despite their large difference in KT, and also suggested the existence of post-gonadal growth functions of KT at high concentrations. Published by Elsevier Inc.

  3. Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

    Directory of Open Access Journals (Sweden)

    Danielle Botelho

    2018-03-01

    Full Text Available Here we examine the organ level toxicology of both carbon black (CB and silver nanoparticles (AgNP. We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF. C57Bl6/J male mice were intratracheally instilled with saline (control, low (0.05 μg/g or high (0.5 μg/g doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.

  4. SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

    Directory of Open Access Journals (Sweden)

    M. Yu. Yukina

    2016-01-01

    Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

  5. ALTERATION OF IMMUNE FUNCTION IN WOMEN COLLEGIATE SOCCER PLAYERS AND COLLEGE STUDENTS

    Directory of Open Access Journals (Sweden)

    Michael R. McGuigan

    2004-12-01

    Full Text Available The purpose of this study was to monitor the stress-induced alteration in concentrations of salivary immunoglobulin (S-IgA and cortisol and the incidence of upper respiratory tract infections (URTI over the course of a 9-week competitive season in college student-athletes and college students. The subjects consisted of 14 NCAA Division III collegiate female soccer athletes (19.8 ¡À 1.0 years, mean ¡À SD and 14 female college students (22.5 ¡À 2.6 years. Salivary samples were collected for 9 weeks during a competitive soccer season. S-IgA and cortisol concentrations were determined by enzyme linked immunosorbent assay (ELISA. A training and performance questionnaire was given to the subjects every week, to record the subjects' session rating of perceived exertion (RPE for all the training, load, monotony and strain, as well as any injuries or illnesses experienced. The between groups ANOVA procedure for repeated measures showed no changes in salivary concentrations of IgA and cortisol. Chi-square analysis showed that during the 9-week training season injury and illness occurred at a higher rate among the soccer players. There was a significant difference at baseline between soccer and control S-IgA levels (p¡Ü0.05. Decreased levels of S-IgA and increases in the indices of training (load, strain and monotony were associated with an increase in the incidence of illness during the 9-week competitive soccer season.

  6. Landscape structure and management alter the outcome of a pesticide ERA: Evaluating impacts of endocrine disruption using the ALMaSS European Brown Hare model.

    Science.gov (United States)

    Topping, Chris J; Dalby, Lars; Skov, Flemming

    2016-01-15

    There is a gradual change towards explicitly considering landscapes in regulatory risk assessment. To realise the objective of developing representative scenarios for risk assessment it is necessary to know how detailed a landscape representation is needed to generate a realistic risk assessment, and indeed how to generate such landscapes. This paper evaluates the contribution of landscape and farming components to a model based risk assessment of a fictitious endocrine disruptor on hares. In addition, we present methods and code examples for generation of landscape structures and farming simulation from data collected primarily for EU agricultural subsidy support and GIS map data. Ten different Danish landscapes were generated and the ERA carried out for each landscape using two different assumed toxicities. The results showed negative impacts in all cases, but the extent and form in terms of impacts on abundance or occupancy differed greatly between landscapes. A meta-model was created, predicting impact from landscape and farming characteristics. Scenarios based on all combinations of farming and landscape for five landscapes representing extreme and middle impacts were created. The meta-models developed from the 10 real landscapes failed to predict impacts for these 25 scenarios. Landscape, farming, and the emergent density of hares all influenced the results of the risk assessment considerably. The study indicates that prediction of a reasonable worst case scenario is difficult from structural, farming or population metrics; rather the emergent properties generated from interactions between landscape, management and ecology are needed. Meta-modelling may also fail to predict impacts, even when restricting inputs to combinations of those used to create the model. Future ERA may therefore need to make use of multiple scenarios representing a wide range of conditions to avoid locally unacceptable risks. This approach could now be feasible Europe wide given the

  7. Endocrine autoimmune diseases and female infertility.

    Science.gov (United States)

    Sen, Aritro; Kushnir, Vitaly A; Barad, David H; Gleicher, Norbert

    2014-01-01

    An increasing body of evidence suggests that immune-mediated processes affect female reproductive success at multiple levels. Crosstalk between endocrine and immune systems regulates a large number of biological processes that affect target tissues, and this crosstalk involves gene expression, cytokine and/or lymphokine release and hormone action. In addition, endocrine-immune interactions have a major role in the implantation process of the fetal (paternally derived) semi-allograft, which requires a reprogramming process of the maternal immune system from rejection to temporary tolerance for the length of gestation. Usually, the female immune system is supportive of all of these processes and, therefore, facilitates reproductive success. Abnormalities of the female immune system, including autoimmunity, potentially interfere at multiple levels. The relevance of the immune system to female infertility is increasingly recognized by investigators, but clinically is often not adequately considered and is, therefore, underestimated. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future.

  8. Quantitative Trait Locus and Brain Expression of HLA-DPA1 Offers Evidence of Shared Immune Alterations in Psychiatric Disorders

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    Ling Z. Morgan

    2016-03-01

    Full Text Available Genome-wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC were highly significant following genome-wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1 in brain from individual subjects with schizophrenia (SZ, bipolar disorder (BD, major depressive disorder (MDD, and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. Exon microarrays were performed in anterior cingulate cortex (ACC in BD compared to controls, and both HLA-DPA1 and CD74 were decreased in expression in BD. The expression of HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA-DPA1 exons 2-3-4 as suggested by exon microarrays. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future

  9. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

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    Zarbock Ralf

    2012-03-01

    Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

  10. Effect of dietary γ-aminobutyric acid on laying performance, egg quality, immune activity and endocrine hormone in heat-stressed Roman hens.

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    Zhang, Min; Zou, Xiao-Ting; Li, Hui; Dong, Xin-Yang; Zhao, Wenjing

    2012-02-01

    This study was conducted to evaluate the effect of γ-aminobutyric acid (GABA) on laying performance, egg quality, digestive enzyme activity, hormone level and immune activities in Roman hens under heat stress. Roman hens (320 days old) were fed with 0, 25, 50, 75 and 100 mg/kg GABA, respectively during a 60-day experiment. Compared with control, supplementation of 50 mg/kg GABA improved the laying performance and egg quality by significantly increasing egg production, average egg weight and shell strength (P level. Anti-oxidation activity was improved by significantly increasing the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but decreasing malondialdehyde level in serum (P level, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2) ), insulin, triiodothyronine (T(3) ) and free triiodothyronine (FT(3) ) levels, and IgG, IgA and complement (C3)activity in serum (P GABA improved laying performance and physical condition mainly by modulating hormone secretion, enhancing anti-oxidation and immune activity, and maintaining electrolyte balance. Fifty mg/kg was the optimum level for laying hens under heat stress in the present study. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  11. Neuropsychiatry phenotype in asthma: Psychological stress-induced alterations of the neuroendocrine-immune system in allergic airway inflammation

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    Isao Ohno

    2017-09-01

    Full Text Available Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation. The mechanisms underlying this process may involve a pathological series of events from the brain to the lungs, which is attracting attention as a conceptually advanced phenotype in asthma pathogenesis. This review presents insights into the critical role of psychological stress in the development and exacerbation of allergic asthma, with a special focus on our own data that emphasizes on the continuity from the central sensing of psychological stress to enhanced eosinophilic airway inflammation.

  12. Pesticides Provoke Endocrine Disruption A Review

    International Nuclear Information System (INIS)

    Aly, M.A.S.

    2006-01-01

    Increasing numbers of environmental chemicals,including pesticides, have the ability to produce endocrine disruption by various mechanisms. such substances may affect hormone secretion from an endocrine gland and may alter the rate of hormone elimination from the body. environmental chemicals may also disrupt regulatory feedback mechanisms that exist between two endocrine organs; or may interact with a hormone receptor either by mimicking or antagonizing the actions of the natural hormone. these chemicals are referred to endocrine disruptive chemicals (EDC's). EDC's act to alter the blood hormone levels or the subsequent action of hormones . the use of radioimmunoassay(RIA) constitutes a superior and unrivalled tool for the determination and quantification of hormones.the endocrine system participates in virtually all important functions of an organism, such as sexual differentiation before birth, sexual maturation during puberty, reproduction in adulthood, growth, metabolism, digestion, cardiovascular function and excretion. hormones are also implicated in the etiology of certain cancers of hormone- dependent tissues, such as those of the breast, uterus, and prostate gland. therefore, endocrine disruption can potentially produce widespread effects. scientists should not stick to the past belief which presumes that pesticides have limited effect on some hormones. A paradigm shift in which a wider vision of understanding of the wholesome complex effects of pesticides on the whole body rather than a narrow limited understanding should take place

  13. Phosphodiesterases in endocrine physiology and disease.

    Science.gov (United States)

    Vezzosi, Delphine; Bertherat, Jérôme

    2011-08-01

    The cAMP-protein kinase A pathway plays a central role in the development and physiology of endocrine tissues. cAMP mediates the intracellular effects of numerous peptide hormones. Various cellular and molecular alterations of the cAMP-signaling pathway have been observed in endocrine diseases. Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. Indeed, PDEs are the only known mechanism for inactivation of cAMP by catalysis to 5'-AMP. It has been suggested that disruption of PDEs could also have a role in the pathogenesis of many endocrine diseases. This review summarizes the most recent advances concerning the role of the PDEs in the physiopathology of endocrine diseases. The potential significance of this knowledge can be easily envisaged by the development of drugs targeting specific PDEs.

  14. Endocrine Disrupting Contaminants—Beyond the Dogma

    Science.gov (United States)

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  15. From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system.

    Science.gov (United States)

    Dhouib, Ines; Jallouli, Manel; Annabi, Alya; Marzouki, Soumaya; Gharbi, Najoua; Elfazaa, Saloua; Lasram, Mohamed Montassar

    2016-05-01

    The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

  16. Immune disorders in anorexia

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    Sylwia Małgorzata Słotwińska

    2017-10-01

    Full Text Available Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  17. Immune disorders in anorexia.

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    Słotwińska, Sylwia Małgorzata; Słotwiński, Robert

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  18. Endocrine system: part 1.

    Science.gov (United States)

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  19. Epigenetic regulation of non-lymphoid cells by Bisphenol-A, a model endocrine disrupter: Potential Implications for Immunoregulation

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    Deena eKhan

    2015-06-01

    Full Text Available Endocrine disrupting chemicals (EDC abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical and consumer product industries. Many of the EDCs such as Bisphenol A (BPA have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system.

  20. Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease

    Science.gov (United States)

    Anway, Matthew D.; Leathers, Charles; Skinner, Michael K.

    2018-01-01

    The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1–F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1–F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease. PMID:16973726

  1. CONTAMINANT-ASSOCIATED ENDOCRINE DISRUPTION IN REPTILES.

    Science.gov (United States)

    The data presented suggest that contaminants can alter the endocrine and reproductive system of reptiles by mimicking hormones and by various mechanisms other than direct hormonal mimicry. However, these data indicate, as do many other studies using various vertebrates, that a fo...

  2. Short Communication: Immunohistochemical localization of the immune cell marker CD68 in bovine adipose tissue: impact of tissue alterations and excessive fat accumulation in dairy cows.

    Science.gov (United States)

    Häussler, S; Germeroth, D; Laubenthal, L; Ruda, L F; Rehage, J; Dänicke, S; Sauerwein, H

    2017-01-01

    With the onset of lactation energy from feed intake is mostly insufficient to meet the requirements of dairy cows. Lipid mobilization from adipose tissue (AT) could lead to a compromised inflammatory response enhancing the incidence for diseases. In addition, tissue alterations can occur, displaying areas of necrosis and inflammation. Furthermore, over-conditioned cows mobilizing more lipids from AT than thin cows are prone to develop metabolic disorders. This might lead to an increased infiltration of phagocytic immune cells into AT. In the present study, CD68 positive cells were localized in AT from 10 early lactating Holstein cows displaying different grades of AT alterations. Biopsies were sampled from visceral and subcutaneous AT and the number of CD68 positive cells was immunohistochemically determined. In addition, AT biopsies from over-conditioned, non-pregnant, non-lactating cows (n=8) were immunohistochemically analyzed for CD68 positive cells. The percentage of CD68 positive cells was less than 2% in AT biopsies with tissue alterations and in AT from over-conditioned cows. Therefore, immune cell infiltration demonstrated via the localization of CD68 positive cells seems to play only a minor role in AT from over-conditioned cows as well as in different bovine AT depots with tissue alterations. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

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    Mohd eKhubaib

    2016-05-01

    Full Text Available PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.

  4. A benign helminth alters the host immune system and the gut microbiota in a rat model system.

    Science.gov (United States)

    Wegener Parfrey, Laura; Jirků, Milan; Šíma, Radek; Jalovecká, Marie; Sak, Bohumil; Grigore, Karina; Jirků Pomajbíková, Kateřina

    2017-01-01

    Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.

  5. A benign helminth alters the host immune system and the gut microbiota in a rat model system.

    Directory of Open Access Journals (Sweden)

    Laura Wegener Parfrey

    Full Text Available Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.

  6. Efeito do treinamento físico como modulador positivo nas alterações no eixo neuroimunoendócrino em indivíduos com insuficiência cardíaca crônica: possível atuação do fator de necrose tumoral-alfa Efecto del entrenamiento físico como modulador positivo en las alteraciones en el eje neuroinmunoendócrino en indivíduos con insuficiência cardíaca crônica: posible actuación como factor de necrosis tumoral-alfa Effect of physical training as positive modulator on the alterations in the neuro-immune-endocrine axis in patients with chronic heart failure: possible role of the tumoral necrosis factor-alpha

    Directory of Open Access Journals (Sweden)

    Luís Fernando Bicudo Pereira Costa Rosa

    2005-08-01

    responsble por la progresión en el deterioro clínico en la ICC. En este cuadro, la principal citoquina envuelta en el cuadro fisiopatológico de la ICC es el factor de necrosis tumoral-alfa (TNF-alfa. Así, el TF puede actuar en el cuadro de ICC de dos maneras, mejorando el desempeño durante el ejercicio físico, bien como atenuando el cuadro de deterioro de elevada concentración de citoquinas pro-inflamatórias en el sistema cardiovascular, pudiendo representar una importante opción inmunomodulatoria, y de esta forma, permitir una mejora significativa en el cuadro clínico del paciente.Chronic physical exercise or physical training (PT has been widely used in the last years with therapeutic and preventive purposes in a series of pathophysiological conditions, including cardiovascular disease. Besides the cardiovascular benefits, PT seems capable to modulate in pathological conditions, at the presence of an abnormal inflammatory response, including over expression of proinflammatory cytokines through a neuro-immune-endocrine interaction. Nowadays chronic heart failure (CHF is reviewed as the consequence of an interplay of hemodynamic, neurohormonal, immunological and endocrine mechanisms. This abnormal inflammatory response, including the over expression of proinflammatory cytokines may be proposed as responsible for the progression and clinical deterioration in CHF. Tumor necrosis factor-alpha (TNF-alpha is the main proinflammatory cytokines involved in the inflammatory cascade implicated in the pathophysiological of CHF. PT may improve exercise performance by modifying the inflammatory status, as well as by allowing reversing the inflammation-induced harmful effects on the cardiovascular system, and that PT may represent an important immunomodulatory option that may be possible to intervene in the progression of the disease.

  7. Models of Stress in Nonhuman Primates and Their Relevance for Human Psychopathology and Endocrine Dysfunction

    Science.gov (United States)

    Meyer, Jerrold S.; Hamel, Amanda F.

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. PMID:25225311

  8. Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunction.

    Science.gov (United States)

    Meyer, Jerrold S; Hamel, Amanda F

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. © The Author 2014. Published by Oxford University Press on

  9. Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system

    Science.gov (United States)

    Cromer, W. E.; Zawieja, D. C.

    2018-05-01

    Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.

  10. Synergy between the KEAP1/NRF2 and PI3K Pathways Drives Non-Small-Cell Lung Cancer with an Altered Immune Microenvironment.

    Science.gov (United States)

    Best, Sarah A; De Souza, David P; Kersbergen, Ariena; Policheni, Antonia N; Dayalan, Saravanan; Tull, Dedreia; Rathi, Vivek; Gray, Daniel H; Ritchie, Matthew E; McConville, Malcolm J; Sutherland, Kate D

    2018-04-03

    The lung presents a highly oxidative environment, which is tolerated through engagement of tightly controlled stress response pathways. A critical stress response mediator is the transcription factor nuclear factor erythroid-2-related factor 2 (NFE2L2/NRF2), which is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1). Alterations in the KEAP1/NRF2 pathway have been identified in 23% of lung adenocarcinomas, suggesting that deregulation of the pathway is a major cancer driver. We demonstrate that inactivation of Keap1 and Pten in the mouse lung promotes adenocarcinoma formation. Notably, metabolites identified in the plasma of Keap1 f/f /Pten f/f tumor-bearing mice indicate that tumorigenesis is associated with reprogramming of the pentose phosphate pathway. Furthermore, the immune milieu was dramatically changed by Keap1 and Pten deletion, and tumor regression was achieved utilizing immune checkpoint inhibition. Thus, our study highlights the ability to exploit both metabolic and immune characteristics in the detection and treatment of lung tumors harboring KEAP1/NRF2 pathway alterations. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Altered Polarization, Morphology, and Impaired Innate Immunity Germane to Resident Peritoneal Macrophages in Mice with Long-Term Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Hui-Fang Liu

    2012-01-01

    Full Text Available Type 2 diabetes (T2D is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80+ RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time.

  12. Surgical strategies in endocrine tumors

    NARCIS (Netherlands)

    Schreinemakers, J.M.J.

    2010-01-01

    Endocrine surgery has become more custom-made throughout the years. Endocrine tumors can be sporadic or develop as part of familial syndromes. Several familial syndromes are known to cause endocrine tumors. The most common are multiple endocrine neoplasia (MEN) syndromes type 1, 2A and 2B. This

  13. Endocrine system: part 2.

    Science.gov (United States)

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

    2014-06-03

    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  14. Omega-3 polyunsaturated fatty acids enrichment alters performance and immune response in infectious bursal disease challenged broilers

    Directory of Open Access Journals (Sweden)

    Maroufyan Elham

    2012-01-01

    Full Text Available Abstract Background Infectious bursal disease (IBD results in economic loss due to mortality, reduction in production efficiency and increasing the usage of antibiotics. This study was carried out to investigate the modulatory roles of dietary n-3 polyunsaturated fatty acids (PUFA enrichment in immune response and performance of IBD challenged broiler chickens. Methods A total of 300 day old male broiler chicks were assigned to four dietary n-3 PUFA ascending levels as the treatment groups (T1: 0.5; T2: 8.0; T3: 11.5; T4: 16.5 using combinations of tuna oil and sunflower oil. All diets were isocaloric and isonitrogenous. On day 28, all birds were challenged with IBD virus. Antibody titer, cytokine production, bursa lesion pre and post-challenge and lymphoid organ weight were recorded. Results On d 42 the highest body weight was observed in the T2 and T3 and the lowest in T4 chickens. Feed conversion ratio of the T2 broilers was significantly better than the other groups. Although productive parameters were not responded to the dietary n-3 PUFA in a dose-dependent manner, spleen weight, IBD and Newcastle disease antibody titers and IL-2 and IFN-γ concentrations were constantly elevated by n-3 PUFA enrichment. Conclusions Dietary n-3 PUFA enrichment may improve the immune response and IBD resistance, but the optimum performance does not coincide with the optimum immune response. It seems that dietary n-3 PUFA modulates the broiler chicken performance and immune response in a dose-dependent manner. Thus, a moderate level of dietary n-3 PUFA enrichment may help to put together the efficiency of performance and relative immune response enhancement in broiler chickens.

  15. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  16. Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

    Science.gov (United States)

    Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

    2016-08-01

    The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

    Science.gov (United States)

    Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

    2015-11-01

    Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Natural functional SNPs in miR-155 alter its expression level, blood cell counts and immune responses

    Directory of Open Access Journals (Sweden)

    Congcong Li

    2016-08-01

    Full Text Available miR-155 has been confirmed to be a key factor in immune responses in humans and other mammals. Therefore, investigation of variations in miR-155 could be useful for understanding the differences in immunity between individuals. In this study, four SNPs in miR-155 were identified in mice (Mus musculus and humans (Homo sapiens. In mice, the four SNPs were closely linked and formed two miR-155 haplotypes (A and B. Ten distinct types of blood parameters were associated with miR-155 expression under normal conditions. Additionally, 4 and 14 blood parameters were significantly different between these two genotypes under normal and lipopolysaccharide (LPS stimulation conditions, respectively. Moreover, the expression levels of miR-155, the inflammatory response to LPS stimulation and the lethal ratio following Salmonella typhimurium infection were significantly increased in mice harboring the AA genotype. Further, two SNPs, one in the loop region and the other near the 3' terminal of pre-miR-155, were confirmed to be responsible for the differential expression of miR-155 in mice. Interestingly, two additional SNPs, one in the loop region and the other in the middle of miR-155*, modulated the function of miR-155 in humans. Predictions of secondary RNA structure using RNAfold showed that these SNPs affected the structure of miR-155 in both mice and humans. Our results provide novel evidence of the natural functional SNPs of miR-155 in both mice and humans, which may affect the expression levels of mature miR-155 by modulating its secondary structure. The SNPs of human miR-155 may be considered as causal mutations for some immune-related diseases in the clinic. The two genotypes of mice could be used as natural models for studying the mechanisms of immune diseases caused by abnormal expression of miR-155 in humans.

  19. Comparison of altered expression of histocompatibility antigens with altered immune function in murine spleen cells treated with ultraviolet radiation and/or TPA

    International Nuclear Information System (INIS)

    Pretell, J.O.; Cone, R.E.

    1985-01-01

    Previous studies in our laboratory demonstrated that several treatments that inhibited the ability of cells to stimulate the mixed lymphocyte reaction (MLR) also blocked the shedding of histocompatibility antigens and Ia antigens from murine spleen cells. In the present studies, one of these treatments, ultraviolet radiation (UV), was shown to cause an initial loss in the density of H-2K, IA, and IE antigens prior to the block in shedding observed after culture of these cells. Further analysis revealed that the UV-induced loss of antigens could be prevented by the presence of colchicine during irradiation. Biosynthetic analyses revealed the IA antigen synthesis was also inhibited in the UV-irradiated cells. Examination of the effects of a second agent, 12-0-tetradecanoylphorbol-13-acetate (TPA) on the turnover of histocompatibility antigens revealed that the biosynthesis and shedding of these antigens were accelerated by this agent. However, addition of TPA to UV-irradiated cells did not result in a reversal of the UV-induced block in biosynthesis of IA antigens. Results of immune function assays correlated with the biochemical studies: UV-irradiation inhibited the generation of the MLR, but TPA enhanced this reaction, and addition of TPA to mixed lymphocyte cultures with UV-irradiated stimulators did not reverse the UV-induced inhibition. These results suggest that, although the turnover of histocompatibility antigens may be affected by TPA and UV in an antagonistic fashion, additional factors other than the expression of histocompatibility antigens are operating in the inhibition of stimulation of an MLR by UV radiation or its enhancement by TPA

  20. Immunoendocrine alterations following Marine Corps Martial Arts training are associated with changes in moral cognitive processes.

    Science.gov (United States)

    Siedlik, Jacob A; Deckert, Jake A; Clopton, Aaron W; Gigliotti, Nicole; Chan, Marcia A; Benedict, Stephen H; Herda, Trent J; Gallagher, Philip M; Vardiman, John P

    2016-02-01

    Combined physical and psychological stress events have been associated with exacerbated endocrine responses and increased alterations in immune cell trafficking when compared to exercise stress alone. Military training programs are rigorous in nature and often purposefully delivered in environments combining high levels of both physical and mental stress. The objective of this study was to assess physiological and cognitive changes following U.S. Marine Corps Martial Arts training. Seven active-duty, male Marines were observed during a typical Marine Corps Martial Arts training session. Immune parameters, including immunomodulatory cytokines, and hormone concentrations were determined from blood samples obtained at baseline, immediately post training (IP) and at 15min intervals post-training to 1h (R15, R30, R45, R60). Assessments of cognitive moral functioning (moral judgment and intent) were recorded at intervals during recovery. There were significant fluctuations in immunoendocrine parameters. Peak endocrine measures were observed within the IP-R15 time interval. Distributions of circulating immune cells were significantly altered with neutrophils and all lymphocyte subsets elevated at IP. IFN-γ and IL-17a exhibited small, non-significant, parallel increases over the recovery period. Moral functioning was informed by different social identities during the recovery resulting in changes in moral decision-making. These data demonstrate that the Marine Corps Martial Arts Program induces significant alterations in lymphocyte and leukocyte distributions, but does not shift the balance of Th1/Th2 cytokines or induce a systemic inflammatory response. The program does, however, induce alterations in moral decision-making ability associated with the observed endocrine responses, even suggesting a potential interaction between one's social identities and endocrine responses upon moral decision-making. Copyright © 2015. Published by Elsevier Inc.

  1. Levetiracetam differentially alters CD95 expression of neuronal cells and the mitochondrial membrane potential of immune and neuronal cells in vitro

    Directory of Open Access Journals (Sweden)

    Susannah K Rogers

    2014-02-01

    Full Text Available Epilepsy is a neurological seizure disorder that affects over 100 million people worldwide. Levetiracetam, either alone, as monotherapy, or as adjunctive treatment, is widely used to control certain types of seizures. Despite its increasing popularity as a relatively safe and effective anti-convulsive treatment option, its mechanism(s of action are poorly understood. Studies have suggested neuronal, glial, and immune mechanisms of action. Understanding the precise mechanisms of action of Levetiracetam would be extremely beneficial in helping to understand the processes involved in seizure generation and epilepsy. Moreover, a full understanding of these mechanisms would help to create more efficacious treatments while minimizing side effects. The current study examined the effects of Levetiracetam on the mitochondrial membrane potential of neuronal and non-neuronal cells, in vitro, in order to determine if Levetiracetam influences metabolic processes in these cell types. In addition, this study sought to address possible immune-mediated mechanisms by determining if Levetiracetam alters the expression of immune receptor-ligand pairs. The results show that Levetiracetam induces expression of CD95 and CD178 on NGF-treated C17.2 neuronal cells. The results also show that Levetiracetam increases mitochondrial membrane potential on C17.2 neuronal cells in the presence of nerve growth factor. In contrast, Levetiracetam decreases the mitochondrial membrane potential of splenocytes and this effect was dependent on intact invariant chain, thus implicating immune cell interactions. These results suggest that both neuronal and non-neuronal anti-epileptic activities of Levetiracetam involve control over energy metabolism, more specifically, mΔΨ. Future studies are needed to further investigate this potential mechanism of action.

  2. Altered Immune Profiles of Natural Killer Cells in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Qiong-Fang Zhang

    Full Text Available Natural killer (NK cells are the main effective component of the innate immune system that responds to chronic hepatitis B (CHB infection. Although numerous studies have reported the immune profiles of NK cells in CHB patients, they are limited by inconsistent results. Thus, we performed a meta-analysis to characterize reliably the immune profiles of NK cells after CHB infection, specifically frequency, phenotype, and function.A literature search of the computer databases MEDLINE, PUBMED, EMBASE, and Cochrane Center Register of Controlled Trails was performed and 19 studies were selected. The standard mean difference (SMD and 95% confidence interval (CI of each continuous variable was estimated with a fixed effects model when I2 < 50% for the test for heterogeneity, or the random effects model otherwise. Publication bias was evaluated using Begg's and Egger's tests.The meta-analysis of publications that reported frequency of peripheral NK cells showed that NK cell levels in CHB patients were significantly lower compared with that of healthy controls. A higher frequency of CD56bright NK subsets was found in CHB patients, but the CD56dim NK subsets of CHB patients and healthy controls were similar. CHB patients before and after antiviral therapy with nucleotide analogues (NUCs showed no statistical difference in NK frequency. The activating receptors were upregulated, whereas inhibitory receptors were comparable in the peripheral NK cells of CHB individuals and healthy controls. NK cells of CHB patients displayed higher cytotoxic potency as evidenced by CD107a protein levels and conserved potency to produce interferon-gamma (IFNγ, compared with their healthy counterparts.Our results revealed that CHB patients had a lower frequency of NK cells compared with healthy individuals not treatable with antiviral NUC therapy. With an activating phenotype, NK cells in CHB patients showed better cytotoxic potency and conserved IFNγ production.

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

    Directory of Open Access Journals (Sweden)

    R. Andrew Shanely

    2016-08-01

    Full Text Available 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.

  4. Endocrine disruptors in female reproductive tract development and carcinogenesis

    OpenAIRE

    Ma, Liang

    2009-01-01

    Growing concerns over endocrine disrupting chemicals (EDCs) and their effects on human fetal development and adult health have promoted research into the underlying molecular mechanisms of endocrine disruption. Gene targeting technology has allowed insight into the genetic pathways governing reproductive tract development and how exposure to EDCs during a critical developmental window can alter reproductive tract development, potentially forming the basis for adult diseases. This review prima...

  5. Future oceanic warming and acidification alter immune response and disease status in a commercial shellfish species, Mytilus edulis L.

    Directory of Open Access Journals (Sweden)

    Clara L Mackenzie

    Full Text Available Increases in atmospheric carbon dioxide are leading to physical changes in marine environments including parallel decreases in ocean pH and increases in seawater temperature. This study examined the impacts of a six month exposure to combined decreased pH and increased temperature on the immune response and disease status in the blue mussel, Mytilus edulis L. Results provide the first confirmation that exposure to future acidification and warming conditions via aquarium-based simulation may have parallel implications for bivalve health. Collectively, the data suggests that temperature more than pH may be the key driver affecting immune response in M. edulis. Data also suggests that both increases in temperature and/or lowered pH conditions may lead to changes in parasite abundance and diversity, pathological conditions, and bacterial incidence in M. edulis. These results have implications for future management of shellfish under a predicted climate change scenario and future sustainability of shellfisheries. Examination of the combined effects of two stressors over an extended exposure period provides key preliminary data and thus, this work represents a unique and vital contribution to current research efforts towards a collective understanding of expected near-future impacts of climate change on marine environments.

  6. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  7. Management of endocrine orbitopathy

    International Nuclear Information System (INIS)

    Kahaly, G.J.

    2001-01-01

    Endocrine orbitopathy is the most common extrathyroidal manifestation of Basedow's disease and is characterized by a lymphocyte infiltration of the peribulbar space. Infiltrating and activated T cells react with orbital target cells and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema, and enlargement of the extra ocular muscels. Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with endocrine orbitopathy. Immunosuppressive treatment is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of thyroid eye disease. (orig.) [de

  8. The Bidirectional Relationship between Sleep and Immunity against Infections

    Directory of Open Access Journals (Sweden)

    Elizabeth G. Ibarra-Coronado

    2015-01-01

    Full Text Available Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.

  9. What Is Men's Endocrine Health?

    Science.gov (United States)

    ... Search form Search What is Men's Endocrine Health? Men's endocrine health incorporates physical activity and sound nutrition to maintain a strong body; however, a major emphasis includes male sexuality ...

  10. Sleep and the endocrine system.

    Science.gov (United States)

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Oral supplementation of Bifidobacterium longum strain BR-108 alters cecal microbiota by stimulating gut immune system in mice irrespectively of viability.

    Science.gov (United States)

    Makioka, Yuko; Tsukahara, Takamitsu; Ijichi, Tetsuo; Inoue, Ryo

    2018-03-20

    Effect on cecal microbiota and gene expression of various cytokines in ileal Peyer's patches and cecal tissues were compared between viable and heat-killed Bifidobacterium longum strain BR-108 (BR-108) using a mouse model. Irrespectively of viability, oral supplementation of BR-108 altered the cecal microbiota and stimulated gene expression of cytokines such as IL-6 and IL-10 in ileal Peyer's patches and cecal tissue of mice. In addition, BR-108 supplementation significantly affected the relative abundance of bacterial genera and family, Oscillospira, Bacteroides and S24-7. The abundance of these bacterial genera and family strongly correlated with gene expression induced by BR-108. This study demonstrated that the effect of heat-killed BR-108 on the mouse cecal microbiota is similar to that of viable BR-108, most likely due to stimulation of the gut immune system by both heat-killed and viable BR-108 is also similar.

  12. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  13. Imaging of endocrine system

    International Nuclear Information System (INIS)

    Das, B.K.; Noreen Norfaraheen Lee Abdullah

    2012-01-01

    In recent years, the role of nuclear medicine in the study of morphology and pathophysiology of various endocrine organs has greatly expanded. Newly developed radiopharmaceuticals, new instrumentation, innovative study designs and dual isotope techniques have contributed significantly to the evaluation of parathyroid and adrenal diseases. In selected cases, patients with metabolic bone disorders and infertility have greatly been benefited. (author)

  14. Endocrine System (For Parents)

    Science.gov (United States)

    ... Problems With the Endocrine System Print en español Sistema endócrino Although we rarely think about them, the ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  15. The Endocrine Machinery.

    Science.gov (United States)

    Fillman, David

    1987-01-01

    Promotes a reductionist approach to teaching about the endocrine system in high school biology and anatomy courses. Encourages the study of how hormones travel to the cells and affect them. Provides suggestions for activities and discussion questions, along with sample diagrams and flow charts. (TW)

  16. Pediatric endocrine surgery development

    Directory of Open Access Journals (Sweden)

    Ivan I. Dedov

    2017-12-01

    Full Text Available Department of pediatric surgery at the Endocrinology Research Centre has been around for nearly two years. During operation, surgical treatment has received more than 500 patients with various endocrine disorders. The article discusses modern diagnostic approaches and surgical options for diseases included in the new direction of pediatric surgery – endocrine surgery in children. There are discussions about options for radical treatment of Graves disease in children, positive and negative aspects of surgical and radioactive iodine treatment. Is own stats of postoperative hyperparathyroidism. Is proposed to optimize the algorithm of actions in identifying thyroid nodules in children. In primary hyperparathyroidism, the emphasis is on the complexity of the postoperative management of patients related to the feature of children’s age in determining the severity of the reactions on the water-electrolyte disorders. Separately reviewed the literature of the adrenal glands diseases in children, demonstrating their own clinical cases which required surgical intervention. The authors describe the possibilities of modern neurosurgical equipment in the Endocrinology Research Centre in operations on the pituitary gland in children. Patients of different age groups performed transnasal transsphenoidal removal of tumors of the chiasm-sellar region using endoscopic assistance. The article also cited research data of pancreas diseases and their surgical treatment. Much attention is paid to the gender section of endocrine surgery in children. Discusses the tactics in disorders of sex development, gonadal tumors in children, diseases of the breast. In conclusion outlines the prospects for the development of endocrine surgery in children.

  17. Nigerian Endocrine Practice: Submissions

    African Journals Online (AJOL)

    Original Articles should be restricted to clinical or basic studies, particularly translational research, which add new information to the etiology, treatment, and outcomes of endocrine disorders that have not been published previously. These manuscripts should be restricted to 3,500 words, no more than 40 references, and no ...

  18. Nigerian Endocrine Practice

    African Journals Online (AJOL)

    The journal accepts original contributions related to the practice and science of clinical endocrinology, articles updating the clinical endocrinologist on current areas of interest in the diagnosis and treatment of endocrine disorders, articles discussing dilemma facing endocrinologists in the clinical, social, and ethical arena of ...

  19. Endocrine diseases in ferrets

    NARCIS (Netherlands)

    Schoemaker, N.J.; van Zeeland, Y.R.A.

    2013-01-01

    SUMMARY Endocrine diseases are among the most commonly seen conditions in ferrets. Tumours of the islet cells in the pancreas, referred to as insulinomas, and tumours of the adrenal glands, referred to as hyperadrenocorticism, are more commonly described in this species than in any other species.

  20. Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

    Science.gov (United States)

    Anastasiadou, Eleni; Stroopinsky, Dina; Alimperti, Stella; Jiao, Alan L; Pyzer, Athalia R; Cippitelli, Claudia; Pepe, Giuseppina; Severa, Martina; Rosenblatt, Jacalyn; Etna, Marilena P; Rieger, Simone; Kempkes, Bettina; Coccia, Eliana M; Sui, Shannan J Ho; Chen, Christopher S; Uccini, Stefania; Avigan, David; Faggioni, Alberto; Trivedi, Pankaj; Slack, Frank J

    2018-06-26

    Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

  1. Carbendazim has the potential to induce oxidative stress, apoptosis, immunotoxicity and endocrine disruption during zebrafish larvae development.

    Science.gov (United States)

    Jiang, Jinhua; Wu, Shenggan; Wang, Yanhua; An, Xuehua; Cai, Leiming; Zhao, Xueping; Wu, Changxing

    2015-10-01

    Increasing evidence have suggested deleterious effects of carbendazim on reproduction, apoptosis, immunotoxicity and endocrine disruption in mice and rats, however, the developmental toxicity of carbendazim to aquatic organisms remains obscure. In the present study, we utilized zebrafish as an environmental monitoring model to characterize the effects of carbendazim on expression of genes related to oxidative stress, apoptosis, immunotoxicity and endocrine disruption during larval development. Different trends in gene expression were observed upon exposing the larvae to 4, 20, 100, and 500 μg/L carbendazim for 4 and 8d. The mRNA levels of catalase, glutathione peroxidase and manganese superoxide dismutase (CAT, GPX, and Mn/SOD) were up-regulated after exposure to different concentrations of carbendazim for 4 or 8d. The up-regulation of p53, Apaf1, Cas8 and the down-regulation of Bcl2, Mdm2, Cas3 in the apoptosis pathway, as well as the increased expression of cytokines and chemokines, including CXCL-C1C, CCL1, IL-1b, IFN, IL-8, and TNFα, suggested carbendazim might trigger apoptosis and immune response during zebrafish larval development. In addition, the alteration of mRNA expression of VTG, ERα, ERβ1, ERβ2, TRα, TRβ, Dio1, and Dio2 indicated the potential of carbendazim to induce endocrine disruption in zebrafish larvae. These data suggested that carbendazim could simultaneously induce multiple responses during zebrafish larval development, and bidirectional interactions among oxidative stress, apoptosis pathway, immune and endocrine systems might be present. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Sodium methyldithiocarbamate inhibits MAP kinase activation through toll-like receptor 4, alters cytokine production by mouse peritoneal macrophages, and suppresses innate immunity.

    Science.gov (United States)

    Pruett, Stephen B; Zheng, Qiang; Schwab, Carlton; Fan, Ruping

    2005-09-01

    Sodium methyldithiocarbamate (SMD; trade name, Metam Sodium) is an abundantly used soil fumigant that can cause adverse health effects in humans, including some immunological manifestations. The mechanisms by which SMD acts, and its targets within the immune system are not fully understood. Initial experiments demonstrated that SMD administered by oral gavage substantially decreased IL-12 production and increased IL-10 production induced by lipopolysaccharide in mice. The present study was conducted to further characterize these effects and to evaluate our working hypothesis that the mechanism for these effects involves alteration in signaling through toll-like receptor 4 and that this would suppress innate immunity to infection. SMD decreased the activation of MAP kinases and AP-1 but not NF-kappaB in peritoneal macrophages. The expression of mRNA for IL-1alpha, IL-1beta, IL-18, IFN-gamma, IL-12 p35, IL-12 p40, and macrophage migration inhibitory factor (MIF) was inhibited by SMD, whereas mRNA for IL-10 was increased. SMD increased the IL-10 concentration in the peritoneal cavity and serum and decreased the concentration of IL-12 p40 in the serum, peritoneal cavity, and intracellularly in peritoneal cells (which are >80% macrophages). Similar effects on LPS-induced cytokine production were observed following dermal administration of SMD. The major breakdown product of SMD, methylisothiocyanate (MITC), caused similar effects on cytokine production at dosages as low as 17 mg/kg, a dosage relevant to human exposure levels associated with agricultural use of SMD. Treatment of mice with SMD decreased survival following challenge with non-pathogenic Escherichia coli within 24-48 h, demonstrating suppression of innate immunity.

  3. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

    Science.gov (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  4. Host immunity, nutrition and coinfection alter longitudinal infection patterns of schistosomes in a free ranging African buffalo population.

    Directory of Open Access Journals (Sweden)

    Brianna R Beechler

    2017-12-01

    Full Text Available Schistosomes are trematode parasites of global importance, causing infections in millions of people, livestock, and wildlife. Most studies on schistosomiasis, involve human subjects; as such, there is a paucity of longitudinal studies investigating parasite dynamics in the absence of intervention. As a consequence, despite decades of research on schistosomiasis, our understanding of its ecology in natural host populations is centered around how environmental exposure and acquired immunity influence acquisition of parasites, while very little is known about the influence of host physiology, coinfection and clearance in the absence of drug treatment. We used a 4-year study in free-ranging African buffalo to investigate natural schistosome dynamics. We asked (i what are the spatial and temporal patterns of schistosome infections; (ii how do parasite burdens vary over time within individual hosts; and (iii what host factors (immunological, physiological, co-infection and environmental factors (season, location explain patterns of schistosome acquisition and loss in buffalo? Schistosome infections were common among buffalo. Microgeographic structure explained some variation in parasite burdens among hosts, indicating transmission hotspots. Overall, parasite burdens ratcheted up over time; however, gains in schistosome abundance in the dry season were partially offset by losses in the wet season, with some hosts demonstrating complete clearance of infection. Variation among buffalo in schistosome loss was associated with immunologic and nutritional factors, as well as co-infection by the gastrointestinal helminth Cooperia fuelleborni. Our results demonstrate that schistosome infections are surprisingly dynamic in a free-living mammalian host population, and point to a role for host factors in driving variation in parasite clearance, but not parasite acquisition which is driven by seasonal changes and spatial habitat utilization. Our study illustrates

  5. Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection.

    Science.gov (United States)

    Wu, Chun; Chen, Xiaopan; Shu, Jing; Lee, Chun-Ting

    2017-05-23

    Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data indicates that diabetic skin is characterized by increased expression of genes that are related to immune responses (CCL20, CXCL9, CXCL10, CXCL11, CXCL13, and CCL18), JAK/STAT signaling pathway (JAK3, STAT1, and STAT2), tumor necrosis factor superfamily (TNFSF10 and TNFSF15), and infectious disease pathways (OAS1, OAS2, OAS3, and IFIH1). Genes in cell adhesion molecules pathway (NCAM1 and L1CAM) and collagen family (PCOLCE2 and COL9A3) are downregulated, suggesting structural changes in the skin of T2DM. For the first time, to the best of our knowledge, this pioneer analytic study reports comprehensive unbiased gene expression changes and dysregulated pathways in the non-diseased skin of T2DM patients. This comprehensive understanding derived from whole-genome expression profiles could advance our knowledge in determining molecular targets for the prevention and treatment of T2DM-associated skin disorders.

  6. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

    Science.gov (United States)

    Straley, Megan E; Van Oeffelen, Wesley; Theze, Sarah; Sullivan, Aideen M; O'Mahony, Siobhain M; Cryan, John F; O'Keeffe, Gerard W

    2017-07-01

    The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Endocrine autoimmune disease: genetics become complex.

    Science.gov (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  8. OXIDATIVE STRESS-DEPENDENT ALTERED IMMUNE RESPONSES AND CELL DEATH IN SUBSTANTIA NIGRA AFTER OZONE EXPOSURE IN RAT

    Directory of Open Access Journals (Sweden)

    Selva eRivas - Arancibia

    2015-05-01

    Full Text Available Parkinson’s disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent 1 spectrophotometric analysis for protein oxidation; 2 western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and 3 immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson’s disease.

  9. Endocrine Abnormalities in Patients with Chronic Kidney Disease.

    Science.gov (United States)

    Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

    2015-01-01

    In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

  10. Diabetic and endocrine emergencies

    OpenAIRE

    Kearney, T; Dang, C

    2007-01-01

    Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004–5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hyperca...

  11. Radiotherapy of endocrine orbitopathy

    International Nuclear Information System (INIS)

    Weischedel, U.; Wieland, C.

    1985-01-01

    After a review of the history and a discussion of recent theories about pathogenesis of endocrine ophthalmopathy the authros give a report on their radiotherapeutical treatment results with cobalt-60-γ-rays in 50 patients. Amelioration was achieved in 50% of the cases, in the other 50% no progression was seen. Radiotherapy is of antiphlogistic and functional effectivity and should be integrated in the treatment regime in early stages. (orig.) [de

  12. [Endocrine function in obesity].

    Science.gov (United States)

    Álvarez-Castro, Paula; Sangiao-Alvarellos, Susana; Brandón-Sandá, Iria; Cordido, Fernando

    2011-10-01

    Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  13. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

    Science.gov (United States)

    Gericke, G S

    2010-05-01

    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  14. Occupational exposure to diesel engine exhaust and alterations in immune/inflammatory markers: a cross-sectional molecular epidemiology study in China.

    Science.gov (United States)

    Bassig, Bryan A; Dai, Yufei; Vermeulen, Roel; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Shiels, Meredith S; Kemp, Troy J; Pinto, Ligia A; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Wong, Jason Y Y; Bin, Ping; Hosgood, H Dean; Hildesheim, Allan; Silverman, Debra T; Rothman, Nathaniel; Zheng, Yuxin; Lan, Qing

    2017-10-26

    The relationship between diesel engine exhaust (DEE), a known lung carcinogen, and immune/inflammatory markers that have been prospectively associated with lung cancer risk is not well understood. To provide insight into these associations, we conducted a cross-sectional molecular epidemiology study of 54 males highly occupationally exposed to DEE and 55 unexposed male controls from representative workplaces in China. We measured plasma levels of 64 immune/inflammatory markers in all subjects using Luminex bead-based assays, and compared our findings to those from a nested case-control study of these markers and lung cancer risk, which had been conducted among never-smoking women in Shanghai using the same multiplex panels. Levels of nine markers that were associated with lung cancer risk in the Shanghai study were altered in DEE-exposed workers in the same direction as the lung cancer associations. Among these, associations with the levels of CRP (β= -0.53; P = 0.01) and CCL15/MIP-1D (β = 0.20; P = 0.02) were observed in workers exposed to DEE and with increasing elemental carbon exposure levels (Ptrends marker positively associated with an increased lung cancer risk, CCL2/MCP-1, were higher among DEE-exposed workers compared with controls in never and former smokers, but not in current smokers (Pinteraction = 0.01). The immunological differences in these markers in DEE-exposed workers are consistent with associations observed for lung cancer risk in a prospective study of Chinese women and may provide some insight into the mechanistic processes by which DEE causes lung cancer. Published by Oxford University Press 2017.

  15. Dietary β-glucan (MacroGard®) enhances survival of first feeding turbot (Scophthalmus maximus) larvae by altering immunity, metabolism and microbiota.

    Science.gov (United States)

    Miest, Joanna J; Arndt, Carmen; Adamek, Mikolaj; Steinhagen, Dieter; Reusch, Thorsten B H

    2016-01-01

    Reflecting the natural biology of mass spawning fish aquaculture production of fish larvae is often hampered by high and unpredictable mortality rates. The present study aimed to enhance larval performance and immunity via the oral administration of an immunomodulator, β-glucan (MacroGard(®)) in turbot (Scophthalmus maximus). Rotifers (Brachionus plicatilis) were incubated with or without yeast β-1,3/1,6-glucan in form of MacroGard(®) at a concentration of 0.5 g/L. Rotifers were fed to first feeding turbot larvae once a day. From day 13 dph onwards all tanks were additionally fed untreated Artemia sp. nauplii (1 nauplius ml/L). Daily mortality was monitored and larvae were sampled at 11 and 24 dph for expression of 30 genes, microbiota analysis, trypsin activity and size measurements. Along with the feeding of β-glucan daily mortality was significantly reduced by ca. 15% and an alteration of the larval microbiota was observed. At 11 dph gene expression of trypsin and chymotrypsin was elevated in the MacroGard(®) fed fish, which resulted in heightened tryptic enzyme activity. No effect on genes encoding antioxidative proteins was observed, whilst the immune response was clearly modulated by β-glucan. At 11 dph complement component c3 was elevated whilst cytokines, antimicrobial peptides, toll like receptor 3 and heat shock protein 70 were not affected. At the later time point (24 dph) an anti-inflammatory effect in form of a down-regulation of hsp 70, tnf-α and il-1β was observed. We conclude that the administration of MacroGard(®) induced an immunomodulatory response and could be used as an effective measure to increase survival in rearing of turbot. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

    Science.gov (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2014-01-01

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

  17. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?

    Science.gov (United States)

    Busse, Stefan; Busse, Mandy; Schiltz, Kolja; Bielau, Hendrik; Gos, Tomasz; Brisch, Ralf; Mawrin, Christian; Schmitt, Andrea; Jordan, Wolfgang; Müller, Ulf J; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

    2012-11-01

    Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain's mononuclear phagocyte system (microglial cells) is activated during acute psychosis. Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P=0.047, right: P=0.038; CD20: left: P=0.020, right: P=0.010) and controls (CD3: left: P=0.057, right: P=0.069; CD20: left: P=0.008, right: P=0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P=0.030, right: P=0.012). A similar trend emerged when this group was compared to controls (left: P=0.090, right: P=0.090). BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years

    Directory of Open Access Journals (Sweden)

    Jadrana T. F. Toich

    2018-01-01

    Full Text Available Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA and seed-based correlation analysis (SCA, we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC in 7 year old children. HIV infected (HIV+ children were from the Children with HIV Early Antiretroviral Therapy (CHER trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs between HIV+ and uninfected children (27 HIV+, 18 uninfected, whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate. Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FC increases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.

  19. Direct and indirect endocrine disruption : aromatase and estrogen receptor-mediated processes in breast cancer development

    NARCIS (Netherlands)

    Heneweer, Marjoke

    2005-01-01

    Endocrine disrupting chemicals (EDCs) have been defined by the World Health Organization as: “exogenous substances or mixtures that alters function(s) of the endocrine system and causes adverse health effects in an intact organism, or its progeny, or (sub)populations”. Synthetic, as well as,

  20. Distribution of intrahepatic T, NK and CD3(+)CD56(+)NKT cells alters after liver transplantation: Shift from innate to adaptive immunity?

    Science.gov (United States)

    Werner, Jens M; Lang, Corinna; Scherer, Marcus N; Farkas, Stefan A; Geissler, Edward K; Schlitt, Hans J; Hornung, Matthias

    2011-07-01

    The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances. Core biopsies of transplanted livers were stained with antibodies against CD3 and CD56. Several cell populations including T (CD3(+)CD56(-)), NK (CD3(-)CD56(+)) and NKT cells (CD3(+)CD56(+)) were studied by fluorescence microscopy. Cell numbers were analyzed in relation to the time interval after LTx, immunosuppressive therapy and stage of acute graft rejection (measured with the rejection activity index: RAI) compared to tumor free liver tissue from patients after liver resection due to metastatic disease as control. Recruitment of CD3(+)CD56(+)NKT cells revealed a significant decrease during high RAI scores in comparison to low and middle RAI scores (RAI 7-9: 0.03±0.01/HPF vs. RAI 4-6: 0.1±0.005/HPF). CD3(+)CD56(+)NKT cells were also lower during immunosuppressive therapy with tacrolimus (0.03±0.01/HPF) than with cyclosporine (0.1±0.003/HPF), cyclosporine/MMF (0.1±0.003/HPF) or sirolimus (0.1±0.01/HPF) treatment. Intrahepatic T cell numbers increased significantly 50days after LTx compared to control liver tissue (4.5±0.2/HPF vs. 1.9±0.1/HPF). In contrast, NK cells (0.3±0.004/HPF) were significantly fewer in all biopsies after LTx compared to the control (0.7±0.04/HPF). These data indicate significant alterations in the hepatic recruitment of T, NK and CD3(+)CD56(+)NKT cells after LTx. The increase in T cells and the decrease in NK and CD3(+)CD56(+)NKT cells suggest a shift from innate to adaptive hepatic immunity in the liver graft. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Psycho-Neuro-Endocrine-Immunology: A Psychobiological Concept.

    Science.gov (United States)

    França, Katlein; Lotti, Torello M

    2017-01-01

    Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) is a scientific field of study that investigates the link between bidirectional communications among the nervous system, the endocrine system, and the immune system and the correlations of this cross-talk with physical health. The P.N.E.I. innovative medical approach represents a paradigm shift from a strictly biomedical view of health and disease taken as hermetically sealed compartments to a more interdisciplinary one. The key element of P.N.E.I. approach is represented by the concept of bidirectional cross-talk between the psychoneuroendocrine and immune systems. The Low Dose Medicine is one of the most promising approaches able to allow the researchers to design innovative therapeutic strategies for the treatment of skin diseases based on the rebalance of the immune response.

  2. Radiological imaging in endocrine hypertension

    Directory of Open Access Journals (Sweden)

    Chandan J Das

    2011-01-01

    Full Text Available While different generations of assays have played important role in elucidating causes of different endocrine disorders, radiological techniques are instrumental in localizing the pathology. This statement cannot be truer in any disease entity other than endocrine hypertension. This review makes an effort to highlight the role of different radiological modalities, especially ultrasonography, computed tomography and magnetic resonance imaging, in the evaluation of different causes of endocrine hypertension.

  3. Fusobacterium nucleatum Alters Atherosclerosis Risk Factors and Enhances Inflammatory Markers with an Atheroprotective Immune Response in ApoE(null Mice.

    Directory of Open Access Journals (Sweden)

    Irina M Velsko

    Full Text Available The American Heart Association supports an association between periodontal disease (PD and atherosclerotic vascular disease (ASVD but does not as of yet support a causal relationship. Recently, we have shown that major periodontal pathogens Porphyromonas gingivalis and Treponema denticola are causally associated with acceleration of aortic atherosclerosis in ApoEnull hyperlipidemic mice. The aim of this study was to determine if oral infection with another significant periodontal pathogen Fusobacterium nucleatum can accelerate aortic inflammation and atherosclerosis in the aortic artery of ApoEnull mice. ApoEnull mice (n = 23 were orally infected with F. nucleatum ATCC 49256 and euthanized at 12 and 24 weeks. Periodontal disease assessments including F. nucleatum oral colonization, gingival inflammation, immune response, intrabony defects, and alveolar bone resorption were evaluated. Systemic organs were evaluated for infection, aortic sections were examined for atherosclerosis, and inflammatory markers were measured. Chronic oral infection established F. nucleatum colonization in the oral cavity, induced significant humoral IgG (P=0.0001 and IgM (P=0.001 antibody response (12 and 24 weeks, and resulted in significant (P=0.0001 alveolar bone resorption and intrabony defects. F. nucleatum genomic DNA was detected in systemic organs (heart, aorta, liver, kidney, lung indicating bacteremia. Aortic atherosclerotic plaque area was measured and showed a local inflammatory infiltrate revealed the presence of F4/80+ macrophages and CD3+ T cells. Vascular inflammation was detected by enhanced systemic cytokines (CD30L, IL-4, IL-12, oxidized LDL and serum amyloid A, as well as altered serum lipid profile (cholesterol, triglycerides, chylomicrons, VLDL, LDL, HDL, in infected mice and altered aortic gene expression in infected mice. Despite evidence for systemic infection in several organs and modulation of known atherosclerosis risk factors, aortic

  4. Neurobehavioral endocrine regulation of small mammal populations

    International Nuclear Information System (INIS)

    Christian, J.J.

    1978-01-01

    A brief review is given of the hypothesis that density-dependent behavioral-endocrine negative feedbacks can regulate and often limit the growth of populations of many species of small mammals. Recent laboratory studies are summarized that show how stress, particularly psychogenic, which results in increased adrenocortical secretion also alters gonadotropin secretion and inhibits reproduction. Chronic stress due to crowding, immobilization, et al. inhibits the release of LH and FSH, particularly by abolishing the pulsatile release of LH, and also causes a rise in prolactin (at least acutely). Stimulation of the hypothalamo-pituitary-adrenocortical system is accompanied by an inversely proportional inhibition of growth hormone secretion. Decreasing photoperiod enhances the sensitivity of the hypothalamus to inhibition of gonadotropin secretion by androgens and estrogens. Other endocrine responses to increased density or subordinate social rank also are summarized. How these facts fit into the negative feedback scheme is discussed, including the greatly prolonged effects of diminished lactation. The changed quality of the animals associated with changes in density discussed by Lidicker also can be explained by the above responses to density. Data on changes in growth and reproductive function which are consistent with the behavioral-endocrine feedback hypothesis are presented for several populations of small mammals, including some previously unpublished data for Microtus pennsylvanicus

  5. Effects of endocrine disrupting heavy metals on pituitary and ...

    African Journals Online (AJOL)

    Association of hypogonadism and visceral obesity (VO) was recently demonstrated in male auto-mechanics occupationally exposed to endocrine disruptors (ED)-lead, cadmium, mercury and arsenic, known to alter the hypothalamic-pituitary-testicular axis. The effects of exposure to these EDs on pituitary and gonadal ...

  6. Endocrine Disruptor Screening Program: Tier I Screening Battery

    Science.gov (United States)

    In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system,' the Food Quality Protection Act and subsequent amendments to the Safe Drinking Water Act and Federal Food, Drug and Cosmetic A...

  7. Two Virus Based Endocrine Disruptor Assays Effective Across Vertebrate Classes.

    Science.gov (United States)

    The presence of hormone mimics, or endocrine disrupting compounds (EDC’s), in the environment are increasing. Sources range from agricultural run–off, pharmaceuticals in waste water, to industrial operations. Current levels of contamination are sufficient to alter sexual develo...

  8. Metabolic targets of endocrine disrupting chemicals assessed by cord blood transcriptome profiling

    DEFF Research Database (Denmark)

    Remy, Sylvie; Govarts, Eva; Wens, Britt

    2016-01-01

    Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic...

  9. STRATEGIES TO REDUCE OR REPLACE THE USE OF ANIMALS IN THE ENDOCRINE SCREENING AND TESTING PROGRAM.

    Science.gov (United States)

    Abstract: The US Environmental Protection Agency (EPA) is developing a screening and testing program for endocrine disrupting chemicals (EDCs) to detect alterations of hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen and thyroid hormone synthesis and androgen (AR...

  10. Your Endocrine System (For Kids)

    Science.gov (United States)

    ... Kids / Your Endocrine System Print en español Tu sistema endocrino You might say endocrine (say: EN-doh- ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  11. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  12. Indoleamine 2,3-Dioxygenase (IDO) Enzyme Links Innate Immunity and Altered T-Cell Differentiation in Non-ST Segment Elevation Acute Coronary Syndrome.

    Science.gov (United States)

    Zara, Chiara; Severino, Anna; Flego, Davide; Ruggio, Aureliano; Pedicino, Daniela; Giglio, Ada Francesca; Trotta, Francesco; Lucci, Claudia; D'Amario, Domenico; Vinci, Ramona; Pisano, Eugenia; La Rosa, Giulio; Biasucci, Luigi Marzio; Crea, Filippo; Liuzzo, Giovanna

    2017-12-26

    Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS). The amount of tryptophan catabolite; kynurenine; was evaluated in the culture supernatants of mature-MDDCs by ELISA assay. Autologous mixed lymphocyte reaction (MLR) between mature-MDDCs and naïve T-cells was carried out to study the differentiation towards T-helper 1 (Th1) and induced regulatory T-cells (iTreg). Analysis of IDO mRNA transcripts in mature-MDDCs revealed a significant reduction in cells isolated from NSTEMI (625.0 ± 128.2; mean ± SEM) as compared with those from SA (958.5 ± 218.3; p = 0.041) and from HC (1183.6 ± 231.6; p = 0.034). Furthermore; the concentration of kynurenine was lower in NSTEMI patients (2.78 ± 0.2) and SA (2.98 ± 0.25) as compared with HC (5.1 ± 0.69 ng/mL; p = 0.002 and p = 0.016; respectively). When IDO-competent mature-MDDCs were co-cultured with allogeneic naïve T-cells, the ratio between the percentage of generated Th1 and iTreg was higher in NSTEMI (4.4 ± 2.9) than in SA (1.8 ± 0.6; p = 0.056) and HC (0.9 ± 0.3; p = 0.008). In NSTEMI, the tolerogenic mechanism of the immune response related to IDO production by activated MDDCs is altered, supporting their role in T-cell dysregulation.

  13. Indoleamine 2,3-Dioxygenase (IDO Enzyme Links Innate Immunity and Altered T-Cell Differentiation in Non-ST Segment Elevation Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Chiara Zara

    2017-12-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO, an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs from non-ST segment elevation myocardial infarction (NSTEMI patients, stable angina (SA patients and healthy controls (HC by real-time quantitative polymerase chain reaction (RT-qPCR before and after in vitro maturation with lipopolysaccharide (LPS. The amount of tryptophan catabolite; kynurenine; was evaluated in the culture supernatants of mature-MDDCs by ELISA assay. Autologous mixed lymphocyte reaction (MLR between mature-MDDCs and naïve T-cells was carried out to study the differentiation towards T-helper 1 (Th1 and induced regulatory T-cells (iTreg. Analysis of IDO mRNA transcripts in mature-MDDCs revealed a significant reduction in cells isolated from NSTEMI (625.0 ± 128.2; mean ± SEM as compared with those from SA (958.5 ± 218.3; p = 0.041 and from HC (1183.6 ± 231.6; p = 0.034. Furthermore; the concentration of kynurenine was lower in NSTEMI patients (2.78 ± 0.2 and SA (2.98 ± 0.25 as compared with HC (5.1 ± 0.69 ng/mL; p = 0.002 and p = 0.016; respectively. When IDO-competent mature-MDDCs were co-cultured with allogeneic naïve T-cells, the ratio between the percentage of generated Th1 and iTreg was higher in NSTEMI (4.4 ± 2.9 than in SA (1.8 ± 0.6; p = 0.056 and HC (0.9 ± 0.3; p = 0.008. In NSTEMI, the tolerogenic mechanism of the immune response related to IDO production by activated MDDCs is altered, supporting their role in T-cell dysregulation.

  14. Endocrine disorders in mitochondrial disease.

    Science.gov (United States)

    Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

    2013-10-15

    Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V

    2001-01-01

    of alkylphenols, these are disseminated in the environment with sewage sludge, and domestic animals and humans are likely to be exposed via the food chain. Using the pig as an in vivo model, we studied the effect of intrauterine exposure to tertiary octylphenol (OP) on essential reproductive parameters over 3......With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...

  16. Endocrine Actions of Osteocalcin

    Directory of Open Access Journals (Sweden)

    Aurora Patti

    2013-01-01

    Full Text Available Osteocalcin is the most abundant noncollagenous protein of bone matrix. Once transcribed, this protein undergoes posttranslational modifications within osteoblastic cells before its secretion, including the carboxylation of three glutamic residues in glutamic acid, which is essential for hydroxyapatite binding and deposition in the extracellular matrix of bone. Recent provocative data from experimental observations in mice showed that the circulating undercarboxylated fraction of osteocalcin increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral fat in both genders, while it enhances testosterone production by the testes in males. Moreover, both total and undercarboxylated osteocalcins increase following physical activity with potential positive effects on glucose tolerance. Despite that these evidences have been only in part confirmed in humans, further prospective investigations are needed to definitively establish the endocrine role of osteocalcin both in the general population and cohorts of patients with diabetes or other metabolic disorders.

  17. Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    2009-09-01

    Full Text Available Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens.Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response.These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.

  18. Immune disorders in anorexia

    OpenAIRE

    SŁOTWIŃSKA, SYLWIA MAŁGORZATA; SŁOTWIŃSKI, ROBERT

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters pla...

  19. Reproduction Alters Hydration State but Does Not Impact the Positive Effects of Dehydration on Innate Immune Function in Children's Pythons (Antaresia childreni).

    Science.gov (United States)

    Brusch, George A; Billy, Gopal; Blattman, Joseph N; DeNardo, Dale F

    Resource availability can impact immune function, with the majority of studies of such influences focusing on the allocation of energy investment into immune versus other physiological functions. When energy is a limited resource, performance trade-offs can result, compromising immunity. Dehydration is also considered a physiological challenge resulting from the limitation of a vital resource, yet previous research has found a positive relationship between dehydration and innate immune performance. However, these studies did not examine the effects of dehydration on immunity when there was another concurrent, substantial physiological challenge. Thus, we examined the impact of reproduction and water deprivation, individually and in combination, on immune performance in Children's pythons (Antaresia childreni). We collected blood samples from free-ranging A. childreni to evaluate osmolality and innate immune function (lysis, agglutination, bacterial growth inhibition) during the austral dry season, when water availability is limited and this species is typically reproducing. To examine how reproduction and water imbalance, both separately and combined, impact immune function, we used a laboratory-based 2 × 2 experiment. Our results demonstrate that A. childreni experience significant dehydration during the dry season and that, overall, osmolality, regardless of the underlying cause (seasonal rainfall, water deprivation, or reproduction), is positively correlated with increased innate immune performance.

  20. Hormones in the city: endocrine ecology of urban birds.

    Science.gov (United States)

    Bonier, Frances

    2012-05-01

    Urbanization dramatically changes the landscape, presenting organisms with novel challenges and often leading to reduced species diversity. Urban ecologists have documented numerous biotic and abiotic consequences of urbanization, such as altered climate, species interactions, and community composition, but we lack an understanding of the mechanisms underlying organisms' responses to urbanization. Here, I review findings from the nascent field of study of the endocrine ecology of urban birds. Thus far, no clear or consistent patterns have been revealed, but we do have evidence that urban habitat can shape endocrine traits, and that those traits might contribute to adaptation to the urban environment. I suggest strong approaches for future work addressing exciting questions about the role of endocrine traits in mediating responses to urbanization within species across the globe. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. What Is Women's Endocrine Health?

    Science.gov (United States)

    ... harness the power to prevent endocrine disorders, the Power of Prevention. Childhood Childhood is a time of rapid growth and development to learn healthy living habits and priorities. It can, however, be a great ...

  2. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert

    2008-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  3. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert

    2007-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  4. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert S

    2005-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40...

  5. Skin Manifestations of Endocrine Diseases.

    Science.gov (United States)

    Demirkesen, Cuyan

    2015-01-01

    Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

  6. Trauma and the endocrine system.

    Science.gov (United States)

    Mesquita, Joana; Varela, Ana; Medina, José Luís

    2010-12-01

    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  7. Respiratory manifestations in endocrine diseases

    OpenAIRE

    LENCU, CODRU?A; ALEXESCU, TEODORA; PETRULEA, MIRELA; LENCU, MONICA

    2016-01-01

    The control mechanisms of respiration as a vital function are complex: voluntary ? cortical, and involuntary ? metabolic, neural, emotional and endocrine. Hormones and hypothalamic neuropeptides (that act as neurotrasmitters and neuromodulators in the central nervous system) play a role in the regulation of respiration and in bronchopulmonary morphology. This article presents respiratory manifestations in adult endocrine diseases that evolve with hormone deficit or hypersecretion. In hyperthy...

  8. Endocrine myopathy: Case-based review

    Directory of Open Access Journals (Sweden)

    Babul Reddy Hanmayyagari

    2016-01-01

    Full Text Available Endocrine myopathy means muscle weakness in the presence of an abnormal endocrine state. Most of the endocrine disorders are associated with myopathy and it is usually reversible with correction of the underlying disturbance, though, there is an increasing knowledge of the metabolic effects of hormones, endocrine myopathy is a less recognized and often overlooked entity in clinical practice. Here, we describe this association in three of our patients, then, we discuss systematically about endocrine myopathy.

  9. Tributyltin: Advancing the science on assessing endocrine disruption with an unconventional endocrine-disrupting compound

    Science.gov (United States)

    Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ronald C.; Guiney, Patrick; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P.

    2018-01-01

    Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated—interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

  10. Tributyltin: Advancing the Science on Assessing Endocrine Disruption with an Unconventional Endocrine-Disrupting Compound.

    Science.gov (United States)

    Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ron; Guiney, Patrick D; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P

    Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

  11. Environmental endocrine disruptors: Effects on the human male reproductive system.

    Science.gov (United States)

    Sweeney, M F; Hasan, N; Soto, A M; Sonnenschein, C

    2015-12-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

  12. Immunity by equilibrium.

    Science.gov (United States)

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  13. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome.

    Science.gov (United States)

    Elsenbruch, Sigrid; Lucas, Ayscha; Holtmann, Gerald; Haag, Sebastian; Gerken, Guido; Riemenschneider, Natalie; Langhorst, Jost; Kavelaars, Annemieke; Heijnen, Cobi J; Schedlowski, Manfred

    2006-10-01

    Augmented neuroendocrine stress responses and altered immune functions may play a role in the manifestation of functional gastrointestinal (GI) disorders. We tested the hypothesis that IBS patients would demonstrate enhanced psychological and endocrine responses, as well as altered stress-induced redistribution of circulating leukocytes and lymphocytes, in response to an acute psychosocial stressor when compared with healthy controls. Responses to public speaking stress were analyzed in N = 17 IBS patients without concurrent psychiatric conditions and N = 12 healthy controls. At baseline, immediately following public speaking, and after a recovery period, state anxiety, acute GI symptoms, cardiovascular responses, serum cortisol and plasma adrenocorticotropic hormone (ACTH) were measured, and numbers of circulating leukocytes and lymphocyte subpopulations were analyzed by flow cytometry. Public speaking led to significant cardiovascular activation, a significant increase in ACTH, and a redistribution of circulating leukocytes and lymphocyte subpopulations, including significant increases in natural killer cells and cytotoxic/suppressor T cells. IBS patients demonstrated significantly greater state anxiety both at baseline and following public speaking. However, cardiovascular and endocrine responses, as well as the redistribution of circulating leukocytes and lymphocyte subpopulations after public speaking stress, did not differ for IBS patients compared with controls. In IBS patients without psychiatric comorbidity, the endocrine response as well as the circulation pattern of leukocyte subpopulations to acute psychosocial stress do not differ from healthy controls in spite of enhanced emotional responses. Future studies should discern the role of psychopathology in psychological and biological stress responses in IBS.

  14. Skeletal Muscle Insulin Resistance in Endocrine Disease

    Directory of Open Access Journals (Sweden)

    Melpomeni Peppa

    2010-01-01

    Full Text Available We summarize the existing literature data concerning the involvement of skeletal muscle (SM in whole body glucose homeostasis and the contribution of SM insulin resistance (IR to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS, adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

  15. Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

    Science.gov (United States)

    Morrot, Alexandre; Villar, Silvina R; González, Florencia B; Pérez, Ana R

    2016-01-01

    Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease.

  16. Scintigraphic imaging of endocrine organs

    International Nuclear Information System (INIS)

    Gross, M.D.; Shapiro, B.; Thrall, J.H.; Freitas, J.E.; Beierwaltes, W.H.

    1984-01-01

    The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach

  17. Pulmonary complications of endocrine and metabolic disorders.

    Science.gov (United States)

    Milla, Carlos E; Zirbes, Jacquelyn

    2012-03-01

    There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Endocrine tumor of the digestive tract - clinical case study

    International Nuclear Information System (INIS)

    Szwedziak, K.; Olejniczak, W.; Brichkovkiy, V.

    2008-01-01

    Introduction: Endocrine tumors of the digestive tract (ETDT) are neoplasms which stem from the APUD (amine precursors uptake and decarboxylation) cells. There are neuroendocrine pancreatic and gastroenteral carcinoid tumors which stand for 2% of digestive tract tumors, 0,5% of all human malignant neoplasms. All of them have secretion granulations in the cytoplasm. That is why a number of immune histochemic techniques is used in search for biogenic amines and hormones such as gastrin, CCK, GIP, VIP, motilin, glucagon, GRP, PP, GHRH and the others. In the majority of cases neuroendocrine tumors of the rectum are described as dysfunctional, which means that specific clinical symptoms are not connected with their hormonal overproduction. Material and methods: We describe a case of fifty seven years old male patient admitted to the Department of General and Transplant Surgery for the diagnosis and treatment of the rectal tumor. Per rectum examination revealed hard tumor. The pathologic examination of the biopsy taken from the lesion and CT scanning confirmed the presence of endocrine tumor of the digestive tract. Results: Anterior resection of the rectum was performed, the postoperative course was uneventful. At present patient is subjected to complementary treatment with the use of somatostatin analogue of the prolonged action. Conclusion: The endocrine tumors of the rectum are extremely rare, they occur in this localization in 0,26-0,52 out of 100.000 all rectal tumors. Diagnosis is usually made upon the microscopic examination and the immune histochemic reactions. (author)

  19. Psychosocial approach to endocrine disease.

    Science.gov (United States)

    Sonino, Nicoletta; Tomba, Elena; Fava, Giovanni A

    2007-01-01

    In recent years, there has been growing interest in the psychosocial aspects of endocrine disease, such as the role of life stress in the pathogenesis of some conditions, their association with affective disorders, and the presence of residual symptoms after adequate treatment. In clinical endocrinology, exploration of psychosocial antecedents may elucidate the temporal relationships between life events and symptom onset, as it has been shown to be relevant for pituitary (Cushing's disease, hyperprolactinemia) or thyroid (Graves' disease) conditions, as well as the role of allostatic load, linked to chronic stress, in uncovering a person's vulnerability. After endocrine abnormalities are established, they are frequently associated with a wide range of psychological symptoms: at times, such symptoms reach the level of psychiatric illness (mainly mood and anxiety disorders); at other times, however, they can only be identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR). Indeed, in a population study, the majority of patients suffered from at least one of the three DCPR syndromes considered: irritable mood, demoralization, persistent somatization. In particular, irritable mood was found to occur in 46% of 146 patients successfully treated for endocrine conditions, a rate similar to that found in cardiology and higher than in oncology and gastroenterology. Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses. In patients who showed persistence or even worsening of psychological distress upon proper endocrine treatment, the value of appropriate psychiatric interventions was underscored. As it happened in other fields of clinical medicine, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary for improving

  20. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

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    Cribbs David H

    2008-04-01

    Full Text Available Abstract Background Inflammation is associated with Aβ pathology in Alzheimer's disease (AD and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months Tg2576 mice to a response that reduces Aβ pathology. Methods TG (n = 29 and WT (n = 27 mice were divided into sedentary (SED and exercised (RUN groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. Results IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED mice than in wildtype (WTSED (p = 0.04, p = 0.006. Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07. Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01 and soluble fibrillar Aβ (p = 0.01 were observed in the exercised transgenic animals. Conclusion Exercise shifts the immune response from innate to an adaptive or

  1. Systemic dystrophic alterations of skeleton

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

    1984-01-01

    A roentgenologic picture of dystrophic alterations of bones following hard, acute and chronic infections diseases, distinct disorders of vitanium balance, diseases of endocrine system, disorder of metabolism and diet, long-term exogenous intoxications including medicinal is given. Distinct dystrophic disorders are characterized both by quantitative and qualitative deviations in physiological change of bones

  2. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Endocrine ophthalmopathy and radioiodine therapy

    International Nuclear Information System (INIS)

    Karlsson, F. Anders

    2006-01-01

    Endocrine ophthalmopathy is to some degree present in most patients with Graves' disease. In few cases, a severe form of the condition develops and in the majority of these cases, the course of the eye problems has been influenced by the treatment for thyrotoxicosis. In this regard, radioiodine therapy has been increasingly recognized as carrying a special risk. Here, the current understanding of endocrine ophthalmopathy and the risks associated with the development of severe eye disease are discussed. The results of a retrospective investigation of patients with severe eye disease in our hospital, and the experience with corticosteroid administration following radioiodine in order to reduce the risk of ophthalmopathy, are also presented

  4. Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio).

    Science.gov (United States)

    Jianjie, Chen; Wenjuan, Xue; Jinling, Cao; Jie, Song; Ruhui, Jia; Meiyan, Li

    2016-02-01

    Excessive fluoride in natural water ecosystem has the potential to detrimentally affect thyroid endocrine system, but little is known of such effects or underlying mechanisms in fish. In the present study, we evaluated the effects of fluoride on growth performance, thyroid histopathology, thyroid hormone levels, and gene expressions in the HPT axis in male zebrafish (Danio rerio) exposed to different determined concentrations of 0.1, 0.9, 2.0 and 4.1 M of fluoride to investigate the effects of fluoride on thyroid endocrine system and the potential toxic mechanisms caused by fluoride. The results indicated that the growth of the male zebrafish used in the experiments was significantly inhibited, the thyroid microtrastructure was changed, and the levels of T3 and T4 were disturbed in fluoride-exposed male fish. In addition, the expressional profiles of genes in HPT axis displayed alteration. The expressions of all studied genes were significantly increased in all fluoride-exposed male fish after exposure for 45 days. The transcriptional levels of corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSH), thyroglobulin (TG), sodium iodide symporter (NIS), iodothyronine I (DIO1), and thyroid hormone receptor alpha (TRα) were also elevated in all fluoride-exposed male fish after 90 days of exposure, while the inconsistent expressions were found in the mRNA of iodothyronineⅡ (DIO2), UDP glucuronosyltransferase 1 family a, b (UGT1ab), transthyretin (TTR), and thyroid hormone receptor beta (TRβ). These results demonstrated that fluoride could notably inhibit the growth of zebrafish, and significantly affect thyroid endocrine system by changing the microtrastructure of thyroid, altering thyroid hormone levels and endocrine-related gene expressions in male zebrafish. All above indicated that fluoride could pose a great threat to thyroid endocrine system, thus detrimentally affected the normal function of thyroid of male zebrafish. Copyright © 2015

  5. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  6. Occupational exposure to diesel engine exhaust and alterations in immune/inflammatory markers : a cross-sectional molecular epidemiology study in China

    NARCIS (Netherlands)

    Bassig, Bryan A.; Dai, Yufei; Vermeulen, Roel; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Shiels, Meredith S; Kemp, Troy J; Pinto, Ligia A; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Wong, Jason Y Y; Li, Ping; Hosgood, H. Dean; Hildesheim, Allan; Silverman, Debra T.; Rothman, Nathaniel; Zheng, Yuxin; Lan, Qing

    2017-01-01

    The relationship between diesel engine exhaust (DEE), a known lung carcinogen, and immune/inflammatory markers that have been prospectively associated with lung cancer risk is not well understood. To provide insight into these associations, we conducted a cross-sectional molecular epidemiology study

  7. Endocrine emergencies in dogs and cats.

    Science.gov (United States)

    Koenig, Amie

    2013-07-01

    Success in treatment of endocrine emergencies is contingent on early recognition and treatment. Many endocrine diseases presenting emergently have nonspecific signs and symptoms. In addition, these endocrine crises are often precipitated by concurrent disease, further making early identification difficult. This article concentrates on recognition and emergency management of the most common endocrine crises in dogs and cats. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Vitamin A, endocrine tissues and hormones: interplay and interactions

    Directory of Open Access Journals (Sweden)

    J Brossaud

    2017-09-01

    Full Text Available Vitamin A (retinol is a micronutrient critical for cell proliferation and differentiation. In adults, vitamin A and metabolites such as retinoic acid (RA play major roles in vision, immune and brain functions and tissue remodelling and metabolism. This review presents the physiological interactions of retinoids and endocrine tissues and hormonal systems. Two endocrine systems have been particularly studied. In the pituitary, retinoids target the corticotrophs with a possible therapeutic use in corticotropinomas. In the thyroid, retinoids interfere with iodine metabolism and vitamin A deficiency aggravates thyroid dysfunction caused by iodine-deficient diets. Retinoids use in thyroid cancer appears less promising than expected. Recent and still controversial studies investigated the relations between retinoids and metabolic syndrome. Indeed, retinoids contribute to pancreatic development and modify fat and glucose metabolism. However, more detailed studies are needed before planning any therapeutic use. Finally, retinoids probably play more minor roles in adrenal and gonads development and function apart from their major effects on spermatogenesis.

  9. Altered Immune Response of the Rice Frog Fejervarya limnocharis Living in Agricultural Area with Intensive Herbicide Utilization at Nan Province, Thailand

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    Khattapan Jantawongsri

    2015-01-01

    Full Text Available Herbicides (atrazine, glyphosate and paraquat have been intensively used in Nan Province for a long time. Prior observations indicated that herbicide contamination and adverse health effects were found on the rice frog Fejervarya limnocharis living in paddy fields at Nan Province. Contamination of herbicides may influence disease emergence by acting directly or indirectly upon the immune system of amphibian or by causing disruptions in homeostasis, it is thus interesting to investigate potential effects of herbicide contamination in Nan Province on immune responses of the rice frog living in agricultural areas. Frogs were caught from a paddy field with no history of herbicide utilization (reference site and a paddy field with intensive herbicide utilization (contaminated site during 2010-2011. After dissection, frog livers were fixed in 10% neutral buffer formalin, processed by paraffin method and stained with hematoxylin and eosin. Number of melanomacrophage and melanomacrophage center (MMC were counted under a light microscope and used as markers of non-specific immune response. It was found that there was no significant sex-related difference in these numbers. However, there were significant seasonal differences in these numbers in both reference and contaminated site frogs, suggesting that seasonal difference in herbicide usage tend to affect frog's immune system in agricultural areas. Furthermore, numbers of melanomacrophage and MMC in early wet, late wet and early dry periods were markedly higher in the contaminated site frogs compared to those of the reference site frogs. The observation on amphibian's immune response to environmental contaminants could indicate the impacts of herbicide utilization on other vertebrates, as well as its role in amphibian declines.

  10. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were

  11. Multiple endocrine neoplasia type I

    International Nuclear Information System (INIS)

    Fischer, H.J.; Lois, J.F.; Gomes, A.S.

    1985-01-01

    A case of multiple endocrine neoplasia (Men) consisting of an unusual combination of an insulin-producing islet cell tumour and an adrenal adenoma is reported. CT clearly demonstrated the adrenal mass whereas the pancreatic lesion remained questionable. Conversely angiography located the pancreatic tumour but the adrenal findings were subtle. (orig.)

  12. The Vitamin D Endocrine System.

    Science.gov (United States)

    Norman, Anthony W.

    1985-01-01

    Discusses the physiology and biochemistry of the vitamin D endocrine system, including role of biological calcium and phosphorus, vitamin D metabolism, and related diseases. A 10-item, multiple-choice test which can be used to obtain continuing medical education credit is included. (JN)

  13. Endocrine control of epigenetic mechanisms in male reproduction.

    Science.gov (United States)

    Ankolkar, Mandar; Balasinor, N H

    2016-01-01

    Endocrine control of reproduction is very well known and has been echoed by many research groups. However, recent developments point to the ability of toxic endocrine disrupting chemicals (EDC) to alter epigenetic information of the gametes which gets transferred to the developing embryo and affects the immediate reproductive outcome or even persists transgenerationally. These epigenetic aberrations contribute to the ensuing pathophysiology of reproductive disorders. Investigations of the female in cases of poor reproductive outcome have been the main strategy towards diagnosis. However, despite the male partner contributing half of his genome to the progeny, thorough investigations in the male have been ignored. Environmental pollutants are all pervading and are encountered in our day-to-day life. Many of these pollutants have potential to disrupt the endocrine system. Here, we discuss how the male gametes (spermatozoa) are susceptible to a myriad of epigenetic insults inflicted by exposure to endocrine disruptors and how important is the contribution of the epigenetic marks of the spermatozoa in healthy reproduction. We advocate that sperm epigenetics should be considered as a significant contributor to reproductive health and should be researched further and be subsequently included in routine diagnostic workup in cases of poor reproductive outcome.

  14. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  15. Endocrine Regulation of T-cell Development and Peripheral T-cell Maturation

    OpenAIRE

    Weerd, Kim

    2013-01-01

    markdownabstract__Abstract__ During the last century a large number of studies have demonstrated that complex interplay exists between the immune and the neuro-endocrine systems. This interplay, via shared cytokines, hormones and their respective receptors and nervous innervations, results in a highly organized integrated surveillance system capable of preserving homeostasis of the body to a large numbers of disturbances. Within this surveillance system the immune system recognizes external (...

  16. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner.

    Science.gov (United States)

    Doerflinger, Sylvie Y; Throop, Andrea L; Herbst-Kralovetz, Melissa M

    2014-06-15

    Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia). Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Endocrine Regulation of T-cell Development and Peripheral T-cell Maturation

    NARCIS (Netherlands)

    K. van der Weerd (Kim)

    2013-01-01

    markdownabstract__Abstract__ During the last century a large number of studies have demonstrated that complex interplay exists between the immune and the neuro-endocrine systems. This interplay, via shared cytokines, hormones and their respective receptors and nervous innervations, results in a

  18. B cell, CD8 + T cell and gamma delta T cell infiltration alters alveolar immune cell homeostasis in HIV-infected Malawian adults [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Andrew Mwale

    2017-12-01

    Full Text Available Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI. However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p<0.05. In contrast, there was no difference in the numbers of alveolar CD4 + T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065. Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%, while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (1 × 10 5 vs. 2.8 × 10 5 cells/100ml of BAL fluid, p=0.0001. The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p<0.05. Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.

  19. Endocrine Regulation of Compensatory Growth in Fish

    Directory of Open Access Journals (Sweden)

    Eugene T. Won

    2013-07-01

    Full Text Available Compensatory growth (CG is a period of accelerated growth that occurs following the alleviation of growth-stunting conditions during which an organism can make up for lost growth opportunity and potentially catch-up in size with non-stunted cohorts. Fish show a particularly robust capacity for the response and have been the focus of numerous studies that demonstrate their ability to compensate for periods of fasting once food is made available again. Compensatory growth is characterized by an elevated growth rate resulting from enhanced feed intake, mitogen production and feed conversion efficiency. Because little is known about the underlying mechanisms that drive the response, this review describes the sequential endocrine adaptations that lead to CG; namely during the precedent catabolic phase (fasting that taps endogenous energy reserves, and the following hyperanabolic phase (refeeding when accelerated growth occurs. In order to elicit a CG response, endogenous energy reserves must first be moderately depleted, which alters endocrine profiles that enhance appetite and growth potential. During this catabolic phase, elevated ghrelin and growth hormone (GH production increase appetite and protein-sparing lipolysis, while insulin-like growth factors (IGFs are suppressed, primarily due to hepatic GH resistance. During refeeding, temporal hyperphagia provides an influx of energy and metabolic substrates that are then allocated to somatic growth by resumed IGF signaling. Under the right conditions, refeeding results in hyperanabolism and a steepened growth trajectory relative to constantly fed controls. The response wanes as energy reserves are re-accumulated and homeostasis is restored. We ascribe possible roles for select appetite and growth-regulatory hormones in the context of these catabolic and hyperanabolic phases of the CG response in teleosts, with emphasis on GH, IGFs, cortisol, somatostatin, neuropeptide Y, ghrelin and leptin.

  20. Altered IFN-γ-mediated immunity and transcriptional expression patterns in N-Ethyl-N-nitrosourea-induced STAT4 mutants confer susceptibility to acute typhoid-like disease.

    Science.gov (United States)

    Eva, Megan M; Yuki, Kyoko E; Dauphinee, Shauna M; Schwartzentruber, Jeremy A; Pyzik, Michal; Paquet, Marilène; Lathrop, Mark; Majewski, Jacek; Vidal, Silvia M; Malo, Danielle

    2014-01-01

    Salmonella enterica is a ubiquitous Gram-negative intracellular bacterium that continues to pose a global challenge to human health. The etiology of Salmonella pathogenesis is complex and controlled by pathogen, environmental, and host genetic factors. In fact, patients immunodeficient in genes in the IL-12, IL-23/IFN-γ pathway are predisposed to invasive nontyphoidal Salmonella infection. Using a forward genomics approach by N-ethyl-N-nitrosourea (ENU) germline mutagenesis in mice, we identified the Ity14 (Immunity to Typhimurium locus 14) pedigree exhibiting increased susceptibility following in vivo Salmonella challenge. A DNA-binding domain mutation (p.G418_E445) in Stat4 (Signal Transducer and Activator of Transcription Factor 4) was the causative mutation. STAT4 signals downstream of IL-12 to mediate transcriptional regulation of inflammatory immune responses. In mutant Ity14 mice, the increased splenic and hepatic bacterial load resulted from an intrinsic defect in innate cell function, IFN-γ-mediated immunity, and disorganized granuloma formation. We further show that NK and NKT cells play an important role in mediating control of Salmonella in Stat4(Ity14/Ity14) mice. Stat4(Ity14/Ity14) mice had increased expression of genes involved in cell-cell interactions and communication, as well as increased CD11b expression on a subset of splenic myeloid dendritic cells, resulting in compromised recruitment of inflammatory cells to the spleen during Salmonella infection. Stat4(Ity14/Ity14) presented upregulated compensatory mechanisms, although inefficient and ultimately Stat4(Ity14/Ity14) mice develop fatal bacteremia. The following study further elucidates the pathophysiological impact of STAT4 during Salmonella infection.

  1. Genetics of Common Endocrine Disease: The Present and the Future.

    Science.gov (United States)

    Goodarzi, Mark O

    2016-03-01

    In honor of the 75th issue of the Journal of Clinical Endocrinology and Metabolism, the author was invited to present his perspectives on genetics in human endocrinology. This paper reviews what the field has achieved in the genetics of common endocrine disease, and offers predictions on where the field will move in the future and its impact on endocrine clinical practice. The October 2015 data release of the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Catalog of Published Genome-wide Association Studies was queried regarding endocrinologic diseases and traits. PubMed searches were focused on genetic prediction of disease, genetic findings and drug targets, functional interrogation of genetic loci, use of genetics to subtype disease, missing heritability, systems genomics, and higher order chromatin structures as regulators of gene function. Nearly a quarter of genome wide association study findings concern endocrinologic diseases and traits. While these findings have not yet dramatically altered clinical care, genetics will have a major impact by providing the drug targets of tomorrow, facilitated by experimental and bioinformatic advances that will shorten the time from gene discovery to drug development. Use of genetic findings to subtype common endocrine disease will allow more precise prevention and treatment efforts. Future advances will allow us to move away from the common view of DNA as a string of letters, allowing exploration of higher order structure that likely explains much "missing heritability." The future will see a greater role of genetics at the bedside, with genetic epidemiologic discoveries leading not only to new treatments of endocrine disease, but also helping us prescribe the right drug to the right patients by allowing subclassification of common heterogeneous endocrine conditions. Future technological breakthroughs will reveal the heritable mysteries hidden in chromatin structure, leading to a

  2. Sympathetic and Catecholaminergic Alterations in Sleep Apnea with Particular Emphasis on Children.

    Directory of Open Access Journals (Sweden)

    Fahed eHakim

    2012-01-01

    Full Text Available Sleep is involved in the regulation of major organ functions in the human body, and disruption of sleep potentially can elicit organ dysfunction. Obstructive sleep apnea (OSA is the most prevalent sleep disorder of breathing in adults and children, and its manifestations reflect the interactions between intermittent hypoxia (IH, intermittent hypercapnia, increased intra-thoracic pressure swings, and sleep fragmentation, as elicited by the episodic changes in upper airway resistance during sleep. The sympathetic nervous system is an important modulator of the cardiovascular, immune, endocrine and metabolic systems, and alterations in autonomic activity may lead to metabolic imbalance and organ dysfunction. Here we review how OSA and its constitutive components can lead to perturbation of the autonomic nervous system in general, and to altered regulation of catecholamines, both of which then playing an important role in some of the mechanisms underlying OSA-induced morbidities.

  3. Radiological imaging of endocrine diseases

    International Nuclear Information System (INIS)

    Bruneton, J.N.

    1999-01-01

    Imaging studies are playing an increasingly role in the evaluation of endocrine diseases; accordingly, familiarity with the specific indications for the various modalities, and with the characteristic findings, is essential. This multi-author work, which is intended for both radiologists and endocrinologists, considers the role of all the recent imaging techniques, including ultrasound (particular color Doppler), computed tomography, MRI, and scintigraphy. Following an extensive introduction on the pituitary, subsequent chapters discuss in detail the normal anatomy and pathology of the female and male reproductive systems. Remaining chapters provide state-of-the-art data on the thyroid, parathyroids, pancreatic endocrine tumors, adrenal glands, hormonal tumors (carcinoids and MEN), and imaging of the complications of hormone therapy. (orig.)

  4. Specifying pancreatic endocrine cell fates.

    Science.gov (United States)

    Collombat, Patrick; Hecksher-Sørensen, Jacob; Serup, Palle; Mansouri, Ahmed

    2006-07-01

    Cell replacement therapy could represent an attractive alternative to insulin injections for the treatment of diabetes. However, this approach requires a thorough understanding of the molecular switches controlling the specification of the different pancreatic cell-types in vivo. These are derived from an apparently identical pool of cells originating from the early gut endoderm, which are successively specified towards the pancreatic, endocrine, and hormone-expressing cell lineages. Numerous studies have outlined the crucial roles exerted by transcription factors in promoting the cell destiny, defining the cell identity and maintaining a particular cell fate. This review focuses on the mechanisms regulating the morphogenesis of the pancreas with particular emphasis on recent findings concerning the transcription factor hierarchy orchestrating endocrine cell fate allocation.

  5. Afferent Endocrine Control of Eating

    DEFF Research Database (Denmark)

    Langhans, Wolfgang; Holst, Jens Juul

    2016-01-01

    The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

  6. Early and late endocrine effects in pediatric central nervous system diseases.

    Science.gov (United States)

    Aslan, Ivy R; Cheung, Clement C

    2014-01-01

    Endocrinopathies are frequently linked to central nervous system disease, both as early effects prior to the disease diagnosis and/or late effects after the disease has been treated. In particular, tumors and infiltrative diseases of the brain and pituitary, such as craniopharyngioma, optic pathway and hypothalamic gliomas, intracranial germ cell tumor, and Langerhans cell histiocytosis, can present with abnormal endocrine manifestations that precede the development of neurological symptoms. Early endocrine effects include diabetes insipidus, growth failure, obesity, and precocious or delayed puberty. With improving prognosis and treatment of childhood brain tumors, many survivors experience late endocrine effects related to medical and surgical interventions. Chemotherapeutic agents and radiation therapy can affect the hypothalamic-pituitary axes governing growth, thyroid, gonadal, and adrenal function. In addition, obesity and metabolic alterations are frequent late manifestations. Diagnosing and treating both early and late endocrine manifestations can dramatically improve the growth, well-being, and quality of life of patients with childhood central nervous system diseases.

  7. Endocrine manifestations of celiac disease

    Directory of Open Access Journals (Sweden)

    R Philip

    2012-01-01

    Full Text Available Background: Celiac disease can have extra gastrointestinal tract (GIT presentations, most of which are endocrine. The aim of this study was to present patients diagnosed to have celiac disease from an endocrine department and to study the prevalence of endocrinopathies in celiac disease. Materials and Methods: A total of 36 patients from the endocrinology department (LLRM Medical College, Meerut between January 2011 and July 2012 and who were diagnosed to have celiac disease were included in the study. Results: Short stature was the commonest presentation (25%, other presentations included short stature and delayed puberty (20%, delayed puberty (11%, screening for celiac disease in type-1 DM patients (17%, rickets (6%, anemia not responding to oral therapy (6%, type-1 DM with recurrent hypoglycaemia (6%, and osteomalacia (3%. The endocrine manifestations include (after complete evaluation short stature (58%, delayed puberty (31%, elevated alkaline phospahatase (67%, low calcium (22%, X-rays suggestive of osteomalacia or rickets (8%, capopedal spasm (6%, and night blindness (6%. Anti-TPO antibody positivity was found in 53%, hypothyroidism in 28%, subclinical hypothyroidism in 17%, and type-1 DM in 25% of the patients. A total of 14% patients had no GI symptoms. Conclusion: Celiac disease is an endocrine disrupter as well as the great masquerader having varied presentations including short stature, delayed puberty, and rickets. Some patients who have celiac disease may not have any GI symptoms, making the diagnosis all the more difficult. Also, there is significant incidence of celiac disease with hypothyroidism and type-1 DM, making screening for it important in these diseases.

  8. Pituitary autoantibodies in endocrine disorders

    OpenAIRE

    Bensing, Sophie

    2005-01-01

    Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid...

  9. Alterations in polyadenylation and its implications for endocrine disease

    DEFF Research Database (Denmark)

    Rehfeld, Anders Aagaard; Plass, Mireya; Krogh, Anders

    2013-01-01

    Introduction: Polyadenylation is the process in which the pre-mRNA is cleaved at the poly(A) site and a poly(A) tail is added - a process necessary for normal mRNA formation. Genes with multiple poly(A) sites can undergo alternative polyadenylation (APA), producing distinct mRNA isoforms with dif......Introduction: Polyadenylation is the process in which the pre-mRNA is cleaved at the poly(A) site and a poly(A) tail is added - a process necessary for normal mRNA formation. Genes with multiple poly(A) sites can undergo alternative polyadenylation (APA), producing distinct mRNA isoforms...... with different 3' untranslated regions (3' UTRs) and in some cases different coding regions. Two thirds of all human genes undergo APA. The efficiency of the polyadenylation process regulates gene expression and APA plays an important part in post-transcriptional regulation, as the 3' UTR contains various cis...

  10. SLEEP APNEA IN ENDOCRINE DISORDERS

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    I. V. Misnikova

    2016-01-01

    Full Text Available In the recent years, an association between sleep apnea and a  number of endocrine diseases has been established. The secretion of many hormones after falling asleep is considerably changed, compared to the period of wakefulness. In patients with endocrine disorders, abnormal hormonal secretion and its pathological consequences may contribute to sleep apnea. Sleep fragmentation and intermittent hypoxia arising in sleep apnea result in a decrease in insulin sensitivity, which contributes to the development of type 2 diabetes mellitus. The prevalence of sleep apnea increases in acromegaly, which may affect the risk of cardio-pulmonary complications. There is an association between sleep apnea and testosterone treatment in men, as well as in postmenopausal women. Sleep apnea in hypothyroidism is most frequently related to the development of hypothyroidism per se and can therefore be reversed with thyroid hormone replacement therapy. Timely detection and treatment of sleep apnea in patients with endocrine disorders can improve their survival prognosis and quality of life.

  11. Endocrine manifestations in celiac disease.

    Science.gov (United States)

    Freeman, Hugh James

    2016-10-14

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.

  12. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

    Science.gov (United States)

    Chappell, V. A.; Fenton, S. E.; Flaws, J. A.; Nadal, A.; Prins, G. S.; Toppari, J.; Zoeller, R. T.

    2015-01-01

    The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans—especially during development—may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the

  13. Spectrum of Endocrine Disorders in Central Ghana

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    Osei Sarfo-Kantanka

    2017-01-01

    Full Text Available Background. Although an increasing burden of endocrine disorders is recorded worldwide, the greatest increase is occurring in developing countries. However, the spectrum of these disorders is not well described in most developing countries. Objective. The objective of this study was to profile the frequency of endocrine disorders and their basic demographic characteristics in an endocrine outpatient clinic in Kumasi, central Ghana. Methods. A retrospective review was conducted on endocrine disorders seen over a five-year period between January 2011 and December 2015 at the outpatient endocrine clinic of Komfo Anokye Teaching Hospital. All medical records of patients seen at the endocrine clinic were reviewed by endocrinologists and all endocrinological diagnoses were classified according to ICD-10. Results. 3070 adults enrolled for care in the endocrine outpatient service between 2011 and 2015. This comprised 2056 females and 1014 males (female : male ratio of 2.0 : 1.0 with an overall median age of 54 (IQR, 41–64 years. The commonest primary endocrine disorders seen were diabetes, thyroid, and adrenal disorders at frequencies of 79.1%, 13.1%, and 2.2%, respectively. Conclusions. Type 2 diabetes and thyroid disorders represent by far the two commonest disorders seen at the endocrine clinic. The increased frequency and wide spectrum of endocrine disorders suggest the need for well-trained endocrinologists to improve the health of the population.

  14. Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System.

    Science.gov (United States)

    Rachdaoui, Nadia; Sarkar, Dipak K

    2017-01-01

    Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

  15. Expression of membrane anchored cytokines and B7-1 alters tumor microenvironment and induces protective antitumor immunity in a murine breast cancer model.

    Science.gov (United States)

    Bozeman, Erica N; Cimino-Mathews, Ashley; Machiah, Deepa K; Patel, Jaina M; Krishnamoorthy, Arun; Tien, Linda; Shashidharamurthy, Rangaiah; Selvaraj, Periasamy

    2013-05-07

    Many studies have shown that the systemic administration of cytokines or vaccination with cytokine-secreting tumors augments an antitumor immune response that can result in eradication of tumors. However, these approaches are hampered by the risk of systemic toxicity induced by soluble cytokines. In this study, we have evaluated the efficacy of 4TO7, a highly tumorigenic murine mammary tumor cell line, expressing glycosyl phosphatidylinositol (GPI)-anchored form of cytokine molecules alone or in combination with the costimulatory molecule B7-1 as a model for potential cell or membrane-based breast cancer vaccines. We observed that the GPI-anchored cytokines expressed on the surface of tumor cells greatly reduced the overall tumorigenicity of the 4TO7 tumor cells following direct live cell challenge as evidenced by transient tumor growth and complete regression within 30 days post challenge. Tumors co-expressing B7-1 and GPI-IL-12 grew the least and for the shortest duration, suggesting that this combination of immunostimulatory molecules is most potent. Protective immune responses were also observed following secondary tumor challenge. Further, the 4TO7-B7-1/GPI-IL-2 and 4TO7-B7-1/GPI-IL-12 transfectants were capable of inducing regression of a wild-type tumor growing at a distant site in a concomitant tumor challenge model, suggesting the tumor immunity elicited by the transfectants can act systemically and inhibit the tumor growth at a distant site. Additionally, when used as irradiated whole cell vaccines, 4TO7-B7-1/GPI-IL-12 led to a significant inhibition in tumor growth of day 7 established tumors. Lastly, we observed a significant decrease in the prevalence of myeloid-derived suppressor cells and regulatory T-cells in the tumor microenvironment on day 7 post challenge with 4TO7-B7-1/GPI-IL-12 cells, which provides mechanistic insight into antitumor efficacy of the tumor-cell membrane expressed IL-12. These studies have implications in designing membrane

  16. Supplemental fish oil does not alter immune competence or the pathophysiological response to an intramammary infusion of endotoxin in peri-partum multiparous Holstein cows.

    Science.gov (United States)

    Ballou, Michael A; Gomes, Rodrigo C; DePeters, Edward J

    2009-05-01

    The objective was to determine the effects of supplementing the diet with fish oil during the peri-partum period on the immune competence and the pathophysiological response to a lipopolysaccharide-induced mastitis challenge. Multiparous Holstein cows (n=30) were completely randomized to one of two treatments at 3 weeks pre-partum. Treatments differed only in the source of supplemental lipid and included either Energy Booster or fish oil. Treatment diets were fed from -21 d relative to expected date of parturition until 10 d post partum. Treatments were fed as a bolus prior to the a.m. feeding. The dose of lipid during the pre-partum period was 250 g/d, whereas the amount of lipid supplemented post partum was adjusted to the level of intake, approximately 0.92% of the previous day's dry matter intake. Ex-vivo analyses of immune competence were measured including the antimicrobial activity of whole blood against Escherichia coli, Salmonella typhimurium and Candida albicans as well as the production of interferon-gamma by peripheral blood mononuclear cultures. At 7 days in milk cows were infused with 100 microg of Esch. coli lipopolysaccharide into one rear quarter. Supplementing fish oil increased plasma concentrations of eicosapentaenoic and docosahexaenoic acids, but had no affect on the proportions of arachidonic acid at calving. Fish oil did not influence the production of interferon-gamma or the antimicrobial activity of whole blood against any of the microorganisms. Furthermore, fish oil had no ameliorative effect on either the local or the systemic acute phase response following an intramammary lipopolysaccharide challenge in early lactating Holstein cows. Supplementing fish oil in the diet of peri-partum cows will not protect them from deleterious effects of an excessive acute phase response.

  17. Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.

    Science.gov (United States)

    Rager, Julia E; Bailey, Kathryn A; Smeester, Lisa; Miller, Sloane K; Parker, Joel S; Laine, Jessica E; Drobná, Zuzana; Currier, Jenna; Douillet, Christelle; Olshan, Andrew F; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

    2014-04-01

    The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. Copyright © 2013 Wiley Periodicals, Inc.

  18. Asian Citrus Psyllid Expression Profiles Suggest Candidatus Liberibacter Asiaticus-Mediated Alteration of Adult Nutrition and Metabolism, and of Nymphal Development and Immunity.

    Directory of Open Access Journals (Sweden)

    Meenal Vyas

    Full Text Available The Asian citrus psyllid (ACP Diaphorina citri Kuwayama (Hemiptera: Psyllidae is the insect vector of the fastidious bacterium Candidatus Liberibacter asiaticus (CLas, the causal agent of citrus greening disease, or Huanglongbing (HLB. The widespread invasiveness of the psyllid vector and HLB in citrus trees worldwide has underscored the need for non-traditional approaches to manage the disease. One tenable solution is through the deployment of RNA interference technology to silence protein-protein interactions essential for ACP-mediated CLas invasion and transmission. To identify psyllid interactor-bacterial effector combinations associated with psyllid-CLas interactions, cDNA libraries were constructed from CLas-infected and CLas-free ACP adults and nymphs, and analyzed for differential expression. Library assemblies comprised 24,039,255 reads and yielded 45,976 consensus contigs. They were annotated (UniProt, classified using Gene Ontology, and subjected to in silico expression analyses using the Transcriptome Computational Workbench (TCW (http://www.sohomoptera.org/ACPPoP/. Functional-biological pathway interpretations were carried out using the Kyoto Encyclopedia of Genes and Genomes databases. Differentially expressed contigs in adults and/or nymphs represented genes and/or metabolic/pathogenesis pathways involved in adhesion, biofilm formation, development-related, immunity, nutrition, stress, and virulence. Notably, contigs involved in gene silencing and transposon-related responses were documented in a psyllid for the first time. This is the first comparative transcriptomic analysis of ACP adults and nymphs infected and uninfected with CLas. The results provide key initial insights into host-parasite interactions involving CLas effectors that contribute to invasion-virulence, and to host nutritional exploitation and immune-related responses that appear to be essential for successful ACP-mediated circulative, propagative CLas

  19. Oestrogen levels and humoral immune parameters in Nigerian ...

    African Journals Online (AJOL)

    Objectives: Endocrine and immune interactions mediate breast cancer which is currently incurable. This study attempts at elucidating mechanisms by which breast cancer progresses by determining the levels of oestradiol and humoral immune parameters at different stages of breast cancer compared with women without ...

  20. Vitamin D endocrine system involvement in autoimmune rheumatic diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Pizzorni, Carmen; Sulli, Alberto

    2011-12-01

    Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. [Arterial hypertension secondary to endocrine disorders].

    Science.gov (United States)

    Minder, Anna; Zulewski, Henryk

    2015-06-01

    Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

  2. Update on endocrine disturbances in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Hangaard, J; Hagen, C

    2001-01-01

    The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes...... of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories....

  3. Radiotherapy for unresectable endocrine pancreatic carcinomas

    International Nuclear Information System (INIS)

    Tennvall, J.; Ljungberg, O.; Ahren, B.; Gustavsson, A.; Nillson, L.O.

    1992-01-01

    Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or α-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas. (author)

  4. [Disperse endocrine system and APUD concept].

    Science.gov (United States)

    Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A

    2011-01-01

    This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

  5. Endocrine aspects of cancer gene therapy.

    Science.gov (United States)

    Barzon, Luisa; Boscaro, Marco; Palù, Giorgio

    2004-02-01

    The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene targeting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, including the possibility to exploit hormone and hormone receptor functions for regulating therapeutic gene expression, the use of endocrine-specific genes as new therapeutic tools, the effects of viral vector delivery and transgene expression on the endocrine system, and the endocrine response to viral vector delivery. Present ethical concerns of gene therapy and the risk of germ cell transduction are also discussed, along with potential lines of innovation to improve cell and gene targeting.

  6. ENDOCRINE OPHTHALMOPATHY: ETIOLOGY, PATHOGENESIS, CLINICAL PICTURE, DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    Nikonova L. V.

    2018-03-01

    Full Text Available The relevance of the study of endocrine ophthalmopathy is due to the high prevalence of this disease and a high risk of developing impaired vision that leads to disability of patients. This lecture presents the main genetic, immunological, clinical manifestations of endocrine ophthalmopathy in order to improve the diagnosis and treatment of this pathology. The clinical picture of endocrine ophthalmopathy is various, unique for every patient and depends on the activity and severity of the process, which requires combined etiopathogenetic therapy. The importance of timely diagnosis for endocrine ophthalmopathy with an assessment of the activity of the process for choosing the right tactics for managing patients is very high.

  7. IFN-γ alters the expression of diverse immunity related genes in a cell culture model designed to represent maturing neutrophils.

    Directory of Open Access Journals (Sweden)

    Michael A Ellison

    Full Text Available The cytokine interferon-γ (IFN-γ is approved as a drug to treat chronic granulomatous disease (CGD and osteopetrosis and is also used in hyperimmunoglobulin E syndromes. Patients with CGD have defects in proteins of the NOX2 NADPH oxidase system. This leads to reduced production of microbicidal ROS by PMNs and recurrent life threatening infections. The goal of this study was to better understand how IFN-γ might support phagocyte function in these diseases, and to obtain information that might expand potential uses for IFN-γ. Neutrophils mature in the bone marrow and then enter the blood where they quickly undergo apoptotic cell death with a half-life of only 5-10 hours. Therefore we reasoned that IFN-γ might exert its effects on neutrophils via prolonged exposure to cells undergoing maturation in the marrow rather than by its brief exposure to short-lived circulating cells. To explore this possibility we made use of PLB-985 cells, a myeloblast-like myeloid cell line that can be differentiated into a mature, neutrophil-like state by treatment with various agents including DMSO. In initial studies we investigated transcription and protein expression in PLB-985 cells undergoing maturation in the presence or absence of IFN-γ. We observed IFN-γ induced differences in expression of genes known to be involved in classical aspects of neutrophil function (transmigration, chemotaxis, phagocytosis, killing and pattern recognition as well as genes involved in apoptosis and other mechanisms that regulating neutrophil number. We also observed differences for genes involved in the major histocompatibility complex I (MHCI and MHCII systems whose involvement in neutrophil function is controversial and not well defined. Finally, we observed significant changes in expression of genes encoding guanylate binding proteins (Gbps that are known to have roles in immunity but which have not as yet been linked to neutrophil function. We propose that changes in the

  8. Physiology of the endocrine pancreas.

    Science.gov (United States)

    Engelking, L R

    1997-11-01

    The endocrine pancreas is composed of nests of cells called the islets of Langerhans, which comprise only about 20% of pancreatic cell mass and secrete insulin, glucagon, somatostatin, and pancreatic polypeptide. Insulin is anabolic, increasing storage of glucose, fatty acids and amino acids, while glucagon namely stimulates hepatic glycogenolysis, gluconeogenesis, and ketogenesis. Somatostatin acts as a paracrine agent to inhibit both insulin and glucagon release, and, therefore, to modulate their output. This article explores factors controlling release of these hormones, as well as the way in which they affect fuel metabolism in the whole animal.

  9. Genetic basis of endocrine pathology

    Directory of Open Access Journals (Sweden)

    T.V. Sorokman

    2017-05-01

    Full Text Available The purpose of the review was analysis of literature data relating to the molecular genetic basis and diagnosis of endocrine pathology. We searched for published and unpublished researches using Pubmed as the search engine by the keywords: ‘genes’, ‘endocrine diseases’, ‘molecular diagnostics’, ‘prohormones’, ‘nuclear receptors and transcription factors’, taking into consideration studies conducted over the last 10 years, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants. The criterion for the selection of articles for the study was based on their close relevance to the topic, thus out of 144 analyzed articles, the findings of the researchers covered in 32 articles were crucial. The described nosologies presented various heredi­tary forms of hypopituitarism, disturbances of steroid hormone biosynthesis, abnormal gender formation, monogenic forms of diabetes mellitus, endocrine tumors, etc. Pathology is identified that is associated with a mutation of genes encoding protein prohormones, receptors, steroid biosynthesis enzymes, intracellular signaling molecules, transport proteins, ion channels, and transcription factors. Among the endocrine diseases associated with defects in genes encoding protein prohormones, the defects of the GH1 gene are most common, the defects in the gene CYP21A2 (21-hydroxylase are among diseases associated with defects in genes encoding enzymes. More often mutations of genes encoding proteins belong to the class of G-protein coupled receptors. Most of the mutations associated with MEN-2A are concentrated in the rich cysteine region of the Ret receptor. More than 70 monogenic syndromes are known, in which there is a marked tolerance to glucose and some form of diabetes mellitus is diagnosed, diabetes mellitus caused by mutation of the mitochondrial gene (mutation tRNALeu, UUR is also detected. Of all the monogenic forms of

  10. Endocrine Disease in Aged Horses.

    Science.gov (United States)

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Altering the balance between immune activation versus regulation in the skin to promote CD8+ T-cell activity within epithelial cancers

    DEFF Research Database (Denmark)

    Bridge, Jennifer A.; Overgaard, Nana Haahr; Steptoe, Raymond

    . The expression, in a mouse model (“E7”), of the HPV16 E7 gene in keratinocytes under the control of the K14 promoter, leads to a local immune suppressive environment, as evidenced by the lack of graft rejection when E7 skin grafts are placed on WT recipient mice. Furthermore, well healed (>30 days) E7 skin...... did not reject. As in the WT mice however, rejection could be induced through the coadministration of an anti-CD4 antibody. The data suggest that the removal of a CD4+, non T-reg cell, leads to CD8+ T-cell activity in the skin as evidenced by E7 skin graft destruction....... grafts are not rejected when mice are immunised with E7 peptide in combination with Quil A- or CASAC-based adjuvants. This is despite a substantial increase in E7 peptide/H-2Db pentamer staining in the blood, and marked killing of E7-peptide expressing TC-1 cells when injected i.v., confirming that CD8 T...

  12. Dysregulation in microRNA expression is associated with alterations in immune functions in combat veterans with post-traumatic stress disorder.

    Directory of Open Access Journals (Sweden)

    Juhua Zhou

    Full Text Available While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD.

  13. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  14. Immune activation in lactating dams alters sucklings' brain cytokines and produces non-overlapping behavioral deficits in adult female and male offspring: A novel neurodevelopmental model of sex-specific psychopathology.

    Science.gov (United States)

    Arad, Michal; Piontkewitz, Yael; Albelda, Noa; Shaashua, Lee; Weiner, Ina

    2017-07-01

    Early immune activation (IA) in rodents, prenatal through the mother or early postnatal directly to the neonate, is widely used to produce behavioral endophenotypes relevant to schizophrenia and depression. Given that maternal immune response plays a crucial role in the deleterious effects of prenatal IA, and lactation is a critical vehicle of immunological support to the neonate, we predicted that immune activation of the lactating dam will produce long-term abnormalities in the sucklings. Nursing dams were injected on postnatal day 4 with the viral mimic poly-I:C (4mg/kg) or saline. Cytokine assessment was performed in dams' plasma and milk 2h, and in the sucklings' hippocampus, 6h and 24h following poly-I:C injection. Male and female sucklings were assessed in adulthood for: a) performance on behavioral tasks measuring constructs considered relevant to schizophrenia (selective attention and executive control) and depression (despair and anhedonia); b) response to relevant pharmacological treatments; c) brain structural changes. Maternal poly-I:C injection caused cytokine alterations in the dams' plasma and milk, as well as in the sucklings' hippocampus. Lactational poly-I:C exposure led to sex-dimorphic (non-overlapping) behavioral abnormalities in the adult offspring, with male but not female offspring exhibiting attentional and executive function abnormalities (manifested in persistent latent inhibition and slow reversal) and hypodopaminergia, and female but not male offspring exhibiting despair and anhedonia (manifested in increased immobility in the forced swim test and reduced saccharine preference) and hyperdopaminergia, mimicking the known sex-bias in schizophrenia and depression. The behavioral double-dissociation predicted distinct pharmacological profiles, recapitulating the pharmacology of negative/cognitive symptoms and depression. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes, as found in both disorders. This is

  15. [Endocrine complications of cystic fibrosis in childhood].

    Science.gov (United States)

    Castanet, M; Wieliczko, M-C

    2012-05-01

    Since the 20 last years, the median age of survival has dramatically improved in children suffering from cystic fibrosis and complications such as growth retardation, pubertal delay and low bone mineral density are now more often than not observed in affected adolescents. The severity of the disease and the poor nutritional status due to pancreatic insufficiency and malabsorption are commonly implicated but recent data suggest that the disease could also play a role though the alteration of the chlore chanel (CFTR). Furthermore an increase prevalence of glucose intolerance and diabetes due to the progressive β cells destruction is observed in these children that make the life sometimes difficult for these adolescents already affected by an heavy chronic disease. The monitoring of the children should thus now become pluridisciplinary and include regular clinical evaluation of height and pubertal status, mineral bone density by DEXA and OGTT every two years since 10 years of age. Therefore, in addition to the standard treatment of cystic fibrosis is now added the vitamin D supplementation, the subcutaneous insulin therapy and may be the growth hormone that could be a new therapeutic demonstrating beneficial effects in these chronic disease. However further studies need to be performed to improve the management of these new endocrine complications more and more frequent in children and adolescents suffering from cystic fibrosis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  16. Metabolic Effects of Obesity and Its Interaction with Endocrine Diseases.

    Science.gov (United States)

    Clark, Melissa; Hoenig, Margarethe

    2016-09-01

    Obesity in pet dogs and cats is a significant problem in developed countries, and seems to be increasing in prevalence. Excess body fat has adverse metabolic consequences, including insulin resistance, altered adipokine secretion, changes in metabolic rate, abnormal lipid metabolism, and fat accumulation in visceral organs. Obese cats are predisposed to endocrine and metabolic disorders such as diabetes and hepatic lipidosis. A connection likely also exists between obesity and diabetes mellitus in dogs. No system has been developed to identify obese pets at greatest risk for development of obesity-associated metabolic diseases, and further study in this area is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

    2016-01-01

    ) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group......Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

  18. The anatomy and physiology of the avian endocrine system.

    Science.gov (United States)

    Ritchie, Midge; Pilny, Anthony A

    2008-01-01

    The endocrine system of birds is comparable to that of mammals, although there are many unique aspects to consider when studying the anatomy, physiology, and biochemistry. Avian endocrinology is a field of veterinary medicine that is unfamiliar to many practitioners; however, it is important to have a comprehensive understanding when evaluating companion birds in clinical practice. This article covers the anatomy and physiology of the normal avian, and readers are referred to other articles for a more detailed explanation of altered physiology and pathology.

  19. Humoral immune alterations caused by lead: studies on an adult toad model Alteraciones inmunes humorales causadas por plomo: estudios en un modelo de sapo adulto

    Directory of Open Access Journals (Sweden)

    Carolina E. Rosenberg

    2007-07-01

    Full Text Available There is evidence that environmental metal levels affect the immune function. In the particular case of the impact of heavy metals, information available suggests that the immune system is a target for low-dose Pb exposure. Among vertebrates it was shown that amphibians are capable of forming antibodies against a variety of antigens, causing several responses such as anaphylactic response and rejecting grafts. In this study, the production of antibodies was assessed against sheep red blood cells (SRBC in the anuran Bufo arenarum after six weekly injections of sublethal doses of lead (50 mg.kg-1, as lead acetate. Natural antibodies (natural heteroagglutinins were also quantified against SRBC. Both assessments were carried out employing an ELISA method developed to this end, measuring absorbance (A. For natural anti-SRBC antibodies in both control (C and Pb treated (T toads, there was a non significant tendency to increase the initial absorbances (C initial: 0.69±0.39 A; T initial: 0.54±0.30 A, relative to those registered at the end of the experiments (C final: 0.89±0.49 A; T final: 0.76±0.31A; the T/C ratios also did not show changes. The only significant difference was found between initial and final samples from lead-treated toads (pExiste evidencia de que los niveles de metal ambientales afectan la función inmune. En el caso particular del impacto de metales pesados, la información disponible sugiere que el sistema inmune es un blanco para la exposición a bajas dosis de Pb. Entre los vertebrados, se ha mostrado que los anfibios son capaces de formar anticuerpos contra una variedad de antígenos, que causan diversas respuestas, tales como respuesta anafiláctica y rechazo de injertos. En este estudio, la producción de anticuerpos fue evaluada contra eritrocitos de oveja (EO en el anuro Bufo arenarum, luego de seis inyecciones semanales de dosis subletales de plomo (50 mg.kg-1, como acetato de Pb. Los anticuerpos naturales

  20. Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

    Science.gov (United States)

    Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

    2018-01-01

    Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

  1. Overview of the Pathophysiological Implications of Organotins on the Endocrine System

    Directory of Open Access Journals (Sweden)

    Vinicius Bermond Marques

    2018-03-01

    Full Text Available Organotins (OTs are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis, altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus or peripheral (e.g., adipose tissue mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

  2. Overview of the Pathophysiological Implications of Organotins on the Endocrine System

    Science.gov (United States)

    Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

    2018-01-01

    Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed. PMID:29615977

  3. Endocrine and metabolic diurnal rhythms in young adult men born small vs appropriate for gestational age

    DEFF Research Database (Denmark)

    Brøns, Charlotte; Saltbæk, Pernille N; Friedrichsen, Martin

    2016-01-01

    OBJECTIVE: Sleep disturbances and alterations of diurnal endocrine rhythms are associated with increased risk of type 2 diabetes (T2D). We previously showed that young men born small for gestational age (SGA) and with increased risk of T2D have elevated fat and decreased glucose oxidation rates d...

  4. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

    DEFF Research Database (Denmark)

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie

    2015-01-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures...

  5. Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model

    Science.gov (United States)

    Various assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis via different mechanisms/modes of action (MOA). These assays can be sensitive ...

  6. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

    KAUST Repository

    Juneja, Punita

    2015-03-27

    Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.

  7. [Vitamin D and endocrine diseases].

    Science.gov (United States)

    Schuch, Natielen Jacques; Garcia, Vivian Cristina; Martini, Ligia Araújo

    2009-07-01

    Vitamin D insufficiency/deficiency has been worldwide reported in all age groups in recent years. It has been considered a Public Health matter since decreased levels of vitamin D has been related to several chronic diseases, as type 2 diabetes mellitus (T2DM), obesity and hypertension. Glucose intolerance and insulin secretion has been observed during vitamin D deficiency, both in animals and humans resulting in T2DM. The supposed mechanism underlying these findings is presence of vitamin D receptor in several tissues and cells, including pancreatic beta-cells, adipocyte and muscle cells. In obese individuals, the impaired vitamin D endocrine system, characterized by high levels of PTH and 1,25(OH)(2)D(3) could induce a negative feedback for the hepatic synthesis of 25(OH)D and also contribute to a higher intracellular calcium, which in turn secrete less insulin and deteriorate insulin sensitivity. In hypertension, vitamin D could act on renin-angiotensin system and also in vascular function. Administration of 1,25(OH)(2)D(3) could decreases renin gene expression and inhibit vascular smooth muscle cell proliferation. However, prospective and intervention human studies that clearly demonstrates the benefits of vitamin D status adequacy in the prevention and treatment of endocrine metabolic diseases are lacking. Further research still necessary to assure the maximum benefit of vitamin D in such situations.

  8. Rhinovirus infection results in stronger and more persistent genomic dysregulation: Evidence for altered innate immune response in asthmatics at baseline, early in infection, and during convalescence.

    Directory of Open Access Journals (Sweden)

    Peter W Heymann

    Full Text Available Rhinovirus (HRV is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined.Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis.At baseline, 57 genes were differentially expressed between asthmatics and controls, and the asthmatics had decreased expression of viral replication inhibitors and increased expression of genes involved in inflammation. At 36 hours (before the emergence of peak symptoms, 1329 genes were significantly altered from baseline in the asthmatics compared to 62 genes in the controls. At this time point, asthmatics lacked an increase in IL-10 signaling observed in the controls. At 7 days following HRV inoculation, 222 genes were significantly dysregulated in the asthmatics, whereas only 4 genes were dysregulated among controls. At this time point, the controls but not asthmatics demonstrated upregulation of SPINK5.As judged by the magnitude and persistence of dysregulated genes, asthmatics have a substantially different host response to HRV-A16 infection compared with non-asthmatic controls. Gene expression differences illuminate biologically plausible mechanisms that contribute to a better understanding of the pathogenesis of HRV-induced asthma exacerbations.

  9. Altered hepatic mRNA expression of immune response-associated DNA damage in mice liver induced by potassium bromate: Protective role of vanillin.

    Science.gov (United States)

    Ben Saad, Hajer; Driss, Dorra; Ben Amara, Ibtissem; Boudawara, Ons; Boudawara, Tahia; Ellouz Chaabouni, Samia; Mounir Zeghal, Khaled; Hakim, Ahmed

    2016-12-01

    Chronic exposure to potassium bromate (KBrO 3 ), a toxic halogen existing widely in the environment, environment through contaminated drinking water, has become a global problem of public health. The present study investigates the protective role of vanillin against KBrO 3 induced oxidative stress, distruption in inflammatory cytokines expression, DNA damage, and histopathological changes. Adult mice were exposed orally to KBrO 3 (2g/L of drinking water) for 2 weeks The co-administration of vanillin to the KBrO 3 -treated mice significantly prevented the plasma transaminases increase in. Furthermore, it inhibited hepatic lipid peroxidation (malondialdehyde), advanced oxidation protein product (AOPP) and protein carbonyl (PCO) formation and attenuated the KBrO 3 -mediated depletion of enzymatic and non enzymatic antioxidants catalase, superoxide dismutase, and glutathione peroxidase activities and glutathione level in the liver. In addition, vanillin markedly attenuated the expression levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and COX2 and prevented KBrO 3 -induced hepatic cell alteration and necrosis, as indicated by histopathological data. DNA damage, as assessed by the alkaline comet assay, was also found to be low in the co-treated group. Thus, these findings show that vanillin acts as potent chemopreventive agent against KBrO 3 -mediated liver oxidative stress and genotoxicity through its antioxidant properties. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1796-1807, 2016. © 2015 Wiley Periodicals, Inc.

  10. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  11. Diagnosis and pathology of endocrine diseases

    International Nuclear Information System (INIS)

    Shriver, B.D.

    1988-01-01

    This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands

  12. The application of PET in endocrine tumors

    International Nuclear Information System (INIS)

    Yuan Zhibin

    2003-01-01

    There are wide application of PET in endocrine tumors, including thyroid cancer, parathyroid adenoma, pheochromocytoma and neuroblastoma. Many papers concluded that in diagnosing endocrine tumors, PET does not show apparent advantages comparing with traditional radionuclide imaging methods. But as a useful complementary method, its clinical value has been recognized

  13. Diagnosis and pathology of endocrine diseases

    Energy Technology Data Exchange (ETDEWEB)

    Shriver, B.D.

    1988-01-01

    This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands.

  14. Endocrine pathology: past, present and future.

    Science.gov (United States)

    Asa, Sylvia L; Mete, Ozgur

    2018-01-01

    Endocrine pathology is the subspecialty of diagnostic pathology which deals with the diagnosis and characterisation of neoplastic and non-neoplastic diseases of the endocrine system. This relatively young subspecialty was initially focused mainly on thyroid and parathyroid pathology, with some participants also involved in studies of the pituitary, the endocrine pancreas, and the adrenal glands. However, the endocrine system involves much more than these traditional endocrine organs and the discipline has grown to encompass lesions of the dispersed neuroendocrine cells, including neuroendocrine tumours (NETs) of the lungs, gastrointestinal tract, thymus, breast and prostate, as well as paraganglia throughout the body, not just in the adrenals. Indeed, the production of hormones is the hallmark of the endocrine system, and some aspects of gynecological/testicular, bone and liver pathology also fall into the realm of this specialty. Many of the lesions that are the focus of this discipline are increasing in incidence and their pathology is becoming more complex with increased understanding of molecular pathology and a high incidence of familial disease. The future of endocrine pathology will demand a depth of understanding of structure, function, prognosis and prediction as pathologists play a key role in the multidisciplinary care team of patients with endocrine diseases. It is anticipated that new technologies will allow increased subspecialisation in pathology and growth of this important area of expertise. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  15. Intrinsic imperfections of endocrine replacement therapy

    NARCIS (Netherlands)

    Romijn, J. A.; Smit, J. W. A.; Lamberts, S. W. J.

    2003-01-01

    Hormonal substitution therapy has been extremely successful, with respect to morbidity and mortality, in the treatment of the major syndromes of endocrine insufficiency. However, many patients treated for endocrine insufficiencies still suffer from more or less vague complaints and a decreased

  16. Tailoring endocrine treatment for early breast cancer

    NARCIS (Netherlands)

    Fontein, Duveken Berthe Yvonne

    2014-01-01

    This thesis describes several important aspects of adjuvant endocrine therapy for postmenopausal women with endocrine-sensitive, early-stage breast cancer. In our ongoing efforts to tailor treatment so as to provide the best possible care to each of our patients, we studied the influence of various

  17. Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

    Science.gov (United States)

    Bottaccioli, Anna Giulia; Bottaccioli, Francesco; Minelli, Andrea

    2018-05-15

    In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases. © 2018 New York Academy of Sciences.

  18. Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function.

    Science.gov (United States)

    Azzinnari, Damiano; Sigrist, Hannes; Staehli, Simon; Palme, Rupert; Hildebrandt, Tobias; Leparc, German; Hengerer, Bastian; Seifritz, Erich; Pryce, Christopher R

    2014-10-01

    In neuropsychiatry, animal studies demonstrating causal effects of environmental manipulations relevant to human aetiology on behaviours relevant to human psychopathologies are valuable. Such valid models can improve understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core symptoms or features. Here we exposed adult male C57BL/6 mice to 15-day psychosocial stress with loss of social control but minimal physical wounding. One cohort was assessed in a 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. Socially stressed mice displayed decreased motor activity, increased fear acquisition, decreased 2-way avoid-escape responding (increased helplessness) and increased fatigue. They also displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy without hyper-corticoidism. In a third cohort, psychosocial stress effects on brain gene expression were assessed using next generation sequencing. Gene expression was altered in pathways of inflammation and G-protein coupled receptors in prefrontal cortex and amygdala; in the latter, expression of genes important in dopamine function were de-regulated including down-regulated Drd2, Adora2a and Darpp-32. This model can be applied to identify targets for treating psychopathologies such as helplessness or fatigue, and to screen compounds/biologics developed to act at these targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations.

    Science.gov (United States)

    Monte, Aline Santos; Mello, Bruna Stefânia Ferreira; Borella, Vládia Célia Moreira; da Silva Araujo, Tatiane; da Silva, Francisco Eliclécio Rodrigues; Sousa, Francisca Cléa F de; de Oliveira, Antônio Carlos Pinheiro; Gama, Clarissa Severino; Seeman, Mary V; Vasconcelos, Silvânia Maria Mendes; Lucena, David Freitas De; Macêdo, Danielle

    2017-07-28

    Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Transgenerational Social Stress, Immune Factors, Hormones, and Social Behavior

    Directory of Open Access Journals (Sweden)

    Christopher Anthony Murgatroyd

    2016-01-01

    Full Text Available A social signal transduction theory of depression has been proposed that states that exposure to social adversity alters the immune response and these changes mediate symptoms of depression such as anhedonia and impairments in social behavior. The exposure of maternal rats to the chronic social stress (CSS of a male intruder depresses maternal care and impairs social behavior in the F1 and F2 offspring of these dams. The objective of the present study was to characterize basal peripheral levels of several immune factors and related hormone levels in the adult F2 offspring of CSS exposed dams and assess whether changes in these factors are associated with previously reported deficits in allogrooming behavior. CSS decreased acid glycoprotein (α1AGP and intercellular adhesion molecule-1 (ICAM-1 in F2 females, and increased granulocyte macrophage-colony stimulating factor (GM-CSF in F2 males. There were also sex dependent changes in IL-18, tissue inhibitors of metalloproteinases 1 (TIMP-1, and vascular endothelial growth factor (VEGF. Progesterone was decreased and alpha melanocyte stimulating hormone (α-MSH was increased in F2 males, and brain-derived neurotrophic factor (BDNF was decreased in F2 females. Changes in α1AGP, GM-CSF, progesterone and α-MSH were correlated with decreased allogrooming in the F2 offspring of stressed dams. These results support the hypothesis that transgenerational social stress affects both the immune system and social behavior, and also support previous studies on the adverse effects of early life stress on immune functioning and stress associated immunological disorders, including the increasing prevalence of asthma. The immune system may represent an important transgenerational etiological factor in disorders which involve social and/or early life stress associated changes in social behavior, such as depression, anxiety, and autism, as well as comorbid immune disorders. Future studies involving immune and

  1. Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

    Science.gov (United States)

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2012-08-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction). Copyright © 2012 Wiley Periodicals, Inc.

  2. Endocrine Consequences of Anorexia Nervosa

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Summary Anorexia nervosa (AN) is prevalent in adolescents and young adults, and endocrine changes include hypothalamic amenorrhea, a nutritionally acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1), relative hypercortisolemia, decreases in leptin, insulin, amylin and incretins, and increases in ghrelin, PYY and adiponectin. These changes in turn have deleterious effects on bone, and may affect neurocognition, anxiety, depression and eating disorder psychopathology. Low bone density is particularly concerning; clinical fractures occur and changes in both bone microarchitecture and strength estimates have been reported. Recovery causes improvement of many, but not all, hormonal changes, and deficits in bone accrual may persist despite recovery. Physiologic, primarily transdermal, estrogen replacement increases bone density in adolescents, although catch-up is incomplete. In adults, oral estrogen co-administered with rhIGF-1 in one study, and bisphosphonates in another increased bone density, though not to normal. More studies are necessary to determine the optimal therapeutic approach in AN. PMID:24731664

  3. [Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

    Science.gov (United States)

    Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

    2014-01-01

    The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

  4. Branched-chain amino acid supplementation and the immune response of long-distance athletes.

    Science.gov (United States)

    Bassit, Reinaldo A; Sawada, Letícia A; Bacurau, Reury F P; Navarro, Franciso; Martins, Eivor; Santos, Ronaldo V T; Caperuto, Erico C; Rogeri, Patrícia; Costa Rosa, Luís F B P

    2002-05-01

    Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.

  5. Analyzing endocrine system conservation and evolution.

    Science.gov (United States)

    Bonett, Ronald M

    2016-08-01

    Analyzing variation in rates of evolution can provide important insights into the factors that constrain trait evolution, as well as those that promote diversification. Metazoan endocrine systems exhibit apparent variation in evolutionary rates of their constituent components at multiple levels, yet relatively few studies have quantified these patterns and analyzed them in a phylogenetic context. This may be in part due to historical and current data limitations for many endocrine components and taxonomic groups. However, recent technological advancements such as high-throughput sequencing provide the opportunity to collect large-scale comparative data sets for even non-model species. Such ventures will produce a fertile data landscape for evolutionary analyses of nucleic acid and amino acid based endocrine components. Here I summarize evolutionary rate analyses that can be applied to categorical and continuous endocrine traits, and also those for nucleic acid and protein-based components. I emphasize analyses that could be used to test whether other variables (e.g., ecology, ontogenetic timing of expression, etc.) are related to patterns of rate variation and endocrine component diversification. The application of phylogenetic-based rate analyses to comparative endocrine data will greatly enhance our understanding of the factors that have shaped endocrine system evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Effects of Anorexia Nervosa on the Endocrine System.

    Science.gov (United States)

    Baskaran, Charumathi; Misra, Madhusmita; Klibanski, Anne

    2017-03-01

    Anorexia nervosa (AN) is characterized by severe undernutrition associated with alterations in multiple endocrine axes, which are primarily adaptive to the state of caloric deprivation. Hormonal changes include growth hormone (GH) resistance with low insulin like growth factor-1 (IGF-1) levels, hypothalamic hypogonadism, relative hypercortisolemia and changes in appetite regulating hormones, including leptin, ghrelin, and peptide YY. These alterations contribute to abnormalities in bone metabolism leading to low bone mass, impaired bone microarchitecture, and increased risk for fracture, and may also negatively impact cognition, emotions and mood. The best strategy to improve all biologic outcomes is weight and menstrual recovery. Physiological estrogen replacement improves bone accrual rates and measures of trait anxiety in adolescents with AN. Other therapies including testosterone and IGF-1 replacement, and use of DHEA with oral estrogen-progesterone combination pills, bisphosphonates and teriparatide have also been studied to improve bone outcomes. Copyright© of YS Medical Media ltd.

  7. Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

    Science.gov (United States)

    Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

    2008-01-01

    During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

  8. Neurocutaneous spectrum of multiple endocrine neoplasia-1

    Directory of Open Access Journals (Sweden)

    Shireen Furtado

    2012-01-01

    Full Text Available Multiple endocrine neoplasia type I or Wermer syndrome is characterized by primary hyperparathyroidism, enteropancreatic endocrine tumor, and a pituitary pathology. A 35-year-old male presented with visual field defects, hyperprolactinemia, and hypogonadism. He also had multiple infraumbilical skin-colored nodules. A syndromal association of Wermer syndrome was derived using the dermal, pituitary, parathyroid, and gastrointestinal hormonal manifestations of the tumor. The radiological and histological findings of lesion which underwent biopsy are discussed. The presence of collagenomas, lipomas, and hypopigmented macules in a patient with neuroendocrine symptoms should raise the suspicion of an underlying multiple endocrine neoplasia.

  9. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  10. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  11. Remote postradiation immunodeficiency a disorder of endocrine regulation and thymic function. Role of intersystems interactions

    International Nuclear Information System (INIS)

    Savina, N.P.

    1999-01-01

    A total of 265 reports on radiation effects on the immune, nervous, and endocrine systems are reviewed. The role of the thymus, hypothalamus, and pituitary in remote manifestations of immunodeficiency in patients with cancer of the head and neck, treated by radiotherapy, is discussed. The pathogenesis of stubborn postradiation disturbances in immunoendocrine homeostasis after local exposure of the thymus and hypothalamus-pituitary at doses of 1-10 Gy, characterized as a syndrome, is analyzed [ru

  12. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Solt, Anna C; Henríquez-Roldán, Carlos; Torres-Jardón, Ricardo; Nuse, Bryan; Herritt, Lou; Villarreal-Calderón, Rafael; Osnaya, Norma; Stone, Ida; García, Raquel; Brooks, Diane M; González-Maciel, Angelica; Reynoso-Robles, Rafael; Delgado-Chávez, Ricardo; Reed, William

    2008-02-01

    Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

  13. Rebuilding immunity with Remune.

    Science.gov (United States)

    Whitfield, L

    1998-01-01

    Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

  14. Immune System Toxicity and Immunotoxicity Hazard Identification

    Science.gov (United States)

    Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

  15. Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects

    DEFF Research Database (Denmark)

    Bourguignon, Jean-Pierre; Juul, Anders; Franssen, Delphine

    2016-01-01

    Debate makes science progress. In the field of endocrine disruption, endocrinology has brought up findings that substantiate a specific perspective on the definition of endocrine disrupting chemicals (EDCs), the role of the endocrine system and the endpoints of hormone and EDC actions among other...... issues. This paper aims at discussing the relevance of the endocrine perspective with regard to EDC effects on pubertal timing. Puberty involves particular sensitivity to environmental conditions. Reports about the advancing onset of puberty in several countries have led to the hypothesis...

  16. Childhood Immunization

    Science.gov (United States)

    ... 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

  17. Immunizations - diabetes

    Science.gov (United States)

    ... 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 ...

  18. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    DEFF Research Database (Denmark)

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades....

  19. Alcohol, aging, and innate immunity.

    Science.gov (United States)

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  20. Endocrine manifestations of Down syndrome.

    Science.gov (United States)

    Whooten, Rachel; Schmitt, Jessica; Schwartz, Alison

    2018-02-01

    To summarize the recent developments in endocrine disorders associated with Down syndrome. Current research regarding bone health and Down syndrome continues to show an increased prevalence of low bone mass and highlights the importance of considering short stature when interpreting dual energy x-ray absorptiometry. The underlying cause of low bone density is an area of active research and will shape treatment and preventive measures. Risk of thyroid disease is present throughout the life course in individuals with Down syndrome. New approaches and understanding of the pathophysiology and management of subclinical hypothyroidism continue to be explored. Individuals with Down syndrome are also at risk for other autoimmune conditions, with recent research revealing the role of the increased expression of the Autoimmune Regulatory gene on 21st chromosome. Lastly, Down-syndrome-specific growth charts were recently published and provide a better assessment of growth. Recent research confirms and expands on the previously known endocrinopathies in Down syndrome and provides more insight into potential underlying mechanisms.

  1. Physiology of fish endocrine pancreas.

    Science.gov (United States)

    Plisetskaya, E M

    1989-06-01

    From the very beginning of physiological studies on the endocine pancreas, fish have been used as experimental subjects. Fish insulin was one of the first vertebrate insulins isolated and one of the first insulins whose primary and then tertiary structures were reported. Before a second pancreatic hormone, glucagon, was characterized, a physiologically active 'impurity', similar to that in mammalian insulin preparations, was found in fish insulins.Fish have become the most widely used model for studies of biosynthesis and processing of the pancreatic hormones. It seems inconceivable, therefore, that until the recent past cod and tuna insulins have been the only purified piscine islet hormones available for physiological experiments. The situation has changed remarkably during the last decade.In this review the contemporary status of physiological studies on the fish pancreas is outlined with an emphasis on the following topics: 1) contents of pancreatic peptides in plasma and in islet tissue; 2) actions of piscine pancreatic hormones in fish; 3) specific metabolic consequences of an acute insufficiency of pancreatic peptides; 4) functional interrelations among pancreatic peptides which differ from those of mammals. The pitfalls, lacunae and the perspectives of contemporary physiological studies on fish endocrine pancreas are outlined.

  2. Endocrine Dysregulation in Anorexia Nervosa Update

    Science.gov (United States)

    2011-01-01

    Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

  3. Mechanistic evaluation of endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Taxvig, Camilla

    BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects.......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

  4. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

  5. In immune defense: redefining the role of the immune system in chronic disease.

    Science.gov (United States)

    Rubinow, Katya B; Rubinow, David R

    2017-03-01

    The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

  6. Molasses as a possible cause of an ''endocrine disruptive syndrome'' in calves

    Directory of Open Access Journals (Sweden)

    M.S. Masgoret

    2009-09-01

    Full Text Available During the mid 1990s a potentially serious, chronic syndrome was reported in well-managed beef and dairy herds from unrelated parts of South Africa. Farmers reported that it manifested as various combinations of decreased production, decreased weaning masses, apparent immune breakdown in previously immunocompetent animals, increased reproductive disorders, various mineral imbalances in non-deficient areas and goitre, noticeable as enlarged thyroid glands. The farmers associated this syndrome with certain batches of sugar cane molasses and molasses-based products. The syndrome was reminiscent of an ''endocrine disruptive syndrome''. The objective of this study was to evaluate the suspected endocrine disruptive effect of molasses included in cattle feed. Using existing in vitro assays, four batches of molasses syrup were screened for possible inclusion in a calf feeding trial. Two batches were selected for the trial. Thirty-two, 4- to 6-week-old, weaned Holstein bull calves were included in the single phase, three treatment, parallel design experiment. In two of the groups of calves, two different batches of molasses were included in their rations respectively. The control group was fed a ration to which no molasses was added, but which was balanced for energy and mineral content. The mass gain of the calves was recorded over the 6-month study period. The calves were clinically examined every week and clinical pathology parameters, immune responses and endocrine effects were regularly evaluated. Even though endocrine disrupting effects were detected with the in vitro screening assays, these could not be reproduced in the calves in the experiment. The two batches of molasses utilized in the calf feeding trial did not induce major differences in any of the parameters measured, with the exception of a lower mass gain in one of the molasses-fed groups (Group 1, which tended towards significance. The results of the study indicate that the two batches

  7. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  8. Purinergic signaling pathways in endocrine system.

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

    2015-09-01

    Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

  9. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  10. Purinergic Signaling Pathways in Endocrine System

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

    2015-01-01

    Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

  11. Endocrine pancreatic function changes after acute pancreatitis.

    Science.gov (United States)

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  12. Endocrine neoplasms in familial syndromes of hyperparathyroidism.

    Science.gov (United States)

    Li, Yulong; Simonds, William F

    2016-06-01

    Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. © 2016 Society for Endocrinology.

  13. Immune dysfunction in cirrhosis

    Science.gov (United States)

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  14. A review of endocrine changes in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Hangaard, J; Hansen-Nord, M

    1999-01-01

    Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways...... they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain...... and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone...

  15. Endocrine disruptors: Revisiting concepts and dogma in toxicology.

    Science.gov (United States)

    Barouki, Robert

    During the last decades, a large number of observations have shown that some exogenous substances could interfere with hormone levels or hormone action and could induce toxic effects. This has led to the identification of endocrine disruptors more than 25 years ago as a new class of toxic agents (Zoeller et al., 2014). Those widely used agents correspond to a variety of chemical classes, are not identified by their chemical structure or by a specific type of usage, but rather by their mechanisms of action; this is not unprecedented in toxicology since genotoxicants have also been identified by their mechanism of action, i.e. their ability to alter DNA structure and function. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  16. Endocrine Disruption of Vasopressin Systems and Related Behaviors

    Directory of Open Access Journals (Sweden)

    Heather B. Patisaul

    2017-06-01

    Full Text Available Endocrine disrupting chemicals (EDCs are chemicals that interfere with the organizational or activational effects of hormones. Although the vast majority of the EDC literature focuses on steroid hormone signaling related impacts, growing evidence from a myriad of species reveals that the nonapeptide hormones vasopressin (AVP and oxytocin (OT may also be EDC targets. EDCs shown to alter pathways and behaviors coordinated by AVP and/or OT include the plastics component bisphenol A (BPA, the soy phytoestrogen genistein (GEN, and various flame retardants. Many effects are sex specific and likely involve action at nuclear estrogen receptors. Effects include the elimination or reversal of well-characterized sexually dimorphic aspects of the AVP system, including innervation of the lateral septum and other brain regions critical for social and other non-reproductive behaviors. Disruption of magnocellular AVP function has also been reported in rats, suggesting possible effects on hemodynamics and cardiovascular function.

  17. Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

    OpenAIRE

    Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

    2008-01-01

    Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1–F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti...

  18. The effect of lead intoxication on endocrine functions.

    Science.gov (United States)

    Doumouchtsis, K K; Doumouchtsis, S K; Doumouchtsis, E K; Perrea, D N

    2009-02-01

    Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

  19. Radiologic techniques in evaluation endocrine disorders

    International Nuclear Information System (INIS)

    Martino, C.R.; Schultz, C.L.; Butler, H.E.; Haaga, J.R.

    1988-01-01

    This paper discusses evaluation of normal and diseased endocrine organs that has been facilitated by the development of new radiologic-imaging techniques including nuclear medicine, ultrasound, computed tomography, and magnetic resonance imaging. With improvement in resolution and tissue contrast, abnormalities as small as 5 mm can now be imaged with these modalities. Endocrinologists and clinicians involved in the evaluation and diagnosis of patients with endocrine diseases can be substantially aided by a proper radiologic workup. The authors describe and illustrate various radiologic techniques that are useful for evaluating thyroid and parathyroid derangements

  20. Radiation pathomorphology of the gastrointestinal endocrine cells

    International Nuclear Information System (INIS)

    Yuzhakov, V.V.; Yakovleva, N.D.; Kvetnoj, I.M.; Ulitina, E.D.

    1994-01-01

    The paper presents the results of histochemical, electronmicroscopic and radioautographic analysis of the effects of a total single gamma irradiation on the functional morphology of cells of the diffuse endocrine system of the gastrointestinal tract of rats and mice. Irradiation in dosses from 5 to 20 Gy results in reduction of the detectability of argyrophilic and argentaffine cells. Changes in these cells counts are related to the irradiation dose. The reaction observed early after the irradiation is related to changes in the endocrine and endoplasmatic reticulum

  1. Manufacturing doubt about endocrine disrupter science

    DEFF Research Database (Denmark)

    Bergman, Åke; Becher, Georg; Blumberg, Bruce

    2015-01-01

    We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption......) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers...

  2. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Metabolic, endocrine, and related bone diseases

    International Nuclear Information System (INIS)

    Rogers, L.F.

    1987-01-01

    Bone is living tissue, and old bone is constantly removed and replaced with new bone. Normally this exchange is in balance, and the mineral content remains relatively constant. This balance may be disturbed as a result of certain metabolic and endocrinologic disorders. The term dystrophy, referring to a disturbance of nutrition, is applied to metabolic and endocrine bone diseases and should be distinguished from the term dysplasia, referring to a disturbance of bone growth. The two terms are easily confused but are not interchangeable. Metabolic bone disease is caused by endocrine imbalance, vitamin deficiency or excess, and other disturbances in bone metabolism leading to osteoporosis and osteomalacia

  4. Biomonitoring of Human Exposure to Prestige Oil: Effects on DNA and Endocrine Parameters

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2008-01-01

    Full Text Available Since 1960, about 400 tankers spilled more than 377765 tons of oil, with the Prestige accident (Galician coast, NW Spain, November 2002 the most recent. Taking into account the consistent large number of individuals exposed to oil that exists all over the world, it seems surprising the absence in the literature of studies focused on the chronic effects of this exposure on human health. In this work we evaluated the level of DNA damage by means of comet assay, and the potential endocrine alterations (prolactin and cortisol caused by Prestige oil exposure in a population of 180 individuals, classified in 3 groups according to the tasks performed, and 60 controls. Heavy metals in blood were determined as exposure biomarkers, obtaining significant increases of aluminum, nickel and lead in the exposed groups as compared to controls. Higher levels of genetic damage and endocrine alterations were also observed in the exposed population. DNA damage levels were influenced by age, sex, and the use of protective clothes, and prolactin concentrations by the last two factors. Surprisingly, the use of mask did not seem to protect individuals from genetic or endocrine alterations. Moreover, polymorphisms in genes encoding for the main enzymes involved in the metabolism of oil components were analyzed as susceptibility biomarkers. CYP1A1-3’UTR and EPHX1 codons 113 and 139 variant alleles were related to higher damage levels, while lower DNA damage was observed in GSTM1 and GSTT1 null individuals.

  5. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  6. Science and policy on endocrine disrupters must not be mixed

    DEFF Research Database (Denmark)

    Bergman, Åke; Andersson, Anna-Maria; Becher, Georg

    2013-01-01

    The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a r...

  7. Schedule for Rating Disabilities; the Endocrine System. Final rule.

    Science.gov (United States)

    2017-11-02

    This document amends the Department of Veterans Affairs (VA) Schedule for Rating Disabilities (VASRD) by revising the portion of the Schedule that addresses endocrine conditions and disorders of the endocrine system. The effect of this action is to ensure that the VASRD uses current medical terminology and to provide detailed and updated criteria for evaluation of endocrine disorders.

  8. [Stress and auto-immunity].

    Science.gov (United States)

    Delévaux, I; Chamoux, A; Aumaître, O

    2013-08-01

    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

    Directory of Open Access Journals (Sweden)

    Sofiane Boudalia

    2017-06-01

    Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity.

  10. Spreeta-based biosensor for endocrine disruptors

    NARCIS (Netherlands)

    Marchesini, G.R.; Koopal, K.; Meulenberg, E.; Haasnoot, W.; Irth, H.

    2007-01-01

    The construction and performance of an automated low-cost Spreeta¿-based prototype biosensor system for the detection of endocrine disrupting chemicals (EDCs) is described. The system consists primarily of a Spreeta miniature liquid sensor incorporated into an aluminum flow cell holder, dedicated to

  11. Endocrine and Metabolic Aspects of OSA

    Directory of Open Access Journals (Sweden)

    Ravinder Goswami

    2014-03-01

    Full Text Available Obstructive sleep apnea (OSA is characterized by repeated spells of apnea.Collapsibility of hypopharynx due to multiple factors involving pharyngeal dilatormuscles and deposition of fat or fluid in the surrounding soft tissues are importantcontributing factors in its pathogenesis. OSA commonly affects obese individuals.Males are more commonly affected than the females probably due to the disturbingeffect of testosterone on sleep.The impact of OSA on human health include disturbances in endocrine and metabolicsystem affecting hypothalamic-pituitary-gonadal axis, adrenocorticotrophic-cortisolaxis, growth hormone, antidiuretic hormones and insulin resistance. There is atendency for predisposition of the metabolic syndrome or its components includingglycemic dysregulation, hypertension, hyperlipidemia and physical parameters relatedto adiposity. On the other hand, several endocrine disorders such as hypothyroidism,growth hormone excess, polycystic ovarian disease and testosterone replacement areassociated with increased prevalence of OSA.There is limited information on the effect of treatment of OSA by continuous positiveairway pressure (CPAP on the endocrine and metabolic disturbances. There is a needto conduct randomized controlled trials using CPAP therapy in patients with OSA andto study its cause and effect relationship with endocrine and metabolic disturbances.

  12. Dietary exposure to the endocrine disruptor tolylfluanid promotes global metabolic dysfunction in male mice.

    Science.gov (United States)

    Regnier, Shane M; Kirkley, Andrew G; Ye, Honggang; El-Hashani, Essam; Zhang, Xiaojie; Neel, Brian A; Kamau, Wakanene; Thomas, Celeste C; Williams, Ayanna K; Hayes, Emily T; Massad, Nicole L; Johnson, Daniel N; Huang, Lei; Zhang, Chunling; Sargis, Robert M

    2015-03-01

    Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome.

  13. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  14. Appetite-Controlling Endocrine Systems in Teleosts

    Science.gov (United States)

    Rønnestad, Ivar; Gomes, Ana S.; Murashita, Koji; Angotzi, Rita; Jönsson, Elisabeth; Volkoff, Hélène

    2017-01-01

    Mammalian studies have shaped our understanding of the endocrine control of appetite and body weight in vertebrates and provided the basic vertebrate model that involves central (brain) and peripheral signaling pathways as well as environmental cues. The hypothalamus has a crucial function in the control of food intake, but other parts of the brain are also involved. The description of a range of key neuropeptides and hormones as well as more details of their specific roles in appetite control continues to be in progress. Endocrine signals are based on hormones that can be divided into two groups: those that induce (orexigenic), and those that inhibit (anorexigenic) appetite and food consumption. Peripheral signals originate in the gastrointestinal tract, liver, adipose tissue, and other tissues and reach the hypothalamus through both endocrine and neuroendocrine actions. While many mammalian-like endocrine appetite-controlling networks and mechanisms have been described for some key model teleosts, mainly zebrafish and goldfish, very little knowledge exists on these systems in fishes as a group. Fishes represent over 30,000 species, and there is a large variability in their ecological niches and habitats as well as life history adaptations, transitions between life stages and feeding behaviors. In the context of food intake and appetite control, common adaptations to extended periods of starvation or periods of abundant food availability are of particular interest. This review summarizes the recent findings on endocrine appetite-controlling systems in fish, highlights their impact on growth and survival, and discusses the perspectives in this research field to shed light on the intriguing adaptations that exist in fish and their underlying mechanisms. PMID:28458653

  15. Immune System Dysfunction in the Elderly.

    Science.gov (United States)

    Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

    2017-01-01

    Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

  16. Manifestations of Immune Privilege in the Human Reproductive Tract

    Directory of Open Access Journals (Sweden)

    Gary F Clark

    2013-02-01

    Full Text Available Like other mucosal surfaces (e.g., the gastrointestinal tract, the respiratory tract, the human female reproductive tract acts as an initial barrier to foreign antigens. In this role, the epithelial surface and subepithelial immune cells must balance protection against pathogenic insults against harmful inflammatory reactions and acceptance of particular foreign antigens. Two common examples of these acceptable foreign antigens are the fetal allograft and human semen/sperm. Both are purposely deposited into the female genital tract and appropriate immunologic response to these non-self antigens is essential to the survival of the species. In light of the weight of this task, it is not surprising that multiple, redundant and overlapping mechanisms are involved. For instance, cells at the immunologic interface between self (female reproductive tract epithelium and non-self (placental trophoblast cells or human sperm express glycosylation patterns that mimic those on many metastatic cancer cells and successful pathogens. The cytokine/chemokine milieu at this interface is altered through endocrine and immunologic mechanisms to favor tolerance of non-self. The foreign cells themselves also play an integral role in their own immunologic acceptance, since sperm and placental trophoblast cells are unusual and unique in their antigen presenting molecule expression patterns. Here, we will discuss these and other mechanisms that allow the human female reproductive tract to perform this delicate and indispensible balancing act.

  17. Shift Work and Endocrine Disorders

    Directory of Open Access Journals (Sweden)

    M. A. Ulhôa

    2015-01-01

    Full Text Available The objective of this review was to investigate the impact of shift and night work on metabolic processes and the role of alterations in the sleep-wake cycle and feeding times and environmental changes in the occurrence of metabolic disorders. The literature review was performed by searching three electronic databases for relevant studies published in the last 10 years. The methodological quality of each study was assessed, and best-evidence synthesis was applied to draw conclusions. The literature has shown changes in concentrations of melatonin, cortisol, ghrelin, and leptin among shift workers. Melatonin has been implicated for its role in the synthesis and action of insulin. The action of this hormone also regulates the expression of transporter glucose type 4 or triggers phosphorylation of the insulin receptor. Therefore, a reduction in melatonin can be associated with an increase in insulin resistance and a propensity for the development of diabetes. Moreover, shift work can negatively affect sleep and contribute to sedentarism, unhealthy eating habits, and stress. Recent studies on metabolic processes have increasingly revealed their complexity. Physiological changes induced in workers who invert their activity-rest cycle to fulfill work hours include disruptions in metabolic processes.

  18. Innate immunity

    African Journals Online (AJOL)

    Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

  19. AB115. Preliminary study on the immune status of patients with prostate cancer

    OpenAIRE

    He, Jingliang; He, Leye

    2014-01-01

    Objective To preliminarily assess the immune status of patients with prostate cancer through detecting various immune indexs and then analyse the relationship between immune status and clinical factors such as clinical stage, pathological classification and endocrine therapy. Methods Flow cytometry was used to detect the percentage of CD4, CD8and NK cells in peripheral blood lymphocyte (PBL) of 28 patients with PCa, 16 BPH patients and ten healthy men (HM). The expression of perforin and gran...

  20. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  1. The influence of pregnancy on systemic immunity.

    Science.gov (United States)

    Pazos, Michael; Sperling, Rhoda S; Moran, Thomas M; Kraus, Thomas A

    2012-12-01

    Adaptations in maternal systemic immunity are presumed to be responsible for observed alterations in disease susceptibility and severity as pregnancy progresses. Epidemiological evidence as well as animal studies have shown that influenza infections are more severe during the second and third trimesters of pregnancy, resulting in greater morbidity and mortality, although the reason for this is still unclear. Our laboratory has taken advantage of 20 years of experience studying the murine immune response to respiratory viruses to address questions of altered immunity during pregnancy. With clinical studies and unique animal model systems, we are working to define the mechanisms responsible for altered immune responses to influenza infection during pregnancy and what roles hormones such as estrogen or progesterone play in these alterations.

  2. Co-administration of plasmid expressing IL-12 with 14-kDa Schistosoma mansoni fatty acid-binding protein cDNA alters immune response profiles and fails to enhance protection induced by Sm14 DNA vaccine alone.

    Science.gov (United States)

    Fonseca, Cristina T; Pacífico, Lucila G G; Barsante, Michele M; Rassi, Tatiana; Cassali, Geovanni D; Oliveira, Sérgio C

    2006-08-01

    Schistosomiasis is an endemic disease that affects 200 million people worldwide. DNA-based vaccine is a promising strategy to induce protective immunity against schistosomiasis, since both humoral and cellular immune responses are involved in parasite elimination. In this study, we evaluated the ability of Sm14 cDNA alone or in association with a plasmid expressing murine interleukin (IL)-12 to induce protection against challenge infection. Mice were immunized with four doses of the DNA vaccine and the levels of protection were determined by worm burden recovery after challenge infection. Specific antibody production to rSm14 was determined by ELISA, and cytokine production was measured in splenocyte culture supernatants stimulated with rSm14 and in bronchoalveolar lavage of vaccinated mice after challenge infection. DNA immunization with pCI/Sm14 alone induced 40.5% of worm reduction. However, the use of pCI/IL-12 as adjuvant to pCI/Sm14 immunization failed to enhance protection against challenge infection. Protection induced by pCI/Sm14 immunization correlates with specific IgG antibody production against Sm14, Th1 type of immune response with high levels of interferon (IFN)-gamma and low levels of IL-4 in splenocyte culture supernatants and in bronchoalveolar lavage after challenge infection. IL-12 co-administration with pCI/Sm14 induced a significant production of nitric oxide in splenocyte culture supernatants and also lymphocyte suppression, with reduced percentage of T cells producing IFN-gamma and tumor necrosis factor-alpha.

  3. Nutrition, immune function and health of dairy cattle

    DEFF Research Database (Denmark)

    Ingvartsen, Klaus Lønne; Moyes, Kasey

    2013-01-01

    not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our......) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where...... the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response...

  4. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    Directory of Open Access Journals (Sweden)

    P. V. Novokhatny

    2014-02-01

    Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

  5. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

  6. [Chronic heart failure and cachexia: role of endocrine system].

    Science.gov (United States)

    Dei Cas, A; Muoio, A; Zavaroni, I

    2011-12-01

    Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

  7. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  8. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  9. No effects of acclimation to heat on immune and hormonal responses to passive heating in healthy volunteers

    Science.gov (United States)

    Kanikowska, Dominika; Sato, Maki; Sugenoya, Junichi; Iwase, Satoshi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko

    2012-01-01

    Heat acclimation results in whole body-adaptations that increase heat tolerance, and might also result in changed immune responses. We hypothesized that, after heat acclimation, tumor necrosis factor alpha, interleukin 6 and the lymphocyte count would be altered. Heat acclimation was induced in 6 healthy men by 100 min of heat exposure for 9 days. Heat exposure consisted of (1) 10 min of immersion up to chest-level in water at 42°C and (2) 90 min of passive heating by a warm blanket to maintain tympanic temperature at 37.5°C. The climatic chamber was maintained at 40°C and a relative humidity of 50%. Blood samples were analyzed before and after heat acclimation for natural killer (NK) cell activity, counts of lymphocytes B and T, before and after heat acclimation for peripheral blood morphology, interleukin 6, tumor necrosis factor alpha, and cortisol. A Japanese version of the profile of mood states questionnaire was also administered before and after acclimation. The concentrations of white blood cells, lymphocytes B and T, cortisol, interleukin 6, tumor necrosis factor alpha and NK cell activity showed no significant differences between pre- and post-acclimation, but there was a significantly lower platelet count after acclimation and, with the profile of mood states questionnaire, there was a significant rise in anger after acclimation. It is concluded that heat acclimation by passive heating does not induce alterations in immune or endocrine responses.

  10. New-tools to assess the toxicological hazard of endocrine disruptor organoclorine contaminants in Mediterranean cetaceans

    Energy Technology Data Exchange (ETDEWEB)

    M. Cristina Fossi; Marsili, L.; Casini, S. [Dept. of Environmental Sciences, Univ. of Siena (Italy)

    2004-09-15

    The Mediterranean top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants (OCs), incurring high toxicological risk. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Four types of organochlorine endocrine disruptors are commonly found in Mediterranean cetaceans: (1) environmental estrogens, (2) environmental androgens, (3) anti-estrogens and (4) anti-androgens. Endocrine disruptors act by mimicking sex steroid hormones, both estrogens and androgens, by binding to hormone receptors or influencing cell pathways (environmental estrogens and androgens), or by blocking and altering hormone receptor binding (anti-estrogens, antiandrogens). Environmental estrogens are the most common and most widely studied EDCs. The relative estrogenic power of these chemicals, identified by in vitro and in vivo screening methods is rather weak (10{sup -3} or less) compared with the reference power of 17-estradiol or DES. However, the high levels of organochlorine compounds detected in marine mammals, particularly in pinnipeds and odontocetes, and consequently, the high levels of organochlorines with ED capacity, cannot be ignored. Here the hypothesis that some Mediterranean cetaceans (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus) are ''potentially at risk'' due to organochlorines with endocrine disrupting capacity is investigated using new non-lethal tools. As ''diagnostic'' tool we use benzo(a)pyrene monooxygenase (CYP1A1) activity in skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. As ''prognostic'' tool we propose the immunofluorescence technique in fibroblast cell cultures, for a qualitative and quantitative evaluation of the target

  11. Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

    Science.gov (United States)

    Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

    2014-03-01

    Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

  12. Endocrine cells in the denervated intestine

    Science.gov (United States)

    Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

    2000-01-01

    This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

  13. Monogenic autoimmune diseases of the endocrine system.

    Science.gov (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Childhood obesity and endocrine disrupting chemicals

    Directory of Open Access Journals (Sweden)

    Jin Taek Kim

    2017-12-01

    Full Text Available The prevalence of obesity around the world has increased sharply. Strong evidence has emerged over the last decades that human exposure to numerous endocrine disrupting chemicals (EDCs is the cause of obesity and obesity-related metabolic diseases. Many EDCs are manmade chemicals that are released into the environment. EDCs are exogenous compounds that interfere with hormonal regulation and normal endocrine systems, thereby affecting the health of animals and humans. The number of chemicals belonging to EDCs is increasing and some of them are very stable; they persist in the environment (persistent organic pollutants. Although they are banned, their concentrations have been continuously increasing over time. This review gives a brief introduction to common EDCs, and evidence of harmful effects of EDCs on obesity-related diseases; we focus in particular on EDCs’ role in causing mitochondrial dysfunction.

  15. Endoplasmic Reticulum (ER Stress and Endocrine Disorders

    Directory of Open Access Journals (Sweden)

    Daisuke Ariyasu

    2017-02-01

    Full Text Available The endoplasmic reticulum (ER is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR, which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI, Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2 are discussed in this article.

  16. Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

    Science.gov (United States)

    Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

    2017-01-01

    The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

  17. Endocrine consequences of irradiation and cancer chemotherapy

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.

    1981-01-01

    A brief review is presented of endocrine dysfunction as a long-term effect of radiotherapy and cancer chemotherapy, with particular reference to children, and to Hodgkin's disease. The hypothalamus and pituitary, growth hormone and thyroid stimulating hormone, thyroid and parathyroid, and gonads are discussed. Suggestions are made for long-term measures to be taken, such as measuring growth rates, L-thyroxine replacement, sperm storage, etc. (U.K.)

  18. The endolymphatic sac, a potential endocrine gland?

    DEFF Research Database (Denmark)

    Qvortrup, K; Rostgaard, J; Holstein-Rathlou, N H

    1999-01-01

    A previous investigation indicated that the chief cells of the endolymphatic sac produce an endogenous inhibitor of sodium re-absorption in the kidneys, which has tentatively been named "saccin". In this study, the ultrastructure of the endolymphatic sac and in particular the chief cells...... is described, demonstrating that this organ fulfils the morphological criteria of a potential endocrine gland. Accordingly, the chief cells are shown to exhibit all the organelles and characteristics of cells that simultaneously synthesize, secrete, absorb and digest proteins....

  19. Endocrine tumors associated with the vagusnerve

    OpenAIRE

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-01-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural-crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from ...

  20. Essential Medicines for Children: An Endocrine Perspective

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2014-11-01

    Full Text Available The emergence of endocrine disease has created significant challenges for healthcare policy-makers and payers across the world. Policy-makers have to ensure availability of drugs used for various endocrinopathies. One way in which this is facilitated is through the World Health Organization (WHO List of Essential Medicines (LEM. The LEM aims to cover the basic pharmaceutical needs of the majority of people seeking healthcare (1.

  1. Endocrine dysfunction in patients of leprosy

    Directory of Open Access Journals (Sweden)

    Rohit Kumar Singh

    2015-01-01

    Full Text Available Background: Leprosy is a chronic granulomatous disease and affects many internal organs in addition to the skin and peripheral nerves. Endocrine dysfunction is often silent and is often missed in patients of leprosy leading to significant morbidity. We studied the presence of occult endocrine disorders in leprosy patients and compared the same with disease parameters. Materials and Methods: We evaluated 40 patients of leprosy (aged 18-70 years, any duration in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, gonadal function, and dynamic testing was done when deemed necessary. The participants were divided into two groups: Group 1 (Leprosy, n = 40 and Group 2 (Controls, n = 20 and the data were analyzed with appropriate statistical tests. Results: The study participants (35 males, 5 females had a mean age of 36.4 ± 11.3 years, and duration of the disease was 2.5 ± 5.5 years. Eleven out of 40 patients showed results consistent with an endocrine disorder, including subclinical hypothyroidism (n = 4, sick euthyroid syndrome (n = 3, growth hormone (GH deficiency (n = 2, primary hypogonadism (n = 2 and secondary hypogonadism in one patient. One patient had partial hypopituitarism (GH deficiency and secondary hypogonadism and none of the controls showed any hormonal dysfunction. Testosterone levels showed inverse correlation with the number of skin patches (P = 0.0006. Conclusion: Occult endocrine dysfunction is seen in a quarter of patients with leprosy. Thyroid and gonadal axes abnormalities are common, and the severity is more in lepromatous forms of the disease. Further large studies are required to confirm the findings observed in our study.

  2. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    OpenAIRE

    P. V. Novokhatny

    2014-01-01

    Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study...

  3. Monitoring and risk assessment for endocrine disruptors in the aquatic environment: a biomarker approach

    Energy Technology Data Exchange (ETDEWEB)

    Bjerregaard, P.; Korsgaard, B.; Christiansen, L.B.; Pedersen, K.L.; Christensen, L.J.; Pedersen, S.N.; Horn, P. [Odense Univ. (Denmark). Biologisk Inst.

    1998-12-31

    Evidence that a number of chemicals affect wildlife populations or individuals via interaction with endocrine systems has been increasing in recent years. Not all of the mechanisms of action are fully understood, but endocrine disrupting chemicals may work at various biochemical levels, e.g. affecting the synthesis of hormones, interfering with hormone transporting proteins in the blood, affecting the metabolisation of hormones or by direct effects on cellular hormone receptors. In dogwhelks Nucella lapillus tributyltin inhibits the aromatase that converts testosterone to oestrogen thereby masculinising the females (Oehlmann et al. 1996). Metabolites of polychlorinated biphenyls interfere with thyroxin transporting proteins in the blood of seals. Chemicals that induce MFO-activity may indirectly lead to altered hormone levels by increasing the metabolisation of hormones. Alkylphenols react directly with the oestrogen receptor which in turn may lead to feminisation of male organisms exposed. (orig.)

  4. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.

    Science.gov (United States)

    Gore, A C; Chappell, V A; Fenton, S E; Flaws, J A; Nadal, A; Prins, G S; Toppari, J; Zoeller, R T

    2015-12-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health.

  5. Prenatal immune challenge in rats: Altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to Poly IC

    OpenAIRE

    Vorhees, Charles V.; Graham, Devon L.; Braun, Amanda A.; Schaefer, Tori L.; Skelton, Matthew R.; Richtand, Neil M.; Williams, Michael T.

    2012-01-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into th...

  6. Hedgehog signaling: endocrine gland development and function.

    Science.gov (United States)

    Cohen, M Michael

    2010-01-01

    The role of hedgehog signaling is analyzed in relation to the developing endocrine glands: pituitary, ovary, testis, adrenal cortex, pancreas, prostate, and epiphyseal growth. Experimental and pathological correlates of these organs are also discussed. The second section addresses a number of topics. First, the pituitary gland, no matter how hypoplastic, is present in most cases of human holoprosencephaly, unlike animals in which it is always said to be absent. The difference appears to be that animal mutations and teratogenic models involve both copies of the gene in question, whereas in humans the condition is most commonly heterozygous. Second, tests of endocrine function are not reported with great frequency, and an early demise in severe cases of holoprosencephaly accounts for this trend. Reported tests of endocrine function are reviewed. Third, diabetes insipidus has been recorded in a number of cases of holoprosencephaly. Its frequency is unknown because it could be masked by adrenal insufficiency in some cases and may not be recognized in others. Because of the abnormal hypothalamic-infundibular region in holoprosencephaly, diabetes insipidus could be caused by a defect in the supra-optic or paraventricular hypothalamic nuclei or in release of ADH via the infundibulum and posterior pituitary.

  7. Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease.

    Science.gov (United States)

    Anway, Matthew D; Skinner, Michael K

    2008-04-01

    The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.

  8. Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Meirong [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Chen Fang [College of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310018 (China); Wang Cui; Zhang Quan [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Gan Jianying [Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Liu Weiping, E-mail: wliu@zjut.edu.c [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China)

    2010-05-15

    The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study. - Chiral contaminants should consider multiple effects and relate directions of enantioselectivity to their interplaying processes.

  9. Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids

    International Nuclear Information System (INIS)

    Zhao Meirong; Chen Fang; Wang Cui; Zhang Quan; Gan Jianying; Liu Weiping

    2010-01-01

    The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study. - Chiral contaminants should consider multiple effects and relate directions of enantioselectivity to their interplaying processes.

  10. Hormones in the immune system and their possible role. A critical review.

    Science.gov (United States)

    Csaba, György

    2014-09-01

    Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

  11. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  12. Immunizing Adults

    Centers for Disease Control (CDC) Podcasts

    Vaccines aren’t just for kids; adults also need to get immunized. Overall, far too many people 19 years and older aren’t getting the vaccines they need and remain unprotected. In this podcast, Dr. Walter Williams discuss the importance of adults being fully vaccinated.

  13. Deceptive Imprinting and Immune Refocusing in Vaccine Design

    Science.gov (United States)

    A large number of the world’s most widespread and problematic pathogens evade host immune responses by inducing strain specific immunity to immunodominant epitopes with high mutation rates capable of altering antigenic profiles. The immune system appears to be decoyed into reacting to these immunod...

  14. Immune-mediated diseases and microbial exposure in early life

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...

  15. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  16. Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol.

    Science.gov (United States)

    Klopčič, Ivana; Markovič, Tijana; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

    2018-05-16

    A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR). The endocrine disrupting effects were assessed in vitro in MDA-kb2 and GH3.TRE-Luc cell lines and by the XenoScreen YES/YAS assay. Moreover, binding affinity to nuclear receptors (GR and AR) was also measured. Immunomodulatory properties of the compounds were evaluated in lymphoblastoid cell lines. All the tested compounds showed endocrine disrupting and immunomodulatory activities. The results revealed that both DIC and its metabolite 4-HD exhibited significant estrogenic, anti-androgenic (in YAS assay), (anti)-androgenic, (anti)-glucocorticoid and anti-thyroid hormonal activities (in luciferase reporter gene assays). DIC showed direct binding to the GR, while its metabolite 4-HD to the GR and AR. Only metabolite 4-HD showed estrogenic, androgenic (in YAS assay) and thyroid-hormonal activities. PAR had anti-androgenic activity and anti-thyroid hormonal activity. PAR displayed GR agonist activity with competition to its receptor and agonistic activity to AR. All of the compounds significantly modulated pro-inflammatory and immunoregulatory cytokine production in lymphoblastoid cell lines and were thus proven immunomodulatory. The study is useful in determining toxicological effects and contributes to the knowledge of possible side effects of diclofenac, its metabolite and paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Syndromes that Link the Endocrine System and Genitourinary Tract.

    Science.gov (United States)

    Özlük, Yasemin; Kılıçaslan, Işın

    2015-01-01

    The endocrine system and genitourinary tract unite in various syndromes. Genitourinary malignancies may cause paraneoplastic endocrine syndromes by secreting hormonal substances. These entities include Cushing`s syndrome, hypercalcemia, hyperglycemia, polycythemia, hypertension, and inappropriate ADH or HCG production. The most important syndromic scenarios that links these two systems are hereditary renal cancer syndromes with specific genotype/phenotype correlation. There are also some very rare entities in which endocrine and genitourinary systems are involved such as Carney complex, congenital adrenal hyperplasia and Beckwith-Wiedemann syndrome. We will review all the syndromes regarding manifestations present in endocrine and genitourinary organs.

  18. The eunuchs of India: An endocrine eye opener

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2012-01-01

    Full Text Available There are established guidelines for the endocrine and overall treatment of transsexual persons. These guidelines provide information about the optimal endocrine management of male-to-female and female-to-male transsexual persons. India has a large community of eunuchs, also known as hijras, who are men with gender identity disorders. While this community has been studied from a social and medical point of new, no endocrine work has been done in them. This exploratory article tries to discuss the endocrine status, health, and management of the eunuchs.

  19. REST represses a subset of the pancreatic endocrine differentiation program

    DEFF Research Database (Denmark)

    Martin, David; Kim, Yung-Hae; Sever, Dror

    2015-01-01

    in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic...... endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3...

  20. Obesity, Fat Mass and Immune System: Role for Leptin

    Directory of Open Access Journals (Sweden)

    Vera Francisco

    2018-06-01

    Full Text Available Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

  1. Endocrine active chemicals and endocrine disruption in Minnesota streams and lakes: implications for aquatic resources, 1994-2008

    Science.gov (United States)

    Lee, Kathy E.; Schoenfuss, Heiko L.; Barber, Larry B.; Writer, Jeff H.; Blazer, Vicki; Keisling, Richard L.; Ferrey, Mark L.

    2010-01-01

    The U.S. Geological Survey, in cooperation with St. Cloud State University, Minnesota Department of Health, Minnesota Pollution Control Agency, Minnesota Department of Natural Resources, Metropolitan Council Environmental Services, and the University of Minnesota, has conducted field monitoring studies and laboratory research to determine the presence of endocrine active chemicals and the incidence of endocrine disruption in Minnesota streams and lakes during 1994–2008. Endocrine active chemicals are chemicals that interfere with the natural regulation of endocrine systems, and may mimic or block the function of natural hormones in fish or other organisms. This interference commonly is referred to as endocrine disruption. Indicators of endocrine disruption in fish include vitellogenin (female egg yolk protein normally expressed in female fish) in male fish, oocytes present in male fish testes, reduced reproductive success, and changes in reproductive behavior.

  2. Microbial endocrinology: the interplay between the microbiota and the endocrine system.

    Science.gov (United States)

    Neuman, Hadar; Debelius, Justine W; Knight, Rob; Koren, Omry

    2015-07-01

    The new field of microbiome research studies the microbes within multicellular hosts and the many effects of these microbes on the host's health and well-being. We now know that microbes influence metabolism, immunity and even behavior. Essential questions, which are just starting to be answered, are what are the mechanisms by which these bacteria affect specific host characteristics. One important but understudied mechanism appears to involve hormones. Although the precise pathways of microbiota-hormonal signaling have not yet been deciphered, specific changes in hormone levels correlate with the presence of the gut microbiota. The microbiota produces and secretes hormones, responds to host hormones and regulates expression levels of host hormones. Here, we summarize the links between the endocrine system and the gut microbiota. We categorize these interactions by the different functions of the hormones, including those affecting behavior, sexual attraction, appetite and metabolism, gender and immunity. Future research in this area will reveal additional connections, and elucidate the pathways and consequences of bacterial interactions with the host endocrine system. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.

    Science.gov (United States)

    Hofmann, Lars; Forschner, Andrea; Loquai, Carmen; Goldinger, Simone M; Zimmer, Lisa; Ugurel, Selma; Schmidgen, Maria I; Gutzmer, Ralf; Utikal, Jochen S; Göppner, Daniela; Hassel, Jessica C; Meier, Friedegund; Tietze, Julia K; Thomas, Ioannis; Weishaupt, Carsten; Leverkus, Martin; Wahl, Renate; Dietrich, Ursula; Garbe, Claus; Kirchberger, Michael C; Eigentler, Thomas; Berking, Carola; Gesierich, Anja; Krackhardt, Angela M; Schadendorf, Dirk; Schuler, Gerold; Dummer, Reinhard; Heinzerling, Lucie M

    2016-06-01

    Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis. Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

    Science.gov (United States)

    Altieri, Barbara; Muscogiuri, Giovanna; Barrea, Luigi; Mathieu, Chantal; Vallone, Carla V; Mascitelli, Luca; Bizzaro, Giorgia; Altieri, Vincenzo M; Tirabassi, Giacomo; Balercia, Giancarlo; Savastano, Silvia; Bizzaro, Nicola; Ronchi, Cristina L; Colao, Annamaria; Pontecorvi, Alfredo; Della Casa, Silvia

    2017-09-01

    In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

  5. Well differentiated endocrine carcinomas of the pancreas

    Directory of Open Access Journals (Sweden)

    Čolović Radoje

    2011-01-01

    Full Text Available Introduction. For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. Objective. The aim of the study was to point out the importance of such treatment. Methods. Over a 6-year period eight patients (seven female and one male of average age 51 years (ranging from 23 to 71 years were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple’s procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple’s procedure a month later. Results. R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. Conclusion. With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas.

  6. Practice of the integrated endocrine system course

    Institute of Scientific and Technical Information of China (English)

    Wen-han MEI; Rong CAI

    2015-01-01

    The integrated curriculum is an important direction of the medical medical education reform under new situation and challenges of medical development.Shanghai Jiao Tong University School of Medicine has implemented the integrated curriculum reform in recent years.The endocrine system course is one of important intergrated courses and integrates relevant contents of multiple disciplines of basic medicine,diagnostics and medical imaging.Various teaching methods are adopted,such as classroom lecture,discussion,problembased learning,experimental lesson and clinical clerkship,etc.The teaching practice is carried on in several aspects:course arrangement,teaching methods,course website construction,teaching team construction and so on.

  7. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  8. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  10. In vitro steroid profiling system for the evaluation of endocrine disruptors.

    Science.gov (United States)

    Nakano, Yosuke; Yamashita, Toshiyuki; Okuno, Masashi; Fukusaki, Eiichiro; Bamba, Takeshi

    2016-09-01

    Endocrine disruptors (ED) are chemicals that affect various aspects of the endocrine system, often leading to the inhibition of steroidogenesis. Current chemical safety policies that restrict human exposure to such chemicals describe often time-consuming and costly methods for the evaluation of ED effects. We aimed to develop an effective tool for accurate phenotypic chemical toxicology studies. We developed an in vitro ED evaluation system using gas chromatography/mass spectrometry (GC/MS/MS) methods for metabolomic analysis of multi-marker profiles. Accounting for sample preparation and GC/MS/MS conditions, we established a screening method that allowed the simultaneous analysis of 17 steroids with good reproducibility and a linear calibration curve. Moreover, we applied the developed system to H295R human adrenocortical cells exposed to forskolin and prochloraz in accordance with the Organization for Economic Cooperation and Development (OECD) guidelines and observed dose-dependent variations in steroid profiles. While the OECD guidelines include only testosterone and 17β-estradiol, our system enabled a comprehensive and highly sensitive analysis of steroid profile alteration due to ED exposure. The application of our ED evaluation screen could be economical and provide novel insights into the hazards of ED exposure to the endocrine system. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  11. A possible role for the canonical Wnt pathway in endocrine cell development in chicks

    International Nuclear Information System (INIS)

    Pedersen, Anna Hauntoft; Heller, R. Scott

    2005-01-01

    Wnt signalling is involved in many developmental processes such as proliferation, differentiation, cell fate decisions, and morphogenesis. However, little is known about Wnt signalling during pancreas development. Multiple Wnt ligands and Frizzled receptors are expressed in the embryonic mouse pancreas, the surrounding mesenchyme, and have also been detected in the chicken endoderm during development. The aim of this study was to investigate the role of canonical Wnt signalling on endocrine cell development by use of the in ovo electroporation of the chicken endoderm. Overexpression with a constitutive active form of β-catenin in combination with Ngn3 resulted in reduced numbers of glucagon cells. dnLEF-1 or naked-1 did not alter endocrine cell differentiation when co-expressed with Ngn3, but dnLEF-1 appeared to have some potential for inhibiting delamination of Ngn3 cells. In addition, neuronal β-III-tubulin, which had previously been considered a specific marker for neuronal cells, was observed in the pancreas and was upregulated in the electroporated Ngn3 cells and thus may be a new endocrine marker in the chicken

  12. Transformation techniques for cross-sectional and longitudinal endocrine data: application to salivary cortisol concentrations.

    Science.gov (United States)

    Miller, Robert; Plessow, Franziska

    2013-06-01

    Endocrine time series often lack normality and homoscedasticity most likely due to the non-linear dynamics of their natural determinants and the immanent characteristics of the biochemical analysis tools, respectively. As a consequence, data transformation (e.g., log-transformation) is frequently applied to enable general linear model-based analyses. However, to date, data transformation techniques substantially vary across studies and the question of which is the optimum power transformation remains to be addressed. The present report aims to provide a common solution for the analysis of endocrine time series by systematically comparing different power transformations with regard to their impact on data normality and homoscedasticity. For this, a variety of power transformations of the Box-Cox family were applied to salivary cortisol data of 309 healthy participants sampled in temporal proximity to a psychosocial stressor (the Trier Social Stress Test). Whereas our analyses show that un- as well as log-transformed data are inferior in terms of meeting normality and homoscedasticity, they also provide optimum transformations for both, cross-sectional cortisol samples reflecting the distributional concentration equilibrium and longitudinal cortisol time series comprising systematically altered hormone distributions that result from simultaneously elicited pulsatile change and continuous elimination processes. Considering these dynamics of endocrine oscillations, data transformation prior to testing GLMs seems mandatory to minimize biased results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Analysis of Endocrine Disrupting Pesticides by Capillary GC with Mass Spectrometric Detection

    Directory of Open Access Journals (Sweden)

    Svetlana Hrouzková

    2012-09-01

    Full Text Available Endocrine disrupting chemicals, among them many pesticides, alter the