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Sample records for affect endocrine function

  1. Marital Conflict and Endocrine Function: Are Men Really More Physiologically Affected than Women?.

    ERIC Educational Resources Information Center

    Kiecolt-Glaser, Janice K.; And Others

    1996-01-01

    Assessed marital conflict and endocrine function in 90 newlywed couples. Blood samples were examined to provide composite and daytime values for three stress hormones and three related hormones. Data provided a window on endocrine function in couples for whom the day included conflicts. Discusses findings in the context of gender models of marital…

  2. Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

    PubMed

    Guarraci, Fay A; Holifield, Caroline; Morales-Valenzuela, Jessica; Greene, Kasera; Brown, Jeanette; Lopez, Rebecca; Crandall, Christina; Gibbs, Nicole; Vela, Rebekah; Delgado, Melissa Y; Frohardt, Russell J

    2016-03-01

    The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli.

  3. [Affective disorders: endocrine and metabolic comorbidities].

    PubMed

    Cermolacce, M; Belzeaux, R; Adida, M; Azorin, J-M

    2014-12-01

    Links between affective and endocrine-metabolic disorders are numerous and complex. In this review, we explore most frequent endocrine-metabolic comorbidities. On the one hand, these comorbidities imply numerous iatrogenic effects from antipsychotics (metabolic side-effects) or from lithium (endocrine side-effects). On the other hand, these comorbidities are also associated with affective disorders independently from medication. We will successively examine metabolic syndrome, glycemic disturbances, obesity and thyroid disorders among patients with affective disorders. Endocrinemetabolic comorbidities can be individually encountered, but can also be associated. Therefore, they substantially impact morbidity and mortality by increasing cardiovascular risk factors. Two distinct approaches give an account of processes involved in these comorbidities: common environmental factors (iatrogenic effects, lifestyle), and/or shared physiological vulnerabilities. In conclusion, we provide a synthesis of important results and recommendations related to endocrine-metabolic comorbidities in affective disorders : heavy influence on morbidity and mortality, undertreatment of somatic diseases, importance of endocrine and metabolic side effects from main mood stabilizers, impact from sex and age on the prevalence of comorbidities, influence from previous depressive episodes in bipolar disorders, and relevance of systematic screening for subclinical (biological) disturbances.

  4. Anatomical and functional imaging in endocrine hypertension

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2012-01-01

    In endocrine hypertension, hormonal excess results in clinically significant hypertension. The functional imaging (such as radionuclide imaging) complements anatomy-based imaging (such as ultrasound, computed tomography, and magnetic resonance imaging) to facilitate diagnostic localization of a lesion causing endocrine hypertension. The aim of this review article is to familiarize general radiologists, endocrinologists, and clinicians with various anatomical and functional imaging techniques used in patients with endocrine hypertension. PMID:23087854

  5. How does obesity affect the endocrine system? A narrative review.

    PubMed

    Poddar, M; Chetty, Y; Chetty, V T

    2017-03-15

    Obesity is a chronic, relapsing medical condition that results from an imbalance of energy expenditure and consumption. It is a leading cause of preventable illness, disability and premature death. The causes of obesity are multifactorial and include behavioural, socioeconomic, genetic, environmental and psychosocial factors. Rarely are endocrine diseases, e.g., hypothyroidism or Cushing's syndrome, the cause of obesity. What is less understood is how obesity affects the endocrine system. In this review, we will discuss the impact of obesity on multiple endocrine systems, including the hypothalamic-pituitary axis, changes in vitamin D homeostasis, gender steroids and thyroid hormones. We will also examine the renin angiotensin aldosterone system and insulin pathophysiology associated with obesity. We will provide a general overview of the biochemical changes that can be seen in patients with obesity, review possible aetiologies of these changes and briefly consider current guidelines on their management. This review will not discuss endocrine causes of obesity.

  6. Environmental exposures that affect the endocrine system: public health implications.

    PubMed

    DeRosa, C; Richter, P; Pohl, H; Jones, D E

    1998-01-01

    In recent years much attention has been focused on the potential for a wide range of xenobiotic chemicals to interact with and disrupt the endocrine systems of animal and human populations. An overview of the chemicals that have been implicated as endocrine disruptors is presented. The ubiquity in the environment and associated body burdens of these chemicals in human populations are described. Potential mechanisms of action are reviewed, including the role of specific intracellular receptors and their interactions with endogenous and exogenous materials. The subsequent upregulation or downregulation of physiological processes at critical stages of development is discussed. The potential for joint toxic action and interaction of chemical mixtures is also discussed. The acknowledged role of wildlife populations as sentinels of potential human health effects is reviewed, and the weight of evidence for the role and impact of endocrine disruptors is presented. The implications of exposure to endocrine-disrupting chemicals for human health are reviewed, with special emphasis on the potential for transgenerational effects in at-risk populations. Recommendations for future research include the development of (1) structural activity and in vivo and in vitro functional toxicology methods to screen chemicals for their endocrine-disrupting ability, (2) biomarkers of exposure and effect, and (3) in situ sentinel systems.

  7. Endocrine disrupters: the new players able to affect the epigenome

    PubMed Central

    Casati, Lavinia; Sendra, Ramon; Sibilia, Valeria; Celotti, Fabio

    2015-01-01

    Epigenetics represents the way by which the environment is able to program the genome; there are three main levels of epigenetic control on genome: DNA methylation, post-translational histone modification and microRNA expression. The term Epigenetics has been widened by NIH to include “both heritable changes in gene activity and expression but also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable.” These changes might be produced mostly by the early life environment and might affect health influencing the susceptibility to develop diseases, from cancer to mental disorder, during the entire life span. The most studied environmental influences acting on epigenome are diet, infections, wasting, child care, smoking and environmental pollutants, in particular endocrine disrupters (EDs). These are environmental xenobiotics able to interfere with the normal development of the male and female reproductive systems of wildlife, of experimental animals and possibly of humans, disrupting the normal reproductive functions. Data from literature indicate that EDs can act at different levels of epigenetic control, in some cases transgenerationally, in particular when the exposure to these compounds occurs during the prenatal and earliest period of life. Some of the best characterized EDs will be considered in this review. Among the EDs, vinclozolin (VZ), and methoxychlor (MXC) promote epigenetic transgenerational effects. Polychlorinated biphenils (PCBs), the most widespread environmental EDs, affect histone post-translational modifications in a dimorphic way, possibly as the result of an alteration of gene expression of the enzymes involved in histone modification, as the demethylase Jarid1b, an enzyme also involved in regulating the interaction of androgens with their receptor. PMID:26151052

  8. Mitochondria and endocrine function of adipose tissue.

    PubMed

    Medina-Gómez, Gema

    2012-12-01

    Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications. White adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose tissue with higher oxidative capacity. Nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis. Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D. This review discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future.

  9. Autonomic and endocrine control of cardiovascular function

    PubMed Central

    Gordan, Richard; Gwathmey, Judith K; Xie, Lai-Hua

    2015-01-01

    The function of the heart is to contract and pump oxygenated blood to the body and deoxygenated blood to the lungs. To achieve this goal, a normal human heart must beat regularly and continuously for one’s entire life. Heartbeats originate from the rhythmic pacing discharge from the sinoatrial (SA) node within the heart itself. In the absence of extrinsic neural or hormonal influences, the SA node pacing rate would be about 100 beats per minute. Heart rate and cardiac output, however, must vary in response to the needs of the body’s cells for oxygen and nutrients under varying conditions. In order to respond rapidly to the changing requirements of the body’s tissues, the heart rate and contractility are regulated by the nervous system, hormones, and other factors. Here we review how the cardiovascular system is controlled and influenced by not only a unique intrinsic system, but is also heavily influenced by the autonomic nervous system as well as the endocrine system. PMID:25914789

  10. Endocrine disrupting chemicals affect the gonadotropin releasing hormone neuronal network.

    PubMed

    Mueller, Johanna K; Heger, Sabine

    2014-04-01

    Endocrine disrupting chemicals have been shown to alter the pubertal process. The controlling levels of the Gonadotropin releasing hormone (GnRH) network involve GnRH itself, KiSS1, and the transcriptional regulators enhanced at puberty 1 (EAP1), Thyroid Transcription Factor 1 (TTF1), and Yin Yang 1 (YY1). While Genistein and Bisphenol A (BPA) have been shown to advance the advent of puberty, exposure to Dioxin delayed pubertal onset. Utilizing in vitro approaches, we observed that Genistein and BPA suppress inhibitory and activate stimulatory components of the GnRH network, while Dioxin exhibit an inhibitory effect at all regulatory hierarchical levels of the GnRH network. It repressed KiSS1, Gnrh, Ttf1 and Yy1 transcription via the xenobiotic response element (XRE), while EAP1 was not affected. Therefore, EDCs alter the neuroendocrine GnRH regulatory network at all hierarchical levels.

  11. Ferrocene Functionalized Endocrine Modulators as Anticancer Agents

    NASA Astrophysics Data System (ADS)

    Hillard, Elizabeth A.; Vessières, Anne; Jaouen, Gerard

    We present here some of our studies on the synthesis and behaviour of ferrocenyl selective endocrine receptor modulators against cancer cells, particularly breast and prostate cancers. The proliferative/anti-proliferative effects of compounds based on steroidal and non-steroidal endocrine modulators have been extensively explored in vitro. Structure-activity relationship studies of such molecules, particularly the hydroxyferrocifens and ferrocene phenols, have shown the effect of (1) the presence and the length of the N,N-dimethylamino side chain, (2) the presence and position of the phenol group, (3) the role of the ferrocenyl moiety, (4) that of conjugation, (5) phenyl functionalisation and (6) the placement of the phenyl group. Compounds possessing a ferrocene moiety linked to a p-phenol by a conjugated π-system are among the most potent of the series, with IC50 values ranging from 0.090 to 0.6µM on hormone independent breast cancer cells. Based on the SAR data and electrochemical studies, we have proposed an original mechanism to explain the unusual behaviour of these bioorganometallic species and coin the term "kronatropic" to qualify this effect, involving ROS production and bio-oxidation. In addition, the importance of formulation is underlined. We also discuss the behaviour of ferrocenyl androgens and anti-androgens for possible use against prostate cancers. In sum, ferrocene has proven to be a fascinating substituent due to its vast potential for oncology.

  12. Endocrine disruptors and Leydig cell function.

    PubMed

    Svechnikov, K; Izzo, G; Landreh, L; Weisser, J; Söder, O

    2010-01-01

    During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  13. ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

    PubMed Central

    Weiss, Bernard

    2011-01-01

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

  14. Endocrine disruptors as a threat to neurological function.

    PubMed

    Weiss, Bernard

    2011-06-15

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer.

  15. Endocrine and exocrine function of the bovine testis. Chapter 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter is devoted to the endocrine and exocrine function of the normal bovine male testes. The discussion begins with a historical review of the literature dating back to Aristotle’s (300 BC) initial description of the anatomy of the mammalian testes. The first microscopic examination of the t...

  16. Non-functioning Well Differentiated Endocrine Carcinoma of the Pancreas

    PubMed Central

    Terada, Tadashi

    2009-01-01

    The author reports a typical but rare case of non-functioning well differentiated endocrine carcinoma of the pancreas. A 67-year-old man was admitted to our hospital because of abdominal pain. No hormone-related symptoms were recognized. He has no familiar history of pancreatic neoplasms. Various imaging modalities including US, CT and MRI revealed a tumor of the pancreatic body. Distal pancreatectomy and splenectomy were performed. A solid well demarcated tumor was present in the pancreatic body. Peripancreatic lymph nodes showed marked swelling suggestive of metastases. Immunohistyochemically, tumor cells were positive for cytokeratin, synaptophysin, neuron-specific enolase, and CD56; they were negative for chromogranin, gastrin, glucagon, somatostatin, pancreatic polypeptide, and vasoactive intestinal polypeptide. The pathological diagnosis was non-functioning well differentiated endocrine carcinoma of the pancreas. PMID:27990210

  17. Growth and endocrine function after treatment for medulloblastoma.

    PubMed

    Brown, I H; Lee, T J; Eden, O B; Bullimore, J A; Savage, D C

    1983-09-01

    Children with medulloblastoma in Bristol are treated surgically and with craniospinal irradiation, and in some cases chemotherapy. Thirteen medium or long term survivors were investigated to determine their growth and endocrine function. Their rate of growth was considerably reduced through the first year of their illness and after spinal irradiation spinal growth was poor. Nine children developed growth hormone deficiency. They were clinically euthyroid but 7 had raised basal thyroid stimulating hormone values. Gonadal function was abnormal in all but the youngest child. The rate of survival is increasing in children with medulloblastoma but this is associated with appreciable endocrine abnormalities. Some of these problems are present shortly after treatment ends but others may develop later and long term surveillance is therefore essential.

  18. The development and endocrine functions of adipose tissue.

    PubMed

    Poulos, Sylvia P; Hausman, Dorothy B; Hausman, Gary J

    2010-07-08

    White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body's fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and immune systems and play major roles in metabolism. Numerous studies have shown nutrient or hormonal manipulations can greatly influence adipose tissue development. In addition, the associations between various disease states, such as insulin resistance and cardiovascular disease, and disregulation of adipose tissue seen in epidemiological and intervention studies are great. Evaluation of known adipokines suggests these factors secreted from adipose tissue play roles in several pathologies. As the identification of more adipokines and determination of their role in biological systems, and the interactions between adipocytes and other cells types continues, there is little doubt that we will gain a greater appreciation for a tissue once thought to simply store excess energy.

  19. Endocrine disruptors and human corpus luteum: in vitro effects of phenols on luteal cells function.

    PubMed

    Romani, Federica; Tropea, Anna; Scarinci, Elisa; Dello Russo, Cinzia; Lisi, Lucia; Catino, Stefania; Lanzone, Antonio; Apa, Rosanna

    2013-01-01

    Endocrine disruptors are well known to impair fertility. The aim of the present study was to investigate the effects of bisphenol A (BPA) and nonylphenol (p-NP) on human luteal function in vitro. In particular, in luteal cells isolated from 21 human corpora lutea progesterone, prostaglandin (PG) F2α, PGE2 and vascular endothelial growth factor (VEGF) release, as well as VEGF expression were evaluated. BPA and p-NP negatively affected both luteal steroidogenesis and luteotrophic/ luteolytic factors balance, without influencing VEGF mRNA expression. Actually, BPA and p-NP impaired human luteal cells function in vitro, underlining the already suggested correlation between phenols and reproductive failure.

  20. Evaluating the effects of endocrine disruptors on endocrine function during development.

    PubMed Central

    Bigsby, R; Chapin, R E; Daston, G P; Davis, B J; Gorski, J; Gray, L E; Howdeshell, K L; Zoeller, R T; vom Saal, F S

    1999-01-01

    The major concerns with endocrine disruptors in the environment are based mostly on effects that have been observed on the developing embryo and fetus. The focus of the present manuscript is on disruption of three hormonal systems: estrogens, androgens, and thyroid hormones. These three hormonal systems have been well characterized with regard to their roles in normal development, and their actions during development are known to be perturbed by endocrine-disrupting chemicals. During development, organs are especially sensitive to low concentrations of the sex steroids and thyroid hormones. Changes induced by exposure to these hormones during development are often irreversible, in contrast with the reversible changes induced by transient hormone exposure in the adult. Although it is known that there are differences in embryonic/fetal/neonatal versus adult endocrine responses, minimal experimental information is available to aid in characterizing the risk of endocrine disruptors with regard to a number of issues. Issues discussed here include the hypothesis of greater sensitivity of embryos/fetuses to endocrine disruptors, irreversible consequences of exposure before maturation of homeostatic systems and during periods of genetic imprinting, and quantitative information related to the shape of the dose-response curve for specific developmental phenomena. PMID:10421771

  1. Endocrine System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Endocrine System KidsHealth > For Parents > Endocrine System A A A ... to help the body function properly. About the Endocrine System The foundations of the endocrine system are the ...

  2. Annexin 1 and the regulation of endocrine function.

    PubMed

    John, Christopher D; Christian, Helen C; Morris, John F; Flower, Roderick J; Solito, Egle; Buckingham, Julia C

    2004-04-01

    Annexin 1 (ANXA1) was first identified as a mediator of the anti-inflammatory actions of glucocorticoids in the host defence system. Subsequent work revealed that this protein fulfils a wider brief and it is now recognized as an important signalling intermediate in a variety of other systems. Here, we consider the role of ANXA1 in the endocrine system, placing particular emphasis on new insights into the mechanisms and functional significance of the secondary processing of ANXA1, the processes that control the intracellular and transmembrane trafficking of the molecule and the molecular mechanisms of ANXA1 action that have identified a novel role for the protein as a paracrine/juxtacrine mediator of the non-genomic actions of glucocorticoids in the neuroendocrine system.

  3. Endocrine function as a target of perinatal drug effects: methodologic issues.

    PubMed

    Kuhn, C; Ignar, D; Windh, R

    1991-01-01

    The goal of this chapter is to indicate potential endocrine targets of perinatal drug exposure, to describe the methodologic issues involved in detecting changes in hormone secretion, and to provide examples of several endocrine systems in which exposure to drugs during development significantly impaired normal endocrine development. Finally, we attempted to show that endocrine function is both a target and useful marker for detecting effects of drug of abuse on development that provides the advantages of accurate quantitation and relative response stability across ontogeny.

  4. Endocrine system: part 2.

    PubMed

    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.

  5. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    SciTech Connect

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blueher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  6. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men?

    PubMed

    Ebisch, I M W; Pierik, F H; DE Jong, F H; Thomas, C M G; Steegers-Theunissen, R P M

    2006-04-01

    We evaluated pre- and post-intervention endocrine and semen parameters in a double-blind, placebo-controlled intervention study to investigate the underlying mechanism of increased sperm concentration after folic acid and zinc sulphate intervention. A total of 47 fertile and 40 subfertile males participated in a 26-week intervention study consisting of a daily treatment with folic acid (5 mg/day) and zinc sulphate (66 mg/day), or placebo. Pre- and post-intervention semen parameters, serum folate, zinc, follicle-stimulating hormone (FSH), testosterone and inhibin B concentrations were measured. The results indicated that intervention treatment significantly increased sperm concentration in subfertile males. Other semen and endocrine parameters were not affected by intervention treatment. At baseline, positive correlations were found between serum zinc and sperm concentration, motility and inhibin B. Serum zinc and FSH were inversely correlated. As (already) well known from previous research, inhibin B positively correlated with sperm concentration, motility and morphology, and was inversely correlated with FSH. The latter was positively correlated with testosterone. In addition, testosterone and inhibin B were inversely correlated. After intervention, the correlations with zinc disappeared. We conclude that the increase in sperm concentration after folic acid and zinc sulphate intervention is not the result of alterations in FSH, testosterone or inhibin B concentrations. Although zinc and folate have several effects on spermatogenesis, the underlying mechanisms involved are not clear.

  7. Food odors trigger an endocrine response that affects food ingestion and metabolism.

    PubMed

    Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

    2015-08-01

    Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling.

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

    PubMed

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie; Pedersen, Anne Stilling; Mortensen, Mette Sidsel; Jørgensen, Jennifer Solgaard; Vinggaard, Anne Marie; Hass, Ulla

    2015-07-01

    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 of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined. Oestrogens increased mammary outgrowth in prepubertal females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin levels. In conclusion both estrogenic and anti-androgenic chemicals given during foetal life and lactation affected mammary glands in the offspring.

  9. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows.

    PubMed

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blüher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-13

    Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  10. Aging does not affect the sleep endocrine response to total sleep deprivation in humans.

    PubMed

    Murck, H; Antonijevic, I A; Schier, T; Frieboes, R M; Barthelmes, J; Steiger, A

    1999-01-01

    Aging is associated with decreased sleep continuity, slow wave sleep (SWS), growth hormone (GH) release and an increased hypothalamo-pituitary-adrenocortical (HPA) system activity. Total sleep deprivation (TSD) is a strong stimulus for sleep. To determine if aging affects the response to TSD, for the first time the combined effects of TSD on conventional and spectral sleep electroencephalographic (EEG) parameters and GH, cortisol and prolactin secretion were compared in elderly (60-80 years; n = 7) vs. younger subjects (20-30 years; n = 7). MANOVA revealed a reduction of SWS in the elderly. TSD led to an increase in SWS, a decrease in sleep onset latency, rapid eye movement (REM) density and by trend REM-latency without a global group difference. GH was reduced, whereas prolactin was enhanced in the elderly. After TSD GH was unchanged and prolactin secretion was enhanced without group difference. Thus, the plasticity of the sleep-endocrine system in response to TSD is sustained during aging. The possible involvement of the GABAergic system, that seems not to be severely impaired with age, is proposed.

  11. Exploring the Relationship of Autonomic and Endocrine Activity with Social Functioning in Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Smeekens, I.; Didden, R.; Verhoeven, E. W. M.

    2015-01-01

    Several studies indicate that autonomic and endocrine activity may be related to social functioning in individuals with autism spectrum disorder (ASD), although the number of studies in adults is limited. The present study explored the relationship of autonomic and endocrine activity with social functioning in young adult males with ASD compared…

  12. Changes of Pain Perception, Autonomic Function, and Endocrine Parameters during Treatment of Anorectic Adolescents

    ERIC Educational Resources Information Center

    Bar, Karl-Jurgen; Boettger, Silke; Wagner, Gerd; Wilsdorf, Christine; Gerhard, Uwe Jens; Boettger, Michael K.; Blanz, Bernhard; Sauer, Heinrich

    2006-01-01

    Objectives: The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients. Method: Heat pain perception was assessed in 15…

  13. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo.

    PubMed

    Du, Guizhen; Hu, Jialei; Huang, Hongyu; Qin, Yufeng; Han, Xiumei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2013-02-01

    Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo.

  14. Verifying of endocrine disruptor chemical affect to the mouse testes: can raman spectroscopy support histology study?

    NASA Astrophysics Data System (ADS)

    Andriana, Bibin B.; Oshima, Yusuke; Takanezawa, Sota; Tay, Tat W.; Rosawati Soeratman, Catherine Linda; Alam, Mohammad S.; Mitsuoka, Hiroki; Zhu, Xiao B.; Suzuki, Toshiaki; Yamamoto, Yuko S.; Tsunekawa, Naoki; Kanai, Yoshiakira; Kurohmaru, Masamichi; Sato, Hidetoshi

    2009-02-01

    One of suspect environmental endocrine disruptors that affect mouse male reproduction by altering the morphology of Sertoli cells and spermatogenic cells is phthalate. The effects of mono(2-ethylhexyl)phthalate (MEHP), one of metabolites of di(2-ethylhexyl)phthalate , on immature mouse testes in vivo were examined. We have recently shown that MEHP induced Sertoli cells necrosis and spermatogenic cells apoptosis in mice by TUNEL method, F-actin staining, and ultrastructural study, but there is no data for biochemical changing of testes due to those methods could not explore. To verify in detail of it, we conducted Raman spectroscopy study with 785 nm wavelength laser line, 50mW of laser power and 3 minutes of exposure time to analysis the MEHP-treated testicular tissue, which has been fixatived by 4% paraformaldehyde (PFA). Five weeks old (5 w.o) male mice were used in this experiment. As the results, the alterations were observed by Raman spectroscopy that there are significantly differences of DNA, actin filament, type IV collagen and amide I between control group (0 μM MEHP) and treatment group (100 μM MEHP). These results significantly support histology staining observation (such as the apoptotic spermatogenic cells which is associated with DNA fragmentation and F-actin disruption) and ultrastructural observation (such as mitochondria rupture and disintegration of nucleus membrane). Raman spectroscopy can be used for 4% PFA-fixatived tissue observation. However, we recommend that Raman spectroscopy may be able to be expanded as an armamentarium not just for the clarification of histology staining and ultrastructural study, but furthermore, it may be as a non-invasion assessment for screening animal tissue toxicity of chemical in future.

  15. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans.

  16. Bacterial mimetics of endocrine secretory granules as immobilized in vivo depots for functional protein drugs

    PubMed Central

    Céspedes, María Virtudes; Fernández, Yolanda; Unzueta, Ugutz; Mendoza, Rosa; Seras-Franzoso, Joaquin; Sánchez-Chardi, Alejando; Álamo, Patricia; Toledo-Rubio, Verónica; Ferrer-Miralles, Neus; Vázquez, Esther; Schwartz, Simó; Abasolo, Ibane; Corchero, José Luis; Mangues, Ramon; Villaverde, Antonio

    2016-01-01

    In the human endocrine system many protein hormones including urotensin, glucagon, obestatin, bombesin and secretin, among others, are supplied from amyloidal secretory granules. These granules form part of the so called functional amyloids, which within the whole aggregome appear to be more abundant than formerly believed. Bacterial inclusion bodies (IBs) are non-toxic, nanostructured functional amyloids whose biological fabrication can be tailored to render materials with defined biophysical properties. Since under physiological conditions they steadily release their building block protein in a soluble and functional form, IBs are considered as mimetics of endocrine secretory granules. We have explored here if the in vivo implantation of functional IBs in a given tissue would represent a stable local source of functional protein. Upon intratumoral injection of bacterial IBs formed by a potent protein ligand of CXCR4 we have observed high stability and prevalence of the material in absence of toxicity, accompanied by apoptosis of CXCR4+ cells and tumor ablation. Then, the local immobilization of bacterial amyloids formed by therapeutic proteins in tumors or other tissues might represent a promising strategy for a sustained local delivery of protein drugs by mimicking the functional amyloidal architecture of the mammals’ endocrine system. PMID:27775083

  17. Bacterial mimetics of endocrine secretory granules as immobilized in vivo depots for functional protein drugs.

    PubMed

    Céspedes, María Virtudes; Fernández, Yolanda; Unzueta, Ugutz; Mendoza, Rosa; Seras-Franzoso, Joaquin; Sánchez-Chardi, Alejando; Álamo, Patricia; Toledo-Rubio, Verónica; Ferrer-Miralles, Neus; Vázquez, Esther; Schwartz, Simó; Abasolo, Ibane; Corchero, José Luis; Mangues, Ramon; Villaverde, Antonio

    2016-10-24

    In the human endocrine system many protein hormones including urotensin, glucagon, obestatin, bombesin and secretin, among others, are supplied from amyloidal secretory granules. These granules form part of the so called functional amyloids, which within the whole aggregome appear to be more abundant than formerly believed. Bacterial inclusion bodies (IBs) are non-toxic, nanostructured functional amyloids whose biological fabrication can be tailored to render materials with defined biophysical properties. Since under physiological conditions they steadily release their building block protein in a soluble and functional form, IBs are considered as mimetics of endocrine secretory granules. We have explored here if the in vivo implantation of functional IBs in a given tissue would represent a stable local source of functional protein. Upon intratumoral injection of bacterial IBs formed by a potent protein ligand of CXCR4 we have observed high stability and prevalence of the material in absence of toxicity, accompanied by apoptosis of CXCR4(+) cells and tumor ablation. Then, the local immobilization of bacterial amyloids formed by therapeutic proteins in tumors or other tissues might represent a promising strategy for a sustained local delivery of protein drugs by mimicking the functional amyloidal architecture of the mammals' endocrine system.

  18. Microcystin-LR impairs zebrafish reproduction by affecting oogenesis and endocrine system.

    PubMed

    Zhao, Yanyan; Xie, Liqiang; Yan, Yunjun

    2015-02-01

    Previous studies have shown that microcystins (MCs) are able to exert negative effects on the reproductive system of fish. However, few data are actually available on the effects of MC-LR on the reproductive system of female fish. In the present study, female zebrafish were exposed to 2, 10, and 50 μg L(-1) of MC-LR for 21 d, and its effects on oogenesis, sex hormones, transcription of genes on the hypothalamic-pituitary-gonad (HPG) axis, and reproduction were investigated for the first time. It was observed that egg production significantly declined at ⩾ 10 μg L(-1) MC-LR. MC-LR exposure to zebrafish increased the concentrations of 17β-estradiol (E2) and vitellogenin (VTG) at 10 μg L(-1) level, whereas concentrations of E2, VTG and testosterone declined at 50 μg L(-1) MC-LR. The transcriptions of steroidogenic pathway gene (cyp19a, cyp19b, 17βhsd, cyp17 and hmgra) changed as well after the exposure and corresponded well with the alterations of hormone levels. A number of intra- and extra-ovarian factors, such as gnrh3, gnrhr1, fshβ, fshr, lhr, bmp15, mrpβ, ptgs2 and vtg1 which regulate oogenesis, were significantly changed with a different dose-related effect. Moreover, MC-LR exposure to female zebrafish resulted in decreased fertilization and hatching rates, and may suggest the possibility of trans-generational effects of MC-LR exposure. The results demonstrate that MC-LR could modulate endocrine function and oogenesis, eventually leading to disruption of reproductive performance in female zebrafish. These data suggest there is a risk for aquatic population living in MC polluted areas.

  19. Assessment of hypothalamic pituitary function in endocrine disease

    PubMed Central

    Greenwood, F. C.; Landon, J.

    1966-01-01

    The insulin test carried out with adequate safeguards under standardized conditions yields valuable information regarding hypothalamic and pituitary function when plasma levels of sugar, cortisol, and growth hormone are determined. The use of a test based on the plasma cortisol response to the infusion of lysine-vasopressin, a polypeptide with a corticotrophin-releasing action, is also of value as a test of pituitary function. Used in conjunction with the insulin test it enables pituitary disorders to be differentiated from those involving the hypothalamus. PMID:4287115

  20. Thymus-Associated Parathyroid Hormone Has Two Cellular Origins with Distinct Endocrine and Immunological Functions

    PubMed Central

    Liu, Zhijie; Farley, Alison; Chen, Lizhen; Kirby, Beth J.; Kovacs, Christopher S.; Blackburn, C. Clare; Manley, Nancy R.

    2010-01-01

    In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2 −/− mutants. However, the developmental ontogeny and cellular identity of these “thymic” PTH–expressing cells is unknown. We found that the lethality of aparathyroid Gcm2 −/− mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2 −/− mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant

  1. Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers.

    PubMed

    Samuels, E R; Hou, R H; Langley, R W; Szabadi, E; Bradshaw, C M

    2006-11-01

    The noradrenergic locus coeruleus is a major wakefulness-promoting nucleus of the brain, which is also involved in the regulation of autonomic and endocrine functions. The activity of the locus coeruleus is believed to be tonically enhanced by a mesocoerulear dopaminergic pathway arising from the ventral tegmental area of the midbrain. Both modafinil, a wakefulness-promoting drug, and pramipexole, a D(2)/D(3)receptor agonist with sedative properties, may act on this pathway, with modafinil increasing and pramipexole decreasing locus coeruleus activity. The aim of this study was to compare the two drugs on alertness, autonomic and endocrine functions in healthy volunteers. Pramipexole (0.5mg), modafinil (200mg), and their combination were administered to 16 healthy males in a double-blind, placebo-controlled design. Methods included tests of alertness (pupillographic sleepiness test, critical flicker fusion frequency, visual analogue scales), autonomic functions (resting pupil diameter, light and darkness reflex responses, heart rate, blood pressure, salivation, core temperature), and endocrine functions (blood concentrations of prolactin, growth hormone, and thyroid stimulating hormone). Data were analysed by ANOVA. Pramipexole reduced alertness, caused pupil dilatation, increased heart rate, reduced prolactin and thyroid stimulating hormone, and increased growth hormone level. Modafinil caused small increases in blood pressure and core temperature, and reduced prolactin levels. The sedative effect of pramipexole and the autonomic effects of modafinil are consistent with altered activity in the mesocoerulear pathway; the pupil dilatation following pramipexole suggests reduced dopaminergic excitation of the Edinger-Westphal nucleus.

  2. Insulin-Producing Endocrine Cells Differentiated In Vitro From Human Embryonic Stem Cells Function in Macroencapsulation Devices In Vivo

    PubMed Central

    Ambruzs, Dana M.; Moorman, Mark A.; Bhoumik, Anindita; Cesario, Rosemary M.; Payne, Janice K.; Kelly, Jonathan R.; Haakmeester, Carl; Srijemac, Robert; Wilson, Alistair Z.; Kerr, Justin; Frazier, Mauro A.; Kroon, Evert J.; D’Amour, Kevin A.

    2015-01-01

    The PEC-01 cell population, differentiated from human embryonic stem cells (hESCs), contains pancreatic progenitors (PPs) that, when loaded into macroencapsulation devices (to produce the VC-01 candidate product) and transplanted into mice, can mature into glucose-responsive insulin-secreting cells and other pancreatic endocrine cells involved in glucose metabolism. We modified the protocol for making PEC-01 cells such that 73%–80% of the cell population consisted of PDX1-positive (PDX1+) and NKX6.1+ PPs. The PPs were further differentiated to islet-like cells (ICs) that reproducibly contained 73%–89% endocrine cells, of which approximately 40%–50% expressed insulin. A large fraction of these insulin-positive cells were single hormone-positive and expressed the transcription factors PDX1 and NKX6.1. To preclude a significant contribution of progenitors to the in vivo function of ICs, we used a simple enrichment process to remove remaining PPs, yielding aggregates that contained 93%–98% endocrine cells and 1%–3% progenitors. Enriched ICs, when encapsulated and implanted into mice, functioned similarly to the VC-01 candidate product, demonstrating conclusively that in vitro-produced hESC-derived insulin-producing cells can mature and function in vivo in devices. A scaled version of our suspension culture was used, and the endocrine aggregates could be cryopreserved and retain functionality. Although ICs expressed multiple important β cell genes, the cells contained relatively low levels of several maturity-associated markers. Correlating with this, the time to function of ICs was similar to PEC-01 cells, indicating that ICs required cell-autonomous maturation after delivery in vivo, which would occur concurrently with graft integration into the host. Significance Type 1 diabetes (T1D) affects approximately 1.25 million people in the U.S. alone and is deadly if not managed with insulin injections. This paper describes the production of insulin

  3. Sleep and the endocrine system.

    PubMed

    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.

  4. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    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.

  5. The endocrine function of human placenta: an overview.

    PubMed

    Costa, Mariana A

    2016-01-01

    During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications. In fact, altered levels of these hormones have been associated with some pathologies, such as chromosomal anomalies or pre-eclampsia. This review proposes to revise and update the main pregnancy-related hormones, addressing their major characteristics, molecular targets, function throughout pregnancy, regulators of their expression and their potential clinical interest.

  6. RELATIONSHIP BETWEEN ETHINYLESTRADIOL-MEDIATED CHANGES IN ENDOCRINE FUNCTION AND REPRODUCTION IMPAIRMENT IN JAPANESE MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    Many biochemical endpoints currently are used to describe endocrine function in fish; however, the sensitivity of these parameters as biomarkers of impaired reproduction or sexual development is not well understood. In the present study, adult Japanese medaka (Oryzias latipes) we...

  7. New Roles of Carboxypeptidase E in Endocrine and Neural Function and Cancer

    PubMed Central

    Cawley, Niamh X.; Wetsel, William C.; Murthy, Saravana R. K.; Park, Joshua J.; Pacak, Karel

    2012-01-01

    Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protein that subserves many essential nonenzymatic roles in the endocrine and nervous systems. Here, we review the phylogeny, structure, and function of CPE in hormone and neuropeptide sorting and vesicle transport for secretion, alternative splicing of the CPE transcript, and single nucleotide polymorphisms in humans. With this and the analysis of mutant and knockout mice, the data collectively support important roles for CPE in the modulation of metabolic and glucose homeostasis, bone remodeling, obesity, fertility, neuroprotection, stress, sexual behavior, mood and emotional responses, learning, and memory. Recently, a splice variant form of CPE has been found to be an inducer of tumor growth and metastasis and a prognostic biomarker for metastasis in endocrine and nonendocrine tumors. PMID:22402194

  8. Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats.

    PubMed

    Jacobsen, P R; Christiansen, S; Boberg, J; Nellemann, C; Hass, U

    2010-04-01

    Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Consequently, we have initiated a large project where the purpose is to study mixture effects of endocrine disrupting pesticides at low doses. In the initial range-finding mixture studies, rats were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual differentiation of the pups was affected at 25% and higher as anogenital distance was affected in both male and female offspring at birth and the male offspring exhibited malformations of the genital tubercle, increased nipple retention, and decreased prostate and epididymis weights at pup day 13. The results show that doses of endocrine disrupting pesticides, which appear to induce no effects on gestation length, parturition and pup mortality when judged on their own, induced marked adverse effects on these endpoints in concert with other pesticides. In addition, the sexual differentiation of the offspring was affected. This as well as the predictability of the combination effects based on dose-additivity modelling will be studied further in a large dose-response study.

  9. Endocrine system and obesity.

    PubMed

    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.

  10. Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.

    PubMed

    Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

    2014-03-19

    Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

  11. Transcriptional analysis of the mammalian heart with special reference to its endocrine function

    PubMed Central

    McGrath, Monica Forero; de Bold, Adolfo J

    2009-01-01

    Background Pharmacological and gene ablation studies have demonstrated the crucial role of the endocrine function of the heart as mediated by the polypeptide hormones ANF and BNP in the maintenance of cardiovascular homeostasis. The importance of these studies lies on the fact that hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative deficiency of ANF and BNP. These hormones are produced by the atrial muscle cells (cardiocytes), which display a dual secretory/muscle phenotype. In contrast, ventricular cardiocytes display mainly a muscle phenotype. Comparatively little information is available regarding the genetic background for this important phenotypic difference with particular reference to the endocrine function of the heart. We postulated that comparison of gene expression profiles between atrial and ventricular muscles would help identify gene transcripts that underlie the phenotypic differences associated with the endocrine function of the heart. Results Comparison of gene expression profiles in the rat heart revealed a total of 1415 differentially expressed genes between the atria and ventricles based on a 1.8 fold cut-off. The identification of numerous chamber specific transcripts, such as ANF for the atria and Irx4 for the ventricles among several others, support the soundness of the GeneChip data and demonstrates that the differences in gene expression profiles observed between the atrial and ventricular tissues were not spurious in nature. Pathway analysis revealed unique expression profiles in the atria for G protein signaling that included Gαo1, Gγ2 and Gγ3, AGS1, RGS2, and RGS6 and the related K+ channels GIRK1 and GIRK4. Transcripts involved in vesicle trafficking, hormone secretion as well as mechanosensors (e.g. the potassium channel TREK-1) were identified in relationship to the synthesis, storage and secretion of hormones. Conclusion The data developed in this investigation

  12. [The effect of normobaric hypoxia on the functioning of links in the endocrine system].

    PubMed

    Shakhtarin, V V; Kiriachkov, Iu Iu; Palyga, G F; Khmelevskiĭ, Ia M; Sloventantor, V Iu; Simakova, G M; Kruglikov, A P

    1990-01-01

    The paper is concerned with the data on change in the blood level of ACTH, STH, TSH, cortisol, T3, insulin, C-peptide during a 25-minute session of respiration using a gaseous hypoxic mixture with 10% oxygen (GHM-10). The investigation was performed in 23 healthy volunteers. Change in the hormonal status, characteristic of a moderate stress-reaction, was observed in 60% of the examinees. It was found out that during a GHM-10 session a degree of change in function of the studied factors of the endocrine system showed correlation with change in the activity of the autonomic nervous system.

  13. ENDOCRINE-DISRUPTING CHEMICALS: PREPUBERTAL EXPOSURES AND EFFECTS ON SEXUAL MATURATION AND THYROID FUNCTION IN THE MALE RAT. A FOCUS ON THE EDSTAC RECOMMENDATIONS. ENDOCRINE DISRUPTER SCREENING AND TESTING ADVISORY COMMITTEE

    EPA Science Inventory

    Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee.

    Stoker TE, Parks LG, Gray LE, Cooper RL.

  14. Non-coding RNAs: Functions and applications in endocrine-related cancer.

    PubMed

    Venkatesh, Thejaswini; Suresh, Padmanaban S; Tsutsumi, Rie

    2015-11-15

    A significant fraction of the human genome is transcribed as non-coding RNAs (ncRNAs). This non-coding transcriptome has challenged the notion of the central dogma and its involvement in transcriptional and post-transcriptional regulation of gene expression is well established. Interestingly, several ncRNAs are dysregulated in cancer and current non-coding transcriptome research aims to use our increasing knowledge of these ncRNAs for the development of cancer biomarkers and anti-cancer drugs. In endocrine-related cancers, for which survival rates can be relatively low, there is a need for such advancements. In this review, we aimed to summarize the roles and clinical implications of recently discovered ncRNAs, including long ncRNAs, PIWI-interacting RNAs, tRNA- and Y RNA-derived ncRNAs, and small nucleolar RNAs, in endocrine-related cancers affecting both sexes. We focus on recent studies highlighting discoveries in ncRNA biology and expression in cancer, and conclude with a discussion on the challenges and future directions, including clinical application. ncRNAs show great promise as diagnostic tools and therapeutic targets, but further work is necessary to realize the potential of these unconventional transcripts.

  15. Acupuncture Affects Autonomic and Endocrine but Not Behavioural Responses Induced by Startle in Horses

    PubMed Central

    Villas-Boas, Julia Dias; Dias, Daniel Penteado Martins; Trigo, Pablo Ignacio; Almeida, Norma Aparecida dos Santos; de Almeida, Fernando Queiroz; de Medeiros, Magda Alves

    2015-01-01

    Startle is a fast response elicited by sudden acoustic, tactile, or visual stimuli in a variety of animals and in humans. As the magnitude of startle response can be modulated by external and internal variables, it can be a useful tool to study reaction to stress. Our study evaluated whether acupuncture can change cardiac autonomic modulation (heart rate variability); and behavioural (reactivity) and endocrine (cortisol levels) parameters in response to startle. Brazilian Sport horses (n = 6) were subjected to a model of startle in which an umbrella was abruptly opened near the horse. Before startle, the horses were subjected to a 20-minute session of acupuncture in acupoints GV1, HT7, GV20, and BL52 (ACUP) and in nonpoints (NP) or left undisturbed (CTL). For analysis of the heart rate variability, ultrashort-term (64 s) heart rate series were interpolated (4 Hz) and divided into 256-point segments and the spectra integrated into low (LF; 0.01–0.07 Hz; index of sympathetic modulation) and high (HF; 0.07–0.50 Hz; index of parasympathetic modulation) frequency bands. Acupuncture (ACUP) changed the sympathovagal balance with a shift towards parasympathetic modulation, reducing the prompt startle-induced increase in LF/HF and reducing cortisol levels 30 min after startle. However, acupuncture elicited no changes in behavioural parameters. PMID:26413116

  16. Placebo Sleep Affects Cognitive Functioning

    ERIC Educational Resources Information Center

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  17. Long-term effects of treatment on endocrine function in children with brain tumors

    SciTech Connect

    Duffner, P.K.; Cohen, M.E.; Anderson, S.W.; Voorhess, M.L.; MacGillivray, M.H.; Panahon, A.; Brecher, M.L.

    1983-11-01

    Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion of cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.

  18. Long-term effects of treatment on endocrine function in children with brain tumors.

    PubMed

    Duffner, P K; Cohen, M E; Anderson, S W; Voorhess, M L; MacGillivray, M H; Panahon, A; Brecher, M L

    1983-11-01

    Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion of cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.

  19. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

    PubMed Central

    Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

    2015-01-01

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  20. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.

    PubMed

    Pierre, Joseph F; Neuman, Joshua C; Brill, Allison L; Brar, Harpreet K; Thompson, Mary F; Cadena, Mark T; Connors, Kelsey M; Busch, Rebecca A; Heneghan, Aaron F; Cham, Candace M; Jones, Elaina K; Kibbe, Carly R; Davis, Dawn B; Groblewski, Guy E; Kudsk, Kenneth A; Kimple, Michelle E

    2015-09-15

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.

  1. Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; Du Toit, L.B.

    1986-05-01

    The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

  2. Subclinical hypothyroidism affects mitochondrial function.

    PubMed

    Kvetny, J; Wilms, L; Pedersen, P L; Larsen, J

    2010-05-01

    The aim of the present study was to examine mitochondrial function in cells from persons with subclinical hypothyroidism and euthyroid controls. The participating persons were examined clinically and had basal oxygen consumption (VO(2)) determined. The concentrations of thyroid hormones and thyrotropine stimulating hormone were determined, and mitochondrial function in isolated mononuclear blood cells was examined by enzymatic methods [citrate synthase activity (CS)] and by flow cytometry (mitochondrial membrane potential by TMRM fluorescence and mitochondrial mass by MTG fluorescence). The ratio of T(4)/T(3) was lowered in subclinical hypothyroidism patients compared to controls (2.5+/-0.5 vs. 2.9+/-0.4, p=0.005). VO(2) was increased in persons with subclinical hypothyroidism compared to controls (adolescents: 134+/-27 ml O(2)/min*m(2) vs. 119+/-27 ml O(2)/min*m(2), p=0.006, adults: 139+/-14 ml O(2)/min*m(2) vs. 121+/-17 ml O(2)/min*m(2), p=0.001). The mitochondrial function, represented by citrate synthase activity, MTG, and TMRM fluorescence were all increased (CS in subclinical hypothyroidism vs. controls: 0.074+/-0.044 nmol/mg*min vs. 0.056+/-0.021 nmol/mg*min, p=0.005; MTG fluorescence in subclinical hypothyroidism vs. controls: 7,482+/-1,733 a.u. vs. 6,391+/-2,171 a.u., p=0.027; TMRM fluorescence in subclinical hypothyroidism vs. controls: 13,449+/-3,807 a.u. vs. 11,733+/-4,473 a.u, p=0.04). Our results indicate an increased mitochondrial stimulation, eventually caused by increased deiodination of T(4) to intracellular bioactive iodothyronines in adults and adolescents with subclinical hypothyroidism.

  3. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations.

    PubMed

    Roepke, Troy A; Snyder, Mark J; Cherr, Gary N

    2005-01-26

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>E2>EE2>DDD>BisA>P4>E1>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng

  4. Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1).

    PubMed

    Giusti, Francesca; Cianferotti, Luisella; Gronchi, Giorgio; Cioppi, Federica; Masi, Laura; Faggiano, Antongiulio; Colao, Annamaria; Ferolla, Piero; Brandi, Maria Luisa

    2016-06-01

    Primary hyperparathyroidism is the main endocrinopathy associated with Multiple Endocrine Neoplasia type 1 syndrome. Cinacalcet is a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease, and for the reduction of marked hypercalcemia in patients with parathyroid carcinoma and sporadic hyperparathyroidism requiring surgery but for whom parathyroidectomy is contraindicated. It may provide a medical alternative for the management of primary hyperparathyroidism in subjects affected by Multiple Endocrine Neoplasia type 1. In this longitudinal, intervention study, 33 MEN1 patients had been enrolled, 10 males and 23 females with a mean age of 40 ± 11.9 years, range 20-63. Primary hyperparathyroidism was the first clinical manifestation in 12 patients. All subjects commenced with Cinacalcet 30 mg/day, 22 patients starting therapy with calcimimetics as an alternative to surgery, and 11 patients opting for the medication after the onset of persistent post-surgical primary hyperparathyroidism. Duration of follow-up was 12 months. The results of this study show significant reductions in serum calcium. The changes in hormonal secretions of pituitary and gastroenteropancreatic glands were not significant, demonstrating the overall safety of this drug in this disease. Cinacalcet has been well tolerated by 28 patients, whereas five individuals complained of heartburn and grade 1 nausea, which did not prevent the completion of the study. In conclusion, Cinacalcet has resulted to be well tolerated and safe in patients with MEN1 syndrome and the calcium homeostasis was stabilized.

  5. SPECIES DIFFERENCES IN ANDROGEN AND ESTROGEN RECEPTOR STRUCTURE AND FUNCTION AMONG VERTEBRATES AND INVERTEBRATES: INTERSPECIES EXTRAPOLATIONS REGARDING ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Species Differences in Androgen and Estrogen Receptor Structure and Function Among Vertebrates and Invertebrates: Interspecies Extrapolations regarding Endocrine Disrupting Chemicals
    VS Wilson1, GT Ankley2, M Gooding 1,3, PD Reynolds 1,4, NC Noriega 1, M Cardon 1, P Hartig1,...

  6. Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis.

    PubMed

    Jedeon, Katia; Loiodice, Sophia; Salhi, Khaled; Le Normand, Manon; Houari, Sophia; Chaloyard, Jessica; Berdal, Ariane; Babajko, Sylvie

    2016-11-01

    Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality.

  7. Endocrine function following high dose proton therapy for tumors of the upper clivus

    SciTech Connect

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  8. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis.

    PubMed

    Schulz, Karl-Heinz; Gold, Stefan M; Witte, Jan; Bartsch, Katharina; Lang, Undine E; Hellweg, Rainer; Reer, Rüdiger; Braumann, Klaus-Michael; Heesen, Christoph

    2004-10-15

    In recent years it has become clear that multiple sclerosis (MS) patients benefit from physical exercise as performed in aerobic training but little is known about the effect on functional domains and physiological factors mediating these effects. We studied immunological, endocrine and neurotrophic factors as well as coordinative function and quality of life during an 8-week aerobic bicycle training in a waitlist control design. In the immune-endocrine study (1) 28 patients were included, the coordinative extension study (2) included 39 patients. Training was performed at 60% VO(2)max after determining individual exertion levels through step-by-step ergometry. Metabolic (lactate), endocrine (cortisol, adrendocortico-releasing hormone, epinephrine, norepinephrine), immune (IL-6, soluble IL-6 receptor), and neurotrophic (brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF)) parameters were compared from a prestudy and a poststudy endurance test at 60% VO(2)max for 30 min. In study (1), lowered lactate levels despite higher workload levels indicated a training effect. Disease-specific quality of life (as measured by the Hamburg Quality of Life Questionnaire for Multiple Sclerosis, HAQUAMS) significantly increased in the training group. No significant training effects were seen for endocrine and immune parameters or neurotrophins. In study (2), two out of three coordinative parameters of the lower extremities were significantly improved. In summary, low-level aerobic training in MS improves not only quality of life but also coordinative function and physical fitness.

  9. Effect of temperament and prolonged transportation on endocrine and functional variables in young beef bulls.

    PubMed

    Fazio, E; Medica, P; Cravana, C; Cavaleri, S; Ferlazzo, A

    The purpose of this study was to evaluate the effect of prolonged transportation on adrenocorticotropic hormone (ACTH), cortisol, total and free triiodothyronine (T(3), fT(3)) and thyroxine (T(4), fT(4)) concentrations, and functional variables (heart rate (HR), respiratory rate (RR) and rectal temperature (RT)) in calm and temperamental Limousin young beef bulls. Exit velocity measurement was used to classify bulls' temperament as calm (group I: consisted of eight slowest bulls) and temperamental (group II: consisted of five fastest bulls). Calm subjects showed an increase of ACTH (P<0.05) and T(4) (P<0.01) concentrations after transportation compared with before transportation values. Temperamental subjects showed higher ACTH (P<0.01) concentrations before transportation, and lower T(4) (P<0.05) and fT(4) (P<0.001) concentrations after transportation than calm subjects. Related to functional variables, temperamental young beef bulls showed a decrease of RT (P<0.05) after transportation compared with before values, higher RT (P<0.001) before transportation, and higher HR (P<0.001) and RR (P<0.01) after transportation than calm subjects. Data obtained suggest that longer periods of transportation could minimise the magnitude and duration of the endocrine and functional responses to stress of young beef bulls; such responses probably decrease or disappear during transport, in accordance with animal temperament.

  10. Fetal signaling through placental structure and endocrine function: illustrations and implications from a nonhuman primate model.

    PubMed

    Rutherford, Julienne N

    2009-01-01

    The placenta is a transmitter of fetal need and fetal quality, interfacing directly with maternal physiology and ecology. Plasticity of placental structure and function across the developmental timeframe of gestation may serve as an important tool by which a fetus calibrates its growth to shifting maternal ecology and resource availability, and thereby signals its quality and adaptability to a changing environment. Signals of this quality may be conveyed by the size of the placental interface, an important marker of fetal access to maternal resources, or by production of placental insulin-like growth factor-II, a driver of fetoplacental growth. Litter size variation in the common marmoset monkey offers the opportunity to explore intrauterine resource allocation and placental plasticity in an important nonhuman primate model. Triplet marmosets are born at lower birth weights and have poorer postnatal outcomes and survivorship than do twins; triplet placentas differ in placental efficiency, microscopic morphology, and endocrine function. Through placental plasticity, triplet fetuses are able to adjust functional access to maternal resources in a way that allows pregnancy to proceed. However, the costs of such mechanisms may relate to reduced fetal growth and altered postnatal outcomes, with the potential to lead to adverse adult health consequences, suggesting an important link between the placenta itself and the developmental origins of health and disease.

  11. Renal function and endocrine responses to arm exercise in euhydrated individuals with spinal cord injury.

    PubMed

    Kawasaki, Takashi; Nakamura, Takeshi; Sasaki, Yusuke; Sakamoto, Keiko; Ito, Tomoyuki; Goto, Masaki; Shimomatsu, Tomoya; Tajima, Fumihiro

    2012-04-01

    This study investigated the renal and endocrine responses to arm exercise in persons with spinal cord injury (SCI) under euhydration conditions (ad libitum drinking of water) and determined the physiological effects of exercise on renal function in these subjects. Eleven SCI (spinal lesions between T6 and L1, American Spinal Injury Association impairment scale A) and 14 able-bodied (AB) persons first rested for 1 h in a sitting position, before undergoing 2-h arm-crank ergometer exercise at 60% of maximum oxygen consumption followed by a 2-h recovery period. On another day, all subjects participated in a time control study (5 h of rest condition in sitting position). Urine and blood samples were collected hourly. There were no differences in mean blood pressure between the two groups. SCI patients showed attenuated increase in plasma adrenaline and increase in plasma aldosterone compared with AB controls, but similar changes in human atrial natriuretic polypeptide, plasma renin activity and plasma antidiuretic hormone following the exercise. Creatinine clearance, osmolal clearance, free water clearance and fractional excretion of Na(+) did not change during exercise in any of the subjects. These findings suggested that activated aldosterone and attenuated adrenaline responses during exercise in SCI could be due to adaptation to disordered sympathetic nervous system triggered to maintain renal function. The results showed no exercise-related adverse effects on renal function in hydrated subjects with SCI.

  12. The endocrine interface of environmental and egg factors affecting chick quality.

    PubMed

    Decuypere, E; Bruggeman, V

    2007-05-01

    Day-old chicks are the endproduct of the hatchery industry and form important starting material for the broiler farms. The major objective is to obtain a high hatchability of marketable chicks and a low spread of hatch. For the farmers, these chicks have to perform well, which is translated in high viability, high growth rate, high breast meat yield, and low feed conversion. A good-quality 1-d-old chick is hence a crucial hinge between the hatchery and the broiler farm. Moreover, maximal hatchability is not always synonymous with maximal posthatch viability and growth potential of the chick. Quantitative and qualitative scoring of chick quality is assessed. We will briefly discuss some recently developed scoring systems, which will convert differences in qualitative parameters into a quantitative score. Preincubation factors such as egg storage duration and age of broiler breeders, as well as incubation conditions, affect day-old chick quality and subsequent broiler performance. Heat production and metabolism, hormonal balances of thyroid hormones and corticosterone, and gas exchange (O(2), CO(2)) are of fundamental importance for embryonic development and survival during incubation. Results from our studies indicated that embryos with higher pCO(2) levels in the air cell and higher triiodothyronine-thyroxine ratios at internal pipping or in the newly hatched chicks had higher hatchability, chick quality, and posthatch chick growth until 7 d of age. Incubation factors such as temperature, turning conditions, or gaseous environment also affect development, change concentrations of hormones related to metabolism and growth of the embryo, and in this way affect 1-d-old chick quality. Moreover, the spread of the hatch process is affected by incubation conditions as well as by the aforementioned preincubation factors. Depending on the spread of the hatching curve together with the place in the sequence of hatching (early or late) and in interaction with quality of the

  13. Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

    PubMed Central

    Phillips, Kelly-Anne; Aldridge, Julie; Ribi, Karin; Sun, Zhuoxin; Thompson, Alastair; Harvey, Vernon; Thürlimann, Beat; Cardoso, Fatima; Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D.

    2011-01-01

    Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment. PMID:21046229

  14. Maternal stress alters endocrine function of the feto-placental unit in rats.

    PubMed

    Mairesse, Jérôme; Lesage, Jean; Breton, Christophe; Bréant, Bernadette; Hahn, Tom; Darnaudéry, Muriel; Dickson, Suzanne L; Seckl, Jonathan; Blondeau, Bertrand; Vieau, Didier; Maccari, Stefania; Viltart, Odile

    2007-06-01

    Prenatal stress (PS) can cause early and long-term developmental effects resulting in part from altered maternal and/or fetal glucocorticoid exposure. The aim of the present study was to assess the impact of chronic restraint stress during late gestation on feto-placental unit physiology and function in embryonic (E) day 21 male rat fetuses. Chronic stress decreased body weight gain and food intake of the dams and increased their adrenal weight. In the placenta of PS rats, the expression of glucose transporter type 1 (GLUT1) was decreased, whereas GLUT3 and GLUT4 were slightly increased. Moreover, placental expression and activity of the glucocorticoid "barrier" enzyme 11beta-hydroxysteroid dehydrogenase type 2 was strongly reduced. At E21, PS fetuses exhibited decreased body, adrenal pancreas, and testis weights. These alterations were associated with reduced pancreatic beta-cell mass, plasma levels of glucose, growth hormone, and ACTH, whereas corticosterone, insulin, IGF-1, and CBG levels were unaffected. These data emphasize the impact of PS on both fetal growth and endocrine function as well as on placental physiology, suggesting that PS could program processes implied in adult biology and pathophysiology.

  15. Endocrine system: part 1.

    PubMed

    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.

  16. Examining the role of endogenous orexins in hypothalamus-pituitary-adrenal axis endocrine function using transient dual orexin receptor antagonism in the rat.

    PubMed

    Steiner, Michel A; Sciarretta, Carla; Brisbare-Roch, Catherine; Strasser, Daniel S; Studer, Rolf; Jenck, Francois

    2013-04-01

    The orexin neuropeptide system regulates wakefulness and contributes to physiological and behavioral stress responses. Moreover, a role for orexins in modulating hypothalamus-pituitary-adrenal (HPA) axis activity has been proposed. Brain penetrating dual orexin receptor (OXR) antagonists such as almorexant decrease vigilance and have emerged as a novel therapeutic class for the treatment of insomnia. Almorexant was used here as a pharmacological tool to examine the role of endogenous orexin signaling in HPA axis endocrine function under natural conditions. After confirming the expression of prepro-orexin and OXR-1 and OXR-2 mRNA in hypothalamus, pituitary and adrenal glands, the effects of systemic almorexant were investigated on peripheral HPA axis hormone release in the rat under baseline, stress and pharmacological challenge conditions. Almorexant did not alter basal or stress-induced corticosterone release despite affecting wake and sleep stages (detected by radiotelemetric electroencephalography/electromyography) during the stress exposure. Moreover, almorexant did not affect the release of adrenocorticotropin (ACTH) and corticosterone at different time points along the diurnal rhythm, nor corticotrophin-releasing hormone (CRH)- and ACTH-stimulated neuroendocrine responses, measured in vivo under stress-free conditions. These results illustrate that dual OXR antagonists, despite modulating stress-induced wakefulness, do not interfere with endocrine HPA axis function in the rat. They converge to suggest that endogenous orexin signaling plays a minor role in stress hormone release under basal conditions and under challenge.

  17. Endocrine and metabolic function in male Carioca High-conditioned Freezing rats.

    PubMed

    Mousovich-Neto, F; Lourenço, A L; Landeira-Fernandez, J; Corrêa da Costa, V M

    2015-04-01

    The aim of this study was to characterize Carioca High-conditioned Freezing rats (CHF) regarding their endocrine and metabolic backgrounds. We found an increase in serum corticosterone (CTRL: 96.7 ± 21.65 vs CHF: 292.0 ± 4 0.71 ng/ml) and leptin (CTRL: 9.5 ± 1.51 vs CHF: 19.2 ± 4.32 ng/ml). Serum testosterone (CTRL: 3.3 ± 0.29 vs CHF: 2.0 ± 0.28 ng/ml) and T3 (CTRL: 52.4 ± 2.74 vs CHF: 42.7 ± 2.94 ng/dl) were decreased in the CHF group, but serum TSH and T4 were unaffected. Body weight and food intake were unchanged, nevertheless retroperitoneal fat (CTRL: 2.2 ± 0.24 vs CHF: 4.8 ± 0.64 g) and epididymal fat (CTRL: 2.6 ± 0.20 vs CHF: 4.8 ± 0.37 g) depot weights were around 2-fold higher in CHF animals. BAT weight was similar in both groups. Serum triglycerides (CTRL: 41.4 ± 6.03 vs CHF: 83.2 ± 17.09 mg/dl) and total cholesterol (CTRL: 181.6 ± 5.61 vs CHF: 226.4 ± 13.04 mg/dl) were higher in the CHF group. Fasting glycemia (CTRL: 68.7 ± 3.04 vs CHF: 82.3 ± 2.99 mg/dl) was also higher in the CHF group, however glucose tolerance test response and serum insulin levels were similar between the groups. Oxygen consumption (CTRL: 10.5 ± 0.40 vs CHF: 7.9 ± 0.58 VO2ml/min/kg(0.75)) and BAT D2 activity (CTRL: 0.7 ± 0.17 vs CHF: 0.3 ± 0.04 fmolT4/min/mg ptn) were lower in the CHF group. Our data show that anxiety could impair endocrine and metabolic functions and may contribute to the development of metabolic diseases.

  18. Physiological and therapeutical roles of ginger and turmeric on endocrine functions.

    PubMed

    Al-Suhaimi, Ebtesam A; Al-Riziza, Noorah A; Al-Essa, Reham A

    2011-01-01

    The natural product ginger (Zingiber officinale) has active constituents gingerol, Shogaol and Zerumbone, while turmeric (Curcuma longa) contains three active major curcuminoids, namely, curcumin, demethoxycurcumin, and bisdemethoxycurcumin. They have the same scientific classification and are reported to have anti-inflammatory and many therapeutic effects. This article reviews the physiological and therapeutic effects of ginger and turmeric on some endocrine gland functions, and signal pathways involved to mediate their actions. With some systems and adipose tissue, ginger and turmeric exert their actions through some/all of the following signals or molecular mechanisms: (1) through reduction of high levels of some hormones (as: T4, leptin) or interaction with hormone receptors; (2) by inhibition of cytokines/adipokine expression; (3) acting as a potent inhibitor of reactive oxygen species (ROS)-generating enzymes, which play an essential role between inflammation and progression of diseases; (4) mediation of their effects through the inhibition of signaling transcription factors; and/or (5) decrease the proliferative potent by down-regulation of antiapoptotic genes, which may suppress tumor promotion by blocking signal transduction pathways in the target cells. These multiple mechanisms of protection against inflammation and oxidative damage make ginger and curcumin particularly promising natural agents in fighting the ravages of aging and degenerative diseases, and need to be paid more attention by studies.

  19. Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with β-thalassemia major.

    PubMed

    Casale, Maddalena; Citarella, Serena; Filosa, Aldo; De Michele, Elisa; Palmieri, Francesco; Ragozzino, Alfonso; Amendola, Giovanni; Pugliese, Umberto; Tartaglione, Immacolata; Della Rocca, Filomena; Cinque, Patrizia; Nobili, Bruno; Perrotta, Silverio

    2014-12-01

    Iron overload in β-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.

  20. The endocrine system in diabetes mellitus.

    PubMed

    Alrefai, Hisham; Allababidi, Hisham; Levy, Shiri; Levy, Joseph

    2002-07-01

    The pathophysiology of diabetes mellitus is complex and not fully understood. However, it emerges as an abnormal metabolic condition associated with a systemic damage to the vascular bed. Cumulative evidence also reveals that the endocrine system is not intact in patients with diabetes mellitus. It is not clear whether the changes observed in the endocrine system represent a primary defect or reflect the effects of the impaired insulin action and abnormal carbohydrate and lipid metabolism on the hormonal milieu. Review of the literature reveals that the function of the entire endocrine system including the functions of hormones from the hypothalamus, pituitary, adrenal, thyroid, parathyroid, the vitamin D system, the gonads, and the endocrine function of the adipose tissue, is impaired. Good metabolic control and insulin treatment may reverse some of these abnormalities. It remains unanswered as to what extent these changes in the endocrine system contribute to the vascular pathologies observed in individuals affected by diabetes mellitus and whether part of the abnormalities observed in the endocrine system reflect a basic cellular defect in the diabetic syndrome.

  1. Endocrine glands

    MedlinePlus Videos and Cool Tools

    ... and nervous systems work very closely together. The brain continuously sends instructions to the endocrine system, and ... master switchboard because it's the part of the brain that controls the endocrine system. The pituitary gland, ...

  2. GATA factors in endocrine neoplasia

    PubMed Central

    Pihlajoki, Marjut; Färkkilä, Anniina; Soini, Tea; Heikinheimo, Markku; Wilson, David B.

    2015-01-01

    GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted. PMID:26027919

  3. Circadian rhythm of the Leydig cells endocrine function is attenuated during aging.

    PubMed

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Bjelic, Maja M; Radovic, Sava M; Andric, Silvana A; Kostic, Tatjana S

    2016-01-01

    Although age-related hypofunction of Leydig cells is well illustrated across species, its circadian nature has not been analyzed. Here we describe changes in circadian behavior in Leydig cells isolated from adult (3-month) and aged (18- and 24-month) rats. The results showed reduced circadian pattern of testosterone secretion in both groups of aged rats despite unchanged LH circadian secretion. Although arrhythmic, the expression of Insl3, another secretory product of Leydig cells, was decreased in both groups. Intracellular cAMP and most important steroidogenic genes (Star, Cyp11a1 and Cyp17a1), together with positive steroidogenic regulator (Nur77), showed preserved circadian rhythm in aging although rhythm robustness and expression level were attenuated in both aged groups. Aging compromised cholesterol mobilization and uptake by Leydig cells: the oscillatory transcription pattern of genes encoding HDL-receptor (Scarb1), hormone sensitive lipase (Lipe, enzyme that converts cholesterol esters from lipid droplets into free cholesterol) and protein responsible for forming the cholesterol esters (Soat2) were flattened in 24-month group. The majority of examined clock genes displayed circadian behavior in expression but only a few of them (Bmal1, Per1, Per2, Per3 and Rev-Erba) were reduced in 24-month-old group. Furthermore, aging reduced oscillatory expression pattern of Sirt1 and Nampt, genes encoding key enzymes that connect cellular metabolism and circadian network. Altogether circadian amplitude of Leydig cell's endocrine function decreased during aging. The results suggest that clock genes are more resistant to aging than genes involved in steroidogenesis supporting the hypothesis about peripheral clock involvement in rhythm maintenance during aging.

  4. Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour.

    PubMed

    Shynlova, Oksana; Tsui, Prudence; Jaffer, Shabana; Lye, Stephen J

    2009-05-01

    In this review, we describe a new model to explain the regulation of myometrial function during pregnancy and labour. We propose that the myometrium undergoes dramatic changes in phenotype from early pregnancy until the onset of labour, characterized by an early proliferative phase, an intermediate phase of cellular hypertrophy and matrix elaboration, a third phase in which the cells assume a contractile phenotype and the final phase in which cells become highly active and committed to labour. The last phase of myometrial differentiation is postpartum uterine involution, completing the reproductive cycle following pregnancy and labour by returning the uterus to its non-pregnant receptive state. We further propose that phenotypic modulation of the uterine myocytes is the result of integration of endocrine signals and mechanical stimulation of the uterus by the growing fetus. Our previous studies have shown that these signals are important in regulating the onset of labour and we now have indications that they regulate earlier myometrial smooth muscle differentiation. We show that the high rate of myometrial cell proliferation in early pregnancy which reflects important aspects of many smooth muscle populations during development. The proliferative phenotype was associated with dramatic changes in the expression of IGF family proteins and coincided with an up-regulation of the anti-apoptotic pathway. Preliminary evidence suggests that myometrial hyperplasia was controlled by the PI3K-Akt-mTOR signaling pathway. The modulation of the mTOR pathway by rapamycin blocked the proliferative activity of the uterine myocytes. The growth and remodeling of the myometrium during pregnancy was associated with increased synthesis of extra cellular matrix (ECM) proteins and their corresponding integrin receptors. Our results show a decrease in expression of fibrillar collagens and a coordinated temporal increase in expression of components of the basement membrane near term

  5. Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers

    PubMed Central

    Samuels, Ebony R; Hou, Ruihua H; Langley, Robert W; Szabadi, Elemer; Bradshaw, Christopher M

    2007-01-01

    What is already known about this subject It is known that the dopamine receptor agonist pramipexole, used for the treatment of Parkinson's disease, often causes nausea that can be treated in patients by the co-administration of an antiemetic, for example domperidone. In experimental studies of pramipexole it may be necessary to administer domperidone alongside pramipexole to alleviate nausea, and as such it is necessary to know how the co-administration of domperidone may alter the observed effects of pramipexole. What this study adds Results from our study indicate that the co-administration of pramipexole and domperidone may reduce the likelihood of observing an effect that is present when pramipexole is administered alone. Although domperidone is mainly a peripherally acting drug, it appears that a high enough concentration of the drug crosses the blood–brain barrier to partially antagonize some of the autonomic actions of pramipexole. Therefore, this report provides a cautionary note to the use of domperidone alongside pramipexole where the results of interest are those from pramipexole alone. Aims To investigate the effects of the D2-receptor agonist pramipexole with and without the co-administration of the peripherally acting D2-receptor antagonist domperidone on measures of alertness, autonomic and endocrine function. Methods Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double-blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid-stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons. Results The pre-post treatment changes in VAS alertness were

  6. Functional and Morphological Changes in Endocrine Pancreas following Cola Drink Consumption in Rats

    PubMed Central

    2015-01-01

    Aim We report the effects of long-term cola beverage drinking on glucose homeostasis, endocrine pancreas function and morphology in rats. Methods Wistar rats drank: water (group W), regular cola beverage (group C, sucrose sweetened) or “light” cola beverage (group L, artificially sweetened). After 6 months, 50% of the animals in each group were euthanized and the remaining animals consumed water for the next 6 months when euthanasia was performed. Biochemical assays, insulinemia determination, estimation of insulin resistance (HOMA-IR), morphometry and immunohistochemistry evaluations were performed in pancreas. Results Hyperglycemia (16%, p<0.05), CoQ10 (coenzyme-Q10) decrease (−52%,p<0.01), strong hypertriglyceridemia (2.8-fold, p<0.01), hyperinsulinemia (2.4 fold, p<0.005) and HOMA-IR increase (2.7 fold, p<0.01) were observed in C. Group C showed a decrease in number of α cells (−42%, p<0.01) and β cells (−58%, p<0.001) and a moderate increase in α cells’ size after wash-out (+14%, p<0.001). Group L showed reduction in β cells’ size (−9%, p<0.001) and only after wash-out (L12) a 19% increase in size (p<0.0001) with 35% decrease in number of α cells (p<0.01). Groups C and L showed increase in α/β-cell ratio which was irreversible only in C (α/β = +38% in C6,+30% in C12, p<0.001vs.W6). Regular cola induced a striking increase in the cytoplasmic expression of Trx1 (Thioredoxin-1) (2.25-fold in C6 vs. W6; 2.7-fold in C12 vs. W12, p<0.0001) and Prx2 (Peroxiredoxin-2) (3-fold in C6 vs. W6; 2-fold in C12 vs. W12, p<0.0001). Light cola induced increase in Trx1 (3-fold) and Prx2 (2-fold) after wash-out (p<0.0001, L12 vs. W12). Conclusion Glucotoxicity may contribute to the loss of β cell function with depletion of insulin content. Oxidative stress, suggested by increased expression of thioredoxins and low circulating levels of CoQ10, may follow sustained hyperglycemia. A likely similar panorama may result from the effects of artificially

  7. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-02-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

  8. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed Central

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-01-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter. PMID:9539004

  9. Cushing's syndrome presenting as treatment-resistant bipolar affective disorder: A step in understanding endocrine etiology of mood disorders

    PubMed Central

    Ummar, I. Syed; Rajaraman, Venkateswaran; Loganathan, N.

    2015-01-01

    Cushing's syndrome (CS) is the multisystem disorder which is due to cortisol excess. It is very difficult to diagnose in early stages, especially when psychiatric manifestations are the predominant complaints. It could result in significant morbidity and mortality. We report a case of resistant bipolar affective disorder secondary to CS. Early diagnosis and treatment will lead to better functional outcome and prevention of neurocognitive side-effects of excessive cortisol. PMID:26124528

  10. Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans

    PubMed Central

    Farmer, Adam D; Ban, Vin F; Coen, Steven J; Sanger, Gareth J; Barker, Gareth J; Gresty, Michael A; Giampietro, Vincent P; Williams, Steven C; Webb, Dominic L; Hellström, Per M; Andrews, Paul L R; Aziz, Qasim

    2015-01-01

    Abstract An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions. Key points Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although

  11. Long-term endocrine sequelae after treatment of medulloblastoma: prospective study of growth and thyroid function.

    PubMed

    Oberfield, S E; Allen, J C; Pollack, J; New, M I; Levine, L S

    1986-02-01

    Endocrine evaluations were performed prospectively in 22 patients with medulloblastoma (ages 2 1/2 to 23 1/2 years at diagnosis), after craniospinal radiation with or without adjuvant chemotherapy. The mean craniospinal hypothalamic-pituitary). and thyroid radiation doses were 3600 and 2400 rads, respectively. Fourteen (73%) of 19 patients who had not yet completed their growth experienced a decrease in growth velocity. However, only three of 10 of these children, who underwent growth hormone stimulation tests, had evidence of deficient growth hormone responses, suggesting that growth hormone secretory or regulatory dysfunction, rather than absolute growth hormone deficiency, is present in the majority of these children. Elevated thyroid-stimulating hormone levels were noted in 15 of 22 patients; one patient had hypothalamic hypothyroidism. Thus, the late effects of therapy for medulloblastoma include frequent endocrine morbidity involving hypothalamic-pituitary and thyroid dysfunction.

  12. Bisphenol A affects androgen receptor function via multiple mechanisms.

    PubMed

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  13. Endocrine Diseases

    MedlinePlus

    ... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  14. Endocrine Disruptors

    MedlinePlus

    ... and wildlife. 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 plasticizers such as bisphenol A. Endocrine disruptors ...

  15. Endocrine Disruptors

    PubMed Central

    2015-01-01

    Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices. PMID:26740809

  16. ANALYTICAL CHALLENGES OF ENVIRONMENTAL ENDOCRINE DISRUPTOR MONITORING

    EPA Science Inventory

    Reported increases in the incidence of endocrine-related conditions have led to speculation about environmental causes. Environmental scientists are focusing increased research effort into understanding the mechanisms by which endocrine disruptors affect human and ecological h...

  17. Endocrine System (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Endocrine System KidsHealth > For Teens > Endocrine System A A A ... is called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  18. Effects of sleep deprivation on autonomic and endocrine functions throughout the day and on exercise tolerance in the evening.

    PubMed

    Konishi, Masayuki; Takahashi, Masaki; Endo, Naoya; Numao, Shigeharu; Takagi, Shun; Miyashita, Masashi; Midorikawa, Taishi; Suzuki, Katsuhiko; Sakamoto, Shizuo

    2013-01-01

    The aim of this study was to investigate the effects of sleep deprivation on autonomic and endocrine functions during the day and on exercise tolerance in the evening. Ten healthy young males completed two, 2-day control and sleep deprivation trials. For the control trial, participants were allowed normal sleep from 23:00 to 07:00 h. For the sleep deprivation trial, participants did not sleep for 34 h. Autonomic activity was measured from 19:00 h on day 1 to 16:00 h on day 2 by frequency-domain measures of heart rate variability. Endocrine function was examined by measuring adrenocorticotropic hormone and cortisol from venous blood samples collected on day 2 at 09:00, 13:00, and 17:00 h and immediately after an exercise tolerance testing. Autonomic regulation, particularly parasympathetic regulation estimated from the high-frequency component of heart rate variability analysis, was significantly higher in the sleep deprivation trial than in the control trial in the morning and afternoon of day 2. Plasma adrenocorticotropic hormone concentrations were significantly higher at 09:00 and 13:00 h of day 2 under sleep deprivation. Heart rate during exercise was significantly lower following sleep deprivation. Therefore, the effects of sleep deprivation on autonomic regulation depend on the time of the day.

  19. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes.

    PubMed

    Rafacho, Alex; Ortsäter, Henrik; Nadal, Angel; Quesada, Ivan

    2014-12-01

    Glucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because of their anti-inflammatory, antiallergic and immunosuppressive effects, among other actions. Nevertheless, GCs can produce undesired diabetogenic side effects through interactions with the regulation of glucose homeostasis. Under conditions of excess and/or long-term treatment, GCs can induce peripheral insulin resistance (IR) by impairing insulin signalling, which results in reduced glucose disposal and augmented endogenous glucose production. In addition, GCs can promote abdominal obesity, elevate plasma fatty acids and triglycerides, and suppress osteocalcin synthesis in bone tissue. In response to GC-induced peripheral IR and in an attempt to maintain normoglycaemia, pancreatic β-cells undergo several morphofunctional adaptations that result in hyperinsulinaemia. Failure of β-cells to compensate for this situation favours glucose homeostasis disruption, which can result in hyperglycaemia, particularly in susceptible individuals. GC treatment does not only alter pancreatic β-cell function but also affect them by their actions that can lead to hyperglucagonaemia, further contributing to glucose homeostasis imbalance and hyperglycaemia. In addition, the release of other islet hormones, such as somatostatin, amylin and ghrelin, is also affected by GC administration. These undesired GC actions merit further consideration for the design of improved GC therapies without diabetogenic effects. In summary, in this review, we consider the implication of GC treatment on peripheral IR, islet function and glucose homeostasis.

  20. SCIENTIFIC AND TECHNOLOGICAL SUPPORT ON IN VITRO ASSAYS FOR THE AGENCY'S ENDOCRINE DISRUPTOR SCREENING PROGRAM

    EPA Science Inventory

    In response to the 1996 legislative mandate for an endocrine screening and testing program, we are helping develop, standardize and validate relatively sensitive, robust and relatively simple methods for in vitro screening of chemicals that affect estrogen, and androgen function ...

  1. Relative functions of Gαs and its extra-large variant XLαs in the endocrine system.

    PubMed

    Bastepe, M

    2012-09-01

    Gαs is a ubiquitous signaling protein necessary for the actions of many neurotransmitters, hormones, and autocrine/paracrine factors. Loss-of-function mutations within the gene encoding Gαs, GNAS, are responsible for multiple human diseases, including Albright's Hereditary Osteodystrophy, progressive osseous heteroplasia, and pseudohypoparathyroidism. Gain-of-function mutations in the same gene are found in various endocrine and nonendocrine tumors and in patients with McCune-Albright Syndrome and fibrous dysplasia of bone. In addition to Gαs, GNAS gives rise to multiple additional coding and noncoding transcripts. Among those, XLαs is a paternally expressed product that is partially identical to Gαs. This article reviews the cellular actions of Gαs and XLαs, focusing on the significance of XLαs relative to Gαs in mammalian physiology and human disease.

  2. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  3. A mutation in the RET proto-oncogene in Hirschsprung's disease affects the tyrosine kinase activity associated with multiple endocrine neoplasia type 2A and 2B.

    PubMed Central

    Cosma, M P; Panariello, L; Quadro, L; Dathan, N A; Fattoruso, O; Colantuoni, V

    1996-01-01

    We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the phosphorylation potential. Co-transfection experiments with single and double mutants carrying plasmids RET2A and RET2AHS in different ratios drastically reduced the phosphorylation levels of the RET2A protein, suggesting a dominant-negative effect of the HSCR mutation. Also, the phosphorylation associated with the multiple endocrine neoplasia type 2B (MEN2B) allele was affected in experiments with single and double mutants carrying plasmids co-transfected under the same conditions. Finally, analysis of the enzymic activity of MEN2A and MEN2B tumours confirmed the relative levels of tyrosine phosphorylation observed in Cos cells, indicating that this condition, in vivo, may account for the RET transforming potential. PMID:8670046

  4. Phytosteroids beyond estrogens: Regulators of reproductive and endocrine function in natural products.

    PubMed

    Dean, Matthew; Murphy, Brian T; Burdette, Joanna E

    2017-02-15

    Foods and botanical supplements can interfere with the endocrine system through the presence of phytosteroids - chemicals that interact with steroids receptors. Phytoestrogens are well studied, but compounds such as kaempferol, apigenin, genistein, ginsenoside Rf, and glycyrrhetinic acid have been shown to interact with non-estrogen nuclear receptors. These compounds can have agonist, antagonist, or mixed agonist/antagonist activity depending on compound, receptor, cell line or tissue, and concentration. Some phytosteroids have also been shown to inhibit steroid metabolizing enzymes, resulting in biological effects through altered endogenous steroid concentrations. An interesting example, compound A (4-[1-chloro-2-(methylamino)ethyl]phenyl acetate hydrochloride (1:1)) is a promising selective glucocorticoid receptor modulator (SGRM) based on a phytosteroid isolated from Salsola tuberculatiformis Botschantzev. Given that $6.9 billion of herbal supplements are sold each year, is clear that further identification and characterization of phytosteroids is needed to ensure the safe and effective use of botanical supplements.

  5. Endocrine disorders and the neurologic manifestations

    PubMed Central

    2014-01-01

    The nervous system and the endocrine system are closely interrelated and both involved intimately in maintaining homeostasis. Endocrine dysfunctions may lead to various neurologic manifestations such as headache, myopathy, and acute encephalopathy including coma. It is important to recognize the neurologic signs and symptoms caused by the endocrine disorders while managing endocrine disorders. This article provides an overview of the neurologic manifestations found in various endocrine disorders that affect pediatric patients. It is valuable to think about 'endocrine disorder' as a cause of the neurologic manifestations. Early diagnosis and treatment of hormonal imbalance can rapidly relieve the neurologic symptoms. Better understanding of the interaction between the endocrine system and the nervous system, combined with the knowledge about the pathophysiology of the neurologic manifestations presented in the endocrine disorders might allow earlier diagnosis and better treatment of the endocrine disorders. PMID:25654063

  6. Endocrine disorders and medically assisted procreation.

    PubMed

    Luk, J

    2011-04-01

    A normal endocrine environment is imperative to maintain normal reproduction in women. The major endocrine organs that play a part in the reproductive system include hypothalamic pituitary axis, adrenal gland, thyroid gland, and the ovary. Each endocrine organ is in close communication and relationship with one another. Any endocrine disorders that significantly affect any of these organs would disrupt reproduction resulting in infertility. In this review, we will provide an overview of the common endocrine disorders and the available medical management including assisted reproductive technology (ART) and hormonal supplementation to overcome the endocrine disorders in order to achieve fertility for the female patients.

  7. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  8. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

  9. Effects of Alcohol on the Endocrine System

    PubMed Central

    Rachdaoui, Nadia; Sarkar, Dipak K.

    2013-01-01

    Synopsis The endocrine system ensures a proper communication between various organs of the body to maintain a constant internal environment. The endocrine system also plays an essential role in enabling the body to respond and appropriately cope with changes in the internal or external environments, such as respond to stress and injury. These functions of the endocrine system to maintain body homeostasis are aided by its communication with the nervous system, immune system and body’s circadian mechanism. 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 physiological 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. PMID:24011889

  10. Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy

    PubMed Central

    De Sanctis, Vincenzo; Elsedfy, Heba; Soliman, Ashraf T.; Elhakim, Ihab Zaki; Kattamis, Christos; Soliman, Nada A.; Elalaily, Rania

    2016-01-01

    Introduction It is well known that the older generation of adult TM patients has a higher incidence of morbidities and co-morbidities. At present, little information is available on adult TM patients with multiple endocrine complications (MEC). The main objectives of this longitudinal retrospective survey were: 1) to establish the incidence and progression of MEC (3 or more) in TM patients; 2) to compare the clinical, laboratory and imaging data to a sex and age-matched group of TM patients without MEC; 3) to assess the influence of iron overload represented by serum ferritin (peak and mean annual value at the last endocrine observation). Patients and methods The study was started in January 1974 and was completed by the same physician at the end of December 2015. The registry database of the regularly followed TM patients from diagnosis included 145 adults (> 18 years). All TM patients were of Italian ethnic origin. Eleven out of 145 patients (7.5 %) developed MEC. Twenty-four other patients (12 females and 12 males) had a normal endocrine function (16.5 %) and served as controls. Results In our survey, four important, relevant aspects emerged in the MEC group. These included the late age at the start of chelation therapy with desferrioxamine mesylate (DFO); the higher serum ferritin peak (8521.8 ± 5958.9 vs 3575.2 ± 1801.4 ng/ml); the upper proportion of splenectomized (81.8 % vs. 28.5%) patients and poor compliance registered mainly during the peripubertal and pubertal age (72.7 % vs.16.6 %) in TM patients developing MEC versus those without endocrine complications. Furthermore, a negative correlation was observed in all TM patients between LIC and final height (r: −0.424; p = 0.031). Conclusions Our study supports the view that simultaneous involvement of more than one endocrine gland is not uncommon (7.5 %). It mainly occurred in TM patients who started chelation therapy with DFO late in life and who had irregular/poor compliance to treatment. Therefore

  11. Exocrine and endocrine testicular function during the treatment of experimental orchitis and nonspecific orchoepididymitis by low-energy laser radiation

    NASA Astrophysics Data System (ADS)

    Reznikov, Leonid L.; Pupkova, Ludmila S.; Bell, H.; Murzin, Alexander G.

    1995-05-01

    Investigations into the biological effects of low-energy laser radiation (LLR) are characterized by a score of challenges, which are due primarily to a cascade of laser-induced and sometimes antagonistic processes. To investigate these processes on various biologic levels, we analyzed local and general effects of LLR on the exocrine and endocrine functions of the accessory sex glands in experimentally induced orchitis and orchoepididymitis in rabbits, and in clinical studies on male patients. The results indicate that LLR may alter the inflammatory response, including the exudative reaction, macrophage migration, and fibroblast activity. Furthermore, LLR may result in changes in serum concentrations of LH, FSH, and ACTH, prolactin, testosterone, cortisol and aldosterone. Some of these changes may be at least partially responsible for the well-known anti-inflammatory effects of LLR.

  12. Long-term effects of cranial irradiation on endocrine function in children with brain tumors. A prospective study

    SciTech Connect

    Duffner, P.K.; Cohen, M.E.; Voorhess, M.L.; MacGillivray, M.H.; Brecher, M.L.; Panahon, A.; Gilani, B.B.

    1985-11-01

    This study prospectively evaluated the endocrine function of 11 children treated with cranial irradiation (CRT) for brain tumors. All tumors were remote from the hypothalamic-pituitary axis. Children were studied before treatment and at 3, 6, and 12 months after the completion of CRT. T4, thyroid-stimulating hormone, prolactin, plasma cortisol, and urinary follicle-stimulating hormone and luteinizing hormone values were normal before and after treatment in all patients. Growth hormone (GH) deficiency was identified in 0 of 7 patients before treatment, in 2 of 7 patients 3 months post-CRT, in 9 of 11 patients 6 months post-CRT, and in 7 of 8 patients 12 months post-CRT. Growth deceleration was identified in five of seven prepubertal patients. GH deficiency is an extremely common sequelae of CRT, beginning as early as 3 months after the completion of CRT. The deficit is progressive over time.

  13. The Endocrine Machinery.

    ERIC Educational Resources Information Center

    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)

  14. Congenital hypogonadotropic hypogonadism and Kallmann syndrome as models for studying hormonal regulation of human testicular endocrine functions.

    PubMed

    Trabado, Séverine; Lamothe, Sophie; Maione, Luigi; Bouvattier, Claire; Sarfati, Julie; Brailly-Tabard, Sylvie; Young, Jacques

    2014-05-01

    Men with Kallmann syndrome (KS) and those with congenital isolated hypogonadotropic hypogonadism with normal olfaction share a chronic, usually profound deficit, in FSH and LH, the two pituitary gonadotropins. Many studies indicate that this gonadotropin deficiency is already present during fetal life, thus explaining the micropenis, cryptorchidism and marked testicular hypotrophy already present at birth. In addition, neonatal activation of gonadotropin secretion is compromised in boys with severe CHH/Kallmann, preventing the first phase of postnatal testicular activation. Finally, CHH is characterized by the persistence, in the vast majority of cases, of gonadotropin deficiency at the time of puberty and during adulthood. This prevents the normal pubertal testicular reactivation required for physiological sex steroid and testicular peptide production, and for spermatogenesis. CHH/KS thus represents a pathological paradigm that can help to unravel, in vivo, the role of each gonadotropin in human testicular exocrine and endocrine functions at different stages of development. Recombinant gonadotropins with pure LH or FSH activity have been used to stimulate Leydig's cells and Sertoli's cells, respectively, and thereby to clarify their paracrine interaction in vivo. The effects of these pharmacological probes can be assessed by measuring the changes they provoke in circulating testicular hormone concentrations. This review discusses the impact of chronic gonadotropin deficiency on the endocrine functions of the interstitial compartment, which contains testosterone-, estradiol- and INSL3-secreting Leydig's cells. It also examines the regulation of inhibin B and anti-Mullerian hormone (AMH) secretion in the seminiferous tubules, and the insights provided by studies of human testicular stimulation with recombinant gonadotropins, used either individually or in combination.

  15. Application of endocrine disruptor screening program fish short-term reproduction assay: Reproduction and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus) exposed to Bermuda pond sediment.

    PubMed

    Fort, Douglas J; Mathis, Michael; Fort, Chelsea E; Fort, Hayley M; Bacon, Jamie P

    2015-06-01

    A modified tier 1 Endocrine Disruptor Screening Program (EDSP) 21-d fish short-term reproduction assay (FSTRA) was used to evaluate the effects of sediment exposure from freshwater and brackish ponds in Bermuda on reproductive fecundity and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus). Reproductively active male and female fish were exposed to control sediment and sediment from 2 freshwater ponds (fathead minnow) and 2 marine ponds (killifish) contaminated with polyaromatic hydrocarbons and metals via flow-through exposure for 21 d. Reproductive fecundity was monitored daily. At termination, the status of the reproductive endocrine system was assessed by the gonadosomatic index, gonadal histology, plasma steroids (estrogen [E2], testosterone [T], and 11-ketotestosterone [11-KT]), steroidogenic enzymes (aromatase and combined 3β/17β -hydroxysteroid dehydrogenase [3β/17β-HSD]), and plasma vitellogenin (VTG). Decreased reproductive fecundity, lower male body weight, and altered endocrinological measures of reproductive status were observed in both species. Higher plasma T levels in female minnows and 11-KT levels in both male and female minnows and female killifish exposed to freshwater and brackish sediments, respectively. Decreased female E2 and VTG levels and gonadal cytochrome P19 (aromatase) activity were also found in sediment exposed females from both species. No effect on female 3β/17β-HSD activity was found in either species. The FSTRA provided a robust model capable of modification to evaluate reproductive effects of sediment exposure in fish.

  16. Effects of acute exercise on pancreatic endocrine function in subjects with type 2 diabetes.

    PubMed

    Knudsen, S H; Karstoft, K; Winding, K; Holst, J J; Pedersen, B K; Solomon, T P J

    2015-02-01

    We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in subjects with type 2 diabetes (T2D) and examined the influence of subjects' diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with glucagon-like peptide-1 (GLP-1) infusion and arginine injection, the morning after a 1-h walk or no exercise. Subjects were stratified by high and low fasting plasma glucose (FPG) levels and by glycated haemoglobin (HbA1c) levels, as well as by current use/non-use of antidiabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (p < 0.05 to <0.01). In subjects with low FPG levels, exercise increased GLP-1-stimulated insulin secretion (p < 0.05), with the same trend being observed for arginine (p = 0.08). The same trends were seen for subjects with low HbA1c levels. Furthermore, exercise increased GLP-1- and arginine-stimulated insulin secretion (p < 0.05) in subjects who were antidiabetic drug-naïve. Exercise-induced increases in insulin secretion are blunted in subjects with T2D with high rates of hyperglycaemia and in those using antidiabetic drugs.

  17. Multiple Endocrine Neoplasia Syndromes

    PubMed Central

    Pont, Allan

    1980-01-01

    The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue. PMID:6247851

  18. DIFFERENCES IN THE STRUCTURE AND FUNCTION OF FATHEAD MINNOW AND HUMAN ERA: IMPLICATIONS FOR IN VITRO TESTING OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Mammalian receptors and assay systems are generally used for in vitro analysis of endocrine disrupting chemicals (EDC) with the assumption that minor differences in amino acid sequences among species do not translate into significant differences in receptor function. We have fou...

  19. Does iron deficiency anemia affect olfactory function?

    PubMed

    Dinc, Mehmet Emre; Dalgic, Abdullah; Ulusoy, Seckin; Dizdar, Denizhan; Develioglu, Omer; Topak, Murat

    2016-07-01

    Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin' Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values.

  20. Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men.

    PubMed Central

    Telisman, S; Cvitković, P; Jurasović, J; Pizent, A; Gavella, M; Rocić, B

    2000-01-01

    Blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin (EP), blood cadmium (BCd), serum zinc (SZn), seminal fluid zinc (SfZn), serum copper (SCu), and parameters of semen quality and of reproductive endocrine function were measured in 149 healthy male industrial workers 20-43 years of age. The group contained 98 subjects with slight to moderate occupational exposure to Pb and 51 reference subjects. All of the subjects lived in Zagreb, Croatia. Significant (p < 0.05) correlations of BPb, ALAD, and/or EP with reproductive parameters indicated a Pb-related decrease in sperm density, in counts of total, motile, and viable sperm, in the percentage and count of progressively motile sperm, in parameters of prostate secretory function (SfZn, acid phosphatase, and citric acid in seminal fluid), and an increase in abnormal sperm head morphology, serum testosterone, and estradiol. These associations were confirmed by results of multiple regression, which also showed significant (p < 0. 05) influence of BCd, SZn, SCu, smoking habits, alcohol consumption, or age on certain reproductive parameters. These effects were mainly of lower rank and intensity as compared to Pb-related reproductive effects, whereas BCd contributed to a decrease in sperm motility and an increase in abnormal sperm morphology and serum testosterone. No significant Pb- or Cd-related influence was found on levels of the lactate dehydrogenase isoenzyme LDH-C(4) and fructose in seminal fluid or on follicle-stimulating hormone, luteinizing hormone, and prolactin in serum. The seminal fluid concentrations of Pb (SfPb) and Cd (SfCd) were measured in 118 of the 149 subjects, and a highly significant (p < 0.0001) correlation was found between BPb and SfPb levels (r = 0.571) and between BCd and SfCd levels (r = 0.490). The overall study results indicate that even moderate exposures to Pb (BPb < 400 microg/L) and Cd (BCd < 10 microg/L) can significantly reduce human

  1. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions.

    PubMed

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant.

  2. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions

    PubMed Central

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant. PMID:26186596

  3. [The central mechanisms of the stimulating influence of intervalic hypoxic conditioning on the endocrine function of the pancreas in rats].

    PubMed

    Abramov, A V

    1997-01-01

    In the investigation of Wistar rats the morpho-functional state of the neurons of the dorsal motor nucleus of n. vagus (DVC), locus coeruleus (LC) and peptidergic neurons of medical parvocellular subnuclei of paraventricular nucleus of hypothalamus (PVHmp) in the conditions of intermittent hypoxic training (IHT) (6 hours a day on the altitude 6000 m for 21 day) was studied. Immunocytochemical method was used to determine the functional state of peptidergic neurons of PVMmp and of the median eminence of hypothalamus, which are synthesizing neurotensin, cholecystokinin, bombesin, leu- and met-enkephalins, calcitonin-gene-related peptide and vasointestinal peptide. It was established that IHT leads to the activation of peptidergic neurons of PVHmp, neurons of DVC and to the lesser restrain of LC. It is demonstrated that these structures may take part in realisation of IHT's stimulating effect on the state of pancreatic beta-cells. In consists of insulin-stimulating and insulocyteprotective effects, that can be realised by the hypothalamic and neuroconducting ways of regulation of endocrine pancreas, with direct participation of hypothalamic neuropeptides.

  4. Evolutionary diversification in stickleback affects ecosystem functioning.

    PubMed

    Harmon, Luke J; Matthews, Blake; Des Roches, Simone; Chase, Jonathan M; Shurin, Jonathan B; Schluter, Dolph

    2009-04-30

    Explaining the ecological causes of evolutionary diversification is a major focus of biology, but surprisingly little has been said about the effects of evolutionary diversification on ecosystems. The number of species in an ecosystem and their traits are key predictors of many ecosystem-level processes, such as rates of productivity, biomass sequestration and decomposition. Here we demonstrate short-term ecosystem-level effects of adaptive radiation in the threespine stickleback (Gasterosteus aculeatus) over the past 10,000 years. These fish have undergone recent parallel diversification in several lakes in coastal British Columbia, resulting in the formation of two specialized species (benthic and limnetic) from a generalist ancestor. Using a mesocosm experiment, we demonstrate that this diversification has strong effects on ecosystems, affecting prey community structure, total primary production, and the nature of dissolved organic materials that regulate the spectral properties of light transmission in the system. However, these ecosystem effects do not simply increase in their relative strength with increasing specialization and species richness; instead, they reflect the complex and indirect consequences of ecosystem engineering by sticklebacks. It is well known that ecological factors influence adaptive radiation. We demonstrate that adaptive radiation, even over short timescales, can have profound effects on ecosystems.

  5. ALTERATIONS IN DEVELOPMENT OF REPRODUCTIVE AND ENDOCRINE SYSTEMS OF WILDLIFE POPULATIONS EXPOSED TO ENDOCRINE-DISRUPTING CONTAMINANTS.

    EPA Science Inventory

    Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target ...

  6. No improvement of pancreas transplant endocrine function by exogenous insulin infusion (islet rest) in the postoperative period.

    PubMed

    Dafoe, D C; Campbell, D A; Rosenberg, L; Merion, R M; Ucros, I; Vinik, A I; Klandorf, H; Turcotte, J G

    1989-07-01

    The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n = 8) received constant insulin infusion for 7 days after transplantation; the control group (n = 5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27 +/- 0.04 ng/ml) as compared to the control group (0.66 +/- 0.08 ng/ml) (P less than 0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were -1.79 and -1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

  7. [Endocrine disease symptoms].

    PubMed

    Reincke, M

    2013-10-01

    Diseases of the endocrine system can be classified according to the prevalence into two categories: very frequent endocrinopathies, which affect a population of several millions in Germany and include diabetes mellitus, endemic goiter, osteoporosis and obesity. On the other hand there are a large number of rare endocrine diseases which share the paradox of other rare diseases: they are also often falsely suspected in patients who are not affected but at the same time there are sometimes long delays in diagnosis in those who do have the disease. In cases of adrenal insufficiency, absolute glucocorticoid deficiency can progress to an adrenal crisis which is fatal if not treated. Patients with de Quervain thyroiditis often suffer from prolonged episodes of fever with tender, diffuse goiter and neck pain. Pheochromocytomas should be recognized early in the course of disease because of life-threatening cardiovascular complications. This article highlights the essential characteristics in order to increase awareness.

  8. [Neurotrophic control in the development and function of two endocrine organs: the ovary and the pancreas].

    PubMed

    Cabrera-Vásquez, Siraam

    2007-01-01

    Neurotrophins (NTs) are important for the survival, differentiation and function of sympathetic and sensorial neurons of central and peripheral nervous system. However, similar functions have been described of NTs in non-neural organs. Nerve Growth factor (NGF) participates in the foliculogenesis and ovulation in the ovary, as well as in the islet morphogenesis and insulin secretion of the pancreatic beta cell. The NTs act by binding to two distinct classes of transmembranal receptors: p75 and Trks. Both receptor types lead to activation of intracellular signaling cascades that end with cell survival or apoptosis. In this review different actions of the NTs in the ovarian and the pancreas are described.

  9. Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

    PubMed Central

    Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.

    2015-01-01

    Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

  10. Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

    PubMed

    Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; Joseph, Vincent; Kinkead, Richard

    2015-04-01

    Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia.

  11. Maternal stress and plural breeding with communal care affect development of the endocrine stress response in a wild rodent.

    PubMed

    Bauer, Carolyn M; Hayes, Loren D; Ebensperger, Luis A; Ramírez-Estrada, Juan; León, Cecilia; Davis, Garrett T; Romero, L Michael

    2015-09-01

    Maternal stress can significantly affect offspring fitness. In laboratory rodents, chronically stressed mothers provide poor maternal care, resulting in pups with hyperactive stress responses. These hyperactive stress responses are characterized by high glucocorticoid levels in response to stressors plus poor negative feedback, which can ultimately lead to decreased fitness. In degus (Octodon degus) and other plural breeding rodents that exhibit communal care, however, maternal care from multiple females may buffer the negative impact on pups born to less parental mothers. We used wild, free-living degus to test this hypothesis. After parturition, we manipulated maternal stress by implanting cortisol pellets in 0%, 50-75%, or 100% of adult females within each social group. We then sampled pups for baseline and stress-induced cortisol, negative feedback efficacy, and adrenal sensitivity. From groups where all mothers were implanted with cortisol, pups had lower baseline cortisol levels and male pups additionally had weaker negative feedback compared to 0% or 50-75% implanted groups. Contrary to expectations, stress-induced cortisol did not differ between treatment groups. These data suggest that maternal stress impacts some aspects of the pup stress response, potentially through decreased maternal care, but that presence of unstressed mothers may mitigate some of these effects. Therefore, one benefit of plural breeding with communal care may be to buffer post-natal stress.

  12. [Photoperiodic control of gonadal endocrine function in silver-gray foxes and its alteration during domestication].

    PubMed

    Osadchuk, L V; Trut, L N

    1988-01-01

    Studies have been made on the level of estradiol and progesterone in domesticated and nondomesticated female silver foxes under different photoperiodic regime. The duration of the "light--darkness" cycle was equal to 24 h. Total duration of the light period was equal to 9 1/2 h; illumination was natural for 7 h, being artificial for the rest 2 1/2 h in a dark part of a day. It was demonstrated that additional illumination affects the hormonal level and sexual activity, the effect being dependent on the particular time of illumination. Nocturnal illumination significantly increased the level of sex hormones in the blood, domesticated animals being more sensitive as compared to nondomesticated ones.

  13. The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function.

    PubMed

    Goldstein, R S; Mayor, G H; Gingerich, R L; Hook, J B; Rosenbaum, R W; Bond, J T

    1983-07-01

    Three divalent platinum compounds, cis-dichlorodiammineplatinum (cis-DDP), trans-dichlorodiammineplatinum (trans-DDP), and ammonium tetrachloroplatinate, were examined for their effects on glucose metabolism in male F-344 rats. Rats were treated with a single iv dose of cis-DDP (0, 2.5, or 5 mg/kg), trans-DDP (0, 5, 7.5, or 15 mg/kg) or tetrachloroplatinate (0, 6, or 18 mg/kg). Glucose tolerance was evaluated 2, 4, 7, and 14 days following platinum treatment by serially measuring plasma glucose before and following an ip glucose load. Administration of 5 mg/kg cis-DDP impaired glucose tolerance on Days 2 and 4, but not on Days 7 and 14. Plasma immunoreactive glucagon (IRG) was elevated at all times following cis-DDP treatment and thus was not correlated with the transient impairment in glucose tolerance. Plasma immunoreactive insulin (IRI) response to a glucose load was deficient relative to the degree of hyperglycemia in cis-DDP-treated (5 mg/kg) animals on Days 2 and 4. However, neither histopathological damage of the pancreas nor pancreatic stores of IRI were affected by cis-DDP treatment. In contrast to cis-DDP, equimolar or greater than equimolar doses of trans-DDP or tetrachloroplatinate did not significantly affect glucose tolerance at any time examined. These results indicate that cis-DDP-mediated glucose intolerance is unique to the geometry of the complex and is related to properties other than the presence of a divalent platinum atom. Furthermore, glucose intolerance following cis-DDP treatment appears to be related to a relative deficiency in insulin secretion.

  14. [Xenoestrogens: endocrine disrupting compounds].

    PubMed

    Wozniak, Milena; Murias, Marek

    2008-11-01

    In recent years much attention has been paid to the issues of chemicals that disrupt the normal function of endocrine system, namely xenoestrogens. These chemicals can mimic the activity of endogenous estrogens, antagonize their interaction with estrogen receptors or disrupt the synthesis, metabolism and functions of endogenous female hormones. Due to the fact that they act thanks to many different mechanisms, it is very difficult to estimate their estrogenic activity by means of a simple tests. The important issue remains the fact that xenoestrogens may have a positive or negative influence on the function of the endocrine system. It seems to be very important that there are many sources of xenoestrogens, that is not only vegetables and fruit (phytoestrogens), but also metals (Co, Cu, Ni, Cr, Pb), dental appliances (alkilphenols), food containers or blood containers (PVC--polyvinyl chloride, DEHP--di-(2-ethylhexyl) phthalate), cosmetics (parabens) and pesticides (DDT--dichlor-diphenyl-trichlorethylane, endosulfane).

  15. Effect of surgery and radiotherapy on visual and endocrine function in nonfunctioning pituitary adenomas.

    PubMed

    Colao, A; Cerbone, G; Cappabianca, P; Ferone, D; Alfieri, A; Di Salle, F; Faggiano, A; Merola, B; de Divitiis, E; Lombardi, G

    1998-05-01

    The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA) subjected to 1-10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness

  16. Endocrine Effects of Circadian Disruption.

    PubMed

    Bedrosian, Tracy A; Fonken, Laura K; Nelson, Randy J

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems.

  17. Bovine herpesvirus 4 is tropic for bovine endometrial cells and modulates endocrine function.

    PubMed

    Donofrio, Gaetano; Herath, Shan; Sartori, Chiara; Cavirani, Sandro; Flammini, Cesidio Filippo; Sheldon, Iain Martin

    2007-07-01

    Bovine postpartum uterine disease, metritis, affects about 40% of animals and is widely considered to have a bacterial aetiology. Although the gamma-herpesvirus bovine herpesvirus 4 (BoHV-4) has been isolated from several outbreaks of metritis or abortion, the role of viruses in endometrial pathology and the mechanisms of viral infection of uterine cells are often ignored. The objectives of the present study were to explore the interaction, tropism and outcomes of BoHV-4 challenge of endometrial stromal and epithelial cells. Endometrial stromal and epithelial cells were purified and infected with a recombinant BoHV-4 carrying an enhanced green fluorescent protein (EGFP) expression cassette to monitor the establishment of infection. BoHV-4 efficiently infected both stromal and epithelial cells, causing a strong non-apoptotic cytopathic effect, associated with robust viral replication. The crucial step for the BoHV-4 endometriotropism appeared to be after viral entry as there was enhanced transactivation of the BoHV-4 immediate early 2 gene promoter following transient transfection into the endometrial cells. Infection with BoHV-4 increased cyclooxygenase 2 protein expression and prostaglandin estradiol secretion in endometrial stromal cells, but not epithelial cells. Bovine macrophages are persistently infected with BoHV-4, and co-culture with endometrial stromal cells reactivated BoHV-4 replication in the persistently infected macrophages, suggesting a symbiotic relationship between the cells and virus. In conclusion, the present study provides evidence of cellular and molecular mechanisms, supporting the concept that BoHV-4 is a pathogen associated with uterine disease.

  18. Artemisia scoparia Enhances Adipocyte Development and Endocrine Function In Vitro and Enhances Insulin Action In Vivo

    PubMed Central

    Richard, Allison J.; Fuller, Scott; Fedorcenco, Veaceslav; Beyl, Robbie; Burris, Thomas P.; Mynatt, Randall; Ribnicky, David M.; Stephens, Jacqueline M.

    2014-01-01

    Background Failure of adipocytes to expand during periods of energy excess can result in undesirable metabolic consequences such as ectopic fat accumulation and insulin resistance. Blinded screening studies have indicated that Artemisia scoparia (SCO) extracts can enhance adipocyte differentiation and lipid accumulation in cultured adipocytes. The present study tested the hypothesis that SCO treatment modulates fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo. Methods In vitro experiments utilized a Gal4-PPARγ ligand binding domain (LBD) fusion protein-luciferase reporter assay to examine PPARγ activation. To investigate the ability of SCO to modulate adipogenesis and mature fat cell function in 3T3-L1 cells, neutral lipid accumulation, gene expression, and protein secretion were measured by Oil Red O staining, qRT-PCR, and immunoblotting, respectively. For the in vivo experiments, diet-induced obese (DIO) C57BL/6J mice were fed a high-fat diet (HFD) or HFD containing 1% w/w SCO for four weeks. Body weight and composition, food intake, and fasting glucose and insulin levels were measured. Phospho-activation and expression of insulin-sensitizing proteins in epididymal adipose tissue (eWAT) were measured by immunoblotting. Results Ethanolic extracts of A. scoparia significantly activated the PPARγ LBD and enhanced lipid accumulation in differentiating 3T3-L1 cells. SCO increased the transcription of several PPARγ target genes in differentiating 3T3-L1 cells and rescued the negative effects of tumor necrosis factor α on production and secretion of adiponectin and monocyte chemoattractant protein-1 in fully differentiated fat cells. DIO mice treated with SCO had elevated adiponectin levels and increased phosphorylation of AMPKα in eWAT when compared to control mice. In SCO-treated mice, these changes were also associated with decreased fasting insulin and glucose levels. Conclusion SCO has metabolically beneficial

  19. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function.

    PubMed

    Ganong, W F

    2000-01-01

    1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

  20. Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male subjects.

    PubMed

    Jurasović, Jasna; Cvitković, Petar; Pizent, Alica; Colak, Bozo; Telisman, Spomenka

    2004-12-01

    In 123 Croatian men with no occupational exposure to metals, the influence of cadmium on reproductive parameters was examined after adjusting for age, smoking, alcohol, and biomarkers of lead, copper, zinc, and selenium. The following variables were measured: blood cadmium (BCd), blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin, serum copper (SCu), serum zinc (SZn), serum selenium (SSe), activity of glutathione peroxidase (GPx) in blood, testis size, semen quality (including sperm concentration, motility, viability, and morphology), indicators in seminal fluid (the lactate dehydrogenase isoenzyme LDH-C4, fructose, zinc, acid phosphatase, and citric acid), and hormones in serum (follicle-stimulating hormone--FSH, luteinizing hormone, prolactin, testosterone, and estradiol). The median and range BCd values were 2.94 (0.49-11.93) microg/L in 61 smokers and 0.59 (0.20-3.71) microg/L in 62 nonsmokers (p < 0.0001). Smoking habits (cigarettes/day) highly significantly correlated with BCd (p < 0.0001). After adjusting for potential confounding variables by multiple regression, BCd was significantly associated with a decrease in testis size (p < 0.03) and an increase in serum estradiol (p < 0.005), FSH (p < 0.03), and testosterone (p < 0.04). Smoking was significantly associated with a decrease in serum prolactin (p < 0.006) and LDH-C4 in seminal fluid (p < 0.03). Several reproductive parameters were significantly associated with BPb and ALAD, biomarkers of lead, and/or with SCu, SZn, SSe, and GPx. The necessity of controlling for various metals, and other potential confounders when assessing the influence of a particular metal on reproductive function in men, is emphasized.

  1. Effects of nutritional restriction on metabolic, endocrine, and ovarian function in llamas (Lama glama).

    PubMed

    Norambuena, M C; Silva, M; Urra, F; Ulloa-Leal, C; Fernández, A; Adams, G P; Huanca, W; Ratto, M H

    2013-05-01

    The objectives of the study were to determine the effects of nutritional restriction on ovarian function in llamas. Mature female llamas were assigned randomly to a Control group, fed 100% of maintenance energy requirements (MER) (n=8), or a Restricted group (n=8) fed from 70% to 40% of MER until a body condition score of 2.5 was attained. Blood samples were taken every-other-day to determine plasma concentrations of LH, estradiol, leptin and metabolic markers, and follicular dynamics were monitored daily by ultrasonography for 30 days (Experiment 1). Llamas were then treated with GnRH to compare the ovulatory response and corpus luteus (CL) development between groups (Experiment 2). Blood samples were taken to measure LH, leptin, progesterone and metabolic markers and ovarian structures were assessed as in Experiment 1. Llamas in the Restricted group had lower body mass and body condition scores than those in the Control group (P<0.001). Plasma concentrations of cholesterol, non-esterified fatty acids, triglycerides, and urea were higher in the Restricted group (P<0.05) than in the Control group. The day-to-day diameter profiles of the dominant follicles were smaller (P<0.05) in the Restricted group than in the Control group but plasma estradiol concentration did not differ. The ovulation rate and LH secretion in response to GnRH did not differ. Day-to-day profiles of CL diameter, plasma progesterone and leptin concentrations were smaller (P<0.01) in the Restricted group. In conclusion, nutritional restriction in llamas was associated with suppressed follicle and CL development, and lower plasma concentrations of progesterone and leptin.

  2. Endocrine-disrupting chemicals and skin manifestations.

    PubMed

    Ju, Qiang; Zouboulis, Christos C

    2016-09-01

    Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin. In addition, their effects on keratinocytes, melanocytes, sebocytes, inflammatory and immunological cells, and skin stem cells produce inflammatory and allergic skin diseases, chloracne, disorders of skin pigmentation, skin cancer, and skin aging. Mechanisms, which EDCs use to induce these skin disorders are complicated, and involve the interference of endogenous hormones and most importantly the activation of the aryl hydrocarbon receptor signal pathway. Further studies on EDCs and skin diseases are necessary to elucidate these mechanisms.

  3. Elucidating the links between endocrine disruptors and neurodevelopment.

    PubMed

    Schug, Thaddeus T; Blawas, Ashley M; Gray, Kimberly; Heindel, Jerrold J; Lawler, Cindy P

    2015-06-01

    Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes.

  4. μ and κ Opioid receptor distribution in the monogamous titi monkey (Callicebus cupreus): Implications for social behavior and endocrine functioning

    PubMed Central

    Ragen, Benjamin J.; Freeman, Sara M.; Laredo, Sarah A.; Mendoza, Sally P.; Bales, Karen L.

    2015-01-01

    The opioid system is involved in infant-mother bonds and adult-adult bonds in many species. We have previously shown that μ opioid receptors (MOR) and κ opioid receptors (KOR) are involved in regulating the adult attachment of the monogamous titi monkey. The present study sought to determine the distribution of MOR and KOR in the titi monkey brain using receptor autoradiography. We used [3H]DAMGO to label MORs and [3H]U69,593 to label KORs. MOR binding was heterogeneous throughout the titi monkey brain. Specifically, MOR binding was observed in the cingulate gyrus, striatum, septal regions, diagonal band, amygdala, hypothalamus, hippocampus, and thalamus. Binding was particularly dense in the septum, medial amygdala, paraventricular nucleus of the hypothalamus, mediodorsal thalamus with moderate binding in the nucleus accumbens. Consistent with other primate species, MOR were also observed in “neurochemically unique domains of the accumbens and putamen” (NUDAPs). In general KOR binding was more homogenous. KORs were primarily found in the cingulate gyrus, striatum, amygdala and hippocampus. Dense KOR binding was observed in the claustrum. Relative MOR and KOR binding in the titi monkey striatum was similar to other humans and primates, but was much lower compared to rodents. Relative MOR binding in the titi monkey hypothalamus was much greater than that found in rodents. This study was the first to examine MOR and KOR binding in a monogamous primate. The location of these receptors gives insight into where ligands may be acting to regulate social behavior and endocrine function. PMID:25637809

  5. μ and κ opioid receptor distribution in the monogamous titi monkey (Callicebus cupreus): implications for social behavior and endocrine functioning.

    PubMed

    Ragen, B J; Freeman, S M; Laredo, S A; Mendoza, S P; Bales, K L

    2015-04-02

    The opioid system is involved in infant-mother bonds and adult-adult bonds in many species. We have previously shown that μ opioid receptors (MORs) and κ opioid receptors (KORs) are involved in regulating the adult attachment of the monogamous titi monkey. The present study sought to determine the distribution of MOR and KOR in the titi monkey brain using receptor autoradiography. We used [(3)H][D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) to label MORs and [(3)H]U69,593 to label KORs. MOR binding was heterogeneous throughout the titi monkey brain. Specifically, MOR binding was observed in the cingulate gyrus (CG), striatum, septal regions, diagonal band, amygdala, hypothalamus, hippocampus, and thalamus. Binding was particularly dense in the septum, medial amygdala, paraventricular nucleus of the hypothalamus, mediodorsal thalamus with moderate binding in the nucleus accumbens. Consistent with other primate species, MOR were also observed in "neurochemically unique domains of the accumbens and putamen" (NUDAPs). In general KOR binding was more homogenous. KORs were primarily found in the CG, striatum, amygdala and hippocampus. Dense KOR binding was observed in the claustrum. Relative MOR and KOR binding in the titi monkey striatum was similar to other humans and primates, but was much lower compared to rodents. Relative MOR binding in the titi monkey hypothalamus was much greater than that found in rodents. This study was the first to examine MOR and KOR binding in a monogamous primate. The location of these receptors gives insight into where ligands may be acting to regulate social behavior and endocrine function.

  6. Bromocriptine and endocrine disorders.

    PubMed

    Spark, R F; Dickstein, G

    1979-06-01

    Bromocriptine, a dopaminergic agonist, has been used to treat many endocrine disorders. In hyperprolactinemia associated with galactorrhea, amenorrhea, oligospermia, and impotence, bromocriptine reduces prolactin levels to normal and allows for satisfactory return of sexual and reproductive function in 90% of patients. In acromegaly, bromocriptine brings about subjective improvement in 75% of patients with reduction in growth-hormone levels to normal in 22% of patients. Bromocriptine has been used in premenstrual tension, functional infertility, Nelson's syndrome, and Cushing's disease with variable benefit. In low doses, side-effects are minimal. In higher doses, digital vasospasm and gastrointestinal bleeding have occurred. Although bromocriptine has been used in a wide variety of endocrine disorders, it appears to be most useful in treatment of male and female infertility associated with hyperprolactinemia.

  7. Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status

    PubMed Central

    Zhong, Shou-Qiang; Chen, Zan-Xiong; Kong, Min-Li; Xie, Yan-Qi; Zhou, Yang; Qin, Xiao-Di; Paul, Gunther; Zeng, Xiao-Wen; Dong, Guang-Hui

    2016-01-01

    Little information exists about the evaluation of potential developmental immunotoxicity induced by perfluorooctane sulfonate (PFOS), a synthetic persistent and increasingly ubiquitous environmental contaminant. To assess potential sex-specific impacts of PFOS on immunological health in the offspring, using male and female C57BL/6 mice, pups were evaluated for developmental immunotoxic effects after maternal oral exposure to PFOS (0.1, 1.0 and 5.0 mg PFOS/kg/day) during Gestational Days 1–17. Spontaneous TH1/TH2-type cytokines, serum levels of testosterone and estradiol were evaluated in F1 pups at four and eight weeks of age. The study showed that male pups were more sensitive to the effects of PFOS than female pups. At eight weeks of age, an imbalance in TH1/TH2-type cytokines with excess TH2 cytokines (IL-4) was found only in male pups. As for hormone levels, PFOS treatment in utero significantly decreased serum testosterone levels and increased estradiol levels only in male pups, and a significant interaction between sex and PFOS was observed for serum testosterone at both four weeks of age (pinteraction = 0.0049) and eight weeks of age (pinteraction = 0.0227) and for estradiol alternation at four weeks of age (pinteraction = 0.0351). In conclusion, testosterone-mediated endocrine function may be partially involved in the TH1/TH2 imbalance induced by PFOS, and these deficits are detectable among both young and adult mice and may affect males more than females. PMID:27626407

  8. How Does Maternal Employment Affect Children's Socioemotional Functioning?

    ERIC Educational Resources Information Center

    Lam, Gigi

    2015-01-01

    The maternal employment becomes an irreversible trend across the globe. The effect of maternal employment on children's socioemotional functioning is so pervasive that it warrants special attention to investigate into the issue. A trajectory of analytical framework of how maternal employment affects children's socioemotional functioning originates…

  9. Endocrine disrupters--a threat to women's health?

    PubMed

    Waring, R H; Harris, R M

    2011-02-01

    Endocrine disruption has been a topic of public concern for many years and its study remains high on the scientific agenda. Endocrine disrupters (EDs) are compounds which may be of industrial or natural origin and which act to dysregulate steroid function and metabolism. As well as their actions on nuclear steroid receptors, EDs can inhibit the pathways of steroid synthesis and degradation. They not only affect reproductive function but also affect a range of tissues which are steroid sensitive such as the central nervous system and thyroid. Results from the latest studies suggest that EDs may also affect the immune system, glucose homeostasis and can act as epigenetic modulators resulting in transgenerational effects. Research in this area has led to the development of drugs used in the treatment of several types of hormone-sensitive cancer. However, despite many years of effort, the effects on human health of long-term environmental exposure to EDs, whether singly or as mixtures, remain unknown.

  10. [Disperse endocrine system and APUD concept].

    PubMed

    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.

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

    EPA Science Inventory

    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...

  12. Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

    PubMed Central

    Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

    2011-01-01

    Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism. PMID:20736991

  13. Effect of endocrine disruptor pesticides: a review.

    PubMed

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-06-01

    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.

  14. Endocrine disruption, parasites and pollutants in wild freshwater fish.

    PubMed

    Jobling, S; Tyler, C R

    2003-01-01

    Disruption of the endocrine system has been shown to occur in wild freshwater fish populations across the globe. Effects range from subtle changes in the physiology and sexual behaviour of fish to permanently altered sexual differentiation, impairment of gonad development and/or altered fertility. A wide variety of adverse environmental conditions may induce endocrine disruption, including sub-optimal temperatures, restricted food supply, low pH, environmental pollutants, and/or parasites. Furthermore, it is conceivable that any/all of these factors could act simultaneously to cause a range of disparate or inter-related effects. Some of the strongest evidence for a link between an adverse health effect, as a consequence of endocrine disruption, and a causative agent(s) is between the condition of intersex in wild roach (Rutlius rutilus) in UK rivers and exposure to effluents from sewage treatment works. The evidence to indicate that intersex in roach (and other cyprinid fish living in these rivers) is caused by chemicals that mimic and/or disrupt hormone function/balance in treated sewage effluent is substantial. There are a few parasites that affect the endocrine system directly in fish, including the tape worm Ligula intestinalis and a few parasites from the micropsora phylum. L. intestinalis acts at the level of the hypothalamus restricting GnRH secretion (resulting in poorly developed gonads) and is one of the very few examples where an endocrine disrupting event has been shown to result in a population-level effect (reducing it). It is well established that many parasites affect the immune system and thus the most common effect of parasites on the endocrine system in fish is likely to be an indirect one.

  15. Prediction of Endocrine System Affectation in Fisher 344 Rats by Food Intake Exposed with Malathion, Applying Naïve Bayes Classifier and Genetic Algorithms

    PubMed Central

    Mora, Juan David Sandino; Hurtado, Darío Amaya; Sandoval, Olga Lucía Ramos

    2016-01-01

    Background: Reported cases of uncontrolled use of pesticides and its produced effects by direct or indirect exposition, represent a high risk for human health. Therefore, in this paper, it is shown the results of the development and execution of an algorithm that predicts the possible effects in endocrine system in Fisher 344 (F344) rats, occasioned by ingestion of malathion. Methods: It was referred to ToxRefDB database in which different case studies in F344 rats exposed to malathion were collected. The experimental data were processed using Naïve Bayes (NB) machine learning classifier, which was subsequently optimized using genetic algorithms (GAs). The model was executed in an application with a graphical user interface programmed in C#. Results: There was a tendency to suffer bigger alterations, increasing levels in the parathyroid gland in dosages between 4 and 5 mg/kg/day, in contrast to the thyroid gland for doses between 739 and 868 mg/kg/day. It was showed a greater resistance for females to contract effects on the endocrine system by the ingestion of malathion. Females were more susceptible to suffer alterations in the pituitary gland with exposure times between 3 and 6 months. Conclusions: The prediction model based on NB classifiers allowed to analyze all the possible combinations of the studied variables and improving its accuracy using GAs. Excepting the pituitary gland, females demonstrated better resistance to contract effects by increasing levels on the rest of endocrine system glands. PMID:27833725

  16. The endocrine control of reproduction in Nereidae: a new multi-hormonal model with implications for their functional role in a changing environment

    PubMed Central

    Lawrence, A. J.; Soame, J. M.

    2009-01-01

    Nereidae are vital to the functioning of estuarine ecosystems and are major components in the diets of over-wintering birds and commercial fish. They use environmental cues to synchronize reproduction. Photoperiod is the proximate cue, initiating vitellogenesis in a temperature-compensated process. The prevailing paradigm in Nereidae is of a single ‘juvenile’ hormone controlling growth and reproduction. However, a new multi-hormone model is presented here that integrates the environmental and endocrine control of reproduction. This is supported by evidence from in vitro bioassays. The juvenile hormone is shown to be heat stable and cross reactive between species. In addition, a second neuro-hormone, identified here as a gonadotrophic hormone, is shown to be present in mature females and is found to promote oocyte growth. Furthermore, dopamine and melatonin appear to switch off the juvenile hormone while serotonin and oxytocin promote oocyte growth. Global warming is likely to uncouple the phase relationship between temperature and photoperiod, with significant consequences for Nereidae that use photoperiod to cue reproduction during the winter in northern latitudes. Genotypic adaptation of the photoperiodic response may be possible, but significant impacts on fecundity, spawning success and recruitment are likely in response to short-term extreme events. Endocrine-disrupting chemicals may also impact on putative steroid hormone pathways in Nereidae with similar consequences. These impacts may have significant implications for the functional role of Nereidae and highlight the importance of comparative endocrinology studies in these and other invertebrates. PMID:19833648

  17. Endocrine controls of keratin expression.

    PubMed

    Ramot, Yuval; Paus, Ralf; Tiede, Stephan; Zlotogorski, Abraham

    2009-04-01

    Keratins are a family of intermediate filaments that serve various crucial roles in skin physiology. For mammalian skin to function properly, and to produce epidermal and hair keratins that are optimally adapted for their environment, it is critical that keratin gene and protein expression are stringently controlled. Given that the skin is not only targeted by multiple hormones, but also constitutes a veritable peripheral endocrine organ, it is not surprizing that intracutaneous keratin expression is underlined by tight endocrine controls. These controls encompass thyroid hormones, steroid hormones such as glucocorticoids (GCs), retinoic acid (RA) and vitamin D, and several neuroendocrine mediators. Here, we review why a better understanding of the endocrine controls of keratin expression is not only required for an improved insight into normal human skin and hair function, but may also open new therapeutic avenues in a wide range of skin and hair diseases.

  18. Endocrine abnormalities in anorexia nervosa.

    PubMed

    Lawson, Elizabeth A; Klibanski, Anne

    2008-07-01

    Anorexia nervosa (AN) is a psychiatric disease associated with notable medical complications and increased mortality. Endocrine abnormalities, including hypogonadotropic hypogonadism, hypercortisolemia, growth hormone resistance and sick euthyroid syndrome, mediate the clinical manifestations of this disease. Alterations in anorexigenic and orexigenic appetite-regulating pathways have also been described. Decreases in fat mass result in adipokine abnormalities. Although most of the endocrine changes that occur in AN represent physiologic adaptation to starvation, some persist after recovery and might contribute to susceptibility to AN recurrence. In this Review, we summarize key endocrine alterations in AN, with a particular focus on the profound bone loss that can occur in this disease. Although AN is increasingly prevalent among boys and men, the disorder predominantly affects girls and women who are, therefore, the focus of this Review.

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

    PubMed

    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.

  20. Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover.

    PubMed

    Scillitani, A; Dicembrino, F; Chiodini, I; Minisola, S; Fusilli, S; Di Giorgio, A; Garrubba, M; D'Aloiso, L; Frusciante, V; Torlontano, M; Modoni, S; Trischitta, V; Trischitta, V; Carnevale, V

    2002-10-01

    This study aimed to clinically validate the global skeletal uptake (GSU) of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), and to compare it with a marker of bone formation (i.e. serum osteocalcin or OC) and an index of bone resorption (i.e. urinary deoxypyridinoline or U-DPD) in different endocrine disorders affecting the skeleton. We studied 29 female patients with thyrotoxicosis (TT), 27 with primary hyperparathyroidism (PHPT), 16 with acromegaly (AC), 15 with Cushing's syndrome (CS), and altogether 110 healthy women matched for age, BMI and menstrual status. In all subjects total body digital scan images (TBDS) were acquired at 5 min and at 4 h after the administration of (99m)Tc-MDP; the whole body retention (WBR) of the tracer was measured by counting two identical sets of rectangular ROIs, and GSU was subsequently calculated by drawing an irregular ROI on 4 h TBDS images. Serum OC was assessed by IRMA and urinary DPD by fluorometric detection after reverse phase high pressure chromatography. In TT patients GSU (40.0 +/- 5.1 vs 36.5 +/- 4.8%), OC (19.1 +/- 11.8 vs 7.1 +/- 2.9 microg/l) and U-DPD (62.4 +/- 42.7 vs 19.5 +/- 5.3 pmol/pmol) were significantly ( p<0.01) higher than in controls. PHPT patients showed GSU (47.2 +/- 6.6 vs 37.8 +/- 5.3%), OC (38.6 +/- 40.9 vs 8.2 +/- 2.5 microg/l), and U-DPD (55.0 +/- 51.3 vs 21.9 +/- 6.1 pmol/pmol) values significantly ( p<0.001) higher than controls. In CS patients, GSU (39.6 +/- 6.4 vs 32.7 +/- 3.5%; p<0.01) and U-DPD (22.8 +/- 8.4 vs 16.5 +/- 2.7 pmol/pmol; p<0.05) were higher, whereas OC (3.6 +/- 2.4 vs 5.2 +/- 1.9 mg/l; p<0,05) was lower than in controls. In AC patients, GSU (34.9 +/- 5.3 vs 35.2 +/- 3.4%) did not differ significantly from controls, whereas OC (16.8 +/- 8.8 vs 6.9 +/- 2.9 microg/l; p<0.001) and U-DPD (30.9 +/- 13.6 vs 21.0 +/- 5.7 pmol/pmol; p<0.01) were higher. Stepwise multivariate linear regression analysis was performed with disease activity, creatinine clearance, age, and years since

  1. Avian endocrine responses to environmental pollutants

    USGS Publications Warehouse

    Rattner, B.A.; Eroschenko, V.P.; Fox, G.A.; Fry, D.M.; Gorsline, J.

    1984-01-01

    Many environmental contaminants are hazardous to populations of wild birds. Chlorinated hydrocarbon pesticides and industrial pollutants are thought to be responsible for population declines of several species of predatory birds through eggshell thinning. Studies have demonstrated that these contaminants have estrogenic potency and may affect the functioning of the gonadal and thyroidal endocrine subsystems. Petroleum crude oil exerts toxicity externally, by oiling of plumage, and internally, by way of ingestion of oil while feeding or preening. Extensive ultrastructural damage to the inner zone of the adrenal, diminished adrenal responsiveness to adrenocorticotrophic hormone, and reduced corticosterone secretion rate suggest that low levels of plasma corticosterone reflect a direct effect of petroleum on the adrenal gland. Suppressive effects of oil on the ovary and decreases in circulating prolactin have been associated with impaired reproductive function. Large-scale field studies of free-living seabirds have confirmed some of the inhibitory effects of oil on reproduction that have been observed in laboratory studies. Organophosphorus insecticides, representing the most widely used class of pesticides in North America, have been shown to impair reproductive function, possibly by altering secretion of luteinizing hormone and progesterone. Relevant areas of future research on the effects of contaminants on avian endocrine function are discussed.

  2. Avian endocrine responses to environmental pollutants.

    PubMed

    Rattner, B A; Eroschenko, V P; Fox, G A; Fry, D M; Gorsline, J

    1984-12-01

    Many environmental contaminants are hazardous to populations of wild birds. Chlorinated hydrocarbon pesticides and industrial pollutants are thought to be responsible for population declines of several species of predatory birds through eggshell thinning. Studies have demonstrated that these contaminants have estrogenic potency and may affect the functioning of the gonadal and thyroidal endocrine subsystems. Petroleum crude oil exerts toxicity externally, by oiling of plumage, and internally, by way of ingestion of oil while feeding or preening. Extensive ultrastructural damage to the inner zone of the adrenal, diminished adrenal responsiveness to adrenocorticotrophic hormone, and reduced corticosterone secretion rate suggest that low levels of plasma corticosterone reflect a direct effect of petroleum on the adrenal gland. Suppressive effects of oil on the ovary and decreases in circulating prolactin have been associated with impaired reproductive function. Large-scale field studies of free-living seabirds have confirmed some of the inhibitory effects of oil on reproduction that have been observed in laboratory studies. Organophosphorus insecticides, representing the most widely used class of pesticides in North America, have been shown to impair reproductive function, possibly by altering secretion of luteinizing hormone and progesterone. Relevant areas of future research on the effects of contaminants on avian endocrine function are discussed.

  3. Introduction to the Endocrine System

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... in Balance › Hormones and Health › Journey Through the Endocrine System Journey Through the Endocrine System Endocrine-related Organs ...

  4. The molecular classification of hereditary endocrine diseases.

    PubMed

    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.

  5. Genetic testing by cancer site: endocrine system.

    PubMed

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  6. Tetrahydroisoquinoline alkaloids mimic direct but not receptor-mediated inhibitory effects of estrogens and phytoestrogens on testicular endocrine function. Possible significance for Leydig cell insufficiency in alcohol addiction

    SciTech Connect

    Stammel, W.; Thomas, H. ); Staib, W.; Kuehn-Velten, W.K. )

    1991-01-01

    Possible effects of various tetrahydroisoquinolines (TIQs) on rat testicular endocrine function were tested in vitro in order to prove whether these compounds may be mediators of the development of Leydig cell insufficiency. TIQ effects on different levels of regulation of testis function were compared in vitro with estrogen effects, since both classes of compounds have structural similarities. Gonadotropin-stimulated testosterone production by testicular Leydig cells was inhibited by tetrahydropapaveroline and isosalsoline, the IC{sub 50} values being comparable to those of estradiol, 2-hydroxyestradiol, and the phytoestrogens, coumestrol and genistein; salsolinol and salsoline were less effective, and salsolidine was ineffective. None of these TIQs interacted significantly with testicular estrogen receptor as analyzed by estradiol displacement. However, tetrahydropapaveroline, isosalsoline and salsolinol competitively inhibited substrate binding to cytochrome P45OXVII, with similar efficiency as the estrogens did; salsoline and salsolidine were again much less effective.

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

    PubMed

    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.

  8. Lexical and Affective Prosody in Children with High Functioning Autism

    PubMed Central

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2012-01-01

    Purpose We investigated perception and production of lexical stress and processing of affective prosody in adolescents with high functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody, but atypical lexical prosody production. Method 16 children with HFA and 15 typically developing (TD) peers participated in three experiments: 1. Perception of affective prosody, 2. Lexical stress perception, 3. Lexical stress production. In Experiment 1, participants labeled sad, happy, and neutral spoken sentences that were low-pass filtered, to eliminate verbal content. In Experiment 2 participants disambiguated word meanings based on lexical stress (HOTdog, vs. hotDOG). In Experiment 3 participants produced these words in a sentence completion task. Productions were analyzed using acoustic measures. Results Accuracy levels showed no group differences. Participants with HFA could determine affect from filtered sentences and disambiguate words based on lexical stress. They produced appropriately differentiated lexical stress patterns but demonstrated atypically long productions indicating reduced ability in natural prosody production. Conclusions Children with HFA were as capable as their TD peers in receptive tasks of lexical stress and affective prosody. Prosody productions were atypically long, despite accurate differentiation of lexical stress patterns. Future research should use larger samples and spontaneous vs. elicited productions. PMID:20530388

  9. Effects of Wastewater Discharges on Endocrine and Reproductive Function of Western Mosquitofish (Gambusia spp.) and Implications for the Threatened Santa Ana Sucker (Catostomus santaanae)

    USGS Publications Warehouse

    Jenkins, Jill A.; Goodbred, Steven L.; Olivier, Heather M.; Draugelis-Dale, Rassa O.; Alvarez, David A.

    2009-01-01

    The Santa Ana River (SAR) in southern California is impacted by effluents from wastewater treatment plants (WWTP), which are sources of organic wastewater compounds (OWCs) and urban runoff. The Santa Ana River is one of only three river basins supporting native populations of the federally listed Santa Ana sucker (Catostomus santaanae) at the time the fish was included on the list 2000. In 2004 and 2005, a U.S. Geological Survey and U.S. Fish and Wildlife Service study was undertaken to determine if the threatened Santa Ana sucker was potentially exposed to OWCs and endocrine disrupting compounds (EDCs) in the SAR by using the western mosquitofish (Gambusia affinis) as a surrogate fish model. Four Santa Ana River sites were chosen along a gradient of proximity to WWTP effluents: (1) a point source of tertiary treated wastewater effluent (TTWE), (2) Rialto Drain (just below a WWTP), (3) Prado Dam (11 kilometers [km] below WWTPs), and (4) Sunnyslope Creek (no WWTP but having urban runoff influence). A reference site having no WWTPs or urban runoff, Thousand Palms, was also sampled. Chemical analyses of passive sampler extracts results showed that 15 OWCs and EDCs were detected in water from the Santa Ana River sites. Many of these compounds contributed to activity from an estrogenic in-vitro assay that showed a significant potential for impacting endocrine and reproductive systems compared to the 25 organochlorine compounds detected in aquatic biota. The site showing compounds having highest influence on sex steroid hormone activities was the point source for TTWE. Sex steroid hormone levels, secondary sex characteristics, organosomatic indices, and sperm quality parameters indicated impairment of endocrine and reproductive function of male western mosquitofish in the Santa Ana River. Exposure to EDCs and consequent impairment in mosquitofish followed the gradient of proximity to WWTP effluents, where the most significant effects were found at TTWE point source and

  10. Intestinal endocrine cells in radiation enteritis

    SciTech Connect

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

    1989-08-01

    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. Diffuse traumatic brain injury affects chronic corticosterone function in the rat

    PubMed Central

    Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan

    2016-01-01

    As many as 20–55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. PMID:27317610

  12. Functional significance of preserved affect recognition in schizophrenia

    PubMed Central

    Fiszdon, Joanna M.; Johannesen, Jason K.

    2009-01-01

    Affect recognition (AR) is a core component of social information processing, thus may be critical to understanding social behavior and functioning in broader aspects of daily living. Deficits in AR are well documented in schizophrenia, however, there is also evidence that many individuals with schizophrenia perform AR tasks at near-normal levels. In the current study, we sought to evaluate the functional significance of AR deficits in schizophrenia by comparing subgroups with normal-range and impaired AR performance on proxy and interviewer-rated measures of real-world functioning. Schizophrenia outpatients were classified as normal-range (N=17) and impaired (N=31) based on a logistic cut point in the sample distribution of BLERT scores, referenced to a normative sample of healthy control subjects (N=56). The derived schizophrenia subgroups were then compared on proxy (UCSD, UPSA, SSPA, MMAA) and interviewer-rated (QLS, ILSS) measures of functioning, as well as battery of neurocognitive tests. Initial analyses indicated superior MMAA and QLS performance in the near-normal AR subgroup. Covariate analyses indicated that group differences in neurocognition fully mediated the observed associations between AR and MMAA and attenuated the observed relationships between AR classification and QLS. These results support three main conclusions. First, AR, like many other domains of psychopathology studied in schizophrenia, is preserved in select subgroups. Second, there is a positive relationship between AR performance and functional outcome measures. Third, neurocognition appears to mediate the relationship between AR and measures of functioning. PMID:20202689

  13. Probing the binding of an endocrine disrupting compound-Bisphenol F to human serum albumin: Insights into the interactions of harmful chemicals with functional biomacromolecules

    NASA Astrophysics Data System (ADS)

    Pan, Fang; Xu, Tianci; Yang, Lijun; Jiang, Xiaoqing; Zhang, Lei

    2014-11-01

    Bisphenol F (BPF) as an endocrine disrupting compounds (EDCs) pollutant in the environment poses a great threat to human health. To evaluate the toxicity of BPF at the protein level, the effects of BPF on human serum albumin (HSA) were investigated at three temperatures 283, 298, and 308 K by multiple spectroscopic techniques. The experimental results showed that BPF effectively quenched the intrinsic fluorescence of HSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and the binding subdomain were measured, and indicated that BPF could spontaneously bind with HSA on subdomain IIA through H-bond and van der Waals interactions. Furthermore, the conformation of HSA was demonstrably changed in the presence of BPF. The work provides accurate and full basic data for clarifying the binding mechanisms of BPF with HSA in vivo and is helpful for understanding its effect on protein function during its transportation and distribution in blood.

  14. Development of a Computational Model for Female Fathead Minnows exposed to Two Endocrine Disrupting Chemicals

    EPA Science Inventory

    Endocrine disrupting chemicals (e.g., estrogens and androgens) are known to affect reproductive functions in fish. A synthetic estrogen used in birth control pills, 17á-ethynylestradiol (EE2), is discharged from wastewater treatment plants into water bodies throughout the United ...

  15. STATUS OF ENDOCRINE DISRUPTOR SCREENING AND TESTING ACTIVITIES IN THE US: IMPLEMENTATION OF THE EDSTAC RECOMMENDATIONS

    EPA Science Inventory

    The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. In 1996, the US Congress passed the Food Quality Protection Act (FQPA) that mandated the US Environmental Protection Ag...

  16. A GLOBAL PERSPECTIVE ON ENDOCRINE DISRUPTION, WITH COMMENTS ON THE US EXPERIENCE

    EPA Science Inventory

    The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. The International Programme on Chemical Safety (IPCS) of the World Health Organization has recently reviewed the curren...

  17. Abnormal GABAergic function and negative affect in schizophrenia.

    PubMed

    Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C

    2014-03-01

    Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

  18. Multiple endocrine neoplasia type 1

    PubMed Central

    Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

    2006-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

  19. Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy

    PubMed Central

    Itoh, Nobuyuki; Ohta, Hiroya; Konishi, Morichika

    2015-01-01

    The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs are secreted signaling molecules by acting via cell-surface FGF receptors (FGFRs). Paracrine FGFs require heparan sulfate as a cofactor for FGFRs. In contrast, endocrine FGFs, comprising FGF19, FGF21, and FGF23, require α-Klotho or β-Klotho as a cofactor for FGFRs. Endocrine FGFs, which are specific to vertebrates, lost heparan sulfate-binding affinity and acquired a systemic signaling system with α-Klotho or β-Klotho during early vertebrate evolution. The phenotypes of endocrine FGF knockout mice indicate that they play roles in metabolism including bile acid, energy, and phosphate/active vitamin D metabolism. Accumulated evidence for the involvement of endocrine FGFs in human genetic and metabolic diseases also indicates their pathophysiological roles in metabolic diseases, potential risk factors for metabolic diseases, and useful biomarkers for metabolic diseases. The therapeutic utility of endocrine FGFs is currently being developed. These findings provide new insights into the physiological and pathophysiological roles of endocrine FGFs and potential diagnostic and therapeutic strategies for metabolic diseases. PMID:26483756

  20. The Effects of Nanomaterials as Endocrine Disruptors

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-01-01

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

  1. The significance of Ciona intestinalis as a stem organism in integrative studies of functional evolution of the chordate endocrine, neuroendocrine, and nervous systems.

    PubMed

    Matsubara, Shin; Kawada, Tsuyoshi; Sakai, Tsubasa; Aoyama, Masato; Osugi, Tomohiro; Shiraishi, Akira; Satake, Honoo

    2016-02-01

    Ascidians are the closest phylogenetic neighbors to vertebrates and are believed to conserve the evolutionary origin in chordates of the endocrine, neuroendocrine, and nervous systems involving neuropeptides and peptide hormones. Ciona intestinalis harbors various homologs or prototypes of vertebrate neuropeptides and peptide hormones including gonadotropin-releasing hormones (GnRHs), tachykinins (TKs), and calcitonin, as well as Ciona-specific neuropeptides such as Ciona vasopressin, LF, and YFV/L peptides. Moreover, molecular and functional studies on Ciona tachykinin (Ci-TK) have revealed the novel molecular mechanism of inducing oocyte growth via up-regulation of vitellogenesis-associated protease activity, which is expected to be conserved in vertebrates. Furthermore, a series of studies on Ciona GnRH receptor paralogs have verified the species-specific regulation of GnRHergic signaling including unique signaling control via heterodimerization among multiple GnRH receptors. These findings confirm the remarkable significance of ascidians in investigations of the evolutionary processes of the peptidergic systems in chordates, leading to the promising advance in the research on Ciona peptides in the next stage based on the recent development of emerging technologies including genome-editing techniques, peptidomics-based multi-color staining, machine-learning prediction, and next-generation sequencing. These technologies and bioinformatic integration of the resultant "multi-omics" data will provide unprecedented insights into the comprehensive understanding of molecular and functional regulatory mechanisms of the Ciona peptides, and will eventually enable the exploration of both conserved and diversified endocrine, neuroendocrine, and nervous systems in the evolutionary lineage of chordates.

  2. The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells

    PubMed Central

    Kang, Hong Soon; Takeda, Yukimasa; Jeon, Kilsoo

    2016-01-01

    The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis. PMID:27270601

  3. Amphibians as model to study endocrine disrupters.

    PubMed

    Kloas, Werner; Lutz, Ilka

    2006-10-13

    Environmental compounds can interfere with endocrine systems of wildlife and humans. These so-called endocrine disrupters (ED) are known to affect reproductive biology and thyroid system. The classical model species for these endocrine systems are amphibians and therefore they can serve as sentinels for detection of the modes of action (MOAs) of ED. Recently, amphibians are being reviewed as suitable models to assess (anti)estrogenic and (anti)androgenic MOAs influencing reproductive biology as well as (anti)thyroidal MOAs interfering with the thyroid system. The development of targeted bioassays in combination with adequate chemical analyses is the prerequisite for a concise risk assessment of ED.

  4. Perspectives in endocrine toxicity of heavy metals--a review.

    PubMed

    Rana, S V S

    2014-07-01

    An attempt has been made to review the endocrine/hormonal implications of a few environmentally significant metals, viz, lead, mercury, cadmium, copper, arsenic and nickel, in man and animals. Special emphasis has been given to the adrenals, thyroid, testis, ovary and pancreas. Toxic metals can cause structural and functional changes in the adrenal glands. Their effects on steroidogenesis have been reviewed. It has been reported that thyroid hormone kinetics are affected by a number of metallic compounds. Occupational exposure to a few of these metals can cause testicular injury and sex hormone disturbances. Protective effects of a few antioxidants on their reproductive toxicity have also been discussed. Information gathered on female reproductive toxicity of heavy metals shows that exposure to these metals can lead to disturbances in reproductive performance in exposed subjects. Certain metals can cause injury to the endocrine pancreas. Exposure to them can cause diabetes mellitus and disturb insulin homeostasis. The need to develop molecular markers of endocrine toxicity of heavy metals has been suggested. Overall information described in this review is expected to be helpful in planning future studies on endocrine toxicity of heavy metals.

  5. Scientific and Regulatory Policy Committee (SRPC) Points to Consider*: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors

    PubMed Central

    Keane, Kevin A.; Parker, George A.; Regan, Karen S.; Picut, Catherine; Dixon, Darlene; Creasy, Dianne; Giri, Dipak; Hukkanen, Renee R.

    2015-01-01

    The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program. PMID:25948506

  6. Can the hydrophilicity of functional monomers affect chemical interaction?

    PubMed

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts.

  7. How does temperature affect the function of tissue macrophages?

    NASA Astrophysics Data System (ADS)

    Lee, Chen-Ting; Repasky, Elizabeth A.

    2011-03-01

    Macrophages create a major danger signal following injury or infection and upon activation release pro-inflammatory cytokines, which in turn help to generate febrile conditions. Thus, like other cells of the body, tissue macrophages are often exposed to naturally occurring elevations in tissue temperature during inflammation and fever. However, whether macrophages sense and respond to temperature changes in a specific manner which modulates their function is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of temperatures on macrophage function, and summarize the possible underlying molecular mechanisms which have been identified. Mild, physiological range hyperthermia has been shown to have both pro- and anti-inflammatory roles in regulating macrophage inflammatory cytokine production and at the meeting presentation, we will show new data demonstrating that hyperthermia can indeed exert both positive and negative signals to macrophages. While some thermal effects are correlated with the induction of heat shock factors/heat shock proteins, overall it is not clear how mild hyperthermia can exert both pro- and anti-inflammatory functions. We also summarize data which shows that hyperthermia can affect other macrophage effector functions, including the anti-tumor cytotoxicity. Overall, these studies may help us to better understand the immunological role of tissue temperature and may provide important information needed to maximize the application of heat in the treatment of various diseases including cancer.

  8. Adrenomedullin and endocrine disorders.

    PubMed

    Letizia, C; Rossi, G; Cerci, S

    2003-12-01

    Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.

  9. Endocrine glands (image)

    MedlinePlus

    Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which ...

  10. [Postpartum endocrine syndrome].

    PubMed

    Ducarme, G; Châtel, P; Luton, D

    2008-05-01

    Postpartum endocrine syndromes occur in the year after delivery. They are due to immunologic and vascular modifications during pregnancy. The Sheehan syndrome is the first described postpartum endocrine syndrome and consists on a hypophyse necrosis in relation with a hypovolemic shock during delivery. The immunologic consequences of the pregnancy are the most frequent, sometimes discrete and transitory. The physiological evolution of the endocrine glands during pregnancy and the most frequent post-partum endocrine syndromes are discussed: postpartum lymphocytic hypophysitis, thyroiditis and Sheehan' syndrome.

  11. MicroRNAs affect dendritic cell function and phenotype

    PubMed Central

    Smyth, Lesley A; Boardman, Dominic A; Tung, Sim L; Lechler, Robert; Lombardi, Giovanna

    2015-01-01

    MicroRNA (miRNA) are small, non-coding RNA molecules that have been linked with immunity through regulating/modulating gene expression. A role for these molecules in T-cell and B-cell development and function has been well established. An increasing body of literature now highlights the importance of specific miRNA in dendritic cell (DC) development as well as their maturation process, antigen presentation capacity and cytokine release. Given the unique role of DC within the immune system, linking the innate and adaptive immune responses, understanding how specific miRNA affect DC function is of importance for understanding disease. In this review we summarize recent developments in miRNA and DC research, highlighting the requirement of miRNA in DC lineage commitment from bone marrow progenitors and for the development of subsets such as plasmacytoid DC and conventional DC. In addition, we discuss how infections and tumours modulate miRNA expression and consequently DC function. PMID:25244106

  12. Can lifestyle modification affect men’s erectile function?

    PubMed Central

    Hehemann, Marah C.

    2016-01-01

    Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification. PMID:27141445

  13. Scorpion venom components that affect ion-channels function

    PubMed Central

    Quintero-Hernández, V.; Jiménez-Vargas, J.M.; Gurrola, G.B.; Valdivia, H.H.F.; Possani, L.D.

    2014-01-01

    SUMMARY The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are now adays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. PMID:23891887

  14. Functional roles affect diversity-succession relationships for boreal beetles.

    PubMed

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  15. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  16. ENDOCRINE DISRUPTORS IN THE ENVIRONMENT

    EPA Science Inventory

    The endocrine system produces hormones which are powerful natural chemicals that regulate important life processes. Endocrine disruptors are human-made chemicals distributed globally which have the potential to interfere with the endocrine system and produce serious biological e...

  17. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  18. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  19. A study on endocrine dysfunction in thalassaemia.

    PubMed

    Ghosh, Soumitra; Bandyopadhyay, Sanjay K; Bandyopadhyay, Ranjana; Roy, Dipankar; Maisnam, Indira; Ghosh, Moloy K

    2008-10-01

    The aim was to study the prevalence and severity of hormonal imbalance affecting growth, gonadal and thyroid function in thalassaemic patients and to find out whether any correlation exists between the degree of tissue iron-overload and several patients characteristics like age, gender, foetal haemoglobin (HbF) level, type of thalassaemia (beta or E-beta), and the presence of specific endocrine abnormality. Sixty-eight consecutive non-chelated, transfusion-dependent patients of beta and E-beta-thalassaemia with significant tissue iron overload (serum ferritin more than 2000 microg/l) were included. Standing height was noted and clinical features of hypogonadism were recorded. Insulin tolerance test was done to assess growth hormone reserve. Serum oestradiol, T3,T4,TSH were measured in fasting clotted sample, while pooled sera (from 3 consevutive morning samples) was used for testosterone, FSH and LH. Hypogonadism was the commonest abnormality, both in males (52.28%) and females (35.89%) followed by growth retardation (20.58%) and reduced growth hormone reserve (7.35%). There was no significant difference in the prevalence of endocrine dysfunction with regard to patient's age, gender, type of thalassaemia (beta or E-beta) amd HbF level. Hypogonadic females had a significantly elevated mean serum ferritin level. Subclinical hypothyroidism was present in 23.52% of patients, related to the duration of disease. No association was found between pituitarty and thyroid dysfunction.

  20. Human infertility: are endocrine disruptors to blame?

    PubMed

    Marques-Pinto, André; Carvalho, Davide

    2013-01-01

    Over recent decades, epidemiological studies have been reporting worrisome trends in the incidence of human infertility rates. Extensive detection of industrial chemicals in human serum, seminal plasma and follicular fluid has led the scientific community to hypothesise that these compounds may disrupt hormonal homoeostasis, leading to a vast array of physiological impairments. Numerous synthetic and natural substances have endocrine-disruptive effects, acting through several mechanisms. The main route of exposure to these chemicals is the ingestion of contaminated food and water. They may disturb intrauterine development, resulting in irreversible effects and may also induce transgenerational effects. This review aims to summarise the major scientific developments on the topic of human infertility associated with exposure to endocrine disruptors (EDs), integrating epidemiological and experimental evidence. Current data suggest that environmental levels of EDs may affect the development and functioning of the reproductive system in both sexes, particularly in foetuses, causing developmental and reproductive disorders, including infertility. EDs may be blamed for the rising incidence of human reproductive disorders. This constitutes a serious public health issue that should not be overlooked. The exposure of pregnant women and infants to EDs is of great concern. Therefore, precautionary avoidance of exposure to EDs is a prudent attitude in order to protect humans and wildlife from permanent harmful effects on fertility.

  1. Endocrine problems in children and adolescents who have disabilities.

    PubMed

    Zacharin, Margaret

    2013-01-01

    The consequences of disability span almost all aspects of life, for families and for an affected individual. Endocrine aspects of disability cover disorders of hypothalamic pituitary dysfunction, bone health, puberty, fertility, sexual function and contraceptive needs. Adequate endocrine assessment for a child with a disability requires extensive and sensitive history to address social issues, general nutrition, vitamin D status, specific hypothalamic pituitary problems, together with parental concerns regarding puberty and contraception. Bone health assessment includes history of minimal trauma fracture, need for intervention or fitness for surgery. Strategic interventions to improve outcome include management of puberty, vitamin D status, biomechanical stimulation with vibration and standing and possible consideration for bisphosphonate in special circumstances. Both early and late puberty cause major family concerns. The paediatrician must be aware of a range of management options to improve outcomes for the child and family.

  2. Ecological risk assessment of endocrine disruptors.

    PubMed Central

    Hutchinson, T H; Brown, R; Brugger, K E; Campbell, P M; Holt, M; Länge, R; McCahon, P; Tattersfield, L J; van Egmond, R

    2000-01-01

    The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna. PMID:11102288

  3. Functional Roles Affect Diversity-Succession Relationships for Boreal Beetles

    PubMed Central

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of “functional” groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience. PMID:23977350

  4. The endocrine quiz.

    PubMed

    Kalra, Sanjay; Baruah, Manash P; Nagesh, V Sri

    2014-05-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject.

  5. The endocrine quiz

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Nagesh, V. Sri

    2014-01-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject. PMID:24944922

  6. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  7. Does Bowel Preparation for Colonoscopy Affect Cognitive Function?

    PubMed Central

    Wadsworth, P.; Blackburne, H.; Dixon, L.; Dobbs, B.; Eglinton, T.; Ing, A.; Mulder, R.; Porter, R.J.; Wakeman, C.; Frizelle, F.A.

    2015-01-01

    Abstract Colonoscopy is a common procedure used in the diagnosis and treatment of a range of bowel disorders. Prior preparation involving potent laxatives is a necessary stage to ensure adequate visualization of the bowel wall. It is known that the sedatives given to most patients during the colonoscopy cause a temporary impairment in cognitive function; however, the potential for bowel preparation to affect cognitive function has not previously been investigated. To assess the effect of bowel preparation for colonoscopy on cognitive function. This was a prospective, nonrandomized controlled study of cognitive function in patients who had bowel preparation for colonoscopy compared with those having gastroscopy and therefore no bowel preparation. Cognitive function was assessed using the Modified Mini Mental State Examination (MMMSE) and selected tests from the Cambridge Neuropsychological Test Automated Battery. Individual test scores and changes between initial and subsequent tests were compared between the groups. Age, gender, and weight were also compared. Forty-three colonoscopy and 25 gastroscopy patients were recruited. The 2 groups were similar for age and gender; however, patients having gastroscopy were heavier. MMMSE scores for colonoscopy and gastroscopy groups, respectively, were 28.6 and 29.5 (P = 0.24) at baseline, 28.7 and 29.8 (P = 0.32) at test 2, 28.1 and 28.5 (P = 0.76) at test 3. Motor screening scores for colonoscopy and gastroscopy groups, respectively, were 349.3 and 354.1 (P = 0.97) at baseline, 307.5 and 199.7 (P = 0.06) at test 2, 212.0 and 183.2 (P = 0.33) at test 3. Spatial working memory scores for colonoscopy and gastroscopy groups, respectively, were 14.4 and 6.7 (P = 0.29) at baseline, 9.7 and 4.3 (P = 0.27) at test 2, 10 and 4.5 (P = 0.33) at test 3. Digit Symbol Substitution Test scores for colonoscopy and gastroscopy groups, respectively, were 36.3 and 37.8 (P = 0.84) at baseline, 36.4 and

  8. Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice.

    PubMed

    Kodo, Kazuki; Sugimoto, Satoru; Nakajima, Hisakazu; Mori, Jun; Itoh, Ikuyo; Fukuhara, Shota; Shigehara, Keiichi; Nishikawa, Taichiro; Kosaka, Kitaro; Hosoi, Hajime

    2017-01-01

    Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO's suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT's endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO

  9. Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice

    PubMed Central

    Kodo, Kazuki; Sugimoto, Satoru; Mori, Jun; Itoh, Ikuyo; Fukuhara, Shota; Shigehara, Keiichi; Nishikawa, Taichiro; Kosaka, Kitaro; Hosoi, Hajime

    2017-01-01

    Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO’s anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO’s suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT’s endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO

  10. Potency matters: thresholds govern endocrine activity.

    PubMed

    Borgert, Christopher J; Baker, Stephen P; Matthews, John C

    2013-10-01

    Whether thresholds exist for endocrine active substances and for endocrine disrupting effects of exogenous chemicals has been posed as a question for regulatory policy by the European Union. This question arises from a concern that the endocrine system is too complex to allow estimations of safe levels of exposure to any chemical with potential endocrine activity, and a belief that any such chemical can augment, retard, or disrupt the normal background activity of endogenous hormones. However, vital signaling functions of the endocrine system require it to continuously discriminate the biological information conveyed by potent endogenous hormones from a more concentrated background of structurally similar, endogenous molecules with low hormonal potential. This obligatory ability to discriminate important hormonal signals from background noise can be used to define thresholds for induction of hormonal effects, without which normal physiological functions would be impossible. From such thresholds, safe levels of exposure can be estimated. This brief review highlights how the fundamental principles governing hormonal effects - affinity, efficacy, potency, and mass action - dictate the existence of thresholds and why these principles also define the potential that exogenous chemicals might have to interfere with normal endocrine functioning.

  11. Viewpoint: Policy Requirements for Protecting Wildlife from Endocrine Disruptors

    PubMed Central

    Lyons, Gwynne

    2006-01-01

    Man-made endocrine-disrupting chemicals (EDCs) present a threat to biodiversity, even in remote areas. To date, numerous wildlife species have been affected by EDCs in the environment, but it is likely that many more species are suffering effects that have not yet been reported. Impaired reproduction, damaged brain function, and deficits of the immune system are of particular concern. In order to bring all endocrine-disrupting chemicals under control, the development of screens and tests to identify EDCs must be expedited. However, the World Wildlife Fund (WWF) considers that sufficient information is already available to merit action on several such substances. In addition, it must be recognized that proving the mechanism of action for some chemicals may take decades. Therefore, it is important to enable certain chemicals to be brought under stricter control on the basis of strong suspicion of endocrine disruption or biochemical signaling disruption. Furthermore, the risk assessment process itself also must be modified, and some suggestions are discussed in this article. WWF maintains that any effect that could reasonably be expected to affect the population level should be taken forward in environmental risk characterization, in particular, behavioral effects should be given more consideration. Current chemical management policies are not protective, and we argue for modifications in them to be made. PMID:16818260

  12. Endocrine disorders & female infertility.

    PubMed

    Unuane, David; Tournaye, Herman; Velkeniers, Brigitte; Poppe, Kris

    2011-12-01

    Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established. Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed. We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.

  13. Endocrine responses to space flights.

    PubMed

    Macho, L; Kvetnansky, R; Fickova, M; Kolena, J; Knopp, J; Tigranian, R A; Popova, I A; Grogoriev, A I

    2001-07-01

    Simultaneously with human space flights several series of observations were performed by using experimental animals--mainly rats--exposed to space flights on board of special satellites BION-COSMOS or in Shuttle Transportation Systems (STS). The aims of these experiments were to study in more details: the mechanisms of the changes in bones and skeletal muscle, the alterations of the function of immune system, the radiation effects on organism, the mechanism of the changes of endocrine functions, the evaluation of the role of hormones in alteration of metabolic processes in organism. The advantages of these animal experiments were the possibilities to analyze not only the plasma samples, but it was possible to obtain samples of organs or tissues: for morphological and biochemical analysis for studies of the changes in enzyme activities and in gene expressions, for measurement of metabolic processes and for investigation of the hormone production in endocrine glands and estimation of the response of tissues to hormones. It was also possible to compare the endocrine response to spaceflight and to other stress stimuli. These animal studies are interesting for verification of some hypothesis in the mechanism of adaptation of human organism to the changes of gravity. The disadvantage was, however, that the animals in almost all experiments could be examined only after space flight. The actual inflight changes were investigated only in two SLS flights. In this short review it is not possible to evaluate all hormonal data available on the response of endocrine system to the conditions of space flights. Therefore we will concentrate on the response of pituitary adrenocortical system, pituitary thyroid and pituitary gonadal functions.

  14. Maternal metabolic stress may affect oviduct gatekeeper function.

    PubMed

    Jordaens, Lies; Van Hoeck, Veerle; Maillo, Veronica; Gutierrez-Adan, Alfonso; Marei, Waleed Fawzy A; Vlaeminck, Bruno; Thys, Sofie; Sturmey, Roger G S; Bols, Peter; Leroy, Jo

    2017-03-03

    We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24h-treatments at day 9: 1) CONTROL (0µM NEFA + 0%EtOH), 2) SOLVENT CONTROL (0µM NEFA + 0.45%EtOH), 3) BASAL NEFA (720µM NEFA + 0.45%EtOH in the basal compartment), 4) APICAL NEFA (720µM NEFA + 0.45%EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment, and related to Transepithelial Electric Resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA-uptake were studied using Bodipy 493/503 and immunolabelling of FA-transporters (FAT/CD36, FABP3 and caveolin1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that APICAL NEFA reduced relative TER-increase (46.85%) during treatment, and increased FITC-albumin flux (27.59%) compared to other treatments. In BASAL NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased, respectively 56.0 % and 33.5% of initial FA-concentrations. APICAL NEFA allowed no FA-transfer, but induced LD-accumulation and upregulated FA-transporter expression (↑CD36, ↑FABP3, ↑CAV1-protein-expression). Gene expression in APICAL NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA), and FA-uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function specific gene expression (=OVGP1, ESR1, FOXJ1). Overall, elevated NEFAs affected BOEC-metabolism and barrier function differently depending on NEFA-exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions.

  15. Impairment of diastolic function in adult patients affected by osteogenesis imperfecta clinically asymptomatic for cardiac disease: casuality or causality?

    PubMed

    Migliaccio, Silvia; Barbaro, Giuseppe; Fornari, Rachele; Di Lorenzo, Gabriella; Celli, Mauro; Lubrano, Carla; Falcone, Stefania; Fabbrini, Elisa; Greco, Emanuela; Zambrano, Anna; Brama, Marina; Prossomariti, Giancarlo; Marzano, Sara; Marini, Mario; Conti, Francesco; D'Eufemia, Patrizia; Spera, Giovanni

    2009-01-09

    Osteogenesis imperfecta (OI) is a rare inherited connective disorder causing increased bone fragility and low bone mass. OI includes severe bone fragility, impaired dentinogenesis, with less common alterations in the joints, blood vessels, heart valves, skin. Interestingly, description of left ventricular rupture, aortic dissection and heart valves incompetence has been previously described. Death may occur in OI patients for cardiac disease in asyntomatic subjects. Aim of our study has been to evaluate the presence of potential subclinical cardiac disorders and to characterize cardiac functional parameters by echocardiography in adults with OI in absence of cardiac symptoms. Forty patients (21 females and 19 males) affected by type I, III, IV OI and 40 control subjects (20 females and 20 males) were evaluated in the study. Patients and controls underwent clinical examination, screening for endocrine and metabolic disorders, 12-lead electrocardiogram and echocardiogram. In particular, all subjects were evaluated by two-dimensional echocardiography with continuous- and pulse-wave Doppler. Patients and controls belonged to NYHA class I and no significant electrocardiographic alteration was documented in both groups. Thirty-eight patients (95%) showed valvular regurgitation compared to one control subject (2.5%; P<0.001). As regards the diastolic function parameters, in OI patients E wave velocity was reduced by 23% (95% CI: 9% to 29%; P<0.001), E/A ratio was reduced by 17% (95% CI: 15% to 26%; P<0.001) while isovolumetric relaxation time (IRT) was increased by 47% (95% CI: 26% to 53%; P<0.001) and E wave deceleration time (DT) was increased by 18% (95% CI: 13% to 26%; P<0.001) compared to controls. In conclusion, our data indicate that adult patients affected by OI have an altered diastolic function in absence of other metabolic alterations. These diastolic echocardiographic parameters might worsen over time, especially if other cardiovascular risk factors (e

  16. Gestational Exposure to Bisphenol A Affects the Function and Proteome Profile of F1 Spermatozoa in Adult Mice

    PubMed Central

    Rahman, Md Saidur; Kwon, Woo-Sung; Karmakar, Polash Chandra; Yoon, Sung-Jae; Ryu, Buom-Yong; Pang, Myung-Geol

    2016-01-01

    Background: Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood. Objectives: The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice. Methods: Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease. Results: BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases. Conclusions: Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238–245; http://dx.doi.org/10.1289/EHP378 PMID:27384531

  17. Steroid hormones as biomarkers of endocrine disruption in wildlife

    SciTech Connect

    Guillette, L.J. Jr.; Rooney, A.A.; Crain, D.A.; Orlando, E.F.

    1999-07-01

    Xenobiotic compounds introduced into the environment by human activity have been shown to adversely affect the endocrine system of wildlife. Various species exhibit abnormalities of (1) plasma sex steroid hormones, (2) altered steroid synthesis form the gonad in vitro and (3) altered steroidogenic enzyme function. These endpoints are sensitive and relatively easy to measure quantitatively with reliability and precision. These observations have led to the conclusion that sex steroid hormones could be markers of exposure to, and altered function from, endocrine disrupting contaminants (EDCs). However, there are serious limitations in the use of steroid hormones as generalized markers of EDC exposure. Steroid hormones exhibit seasonal, ontogenetic, gender and species-specific variation. Moreover, the regulation of sex steroid plasma concentrations is a relatively complex phenomenon capable of short-term (minutes-hours) alteration due to environmental inputs, such as acute stress--an activational response. Alterations in steroids synthesis and degradation also can be a response to altered embryonic development due to EDC exposure--an organizational response. If steroid hormones are to be used as biomarkers, then closely controlled, well designed sampling has to be performed. Additionally, an appreciation of the variation possible in endocrine responses among the species to be studied must be obtained.

  18. One-pot synthesized functionalized mesoporous silica as a reversed-phase sorbent for solid-phase extraction of endocrine disrupting compounds in milks.

    PubMed

    Gañán, Judith; Morante-Zarcero, Sonia; Pérez-Quintanilla, Damián; Marina, María Luisa; Sierra, Isabel

    2016-01-08

    A new procedure for the determination of 12 naturally occurring hormones and some related synthetic chemicals in milk, commonly used as growth promoters in cattle, is reported. The method is based on liquid-liquid extraction followed by solid-phase extraction (SPE) using a new one-pot synthesized ordered mesoporous silica (of the SBA-15 type) functionalized with octadecyl groups (denoted as SBA-15-C18-CO) as reversed-phase sorbent. The analytes were eluted with methanol and then submitted to HPLC with diode array detection. Under optimal conditions, the method quantification limit for the analytes ranged from 0.023 to 1.36μg/mL. The sorbent affored the extraction of estrone, 17β-estradiol, estriol, progesterone, hexestrol, diethylstilbestrol, 4-androstene-3,17-dione, ethinylestradiol, 17α-methyltestosterone, nandrolone, prednisolone and testosterone with mean recoveries ranging from 72% to 105% (except for diethylstilbestrol) with RSD<11%. These results were comparable and, in some cases, even better than those obtained with other extraction methods, therefore SBA-15-C18-CO mesoporous silica possess a high potential as a reversed-phase sorbent for SPE of the 12 mentioned endocrine disrupting compounds in milk samples.

  19. Dietary supplementation of yucca (Yucca schidigera) affects ovine ovarian functions.

    PubMed

    Vlčková, Radoslava; Sopková, Drahomíra; Andrejčáková, Zuzana; Valocký, Igor; Kádasi, Attila; Harrath, Abdel Halim; Petrilla, Vladimír; Sirotkin, Alexander V

    2017-01-15

    Yucca (Yucca schidigera) is a popular medicinal plant due to its many positive effects on animal and human physiology, including their reproductive systems. To examine the effect of supplemental yucca feeding on sheep reproduction, including ovarian functions and their hormonal regulators, ewes were fed (or not fed, control) yucca powder (1.5 g/head/day, 30 days). Macromorphometric indexes of the oviduct, ovary, and ovarian folliculogenesis were measured. Reproductive hormone levels in the blood were measured using a radioimmunoassay. Granulosa cells were aspirated from the ovary, and their proliferation and apoptosis were detected using immunocytochemistry. To assess secretory activity and its response to gonadotropin, ovarian fragments of treated and control ewes were cultured with and without follicle-stimulating hormone (FSH; 0, 0.1, 1, 10, or 100 IU/mL), and the release of reproductive hormones into the culture medium was evaluated. Finally, to examine the direct action of yucca on the ovary, ovarian fragments from control ewes were cultured with and without yucca extract (1, 10, or 100 μg/mL), and the release of reproductive hormones was measured. Yucca supplementation significantly decreased the size of small antral follicles (2 to <5 mm in diameter), increased accumulation of the apoptosis marker bax, and decreased serum progesterone (P4) and estradiol (E2) levels. It inhibited the release of P4 (but not other hormones), to prevent the stimulatory action of FSH on P4 output and promoted insulin-like growth factor I (IGF-I) release by fragments cultured with FSH. However, yucca supplementation did not affect the size of larger follicles and number of follicles, volume and weight of ovaries, length and weight of oviducts, caspase 3 accumulation, cell proliferation, testosterone (T) or IGF-I serum levels, or T or E2 release by cultured ovarian fragments and their response to FSH. Yucca addition to culture medium inhibited P4 and IGF-I, but not T or E2

  20. Multiple endocrine neoplasia type 2.

    PubMed

    Lodish, Maya

    2013-01-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter.

  1. [Contamination, endocrine disruptors and cancer].

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-03-01

    Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations.

  2. Antidiuretic action of angiotensin II in the river lamprey Lampetra fluviatilis: evidence for endocrine control of kidney function in cyclostomes.

    PubMed

    Cobb, C S; Brown, J A; Rankin, J C

    2010-10-01

    Intravenous infusion of angiotensin II ([Asn¹ Val⁵]-Ang II) at 10⁻⁹ mol min⁻¹ kg⁻¹ body mass produced a significant antidiuresis in river lamprey Lampetra fluviatilis, captured during upstream migration and maintained in fresh water. Although the renin-angiotensin hormonal system (RAS) is now recognized in jawless fishes, until this study, the role of homologous Ang II in L. fluviatilis kidney function had not been examined. This study provides the first evidence for an antidiuretic action of Ang II in cyclostomes and, in evolutionary terms, suggests a renal function for the RAS in early vertebrates.

  3. [The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans].

    PubMed

    Komorowski, Jan; Stepień, Henryk

    2007-01-01

    The endocannabinoid system has been recently recognized as an important modulatory system in the function of brain, endocrine, and immune tissues. It appears to play a very important regulatory role in the secretion of hormones related to reproductive functions and response to stress. The important elements of this system are: endocannabinoid receptors (types CB1 and CB2), their endogenous ligands (N-arachidonoylethanolamide, 2-arachidonoyl glycerol), enzymes involved in their synthesis and degradation, as well as cannabinoid antagonists. In humans this system also controls energy homeostasis and mainly influences the function of the food intake centers of the central nervous system and gastrointestinal tract activity. The endocannabinoid system regulates not only the central and peripheral mechanisms of food intake, but also lipids synthesis and turnover in the liver and adipose tissue as well as glucose metabolism in muscle cells. Rimonabant, a new and selective central and peripheral cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factor (metabolic syndrome) in obese patients by increasing HDL-cholesterol and adiponectin blood levels as well as decreasing LDL-cholesterol, leptin, and C-reactive protein (a proinflammatory marker) concentrations. It is therefore possible to speculate about a future clinical use of CB1 antagonists, as a means of improving gonadotrophin pulsatility and fertilization capacity as well as the prevention of cardiovasculary disease and type 2 diabetes mellitus. Drugs acting as agonists of CB1 receptors (Dronabinol, Dexanabinol) are currently proposed for evaluation as drugs to treat neurodegenerative disorders (Alzheimer's and Parkinson's diseases), epilepsy, anxiety, and stroke.

  4. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  5. Effects of acute psychosocial stress exposure on endocrine and affective reactivity in college students differing in the 5-HTTLPR genotype and trait neuroticism.

    PubMed

    Verschoor, Ellen; Markus, C Rob

    2011-07-01

    Enhanced stress vulnerability has been implicated in the pathogenesis of affective disorders. Although both genetic (5-HTTLPR) and cognitive (neuroticism) factors are known to increase stress vulnerability, no experimental study has investigated the interaction between these two factors on psychobiological reactivity following acute stress exposure. This study used a balanced experimental design to examine the interaction between the 5-HTTLPR genotype and trait neuroticism in neuroendocrine and affective stress responses. From a large group of 771 students, 48 carriers of the short/short (S/S) allele and 48 carriers of the long/long (L/L) allele with the lowest and the highest neuroticism scores (77 females, 19 males; mean age ± SD: 20.6 ± 2 years) were selected and exposed to an acute psychosocial stressor. Mood was assessed before and after the stressor, and salivary cortisol concentrations were measured before and at 20, 30, and 60 min after stressor onset. Acute stress increased salivary cortisol concentration regardless of either 5-HTTLPR genotype or neuroticism, but it caused a less profound negative mood change in L/L compared to S/S-allele carriers with the lowest neuroticism scores. The 5-HTTLPR genotype influences affective reactivity to acute stress conditional upon neuroticism, improving resilience to acute stress in L/L-allele carriers if they do not already possess high cognitive-affective (neuroticism) vulnerability.

  6. Functional neuroimaging of human vocalizations and affective speech.

    PubMed

    Frühholz, Sascha; Sander, David; Grandjean, Didier

    2014-12-01

    Neuroimaging studies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory-motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

  7. Endocrine Profiling and Prioritization Using ToxCast Assays

    EPA Science Inventory

    The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) is charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife (http://www.epa.gov/endo/). The prioritization of chemicals for test...

  8. Research on Endocrine Disruptors

    EPA Pesticide Factsheets

    EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

  9. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... Endocrine Neoplasia Syndromes By Patricia A. Daly, MD, University of Virginia;Front Royal Internal Medicine, VA ; Lewis Landsberg, MD, Northwestern University NOTE: This is the Consumer Version. DOCTORS: Click ...

  10. Endocrine Drugs in Aircrew

    DTIC Science & Technology

    2001-06-01

    stresses. common endocrine diseases are diabetes mellitus, thyrotoxicosis, hypothyroidism, nodular goiter , The human adrenal consists of an outer cortex...about 40% goiter or thyroid carcinoma. of patients with primary hypothyroidism. Insulin requirements in diabetics are frequently increased in

  11. Endocrine Disrupting Chemicals (EDCs)

    MedlinePlus

    ... your body handles stress and responds to the environment. Results of animal and human scientific studies support a link between EDCs and ... to cause endocrine, reproductive, or neurological problems in humans. ... environmental contamination. For example, in 1976 an industrial accident ...

  12. Respiratory manifestations in endocrine diseases

    PubMed Central

    LENCU, CODRUŢA; 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 hyperthyroidism, patients develop ventilation disorders, obstructive and central sleep apnea, and pleural collection. The respiratory abnormalities in hyperthyroidism as a result of the hypermetabolic action of thyroid hormones are hyperventilation, myopathy and cardiovascular involvement; recent studies have reported pulmonary arterial hypertension in Graves’ disease, as a result of the association of several mechanisms. Thyroid hypertrophy can induce through compression of the upper airways dyspnea, stridor, wheezing and cough. The respiratory disorders in acromegaly are ventilatory dysfunction and sleep apnea, which contribute to an unfavorable evolution of the disease. Respiratory changes in parathyroid, adrenal and reproductive system diseases have been described. Respiratory disorders should be recognized, investigated and monitored by medical practitioners of various specialties (family physicians, internists, endocrinologists, pneumologists, cardiologists). They are frequently severe, causing an unfavorable evolution of the associated endocrine and respiratory disease. PMID:27857512

  13. Frozen Soil Characteristics That Affect Land Mine Functioning.

    DTIC Science & Technology

    1983-04-01

    ii Introduction .............................................. 1 Backgroun ...Table 3 also presents the results of the mine functioning perform- ance . The M12 mine requires between 1739 and 3287 N to function, as indicated by the

  14. Regulation of synaptic functions in central nervous system by endocrine hormones and the maintenance of energy homoeostasis.

    PubMed

    Pang, Zhiping P; Han, Weiping

    2012-10-01

    Energy homoeostasis, a co-ordinated balance of food intake and energy expenditure, is regulated by the CNS (central nervous system). The past decade has witnessed significant advances in our understanding of metabolic processes and brain circuitry which responds to a broad range of neural, nutrient and hormonal signals. Accumulating evidence demonstrates altered synaptic plasticity in the CNS in response to hormone signals. Moreover, emerging observations suggest that synaptic plasticity underlies all brain functions, including the physiological regulation of energy homoeostasis, and that impaired synaptic constellation and plasticity may lead to pathological development and conditions. Here, we summarize the current knowledge on the regulation of postsynaptic receptors such as AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), NMDA (N-methyl-D-aspartate) and GABA (γ-aminobutyric acid) receptors, and the presynaptic components by hormone signals. A detailed understanding of the neurobiological mechanisms by which hormones regulate energy homoeostasis may lead to novel strategies in treating metabolic disorders.

  15. Hormones and endocrine disruptors in human seminal plasma.

    PubMed

    Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

    2013-07-01

    Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

  16. Endocrine consequences of perinatal methadone exposure.

    PubMed

    Kuhn, C; Bero, L; Ignar, D; Lurie, S; Field, E

    1987-01-01

    In summary, we have shown that marked acute responses as well as persistent changes in hypothalamopituitary responsivity to opiate challenge result from perinatal opioid addiction. We have also shown that different endocrine systems and opioid receptor subtypes develop at different rates, and that the responses of these systems depend upon the relative timing of the treatment regimen and the functional development of the particular opioid system involved. It should be emphasized that these studies have investigated only a single developmental window. The additional critical question of how opioid neuron function is affected by treatment during the period of active neuronal differentiation has not yet been answered. However, these studies do demonstrate the utility of this neuroendocrine model in assessing opioid function following chronic treatment regimens. By using neuroendocrine function as an end point, multiple systems can be studied simultaneously in the same animal. This has a particular advantage in studying the effects of chronic drug exposure on the developing nervous system, because hormone secretion is an easily quantifiable and early maturing functional index which can be used to identify vulnerable (and resistant) systems. Endogenous opioid systems appear to be particularly important in neuroendocrine regulation during the early phase of development, when other neural controls have not yet matured. Our preliminary results suggest that specific opioid systems that mature early may be especially important in the specific neuroendocrine effects of perinatal opiate addiction.

  17. Selenium and endocrine systems.

    PubMed

    Beckett, Geoffrey J; Arthur, John R

    2005-03-01

    The trace element selenium (Se) is capable of exerting multiple actions on endocrine systems by modifying the expression of at least 30 selenoproteins, many of which have clearly defined functions. Well-characterized selenoenzymes are the families of glutathione peroxidases (GPXs), thioredoxin reductases (TRs) and iodothyronine deiodinases (Ds). These selenoenzymes are capable of modifying cell function by acting as antioxidants and modifying redox status and thyroid hormone metabolism. Se is also involved in cell growth, apoptosis and modifying the action of cell signalling systems and transcription factors. During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage. Thyroidal D1 in rats and both D1 and D2 in humans are also up-regulated to increase the production of bioactive 3,5,3'-tri-iodothyronine (T3). In the basal state, GPX3 is secreted into the follicular lumen where it may down-regulate thyroid hormone synthesis by decreasing hydrogen peroxide concentrations. The deiodinases are present in most tissues and provide a mechanism whereby individual tissues may control their exposure to T3. Se is also able to modify the immune response in patients with autoimmune thyroiditis. Low sperm production and poor sperm quality are consistent features of Se-deficient animals. The pivotal link between Se, sperm quality and male fertility is GPX4 since the enzyme is essential to allow the production of the correct architecture of the midpiece of spermatozoa. Se also has insulin-mimetic properties, an effect that is probably brought about by stimulating the tyrosine kinases involved in the insulin signalling cascade. Furthermore, in the diabetic rat, Se not only restores glycaemic control but it also prevents or alleviates the adverse effects that diabetes has on cardiac, renal and platelet function.

  18. CHARACTERIZATION OF ENDOCRINE-DISRUPTION AND CLINICAL MANIFESTATIONS IN LARGE-MOUTH BASS FROM FLORIDA LAKES

    EPA Science Inventory

    Previous efforts from this laboratory, have documented altered endocrine function and sexual differentiation for alligators and turtles from Lake Apopka in Central Florida. This lake has been exposed to a variety of contaminants which are potentially endocrine-disrupting. Therefo...

  19. COMPARISON OF FATHEAD MINNOW AND HUMAN ESTROGEN RECEPTOR BINDING TO ENDOCRINE DISRUPTING COMPOUNDS

    EPA Science Inventory

    Environmental estrogens have the potential to disrupt endocrine function in a myriad of species. However, in vitro assays designed to detect and characterize endocrine disrupting chemicals (EDCs) typically utilize mammalian estrogen receptors. Our overall objective is to charac...

  20. Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo

    PubMed Central

    Colvin, Stephanie C.; Malik, Raleigh E.; Showalter, Aaron D.; Sloop, Kyle W.; Rhodes, Simon J.

    2011-01-01

    The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (Lhx3 W227ter), which is a model for the human LHX3 W224ter disease. The LHX3 gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous Lhx3 W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the Lhx3 W227ter mice have no apparent nervous system deficits. The Lhx3 W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable. PMID:21149718

  1. Pesticides as endocrine-disrupting chemicals

    EPA Science Inventory

    Pesticides are designed to be bioactive against certain targets but can cause toxicity to nontarget species by a variety of other modes of action including disturbance of endocrine function. As such, pesticides have been found to bind and alter the function of hormone receptors, ...

  2. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. We conducted a retrospective chart review of children with BD (ejecti...

  3. Update: Systemic Diseases and the Cardiovascular System (II). The endocrine system and the heart: a review.

    PubMed

    Rhee, Soo S; Pearce, Elizabeth N

    2011-03-01

    Normal endocrine function is essential for cardiovascular health. Disorders of the endocrine system, consisting of hormone hyperfunction and hypofunction, have multiple effects on the cardiovascular system. In this review, we discuss the epidemiology, diagnosis, and management of disorders of the pituitary, thyroid, parathyroid, and adrenal glands, with respect to the impact of endocrine dysfunction on the cardiovascular system. We also review the cardiovascular benefits of restoring normal endocrine function.

  4. Effects of alcohol on the endocrine system.

    PubMed

    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.

  5. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment.

  6. Effects of a Short-term Exposure to the Fungicide Prochloraz on Endocrine Function and Gene Expression in Female Fathead Minnows (Pimephales promelas)

    EPA Science Inventory

    Prochloraz is a fungicide known to cause endocrine disruption through effects on the hypothalamic-pituitary-gonadal (HPG) axis. To determine the short-term impacts of prochloraz on gene expression and steroid production, adult female fathead minnows (Pimephales promelas) were exp...

  7. EFFECT OF THE ANTI-ANDROGENIC ENDOCRINE DISRUPTOR VINCLOZOLIN ON EMBRYONIC TESTIS CORD FORMATION AND POSTNATAL TESTIS DEVELOPMENT AND FUNCTION. (R827405)

    EPA Science Inventory

    Vinclozolin is a systemic dicarboximide fungicide that is used on fruits, vegetables, ornamental plants, and turf grass. Vinclozolin and its metabolites are known to be endocrine disruptors and act as androgen receptor antagonists. The hypothesis tested in the current study is...

  8. The absence of corpus luteum formation alters the endocrine profile and affects follicular development during the first follicular wave in cattle.

    PubMed

    Hayashi, Ken-Go; Matsui, Motozumi; Shimizu, Takashi; Sudo, Natsuko; Sato, Ayako; Shirasuna, Koumei; Tetsuka, Masa; Kida, Katsuya; Schams, Dieter; Miyamoto, Akio

    2008-12-01

    We previously established a bovine experimental model showing that the corpus luteum (CL) does not appear following aspiration of the preovulatory follicle before the onset of LH surge. Using this model, the present study aimed to determine the profile of follicular development and the endocrinological environment in the absence of CL with variable nadir circulating progesterone (P(4)) concentrations during the oestrous cycle in cattle. Luteolysis was induced in heifers and cows and they were assigned either to have the dominant follicle aspirated (CL-absent) or ovulation induced (CL-present). Ultrasound scanning to observe the diameter of each follicle and blood collection was performed from the day of follicular aspiration or ovulation and continued for 6 days. The CL-absent cattle maintained nadir circulating P(4) throughout the experimental period and showed a similar diameter between the largest and second largest follicle, resulting in co-dominant follicles. Oestradiol (E(2)) concentrations were greater in the CL-absent cows than in the CL-present cows at day -1, day 1 and day 2 from follicular deviation. The CL-absent cows had a higher basal concentration, area under the curve (AUC), pulse amplitude and pulse frequency of LH than the CL-present cows. After follicular deviation, the CL-absent cows showed a greater basal concentration, AUC and pulse amplitude of growth hormone (GH) than the CL-present cows. These results suggest that the absence of CL accompanying nadir circulating P(4) induces an enhancement of LH pulses, which involves the growth of the co-dominant follicles. Our results also suggest that circulating levels of P(4) and E(2) affect pulsatile GH secretion in cattle.

  9. Purinergic Signaling Pathways in Endocrine System

    PubMed Central

    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

  10. Purinergic signaling pathways in endocrine system.

    PubMed

    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.

  11. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    PubMed

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  12. REMOVAL OF ENDOCRINE DISRUPTING COMPOUNDS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    A growing body of scientific information has shown that man-made industrial chemicals and pesticides may interfere with the normal functioning of human and wildlife endocrine systems. These agents are referred to collectively as endocrine disrupting compounds (EDCs) and they are ...

  13. Update on the Mammalian Tier 1 Endocrine Disruptor Screening Protocols

    EPA Science Inventory

    The endocrine system provides a number of target sites that may be susceptible to disruption by environmental agents. In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system (http://w...

  14. Factors affecting the development of lung function in Tunisian children.

    PubMed

    Trabelsi, Y; Pariès, J; Harrabi, I; Zbidi, A; Tabka, Z; Richalet, J P; Buvry, A

    2008-01-01

    We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

  15. ENDOCRINE DISRUPTING CONTAMINANTS AND ALLIGATOR EMBRYOS: A LESSON FROM WILDLIFE?

    EPA Science Inventory

    Many xenobiotic compounds introduced into the environment by human activity adversely affect wildlife. A number of these contaminants have been hypothesized to induce non lethal, multigenerational effects by acting as endocrine disrupting agents. One case is that of the alligator...

  16. Genetics Home Reference: multiple endocrine neoplasia

    MedlinePlus

    ... Multiple endocrine neoplasia, type 4 Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 1 Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 2A MalaCards: multiple endocrine ...

  17. Drying process strongly affects probiotics viability and functionalities.

    PubMed

    Iaconelli, Cyril; Lemetais, Guillaume; Kechaou, Noura; Chain, Florian; Bermúdez-Humarán, Luis G; Langella, Philippe; Gervais, Patrick; Beney, Laurent

    2015-11-20

    Probiotic formulations are widely used and are proposed to have a variety of beneficial effects, depending on the probiotic strains present in the product. The impact of drying processes on the viability of probiotics is well documented. However, the impact of these processes on probiotics functionality remains unclear. In this work, we investigated variations in seven different bacterial markers after various desiccation processes. Markers were composed of four different viability evaluation (combining two growth abilities and two cytometric measurements) and in three in vitro functionalities: stimulation of IL-10 and IL-12 production by PBMCs (immunomodulation) and bacterial adhesion to hexadecane. We measured the impact of three drying processes (air-drying, freeze-drying and spray-drying), without the use of protective agents, on three types of probiotic bacteria: Bifidobacterium bifidum, Lactobacillus plantarum and Lactobacillus zeae. Our results show that the bacteria respond differently to the three different drying processes, in terms of viability and functionality. Drying methods produce important variations in bacterial immunomodulation and hydrophobicity, which are correlated. We also show that adherence can be stimulated (air-drying) or inhibited (spray-drying) by drying processes. Results of a multivariate analysis show no direct correlation between bacterial survival and functionality, but do show a correlation between probiotic responses to desiccation-rewetting and the process used to dry the bacteria.

  18. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  19. Chemical Modifications that Affect Nutritional and Functional Properties of Proteins.

    ERIC Educational Resources Information Center

    Richardson, T.; Kester, J. J.

    1984-01-01

    Discusses chemical alterations of selected amino acids resulting from environmental effects (photooxidations, pH extremes, thermally induced effects). Also dicusses use of intentional chemical derivatizations of various functional groups in amino acid residue side chains and how recombinant DNA techniques might be useful in structure/function…

  20. Neurotoxicity of endocrine disruptors: possible involvement in brain development and neurodegeneration.

    PubMed

    Masuo, Yoshinori; Ishido, Masami

    2011-01-01

    Environmental chemicals that act as endocrine disruptors do not appear to pose a risk to human reproduction; however, their effects on the central nervous systems are less well understood. Animal studies suggested that maternal exposure to endocrine-disrupting chemicals (EDC) produced changes in rearing behavior, locomotion, anxiety, and learning/memory in offspring, as well as neuronal abnormalities. Some investigations suggested that EDC exert effects on central monoaminergic neurons, especially dopaminergic neurons. Our data demonstrated that EDC attenuate the development of dopaminergic neurons, which might be involved in developmental disorders. Perinatal exposure to EDC might affect neuronal plasticity in the hippocampus, thereby potentially modulating neuronal development, leading to impaired cognitive and memory functions. Endocrine disruptors also attenuate gender differences in brain development. For example, the locus ceruleus is larger in female rats than in males, but treatments with bisphenol-A (BPA) enlarge this region in males. Some reports indicated that EDC induce hypothyroidism, which might be evidenced as abnormal brain development. Endocrine disruptors might also affect mature neurons, resulting in neurodegenerative disorders such as Parkinson's disease. The current review focused on alterations in the brain induced by EDC, specifically on the possible involvement of EDC in brain development and neurodegeneration.

  1. Your Endocrine System (For Kids)

    MedlinePlus

    ... Dictionary of Medical Words En Español What Other Kids Are Reading Taking Care of Your Ears Taking ... an X-ray Your Endocrine System KidsHealth > For Kids > Your Endocrine System Print A A A en ...

  2. Uncertainties for endocrine disrupters: our view on progress.

    PubMed

    Daston, George P; Cook, Jon C; Kavlock, Robert J

    2003-08-01

    hormonal activity should include androgens and compounds that affect thyroid function, and expanded the mandate to include all chemicals under EPA's jurisdiction, potentially including the 70,000 chemicals regulated under the Toxic Substances Control Act (Endocrine Disruptor Screening and Testing Advisory Committee [EDSTAC], 1998). EDSTAC recommended an extensive process of prioritization, screening, and testing of chemicals for endocrine-disrupting activity, including a screening battery that involves a combination of at least eight in vitro and in vivo assays spanning a number of taxa (EDSTAC, 1998). What started out as a hypothesis has become one of the biggest testing programs conceived in the history of toxicology and the only one that has ever been based on mechanism of action as its premise. As we pass the 10th anniversary of the emergence of the endocrine disruptor hypothesis, it is useful to look back on the progress that has been made in answering the nine questions posed as data gaps in the EPA's research strategy (EPA, 1998a)--not only to see what we have learned, but also to examine whether the questions are still appropriate for the goal, what gaps remain, and what directions should be emphasized in the future.

  3. Development of affective theory of mind across adolescence: disentangling the role of executive functions.

    PubMed

    Vetter, Nora C; Altgassen, Mareike; Phillips, Louise; Mahy, Caitlin E V; Kliegel, Matthias

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

  4. Alginate Overproduction Affects Pseudomonas aeruginosa Biofilm Structure and Function

    PubMed Central

    Hentzer, Morten; Teitzel, Gail M.; Balzer, Grant J.; Heydorn, Arne; Molin, Søren; Givskov, Michael; Parsek, Matthew R.

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development on an abiotic surface. Biofilms formed by an alginate-overproducing strain exhibit a highly structured architecture and are significantly more resistant to the antibiotic tobramycin than a biofilm formed by an isogenic nonmucoid strain. These results suggest that an important consequence of the conversion to mucoidy is an altered biofilm architecture that shows increasing resistance to antimicrobial treatments. PMID:11514525

  5. Nuclear cyclophilins affect spliceosome assembly and function in vitro.

    PubMed

    Adams, B M; Coates, Miranda N; Jackson, S RaElle; Jurica, Melissa S; Davis, Tara L

    2015-07-15

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.

  6. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

    Salzwedel, Andrew P.; Vachet, Clement; Gerig, Guido; Lin, Weili

    2015-01-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  7. How optimization of potential functions affects protein folding.

    PubMed Central

    Hao, M H; Scheraga, H A

    1996-01-01

    The relationship between the optimization of the potential function and the foldability of theoretical protein models is studied based on investigations of a 27-mer cubic-lattice protein model and a more realistic lattice model for the protein crambin. In both the simple and the more complicated systems, optimization of the energy parameters achieves significant improvements in the statistical-mechanical characteristics of the systems and leads to foldable protein models in simulation experiments. The foldability of the protein models is characterized by their statistical-mechanical properties--e.g., by the density of states and by Monte Carlo folding simulations of the models. With optimized energy parameters, a high level of consistency exists among different interactions in the native structures of the protein models, as revealed by a correlation function between the optimized energy parameters and the native structure of the model proteins. The results of this work are relevant to the design of a general potential function for folding proteins by theoretical simulations. PMID:8643516

  8. Does caregiving stress affect cognitive function in older women?

    PubMed

    Lee, Sunmin; Kawachi, Ichiro; Grodstein, Francine

    2004-01-01

    Increasing numbers of women provide care to their ill spouses; however, no studies have examined possible effects of caregiving stress on cognitive function. We administered 6 tests of cognitive function to 13740 Nurses' Health Study participants aged 70-79 years. We collected information on caregiving and numerous potential confounding variables via biennial mailed questionnaires. After adjustment for potential confounders (age, education, mental health index, vitality index, use of antidepressants, and history of high blood pressure, diabetes, and heart disease), we found modest but significantly increased risks of low cognitive function on three of the cognitive tests among women who provided care to a disabled or ill spouse compared with women who did not provide any care. For example, on the TICS, a test of general cognition, the risk of a low score was 31% higher in women who provided care compared with women who did not (RR = 1.31, 95% CI 1.10, 1.56). We found a moderately increased risk of poor performance on several cognitive tests among women who provided care to their disabled or ill husbands.

  9. Microplastics Affect the Ecological Functioning of an Important Biogenic Habitat.

    PubMed

    Green, Dannielle Senga; Boots, Bas; O'Connor, Nessa E; Thompson, Richard

    2017-01-03

    Biological effects of microplastics on the health of bivalves have been demonstrated elsewhere, but ecological impacts on the biodiversity and ecosystem functioning of bivalve-dominated habitats are unknown. Thus, we exposed intact sediment cores containing European flat oysters (Ostrea edulis) or blue mussels (Mytilus edulis) in seawater to two different densities (2.5 or 25 μg L(-1)) of biodegradable or conventional microplastics in outdoor mesocosms. We hypothesized that filtration rates of the bivalves, inorganic nitrogen cycling, primary productivity of sediment dwelling microphytobenthos, and the structure of invertebrate benthic assemblages would be influenced by microplastics. After 50 days, filtration by M. edulis was significantly less when exposed to 25 μg L(-1) of either type of microplastics, but there were no effects on ecosystem functioning or the associated invertebrate assemblages. Contrastingly, filtration by O. edulis significantly increased when exposed to 2.5 or 25 μg L(-1) of microplastics, and porewater ammonium and biomass of benthic cyanobacteria decreased. Additionally the associated infaunal invertebrate assemblages differed, with significantly less polychaetes and more oligochaetes in treatments exposed to microplastics. These findings highlight the potential of microplastics to impact the functioning and structure of sedimentary habitats and show that such effects may depend on the dominant bivalve present.

  10. Nuclear cyclophilins affect spliceosome assembly and function in vitro

    PubMed Central

    Adams, B.M.; Coates, Miranda N.; Jackson, S. RaElle; Jurica, Melissa S.; Davis, Tara L.

    2015-01-01

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing. PMID:25967372

  11. Your Endocrine System (For Kids)

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Endocrine System KidsHealth > For Kids > Your Endocrine System A A A en español Tu sistema endocrino ... a pea, is the "master gland" of the endocrine system. It makes and releases a bunch of hormones ...

  12. Visual function affects prosocial behaviors in older adults.

    PubMed

    Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

    2016-02-01

    Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

  13. Oxidative stress and the ageing endocrine system.

    PubMed

    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.

  14. Exercise and the Regulation of Endocrine Hormones.

    PubMed

    Hackney, Anthony C; Lane, Amy R

    2015-01-01

    The endocrine system has profound regulatory effects within the human body and thus the ability to control and maintain appropriate function within many physiological systems (i.e., homeostasis). The hormones associated with the endocrine system utilize autocrine, paracrine, or endocrine actions on the cells of their target tissues within these physiologic systems to adjust homeostasis. The introduction of exercise as a stressor to disrupt homeostasis can greatly amplify and impact the actions of these hormones. To that end, the endocrine response to an acute exercise session occurs in a progression of phases with the magnitude of the response being relative to the exercise work intensity or volume. Various physiologic mechanisms are considered responsible for these responses, although not all are completely understood or elucidated. Chronic exercise training does not eliminate the acute exercise response but may attenuate the overall effect of the responsiveness as the body adapts in a positive fashion to the training stimulus. Regrettably, an excessive intensity and/or volume of training may lead to maladaptation and is associated with inappropriate endocrine hormonal responses. The mechanisms leading to a deleterious maladaptive state are not well understood and require additional research for elucidation.

  15. ENDOCRINE DISRUPTORS: LESSONS LEARNED

    EPA Science Inventory

    For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

  16. Affected functional networks associated with sentence production in classic galactosemia.

    PubMed

    Timmers, Inge; van den Hurk, Job; Hofman, Paul Am; Zimmermann, Luc Ji; Uludağ, Kâmil; Jansma, Bernadette M; Rubio-Gozalbo, M Estela

    2015-08-07

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients.

  17. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  18. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  19. Unmasking the truth behind endocrine disruptors.

    PubMed

    DiDiego, Michele Lamse; Eggert, Julia A; Pruitt, Rosanne H; Larcom, Lyndon L

    2005-10-01

    The increase in reproductive cancers and developmental problems over the past 70 years has led researchers to suspect environmental influences as a root cause. Evidence from wildlife and laboratory studies suggests that exposure to endocrine disruptors (EnDs) may be the cause. An EnD is a foreign substance or mixture that alters the function of the endocrine system. They can be found in food, water, soil, or air. Research into their possible role provides an opportunity to decrease modifiable risk factors.

  20. [Novel concepts in biology of diffuse endocrine system: results and future investigations].

    PubMed

    Iaglov, V V; Iaglova, N V

    2012-01-01

    Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.

  1. Diagnosis and management of endocrine gland neoplasms

    SciTech Connect

    Weller, R.E.

    1989-05-01

    Functional and nonfunctional neoplasms of the endocrine glands constitute some of the more challenging diagnostic and therapeutic problems in veterinary cancer medicine. The clinical signs are usually the result of an overproduction of hormones that are normally biosynthesized by the neoplastic endocrine gland (orthoendocrine syndromes), as opposed to those that are the result of hormones that are not normally biosynthesized and secreted by those cells that have undergone neoplastic transformation (paraendocrine syndromes, also known as endocrine paraneoplastic syndromes or ectopic hormone syndromes). The biological effects produced by a neoplasm may be out of proportion to the actual size of the tumor. This report focuses on the clinical signs and syndromes associated with neoplasms of the thyroid, adrenal glands and pancreas. Discussion will focus on the mechanisms producing the clinical signs, diagnosis, staging, therapy and prognosis. 2 tabs.

  2. Epigenetic alterations in endocrine-related cancer.

    PubMed

    Rodríguez-Rodero, Sandra; Delgado-Álvarez, Elías; Fernández, Agustín F; Fernández-Morera, Juan L; Menéndez-Torre, Edelmiro; Fraga, Mario F

    2014-08-01

    Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no exception. Recent research has been identifying an ever-growing number of epigenetic alterations in both genomic DNA methylation and histone post-translational modification in tumors of the endocrine system. Novel microarray and ultra-deep sequencing technologies have allowed the identification of genome-wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid, and breast carcinomas. However, in other cancer types, such as the multiple endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to candidate genes alone. Future research should fill this gap and deepen our understanding of the functional role of these alterations in cancer, as well as defining their possible clinical uses.

  3. Purinergic signalling in endocrine organs.

    PubMed

    Burnstock, Geoffrey

    2014-03-01

    There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5'-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.

  4. Low level methylmercury exposure affects neuropsychological function in adults

    PubMed Central

    Yokoo, Edna M; Valente, Joaquim G; Grattan, Lynn; Schmidt, Sérgio Luís; Platt, Illeane; Silbergeld, Ellen K

    2003-01-01

    -dependent effect. Conclusions This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures. PMID:12844364

  5. Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

    PubMed

    Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

    2017-02-01

    Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

  6. Does vitamin C deficiency affect cognitive development and function?

    PubMed

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-09-19

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

  7. Enhanced serotonin transporter function during depression in seasonal affective disorder.

    PubMed

    Willeit, Matthäus; Sitte, Harald H; Thierry, Nikolaus; Michalek, Klaus; Praschak-Rieder, Nicole; Zill, Peter; Winkler, Dietmar; Brannath, Werner; Fischer, Michael B; Bondy, Brigitta; Kasper, Siegfried; Singer, Ernst A

    2008-06-01

    Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (rho=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

  8. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    ERIC Educational Resources Information Center

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  9. Familial Clustering of Executive Functioning in Affected Sibling Pair Families with ADHD

    ERIC Educational Resources Information Center

    Slaats-Willemse, Dorine; Swaab-Barneveld, Hanna; De Sonneville, Leo; Buitelaar, Jan

    2005-01-01

    Objective: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. Method: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the…

  10. Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus).

    PubMed

    Wistuba, Joachim; Luetjens, C Marc; Ehmcke, Jens; Redmann, Klaus; Damm, Oliver S; Steinhoff, Antje; Sandhowe-Klaverkamp, Reinhild; Nieschlag, Eberhard; Simoni, Manuela; Schlatt, Stefan

    2013-04-01

    Marmosets are used as preclinical model in reproductive research. In contrast to other primates, they display short gestation times rendering this species valid for exploration of effects on fertility. However, their peculiar endocrine regulation differs from a those of macaques and humans. We subjected male marmosets to previously clinically tested hormonal regimens that are known to effectively suppress spermatogenesis. Beside a control group, seven groups (each n=6) were investigated for different periods of up to 42 months: regimen I, (four groups) received testosterone undecanoate (TU) and norethisterone enanthate (NETE); regimen II, (two groups) received TU and NETE followed by NETE only; and regimen III, (one group) received NETE only. Testicular volume, cell ploidy and histology, endocrine changes and fertility were monitored weekly. TU and NETE and initial TU and NETE treatment followed by NETE failed to suppress spermatogenesis and fertility. Testicular volumes dropped, although spermatogenesis was only mildly affected; however, testicular cellular composition remained stable. Serum testosterone dropped when NETE was given alone but the animals remained fertile. Compared with controls, no significant changes were observed in sperm motility and fertility. Administration of TU and NETE affected testicular function only mildly, indicating that the regulatory role of chorionic gonadotrophin and testosterone on spermatogenesis is obviously limited and testicular function is maintained, although the endocrine axis is affected by the treatment. In conclusion, marmosets showed a different response to regimens of male contraception from macaques or men and have to be considered as a problematic model for preclinical trials of male hormonal contraception.

  11. [The vitamin D endocrine system].

    PubMed

    Castro, Luiz Claudio Gonçalves de

    2011-11-01

    The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)(2)D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)(2)D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)(2)D directly or indirectly modulates about 3% of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.

  12. Endocrine Consequences of Anorexia Nervosa

    PubMed Central

    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

  13. Endocrine disrupters as obesogens

    PubMed Central

    Grün, Felix; Blumberg, Bruce

    2009-01-01

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity. PMID:19433244

  14. Opioids and endocrine dysfunction

    PubMed Central

    Hester, Joan

    2012-01-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist. PMID:26516462

  15. Endocrine oncology in pregnancy.

    PubMed

    Lansdown, A; Rees, D A

    2011-12-01

    Endocrine tumours occur rarely in pregnant women but present clinicians with unique challenges. A high index of suspicion is often required to make a diagnosis since the symptoms and signs associated with many of these tumours, including insulinoma, adrenocortical carcinoma and phaeochromocytoma, mimic those of normal pregnancy or its complications, such as pre-eclampsia. The evidence base which informs management is very limited hence decisions on investigation and therapy must be individualised and undertaken jointly by the multidisciplinary medical team and the patient. The optimal strategy will depend on the nature and stage of the endocrine tumour, gestational stage, treatments available and patient wishes. Thus, surgical intervention, appropriately timed, may be considered in pregnancy for resectable adrenocortical carcinoma or phaeochromocytoma, but delayed until the postpartum period for well-differentiated thyroid cancer. Medical therapy may be required to reduce the drive to tumour growth, control symptoms of hormone excess and to minimise the risks of surgery, anaesthesia or labour.

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

    USGS Publications Warehouse

    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.

  17. Endocrine effects of the herbicide linuron on the American Goldfinch (Carduelis tristis)

    USGS Publications Warehouse

    Sughrue, K.M.; Brittingham, M.C.; French, J.B.

    2008-01-01

    Certain contaminants alter normal physiological function, morphology, and behavior of exposed organisms through an endocrine mechanism. We evaluated how the herbicide linuron, an endocrine-active compound, affects physiological parameters and secondary sex characteristics of the American Goldfinch (Carduelis tristis). When administered at relatively low doses (control, 1.0, 4.0, and 16.0 mu g linuron per gram of body mass per day), linuron delayed prealternate molt progression in a dose-dependent manner. At the high dose level, linuron exposure lowered hematocrit and female plasma thyroxine concentrations and increased body mass. Neither plasma testosterone concentrations nor the color of plumage or integument of birds in the treatment groups were different from those of the control group. Overall, the physiological effects that were measured suggested disruption of thyroid function. These results highlight the importance of continual monitoring of avian populations for potential effects of exposure to pesticides and other chemicals at sublethal concentrations.

  18. AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo.

    PubMed

    Ribas, Ricardo; Pancholi, Sunil; Guest, Stephanie K; Marangoni, Elisabetta; Gao, Qiong; Thuleau, Aurélie; Simigdala, Nikiana; Polanska, Urszula M; Campbell, Hayley; Rani, Aradhana; Liccardi, Gianmaria; Johnston, Stephen; Davies, Barry R; Dowsett, Mitch; Martin, Lesley-Ann

    2015-09-01

    PI3K/AKT/mTOR signaling plays an important role in breast cancer. Its interaction with estrogen receptor (ER) signaling becomes more complex and interdependent with acquired endocrine resistance. Targeting mTOR combined with endocrine therapy has shown clinical utility; however, a negative feedback loop exists downstream of PI3K/AKT/mTOR. Direct blockade of AKT together with endocrine therapy may improve breast cancer treatment. AZD5363, a novel pan-AKT kinase catalytic inhibitor, was examined in a panel of ER(+) breast cancer cell lines (MCF7, HCC1428, T47D, ZR75.1) adapted to long-term estrogen deprivation (LTED) or tamoxifen (TamR). AZD5363 caused a dose-dependent decrease in proliferation in all cell lines tested (GI50 < 500 nmol/L) except HCC1428 and HCC1428-LTED. T47D-LTED and ZR75-LTED were the most sensitive of the lines (GI50 ∼ 100 nmol/L). AZD5363 resensitized TamR cells to tamoxifen and acted synergistically with fulvestrant. AZD5363 decreased p-AKT/mTOR targets leading to a reduction in ERα-mediated transcription in a context-specific manner and concomitant decrease in recruitment of ER and CREB-binding protein (CBP) to estrogen response elements located on the TFF1, PGR, and GREB1 promoters. Furthermore, AZD5363 reduced expression of cell-cycle-regulatory proteins. Global gene expression highlighted ERBB2-ERBB3, ERK5, and IGFI signaling pathways driven by MYC as potential feedback-loops. Combined treatment with AZD5363 and fulvestrant showed synergy in an ER(+) patient-derived xenograft and delayed tumor progression after cessation of therapy. These data support the combination of AZD5363 with fulvestrant as a potential therapy for breast cancer that is sensitive or resistant to E-deprivation or tamoxifen and that activated AKT is a determinant of response, supporting the need for clinical evaluation.

  19. Endocrine control of spermatogenesis: Role of FSH and LH/ testosterone

    PubMed Central

    Ramaswamy, Suresh; Weinbauer, Gerhard F

    2014-01-01

    Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species. PMID:26413400

  20. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    SciTech Connect

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S. . E-mail: mssantos@ci.uc.pt

    2007-05-15

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17{beta}-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca{sup 2+} delaying the opening of the permeability transition pore. The presence of 25 {mu}M E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H{sub 2}O{sub 2} in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

  1. SCREENING CALIFORNIA SURFACE WATERS FOR ESTROGENIC ENDOCRINE DISRUPTING CHEMICALS (EEDC) WITH A JUVENILE RAINBOW TROUT LIVER VITELLOGENIN MRNA PROCEDURE

    EPA Science Inventory

    Concern regarding the occurrence of chemicals that disrupt endocrine system functions in aquatic species has heightened over the last 15 years. However, little attention has been given to monitoring for estrogenic endocrine disrupting chemicals (EEDCs) in California's freshwater ...

  2. Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation

    PubMed Central

    Fanning, Sean W; Mayne, Christopher G; Dharmarajan, Venkatasubramanian; Carlson, Kathryn E; Martin, Teresa A; Novick, Scott J; Toy, Weiyi; Green, Bradley; Panchamukhi, Srinivas; Katzenellenbogen, Benita S; Tajkhorshid, Emad; Griffin, Patrick R; Shen, Yang; Chandarlapaty, Sarat; Katzenellenbogen, John A; Greene, Geoffrey L

    2016-01-01

    Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and structural biology data to reveal how these mutations lead to a constitutively active and antiestrogen-resistant ERα. We show that these mutant ERs recruit coactivator in the absence of hormone while their affinities for estrogen agonist (estradiol) and antagonist (4-hydroxytamoxifen) are reduced. Further, they confer antiestrogen resistance by altering the conformational dynamics of the loop connecting Helix 11 and Helix 12 in the ligand-binding domain of ERα, which leads to a stabilized agonist state and an altered antagonist state that resists inhibition. DOI: http://dx.doi.org/10.7554/eLife.12792.001 PMID:26836308

  3. Cognitive effects of endocrine-disrupting chemicals in animals.

    PubMed Central

    Schantz, S L; Widholm, J J

    2001-01-01

    A large number of chemical pollutants including phthalates, alkylphenolic compounds, polychlorinated biphenyls and polychlorinated dibenzodioxins, organochlorine pesticides, bisphenol A, and metals including lead, mercury, and cadmium have the ability to disrupt endocrine function in animals. Some of these same chemicals have been shown to alter cognitive function in animals and humans. Because hormonally mediated events play a central role in central nervous system development and function, a number of researchers have speculated that the changes in cognitive function are mediated by the endocrine-like actions of these chemicals. In this paper we review the evidence that cognitive effects of chemicals classified as environmental endocrine disruptors are mediated by changes in hormonal function. We begin by briefly reviewing the role of gonadal steroids, thyroid hormones, and glucocorticoids in brain development and brain function. We then review the endocrine changes and cognitive effects that have been reported for selected endocrine-disrupting chemicals, discuss the evidence for causal relationships between endocrine disruption and cognitive effects, and suggest directions for future research. PMID:11748026

  4. Cognitive effects of endocrine-disrupting chemicals in animals.

    PubMed

    Schantz, S L; Widholm, J J

    2001-12-01

    A large number of chemical pollutants including phthalates, alkylphenolic compounds, polychlorinated biphenyls and polychlorinated dibenzodioxins, organochlorine pesticides, bisphenol A, and metals including lead, mercury, and cadmium have the ability to disrupt endocrine function in animals. Some of these same chemicals have been shown to alter cognitive function in animals and humans. Because hormonally mediated events play a central role in central nervous system development and function, a number of researchers have speculated that the changes in cognitive function are mediated by the endocrine-like actions of these chemicals. In this paper we review the evidence that cognitive effects of chemicals classified as environmental endocrine disruptors are mediated by changes in hormonal function. We begin by briefly reviewing the role of gonadal steroids, thyroid hormones, and glucocorticoids in brain development and brain function. We then review the endocrine changes and cognitive effects that have been reported for selected endocrine-disrupting chemicals, discuss the evidence for causal relationships between endocrine disruption and cognitive effects, and suggest directions for future research.

  5. Predicting the accuracy of facial affect recognition: the interaction of child maltreatment and intellectual functioning.

    PubMed

    Shenk, Chad E; Putnam, Frank W; Noll, Jennie G

    2013-02-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying levels of intellectual functioning. A sample of maltreated (n=50) and nonmaltreated (n=56) adolescent females, 14 to 19 years of age, was recruited to participate in this study. Participants completed demographic and study-related questionnaires and interviews to control for potential psychological and psychiatric confounds such as symptoms of posttraumatic stress disorder, negative affect, and difficulties in emotion regulation. Participants also completed an experimental paradigm that recorded responses to facial affect displays starting in a neutral expression and changing into a full expression of one of six emotions: happiness, sadness, anger, disgust, fear, or surprise. Hierarchical multiple regression assessed the incremental advantage of evaluating the interaction between child maltreatment and intellectual functioning. Results indicated that the interaction term accounted for a significant amount of additional variance in the accurate identification of facial affect after controlling for relevant covariates and main effects. Specifically, maltreated females with lower levels of intellectual functioning were least accurate in identifying facial affect displays, whereas those with higher levels of intellectual functioning performed as well as nonmaltreated females. These results suggest that maltreatment and intellectual functioning interact to predict the recognition of facial affect, with potential long-term consequences for the interpersonal functioning of maltreated females.

  6. Endocrine disturbances in suprasellar germinomas.

    PubMed

    Buchfelder, M; Fahlbusch, R; Walther, M; Mann, K

    1989-03-01

    The authors have investigated hypothalamic-pituitary function in 8 patients (aged 9-27 years) with surgically and histologically proven suprasellar germinomas. Diabetes insipidus was found in 7 patients. All the patients had hypogonadism and hypocortisolism as judged by dynamic endocrine testing. Hypothyroidism was found in 6. Moreover, growth hormone secretion, as assessed by insulin-induced hypoglycemia, was defective in all patients. Comparison of results of insulin-induced hypoglycemia testing and stimulation tests by CRH and GHRH suggested that all patients had a primary suprahypophyseal lesion rather than a primary pituitary defect. The authors conclude that suprasellar germinomas, although uncommon, should be included in the differential diagnosis of juvenile suprasellar tumours and in cases suggestive of idiopathic diabetes insipidus, even if neuroradiological investigation fails to demonstrate a discrete tumour.

  7. Lexical and Affective Prosody in Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2010-01-01

    Purpose: To investigate the perception and production of lexical stress and processing of affective prosody in adolescents with high-functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody but atypical lexical prosody production. Method: Sixteen children with HFA and 15 typically developing (TD) peers…

  8. [Hypotension from endocrine origin].

    PubMed

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie

    2012-11-01

    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  9. Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation.

    PubMed

    Vos, J G; Dybing, E; Greim, H A; Ladefoged, O; Lambré, C; Tarazona, J V; Brandt, I; Vethaak, A D

    2000-01-01

    Many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption at environmentally realistic exposure levels. In wildlife populations, associations have been reported between reproductive and developmental effects and endocrine-disrupting chemicals. In the aquatic environment, effects have been observed in mammals, birds, reptiles, fish, and mollusks from Europe, North America, and other areas. The observed abnormalities vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, changed sexual behavior, and altered immune function. For most reported effects in wildlife, however, the evidence for a causal link with endocrine disruption is weak or nonexisting. Crucial in establishing causal evidence for chemical-induced wildlife effects appeared semifield or laboratory studies using the wildlife species of concern. Impaired reproduction and development causally linked to endocrine-disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. These include: Masculinization (imposex) in female marine snails by tributyltin, a biocide used in antifouling paints, is probably the clearest case of endocrine disruption caused by an environmental chemical. The dogwhelk is particularly sensitive, and imposex has resulted in decline or extinction of local populations worldwide, including coastal areas all over Europe and the open North Sea. DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species. In the vicinity of certain sources (e.g., effluents of water treatment plants) and in the most

  10. Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast.

    PubMed

    Gaytán, Brandon D; Loguinov, Alex V; Lantz, Stephen R; Lerot, Jan-Michael; Denslow, Nancy D; Vulpe, Chris D

    2013-04-01

    Exposure to organochlorinated pesticides such as dieldrin has been linked to Parkinson's and Alzheimer's diseases, endocrine disruption, and cancer, but the cellular and molecular mechanisms of toxicity behind these effects remain largely unknown. Here we demonstrate, using a functional genomics approach in the model eukaryote Saccharomyces cerevisiae, that dieldrin alters leucine availability. This model is supported by multiple lines of congruent evidence: (1) mutants defective in amino acid signaling or transport are sensitive to dieldrin, which is reversed by the addition of exogenous leucine; (2) dieldrin sensitivity of wild-type or mutant strains is dependent upon leucine concentration in the media; (3) overexpression of proteins that increase intracellular leucine confer resistance to dieldrin; (4) leucine uptake is inhibited in the presence of dieldrin; and (5) dieldrin induces the amino acid starvation response. Additionally, we demonstrate that appropriate negative regulation of the Ras/protein kinase A pathway, along with an intact pyruvate dehydrogenase complex, is required for dieldrin tolerance. Many yeast genes described in this study have human orthologs that may modulate dieldrin toxicity in humans.

  11. Endocrine Disruptor Screening Program Reports to Congress

    EPA Pesticide Factsheets

    This page includes EPA reports to congress on pesticide licensing and endocrine disruptor screening activities, Endocrine Disruptor Methods Validation Subcomittee (EDMVS) progress, and Endocrine Disruptor Screening Program (EDSP) implementation progress.

  12. Crosstalk between PKCα and Notch-4 in endocrine-resistant breast cancer cells

    PubMed Central

    Yun, J; Pannuti, A; Espinoza, I; Zhu, H; Hicks, C; Zhu, X; Caskey, M; Rizzo, P; D'Souza, G; Backus, K; Denning, M F; Coon, J; Sun, M; Bresnick, E H; Osipo, C; Wu, J; Strack, P R; Tonetti, D A; Miele, L

    2013-01-01

    The Notch pathway is functionally important in breast cancer. Notch-1 has been reported to maintain an estrogen-independent phenotype in estrogen receptor α (ERα)+ breast cancer cells. Notch-4 expression correlates with Ki67. Notch-4 also plays a key role in breast cancer stem-like cells. Estrogen-independent breast cancer cell lines have higher Notch activity than estrogen-dependent lines. Protein kinase Cα (PKCα) overexpression is common in endocrine-resistant breast cancers and promotes tamoxifen (TAM)-resistant growth in breast cancer cell lines. We tested whether PKCα overexpression affects Notch activity and whether Notch signaling contributes to endocrine resistance in PKCα-overexpressing breast cancer cells.Analysis of published microarray data from ERα+ breast carcinomas shows that PKCα expression correlates strongly with Notch-4. Real-time reverse transcription PCR and immunohistochemistry on archival specimens confirmed this finding. In a PKCα-overexpressing, TAM-resistant T47D model, PKCα selectively increases Notch-4, but not Notch-1, expression in vitro and in vivo. This effect is mediated by activator protein-1 (AP-1) occupancy of the Notch-4 promoter. Notch-4 knockdown inhibits estrogen-independent growth of PKCα-overexpressing T47D cells, whereas Notch-4IC expression stimulates it. Gene expression profiling shows that multiple genes and pathways associated with endocrine resistance are induced in Notch-4IC- and PKCα-expressing T47D cells. In PKCα-overexpressing T47D xenografts, an orally active γ-secretase inhibitor at clinically relevant doses significantly decreased estrogen-independent tumor growth, alone and in combination with TAM. In conclusion, PKCα overexpression induces Notch-4 through AP-1. Notch-4 promotes estrogen-independent, TAM-resistant growth and activates multiple pathways connected with endocrine resistance and chemoresistance. Notch inhibitors should be clinically evaluated in PKCα- and Notch-4-overexpressing

  13. Endocrine disrupters and female reproductive health.

    PubMed

    McLachlan, John A; Simpson, Erica; Martin, Melvenia

    2006-03-01

    There is growing evidence of the impact of estrogenic contaminants in the environment. Studies have shown that male fish in detergent-contaminated water express female characteristics, turtles are sex-reversed by polychlorinated biphenyls (PCBs), male frogs exposed to a common herbicide form multiple ovaries, pseudohermaphroditic offspring are produced by polar bears, and seals in contaminated water have an excess of uterine fibroids. Endocrine-disrupting chemicals (those found in the external environment that can mimic or inhibit endogenous hormones) mostly exhibit estrogenic effects, but a few are anti-estrogenic or anti-androgenic. Many of these compounds are industrial contaminants, such as pesticides and plasticizers, and others are natural phytoestrogens found in plants such as soy and in herbal supplements. Recent work shows that human development can also be feminized by exposure to estrogenic chemicals. Estrogen is the key hormone in the initiation (puberty) and the end (menopause) of reproductive life in women and thus of considerable importance in women's health. The same chemicals that affect wildlife may affect breast growth and lactation, and could have a role in uterine diseases such as fibroids and endometriosis. New studies provide a mechanism of action for estrogenic chemicals and other endocrine disrupters at the molecular level (called epigenetics) that may help explain the long-term effects of endocrine disruption.

  14. Human skin: an independent peripheral endocrine organ.

    PubMed

    Zouboulis, C C

    2000-01-01

    The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth

  15. Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

    PubMed

    Grove, Tyler B; Tso, Ivy F; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Ellingrod, Vicki L; McInnis, Melvin G; Deldin, Patricia J

    2016-09-30

    Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms.

  16. Positive Affect in the Midst of Distress: Implications for Role Functioning

    PubMed Central

    Moskowitz, Judith Tedlie; Shmueli-Blumberg, Dikla; Acree, Michael; Folkman, Susan

    2012-01-01

    Stress has been shown to deplete the self-regulation resources hypothesized to facilitate effective role functioning. However, recent research suggests that positive affect may help to replenish these vital self-regulation resources. Based on revised Stress and Coping theory and the Broaden-and-Build theory of positive emotion, three studies provide evidence of the potential adaptive function of positive affect in the performance of roles for participants experiencing stress. Participants were students (Study 1), caregivers of ill children (Study 2), and individuals recently diagnosed with HIV (Study 3). In cross sectional analyses, using role functioning as an indicator of self-regulation performance, we found that positive affect was significantly correlated with better self regulation performance, independent of the effects of negative affect. The effects were not as strong longitudinally, however, and there was little evidence of a reciprocal association between increases in positive affect and improvements in role functioning over time. The results provide some modest support for hypotheses stemming from the Broaden and Build model of positive emotion and revised Stress and Coping theory, both of which argue for unique adaptive functions of positive affect under stressful conditions. PMID:23175617

  17. Trauma and the endocrine system.

    PubMed

    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.

  18. Sun lotion chemicals as endocrine disruptors.

    PubMed

    Maipas, Sotirios; Nicolopoulou-Stamati, Polyxeni

    2015-01-01

    Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard.

  19. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  20. Phenyl-functionalized magnetic palm-based powdered activated carbon for the effective removal of selected pharmaceutical and endocrine-disruptive compounds.

    PubMed

    Wong, Kien Tiek; Yoon, Yeomin; Snyder, Shane A; Jang, Min

    2016-06-01

    Triethoxyphenylsilane (TEPS)-functionalized magnetic palm-based powdered activated carbon (MPPAC-TEPS) was prepared and characterized using various spectroscopic methods, and then tested for the removal of bisphenol A, carbamazepine, ibuprofen and clofibric acid. Magnetite film on MPPAC-TEPS was homogeneously coated on the outer surface of palm-based powdered activated carbon (PPAC) through a hydrothermal co-precipitation technique. Followed by silanization of phenyl-functionalized organosilane on MPPAC's magnetic film. As results, micro/mesopore surface area and volume increased without significant pore clogging and iron (Fe) dissolution under the acidic conditions was greatly decreased. The unique structural and chemical features of MPPAC-TEPS were found to be the main reasons for the enhanced adsorption rates and removal capacities of POPs. The presence of electrolytes and different pH values greatly affected the sorption efficiencies. The dominant sorption mechanism of POPs by MPPAC-TEPS was determined to be π-π interaction (physisorption), based on thermodynamic (ΔG°) and differential scanning calorimetry (DSC). Thermal regeneration at a low temperature (350 °C) was an effective method to desorb the retained POPs and enabled to reactivate MPPAC-TEPS with sustained sorption rates and capacities, whereas PPAC was largely exhausted. As a new type of sorbent for POPs, MPPAC-TEPS has operational advantages, such as magnetic separation and stable regeneration.

  1. Early effects of liver regeneration on endocrine pancreas: in vivo change in islet morphology and in vitro assessment of systemic effects on β-cell function and viability in the rat model of two-thirds hepatectomy.

    PubMed

    Moreau, F; Seyfritz, E; Toti, F; Sigrist, S; Bietigier, W; Pinget, M; Kessler, L

    2014-12-01

    Liver and pancreas share key roles in glucose homeostasis. Liver regeneration is associated with systemic modifications and depends especially on pancreatic hormones. The aim of the study was to investigate the role of systemic factors released after two-thirds hepatectomy (2/3H) on early possible consequences of liver regeneration on endocrine pancreas structure and function. The pancreas and serum were harvested 1, 2, or 3 days after 2/3H or sham operation in Lewis rats. The HGF and VEGF serum concentrations and plasma microparticles levels were measured. The fate of endocrine pancreas was examined through islets histomorphometry and function in sham and 2/3H rats. β-Cell line RIN-m5F viability was assessed after 24 h of growth in media supplemented with 10% serum from 2/3H or sham rats instead of FCS. Three days after surgery, the pancreas was heavier in 2/3H compared to sham rats (0.56 vs. 0.40% of body weight, p < 0.05) and the proportion of islets of intermediate size was lower in 2/3H rats (5 vs. 15%, p < 0.05). Compared to Sham, sera obtained 3 days after hepatectomy were more efficient to maintain the viability of RIN-m5F cells (99 vs. 67%, p < 0.01). Three days after surgery, no significant differences in serum HGF, a trend to significant increase in VEGF concentration and a significant increase in microparticles levels, were observed in 2/3H vs. sham rats (9.8 vs. 6.5 nM Phtd Ser Eq., p < 0.05). Liver regeneration is associated with early effects on islets and could influence β-cell viability and function by systemic effect.

  2. The Functional Significance of Affect Recognition, Neurocognition, and Clinical Symptoms in Schizophrenia

    PubMed Central

    Hsiao, Sigmund

    2017-01-01

    Objectives The complex relationship and exact extent of the contribution of plausible indictors to social functional outcome in schizophrenia remain unclear. The present study aimed to explore the functional significance of clinical symptoms, neurocognition, and affect recognition simultaneously in schizophrenia. Methods The clinical symptoms, basic neurocognition, facial emotion recognition, and social functioning of 154 subjects, including 74 with schizophrenia and 80 nonclinical comparisons, were assessed. Results We observed that various subdomains of social functioning were extensively related to general intelligence, basic neurocognition, facial emotion recognition, and clinical symptoms, with different association patterns. Multivariate regression analyses revealed that years of education, age, sustained attention, working memory, and facial emotion recognition were significantly associated with global social functioning in schizophrenia. Conclusion Our findings suggest that affect recognition combined with nonsocial neurocognition demonstrated a crucial role in predicting global social function in schizophrenia. PMID:28099444

  3. Morpho-functional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure.

    PubMed

    Manojlović-Stojanoski, Milica N; Filipović, Branko R; Nestorović, Nataša M; Šošić-Jurjević, Branka T; Ristić, Nataša M; Trifunović, Svetlana L; Milošević, Verica Lj

    2014-06-01

    Thyroid hormones (TH) and glucocorticoids strongly contribute to the maturation of fetal tissues in the preparation for extrauterine life. Influence of maternal dexamethasone (Dx) administration on thyroid glands morpho-functional characteristics of near term rat fetuses was investigated applying unbiased stereology. On the 16th day of pregnancy dams received 1.0mg/Dx/kg/b.w., followed by 0.5mg/Dx/kg/b.w. on the 17th and 18th days of gestation. The control females received the same volume of saline. The volume of fetal thyroid was estimated using Cavalieri's principle; the physical/fractionator design was applied for the determination of absolute number of follicular cells in mitosis and immunohistochemically labeled C cells; C cell volume was measured using the planar rotator. The functional activity of thyroid tissue was provided from thyroglobulin (Tg) and thyroperoxidase (TPO) immunohistochemical staining. Applying these design-based modern stereological methods it was shown that Dx treatment of gravid females led to a significant decrease of fetal thyroid gland volume in 19- and 21-day-old fetuses, due to decreased proliferation of follicular cells. The Tg and TPO immunohistochemistry demonstrated that intensive TH production starts and continues during the examined period in control and Dx-exposed fetuses. Under the influence of Dx the absolute number of C cells was lower in both groups of near term fetuses, although unchanged relation between the two populations of endocrine cells, follicular and C cells suggesting that structural relationships within the gland are preserved. In conclusion maternal glucocorticoid administration at the thyroid gland level exerts growth-inhibitory and maturational promoting effects in near term rat fetuses.

  4. [Acne vulgaris: endocrine aspects].

    PubMed

    Dekkers, O M; Thio, B H; Romijn, J A; Smit, J W A

    2006-06-10

    Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development of acne. The skin contains enzymes that convert precursor hormones to the more potent androgens such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be regulated locally. The effects of androgens on the skin are the result of circulating androgens and enzyme activity in local tissues and androgen receptors. Acne is a clinical manifestation of some endocrine diseases. The polycystic ovary syndrome has the highest prevalence. In women with acne that persists after puberty, in 10-200% of cases polycystic ovary syndrome is later diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the androgen-production (oestrogens) or by blocking the androgen receptor (cyproterone, spironolactone).

  5. Voltage-activated Ca2+ channels and their role in the endocrine function of the pituitary gland in newborn and adult mice

    PubMed Central

    Sedej, Simon; Tsujimoto, Tetsuhiro; Zorec, Robert; Rupnik, Marjan

    2004-01-01

    We have prepared fresh pituitary gland slices from adult and, for the first time, from newborn mice to assess modulation of secretory activity via voltage-activated Ca2+ channels (VACCs). Currents through VACCs and membrane capacitance have been measured with the whole-cell patch-clamp technique. Melanotrophs in newborns were significantly larger than in adults. In both newborn and adult melanotrophs activation of VACCs triggered exocytosis. All pharmacologically isolated VACC types contributed equally to the secretory activity. However, the relative proportion of VACCs differed between newborns and adults. In newborn cells L-type channels dominated and, in addition, an exclusive expression of a toxin-resistant R-type-like current was found. The expression of L-type VACCs was up-regulated by the increased oestrogen levels observed in females, and was even more emphasized in the cells of pregnant females and oestrogen-treated adult male mice. We suggest a general mechanism modulating endocrine secretion in the presence of oestrogen and particularly higher sensitivity to treatments with L-type channel blockers during high oestrogen physiological states. PMID:14724188

  6. Development of a functionalized polymeric ionic liquid monolith for solid-phase microextraction of polar endocrine disrupting chemicals in aqueous samples coupled to high-performance liquid chromatography.

    PubMed

    Feng, Juanjuan; Sun, Min; Bu, Yanan; Luo, Chuannan

    2015-09-01

    Ionic liquids (ILs) have been efficiently used as a "designer sorbent" in sample preparation. A novel 1-(3-aminopropyl)-3-(4-vinylbenzyl)imidazolium 4-styrenesulfonate IL monomer was synthesized and copolymerized with 1,6-di(3-vinylimidazolium) hexane bishexafluorophosphate IL as cross-linking agent to prepare a cross-linked polymeric ionic liquids (PILs) monolith. Coupled to high-performance liquid chromatography (HPLC), the PILs monolith was used as a solid-phase microextraction (SPME) sorbent to extract some polar endocrine disrupting chemical (EDCs) such as estrogens, bisphenol A, and phthalate esters in aqueous samples. Preparation and extraction conditions were investigated and optimized to obtain satisfactory extraction efficiency. Limits of detection (LODs) of the proposed method for three steroid estrogens and bisphenol A were 0.25 and 0.2 μg L(-1), respectively, which were lower than or comparable to some other sample preparation methods. Intra- and inter-day repeatability for all the analytes was 2.2-12%. The monolith-to-monolith repeatability was 7.4-15%. The extraction performance of the method for analysis of target estrogens in treated domestic wastewater was investigated and compared with a dispersive liquid-liquid microextraction (DLLME) method. The proposed SPME method provided better sensitivity and higher resistance to matrix interferences.

  7. Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder Dystonia

    DTIC Science & Technology

    2015-08-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0301 TITLE: Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder...Affected in the Movement Disorder Dystonia 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0301 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT The movement disorder dystonia is characterized by involuntary muscle contractions in the limbs, hands, feet or neck. The aim

  8. FOXO factors and breast cancer: outfoxing endocrine resistance.

    PubMed

    Bullock, M

    2016-02-01

    The majority of metastatic breast cancers cannot be cured and present a major public health problem worldwide. Approximately 70% of breast cancers express the estrogen receptor, and endocrine-based therapies have significantly improved patient outcomes. However, the development of endocrine resistance is extremely common. Understanding the molecular pathways that regulate the hormone sensitivity of breast cancer cells is important to improving the efficacy of endocrine therapy. It is becoming clearer that the PI3K-AKT-forkhead box O (FOXO) signaling axis is a key player in the hormone-independent growth of many breast cancers. Constitutive PI3K-AKT pathway activation, a driver of breast cancer growth, causes down-regulation of FOXO tumor suppressor functions. This review will summarize what is currently known about the role of FOXOs in endocrine-resistance mechanisms. It will also suggest potential therapeutic strategies for the restoration of normal FOXO transcriptional activity.

  9. Role of affective self-regulatory efficacy in diverse spheres of psychosocial functioning.

    PubMed

    Bandura, Albert; Caprara, Gian Vittorio; Barbaranelli, Claudio; Gerbino, Maria; Pastorelli, Concetta

    2003-01-01

    This prospective study with 464 older adolescents (14 to 19 years at Time 1; 16 to 21 years at Time 2) tested the structural paths of influence through which perceived self-efficacy for affect regulation operates in concert with perceived behavioral efficacy in governing diverse spheres of psychosocial functioning. Self-efficacy to regulate positive and negative affect is accompanied by high efficacy to manage one's academic development, to resist social pressures for antisocial activities, and to engage oneself with empathy in others' emotional experiences. Perceived self-efficacy for affect regulation essentially operated mediationally through the latter behavioral forms of self-efficacy rather than directly on prosocial behavior, delinquent conduct, and depression. Perceived empathic self-efficacy functioned as a generalized contributor to psychosocial functioning. It was accompanied by prosocial behavior and low involvement in delinquency but increased vulnerability to depression in adolescent females.

  10. Observing functional actions affects semantic processing of tools: evidence of a motor-to-semantic priming.

    PubMed

    De Bellis, Francesco; Ferrara, Antonia; Errico, Domenico; Panico, Francesco; Sagliano, Laura; Conson, Massimiliano; Trojano, Luigi

    2016-01-01

    Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools' function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool-recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact.

  11. [Endocrine xenoestrogenics disrupters: molecular mechanisms and detection methods].

    PubMed

    Mnif, Wissem; Pillon, Arnaud; Balaguer, Patrick; Bartegi, Aghleb

    2007-01-01

    The attention paid to endocriniens modulators for purpose micropolluants (endocrine disrupters) has been increasingly studied these last years particularly on animals. The results of this study raised big concerns from Doctors and Biologists on the eventual risks human health can face. Indeed, endocrine systems of the body play an essential and pervasive role in both the short- and long-term regulation of metabolic processes. Nutritional, behavioural, and reproductive processes are intricately regulated by endocrine systems, as are growth (including bone growth/remodelling), gut, cardiovascular, and kidney function and responses to all forms of stress. Disorders of any of the endocrine system, involving both over- and under-active hormone secretion, result inevitably in disease, the effects of which may extend to many different organs and functions and are often debilitating or life-threatening. Viewed from this general perspective, the threat posed from environmental chemicals with endocrine activity (either agonist or antagonistic) is potentially serious. However, the fact that humans and wildlife are exposed to such chemicals does not necessarily mean that clinically manifest disturbance of the relevant endocrine system will result, because much depends on the level and duration of exposure and on the timing of exposure. Indeed, a large numbers of environmental estrogens are suspected of altering human health as well as the marine ecosystem balance. The objective of this review is to study the different molecular mechanisms of these xenoestrogenes micropolluants, in order to emphasize their potential risk and to present some of the different experimental methods for their detection.

  12. Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

    PubMed Central

    Lundholm, Jeremy; MacIvor, J. Scott; MacDougall, Zachary; Ranalli, Melissa

    2010-01-01

    Background Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. Methodology/Principal Findings We used a replicated modular extensive (shallow growing- medium) green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. Conclusions/Significance Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or facilitation as mechanisms

  13. New aspects of cadmium as endocrine disruptor.

    PubMed

    Takiguchi, Masufumi; Yoshihara, Shin'ichi

    2006-01-01

    Cadmium (Cd) is an industrial and environmental pollutant that exerts adverse effects on a number of organs in humans and animals. Reproductive organs, such as the testis and placenta, are sensitive to the toxic effects of Cd. In animal experiments, high-dose exposure to Cd induced severe testicular interstitial hemorrhage with edema, and increased incidence of fetal death and placental necrosis. Low-dose exposure to Cd affects steroid synthesis in male and female reproductive organs. In 1998, the Ministry of Environment in Japan listed Cd in the strategy plan SPEED98 as one of the chemicals suspected of having possible endocrine disrupting activity. Recently, it has been shown that Cd has potent estrogen- and androgen-like activities in vivo and in vitro, by directly binding to estrogen and androgen receptors. However, the precise mechanisms underlying the effects of Cd as an endocrine disruptor remain to be elucidated. In this review, we will discuss evidence thus far presented concerning the effects of Cd on the endocrine system.

  14. Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases

    PubMed Central

    Erdöl, Şahin; Sağlam, Halil

    2016-01-01

    Objective: Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Methods: Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013. Results: In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency. Conclusion: Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction. PMID:27086477

  15. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity

    SciTech Connect

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [{sup 3}H]{sub 2}O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks

  16. [Multiple endocrine neoplasia type 2].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2012-04-01

    Multiple endocrine neoplasia type 2 syndrome (MEN-2) is a rare hereditary cancer syndrome with autosomal dominant trait of inheritance. The most characteristic feature of this syndrome is a complete penetrance of medullary thyroid cancer. On the basis of differences in variable expression of pheochromocytomas, hyperparathyroidism, and other clinical features, MEN-2 is divided into three clinical variants, referred to as MEN-2A, MEN-2B and familial medullary thyroid cancer. In the most frequent variant, MEN-2A syndrome, apart from thyroid carcinoma, this syndrome includes also unilateral or bilateral pheochromocytoma and hyperparathyroidism. In less common MEN-2B, medullary thyroid cancer and pheochromocytoma occur together with complex nervous and skeletal abnormalities. Familial medullary thyroid cancer is a variant of MEN-2 in which individuals affected develop only this neoplasm without other manifestations of MEN-2. It is well known that MEN-2 is caused by mutations of different codons of the RET proto-oncogene. The identification of mutations associated with this syndrome has led to genetic testing to identify patients at risk for MEN-2. There is a significant genotype-phenotype correlation, which allows a more individualised approach to the timing of prophylactic thyroidectomy. In this paper, we review the current views on the etiopathogenesis, clinical presentation, diagnosis and treatment of MEN-2.

  17. Purinergic receptors in the endocrine and exocrine pancreas

    PubMed Central

    2007-01-01

    The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In β cells, stimulation of P2Y1 receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y1 receptors, there is also evidence for other P2 and adenosine receptors in β cells (P2Y2, P2Y4, P2Y6, P2X subtypes and A1 receptors) and in glucagon-secreting α cells (P2X7, A2 receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y2, P2Y4, P2Y11, P2X4 and P2X7 receptors could regulate secretion, primarily by affecting Cl− and K+ channels and intracellular Ca2+ signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases. PMID:18368520

  18. Self-conscious affects: their adaptive Functions and relationship to depressive mood.

    PubMed

    Uji, Masayo; Kitamura, Toshinori; Nagata, Toshiaki

    2011-01-01

    This study used a structural equation model to examine the influence of resilience on the four self-conscious affects (guilt-proneness, shame-proneness, externalization, and detachment) assessed in the Test of Self-Conscious Affect-3 (TOSCA-3) and their impact on depressive mood. Our subject population consisted of 447 Japanese university students. The first analysis explored which TOSCA-3 affects help an individual adapt to stressful situations. The concept of "resilience" was used as an indicator to evaluate the adaptive functions. We based this on the assumption that an individual with higher resilience is able to use more adaptive affects. In the second analysis, taking the above relationship between resilience and the self-conscious affects into consideration, we examined how those variables as well as a negative life event are related to depressive mood. To assess the resilience level and depressive mood, we adopted the Resilience Scale (RS) and Self-rating Depressive Scale (SDS), respectively. The first analysis showed that the more resilient an individual was, the more prone they were to "detachment" and the less "shame" they experienced. The level of resilience did not have a significant effect on "guilt" or "externalization." In the second analysis we found that "resilience" had a direct inverse effect on depressive mood that was also mediated by "shame" and "detachment." We discuss how the particular self-conscious affects comprising each adaptive function are related to depressive mood.

  19. Handgrip Strength, Positive Affect, and Perceived Health Are Prospectively Associated with Fewer Functional Limitations among Centenarians

    ERIC Educational Resources Information Center

    Franke, Warren D.; Margrett, Jennifer A.; Heinz, Melinda; Martin, Peter

    2012-01-01

    This study assessed the association between perceived health, fatigue, positive and negative affect, handgrip strength, objectively measured physical activity, body mass index, and self-reported functional limitations, assessed 6 months later, among 11 centenarians (age = 102 plus or minus 1). Activities of daily living, assessed 6 months prior to…

  20. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  1. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    McMahon, Camilla M.; Henderson, Heather A.; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2016-01-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical…

  2. The effect of affective bibliotherapy on clients' functioning in group therapy.

    PubMed

    Shechtman, Zipora; Nir-Shfrir, Rivka

    2008-01-01

    Abstract The effect of affective group bibliotherapy (GB) was compared to affective group therapy (GT) on patients' functioning in therapy and their session impression. Three small groups totaling twenty-five in-patients in a hospital in Israel participated in the study. Clients concurrently participated in both group types, undergoing three sessions in each condition. In-therapy behaviors were assessed through the Client Behavior System (CBS; Hill & O'Brien, 1999). Results indicated that in the GB condition compared to the GT condition, clients showed less resistance, used simple responses less frequently, and expressed greater affective exploration. The Session Evaluation Questionnaire (SEQ; Stiles et al., 1994) was used to measure clients' impressions of the sessions. Results indicated that patients evaluated the two treatment conditions equally. Overall, the results support earlier findings, suggesting that affective bibliotherapy can be an effective method of treatment.

  3. Use of suppression subtractive hybridization PCR for the development of cDNA arrays for the detection of endocrine disruption in carp (Cyprinus carpio).

    PubMed

    Moens, Lotte N; Soetaert, Anneleen; van der Ven, Karlijn; Del-Favero, Jurgen; De Coen, Wim M

    2007-03-01

    The potential of a variety of xenobiotic compounds to modulate or disrupt the endocrine system of humans and wildlife is now widely recognized. In the present study, we developed a molecular tool for the evaluation of endocrine disruption in common carp (Cyprinus carpio). Suppression Subtractive Hybridization PCR was applied for the isolation of a relevant gene set, consisting of gender- and hormone-responsive gene fragments. This resulted in 398 different gene fragments that were most related to endocrine functioning. To investigate the applicability of this gene collection for studying endocrine disruption in fish, the gender-related genes were spotted on a cDNA macroarray, and expression profiles were generated for 17beta-estradiol (E2) and cortisol. Therefore, fish were injected with these hormones, and after 24 h and 96 h RNA was extracted and used for macroarray hybridizations. E2 exposure resulted in a total of 35 differentially expressed genes, whereas cortisol only affected 3 genes spotted on the macroarray. These results indicate the discriminating power of the developed array, and its usefulness to describe the toxicological mode of action of endocrine disruptive chemicals.

  4. Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

    PubMed Central

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand. PMID:22991565

  5. Weight control, endocrine hormones and cancer prevention.

    PubMed

    King, Brenee; Jiang, Yu; Su, Xiaoyu; Xu, Jianteng; Xie, Linglin; Standard, Joseph; Wang, Weiqun

    2013-05-01

    The prevalence of obesity is increasing which becomes worrisome due to its association with several diseases and certain types of cancers. While weight control through dietary caloric restriction and/or physical activity protects against cancer in animal models, the underlying mechanisms are not fully defined. Weight loss due to negative energy balance is associated with alterations of multiple growth factors and endocrine hormones. The altered hormones and hormone-related functions appear to be responsible for anti-cancer mechanisms. In this review, we summarize the recent studies related to weight loss and the altered endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of adiponectin and glucocorticoids. The potential molecular targets of these hormone-dependent signalling pathways are also discussed. Considering the increasing trends of obesity throughout the world, a better understanding of the underlying mechanisms between body weight, endocrine hormones and cancer risk may lead to novel approaches to cancer prevention and treatment.

  6. The Caenorhabditis Elegans Unc-31 Gene Affects Multiple Nervous System-Controlled Functions

    PubMed Central

    Avery, L.; Bargmann, C. I.; Horvitz, H. R.

    1993-01-01

    We have devised a method for selecting Caenorhabditis elegans mutants that execute feeding motions in the absence of food. One mutation isolated in this way is an allele of the gene unc-31, first discovered by S. Brenner in 1974, because of its effects on locomotion. We find that strong unc-31 mutations cause defects in four functions controlled by the nervous system. Mutant worms are lethargic, feed constitutively, are defective in egg-laying and produce dauer larvae that fail to recover. We discuss two extreme models to explain this pleiotropy: either unc-31 affects one or a few neurons that coordinately control several different functions, or it affects many neurons that independently control different functions. PMID:8325482

  7. Noncoding RNAs in endocrine malignancy.

    PubMed

    Kentwell, Jessica; Gundara, Justin S; Sidhu, Stan B

    2014-05-01

    Only recently has it been uncovered that the mammalian transcriptome includes a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. Among numerous kinds of ncRNAs, short noncoding RNAs, such as microRNAs, have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. Long noncoding RNAs (lncRNAs) have only recently been implicated in playing a key regulatory role in cancer biology. The deregulation of ncRNAs has been demonstrated to have important roles in the regulation and progression of cancer development. In this review, we describe the roles of both short noncoding RNAs (including microRNAs, small nuclear RNAs, and piwi-interacting RNAs) and lncRNAs in carcinogenesis and outline the possible underlying genetic mechanisms, with particular emphasis on clinical applications. The focus of our review includes studies from the literature on ncRNAs in traditional endocrine-related cancers, including thyroid, parathyroid, adrenal gland, and gastrointestinal neuroendocrine malignancies. The current and potential future applications of ncRNAs in clinical cancer research is also discussed, with emphasis on diagnosis and future treatment.

  8. Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients.

    PubMed

    Watanabe, Hazuki; Atsuta, Naoki; Nakamura, Ryoichi; Hirakawa, Akihiro; Watanabe, Hirohisa; Ito, Mizuki; Senda, Jo; Katsuno, Masahisa; Izumi, Yuishin; Morita, Mitsuya; Tomiyama, Hiroyuki; Taniguchi, Akira; Aiba, Ikuko; Abe, Koji; Mizoguchi, Kouichi; Oda, Masaya; Kano, Osamu; Okamoto, Koichi; Kuwabara, Satoshi; Hasegawa, Kazuko; Imai, Takashi; Aoki, Masashi; Tsuji, Shoji; Nakano, Imaharu; Kaji, Ryuji; Sobue, Gen

    2015-06-01

    Our objective was to elucidate the clinical factors affecting functional decline and survival in Japanese amyotrophic lateral sclerosis (ALS) patients. We constructed a multicenter prospective ALS cohort that included 451 sporadic ALS patients in the analysis. We longitudinally utilized the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) as the functional scale, and determined the timing of introduction of a tracheostomy for positive-pressure ventilation and death. A joint modelling approach was employed to identify prognostic factors for functional decline and survival. Age at onset was a common prognostic factor for both functional decline and survival (p < 0.001, p < 0.001, respectively). Female gender (p = 0.019) and initial symptoms, including upper limb weakness (p = 0.010), lower limb weakness (p = 0.008) or bulbar symptoms (p = 0.005), were related to early functional decline, whereas neck weakness as an initial symptom (p = 0.018), non-use of riluzole (p = 0.030) and proximal dominant muscle weakness in the upper extremities (p = 0.01) were related to a shorter survival time. A decline in the ALSFRS-R score was correlated with a shortened survival time (p < 0.001). In conclusion, the factors affecting functional decline and survival in ALS were common in part but different to some extent. This difference has not been previously well recognized but is informative in clinical practice and for conducting trials.

  9. Small but Powerful: Top Predator Local Extinction Affects Ecosystem Structure and Function in an Intermittent Stream

    PubMed Central

    Rodríguez-Lozano, Pablo; Verkaik, Iraima; Rieradevall, Maria; Prat, Narcís

    2015-01-01

    Top predator loss is a major global problem, with a current trend in biodiversity loss towards high trophic levels that modifies most ecosystems worldwide. Most research in this area is focused on large-bodied predators, despite the high extinction risk of small-bodied freshwater fish that often act as apex consumers. Consequently, it remains unknown if intermittent streams are affected by the consequences of top-predators’ extirpations. The aim of our research was to determine how this global problem affects intermittent streams and, in particular, if the loss of a small-bodied top predator (1) leads to a ‘mesopredator release’, affects primary consumers and changes whole community structures, and (2) triggers a cascade effect modifying the ecosystem function. To address these questions, we studied the top-down effects of a small endangered fish species, Barbus meridionalis (the Mediterranean barbel), conducting an enclosure/exclosure mesocosm experiment in an intermittent stream where B. meridionalis became locally extinct following a wildfire. We found that top predator absence led to ‘mesopredator release’, and also to ‘prey release’ despite intraguild predation, which contrasts with traditional food web theory. In addition, B. meridionalis extirpation changed whole macroinvertebrate community composition and increased total macroinvertebrate density. Regarding ecosystem function, periphyton primary production decreased in apex consumer absence. In this study, the apex consumer was functionally irreplaceable; its local extinction led to the loss of an important functional role that resulted in major changes to the ecosystem’s structure and function. This study evidences that intermittent streams can be affected by the consequences of apex consumers’ extinctions, and that the loss of small-bodied top predators can lead to large ecosystem changes. We recommend the reintroduction of small-bodied apex consumers to systems where they have been

  10. Small but powerful: top predator local extinction affects ecosystem structure and function in an intermittent stream.

    PubMed

    Rodríguez-Lozano, Pablo; Verkaik, Iraima; Rieradevall, Maria; Prat, Narcís

    2015-01-01

    Top predator loss is a major global problem, with a current trend in biodiversity loss towards high trophic levels that modifies most ecosystems worldwide. Most research in this area is focused on large-bodied predators, despite the high extinction risk of small-bodied freshwater fish that often act as apex consumers. Consequently, it remains unknown if intermittent streams are affected by the consequences of top-predators' extirpations. The aim of our research was to determine how this global problem affects intermittent streams and, in particular, if the loss of a small-bodied top predator (1) leads to a 'mesopredator release', affects primary consumers and changes whole community structures, and (2) triggers a cascade effect modifying the ecosystem function. To address these questions, we studied the top-down effects of a small endangered fish species, Barbus meridionalis (the Mediterranean barbel), conducting an enclosure/exclosure mesocosm experiment in an intermittent stream where B. meridionalis became locally extinct following a wildfire. We found that top predator absence led to 'mesopredator release', and also to 'prey release' despite intraguild predation, which contrasts with traditional food web theory. In addition, B. meridionalis extirpation changed whole macroinvertebrate community composition and increased total macroinvertebrate density. Regarding ecosystem function, periphyton primary production decreased in apex consumer absence. In this study, the apex consumer was functionally irreplaceable; its local extinction led to the loss of an important functional role that resulted in major changes to the ecosystem's structure and function. This study evidences that intermittent streams can be affected by the consequences of apex consumers' extinctions, and that the loss of small-bodied top predators can lead to large ecosystem changes. We recommend the reintroduction of small-bodied apex consumers to systems where they have been extirpated, to restore

  11. Affective and physiological sexual response patterns: the effects of instructions on sexually functional and dysfunctional men.

    PubMed

    Heiman, J R; Rowland, D L

    1983-01-01

    To more clearly characterize the patterns of cognitive-affective and physiological responses concomitant with male sexual dysfunction, the present study compared 14 sexually dysfunctional and 16 sexually functional men. All individuals listened to two sexually explicit tapes and engaged in a self-generated fantasy, while genital, heart rate and scaled cognitive affective responses were recorded. Two types of instructions, a performance demand set and a non-demand sensate focus set, preceded the erotic tapes in counterbalanced order. As predicted, dysfunctional men showed less genital tumescence to tapes preceded by the demand than the non-demand instructions. Contrary to expectation, functional men showed greater penile tumescence to the tapes preceded by demand instructions. Self-reported sexual arousal did not follow the penile tumescence pattern but instead indicated that the dysfunctional sample was significantly less subjectively aroused to the tapes and fantasy. There were other significant differences between the groups. Dysfunctional men showed greater general psychological distress, as measured by the SCL-90, including elevated somaticism, anxiety and depression scores. During the experimental session, dysfunctional men also evidenced greater awareness of a variety of physiological responses, as well as more negative and fewer positive cognitive-affective states. These data are discussed in terms of the interaction of affective and physiological responses, differences in contextual meanings of instructional sets given the presence of a dysfunction, and theoretical and clinical conceptualizations of male sexual functioning.

  12. Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence.

    PubMed

    Iudicello, Jennifer E; Woods, Steven P; Vigil, Ofilio; Scott, J Cobb; Cherner, Mariana; Heaton, Robert K; Atkinson, J Hampton; Grant, Igor

    2010-08-01

    Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way of data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent, and 58 used MA at least once during the interval period. A total of 38 non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long-term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use MA were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities than the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.

  13. Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas

    PubMed Central

    Dong, P. Duc Si; Provost, Elayne; Leach, Steven D.; Stainier, Didier Y.R.

    2008-01-01

    The mechanisms regulating pancreatic endocrine versus exocrine fate are not well defined. By analyzing the effects of Ptf1a partial loss of function, we uncovered novel roles for this transcription factor in determining pancreatic fates. In a newly identified hypomorphic ptf1a mutant, pancreatic cells that would normally express ptf1a and become exocrine cells, express the endocrine marker Isl1, indicating a cell fate switch. Surprisingly, a milder reduction of Ptf1a leads to an even greater increase of ectopic endocrine cells, suggesting that Ptf1a also plays a role in promoting endocrine development. We propose that low levels of Ptf1a promote endocrine fate, whereas high levels repress endocrine fate and promote exocrine fate. PMID:18519637

  14. Sustained Endocrine Gland-Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension.

    PubMed

    Sergent, Frédéric; Hoffmann, Pascale; Brouillet, Sophie; Garnier, Vanessa; Salomon, Aude; Murthi, Padma; Benharouga, Mohamed; Feige, Jean-Jacques; Alfaidy, Nadia

    2016-07-01

    Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.

  15. An investigation on pharmacy functions and services affecting satisfaction of patients with prescriptions in community pharmacies.

    PubMed

    Sakurai, Hidehiko; Nakajima, Fumio; Tada, Yuichirou; Yoshikawa, Emi; Iwahashi, Yoshiki; Fujita, Kenji; Hayase, Yukitoshi

    2009-05-01

    Various functions expected by patient expects are needed with progress in the system for separation of dispensing and prescribing functions. In this investigation, the relationship between patient satisfaction and pharmacy function were analyzed quantitatively. A questionnaire survey was conducted in 178 community pharmacies. Questions on pharmacy functions and services totaled 87 items concerning information service, amenities, safety, personnel training, etc. The questionnaires for patients had five-grade scales and composed 11 items (observed variables). Based on the results, "the percentage of satisfied patients" was determined. Multivariate analysis was performed to investigate the relationship between patient satisfaction and pharmacy functions or services provided, to confirm patient's evaluation of the pharmacy, and how factors affected comprehensive satisfaction. In correlation analysis, "the number of pharmacists" and "comprehensive satisfaction" had a negative correlation. Other interesting results were obtained. As a results of factor analysis, three latent factors were obtained: the "human factor," "patients' convenience," and "environmental factor," Multiple regression analysis showed that the "human factor" affected "comprehensive satisfaction" the most. Various pharmacy functions and services influence patient satisfaction, and improvement in their quality increases patient satisfaction. This will result in the practice of patient-centered medicine.

  16. Functions and sources of perceived social support among children affected by HIV/AIDS in China.

    PubMed

    Zhao, Guoxiang; Li, Xiaoming; Fang, Xiaoyi; Zhao, Junfeng; Hong, Yan; Lin, Xiuyun; Stanton, Bonita

    2011-06-01

    While the relationship between perceived social support (PSS) and psychosocial well-being has been well documented in the global literature, existing studies also suggest the existence of multiple domains in definition and measurement of PSS. The current study, utilizing data from 1299 rural children affected by HIV/AIDS in central China, examines the relative importance of PSS functional measures (informational/emotional, material/tangible, affectionate, and social interaction) and PSS structural measures (family/relatives, teachers, friends, and significant others) in predicting psychosocial outcomes including internalizing problems, externalizing problems, and educational resilience. Both functional and structural measures of PSS provided reliable measures of related but unique aspects of PSS. The findings of the current study confirmed the previous results that PSS is highly correlated with children's psychosocial well-being and such correlations vary by functions and sources of the PSS as well as different psychosocial outcomes. The findings in the current study suggested the roles of specific social support functions or resources may need to be assessed in relation to specific psychosocial outcome and the context of children's lives. The strong association between PSS and psychosocial outcomes underscores the importance of adequate social support to alleviate stressful life events and improve psychosocial well-being of children affected by HIV/AIDS. Meanwhile, the study findings call for gender and developmentally appropriate and situation-specific social support for children and families affected by HIV/AIDS.

  17. Functional connectivity in the resting brain as biological correlate of the Affective Neuroscience Personality Scales.

    PubMed

    Deris, Nadja; Montag, Christian; Reuter, Martin; Weber, Bernd; Markett, Sebastian

    2017-02-15

    According to Jaak Panksepp's Affective Neuroscience Theory and the derived self-report measure, the Affective Neuroscience Personality Scales (ANPS), differences in the responsiveness of primary emotional systems form the basis of human personality. In order to investigate neuronal correlates of personality, the underlying neuronal circuits of the primary emotional systems were analyzed in the present fMRI-study by associating the ANPS to functional connectivity in the resting brain. N=120 healthy participants were invited for the present study. The results were reinvestigated in an independent, smaller sample of N=52 participants. A seed-based whole brain approach was conducted with seed-regions bilaterally in the basolateral and superficial amygdalae. The selection of seed-regions was based on meta-analytic data on affective processing and the Juelich histological atlas. Multiple regression analyses on the functional connectivity maps revealed associations with the SADNESS-scale in both samples. Functional resting-state connectivity between the left basolateral amygdala and a cluster in the postcentral gyrus, and between the right basolateral amygdala and clusters in the superior parietal lobe and subgyral in the parietal lobe was associated with SADNESS. No other ANPS-scale revealed replicable results. The present findings give first insights into the neuronal basis of the SADNESS-scale of the ANPS and support the idea of underlying neuronal circuits. In combination with previous research on genetic associations of the ANPS functional resting-state connectivity is discussed as a possible endophenotype of personality.

  18. Nanotoxicity: a growing need for study in the endocrine system.

    PubMed

    Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

    2013-05-27

    Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions.

  19. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23.

    PubMed

    Degirolamo, Chiara; Sabbà, Carlo; Moschetta, Antonio

    2016-01-01

    The endocrine fibroblast growth factors (FGFs), FGF19, FGF21 and FGF23, are critical for maintaining whole-body homeostasis, with roles in bile acid, glucose and lipid metabolism, modulation of vitamin D and phosphate homeostasis and metabolic adaptation during fasting. Given these functions, the endocrine FGFs have therapeutic potential in a wide array of chronic human diseases, including obesity, type 2 diabetes, cancer, and kidney and cardiovascular disease. However, the safety and feasibility of chronic endocrine FGF administration has been challenged, and FGF analogues and mimetics are now being investigated. Here, we discuss current knowledge of the complex biology of the endocrine FGFs and assess how this may be harnessed therapeutically.

  20. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    PubMed

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P < 0.01), anxiety (P = 0.05), depression and anxiety (P = 0.03), antisocial personality (P < 0.001), attention-deficit/hyperactivity (AD/H; P < 0.01), hyperactivity-impulsivity (P < 0.01), and aggressive behavior (P = 0.03) were associated with poorer adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety

  1. Clinical and cognitive factors affecting psychosocial functioning in remitted patients with bipolar disorder.

    PubMed

    Konstantakopoulos, G; Ioannidi, N; Typaldou, M; Sakkas, D; Oulis, P

    2016-01-01

    Impaired interpersonal, social, and occupational functioning is very often observed in patients with bipolar disorder, not only at the acute stages of the illness but in remission as well. This finding raises the question of multiple factors that might affect psychosocial functioning in bipolar patients, such as residual subsyndromal symptoms and neuropsychological deficits. Social cognition impairment, especially impaired Theory of Mind (ToM), might also play an important role in bipolar patients' every-day functioning, similarly to what was found in patients with schizophrenia. The present study aimed to investigate the potential effect of clinical and cognitive factors on the psychosocial functioning of patients with bipolar disorder during remission, assessing ToM along with a broad range of basic cognitive functions. Forty-nine patients with bipolar disorder type I in remission and 53 healthy participants were assessed in general intelligence, working memory, attention, speed processing, verbal learning and memory, and executive functions using a comprehensive battery of neuropsychological tests. The Faux Pas Recognition Test was used to assess ToM. The two groups were matched for gender, age and education level. The Hamilton Rating Scale for Depression (HDRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS) were also administered to the patients. Every-day functioning was assessed with the Global Assessment of Functioning (GAF). In order to examine the contribution of many factors in psychosocial functioning, we used hierarchical multiple regression analysis. Bipolar patients presented significant impairment compared to healthy participants in all the basic cognitive functions tested with the exception of verbal memory. Moreover, patients had significant poorer performance than healthy controls in overall psyand cognitive ToM but not in affective ToM as measured by Faux Pas. Psychosocial functioning in patient group was

  2. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    PubMed

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

    2015-09-01

    Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity.

  3. Negative energy balance in a male songbird, the Abert's Towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    PubMed

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

    2015-07-10

    Energy deficiency can suppress reproductive functions in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none has investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's Towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone (T) responsiveness of the HPG axis. Wild-caught birds were either ad libitum-fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma T response to GnRH challenge. Energy deficiency did, however, decrease the plasma T responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting in decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity.

  4. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

    PubMed Central

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

    2015-01-01

    ABSTRACT Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary–gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. PMID:26333925

  5. The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

    PubMed

    Carpenter, Joanne S; Robillard, Rébecca; Lee, Rico S C; Hermens, Daniel F; Naismith, Sharon L; White, Django; Whitwell, Bradley; Scott, Elizabeth M; Hickie, Ian B

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in

  6. Effects of elevated glucocorticoids on reproduction and development: relevance to endocrine disruptor screening.

    PubMed

    Witorsch, Raphael J

    2016-01-01

    This article reviews the influence of the hypothalamo-pituitary-adrenocortical (HPA) axis on mammalian male and female reproduction and development of offspring and its potential impact on the identification of endocrine disruptive chemicals by in vivo assays. In the adult male rat and baboon, stress suppresses testosterone secretion via a direct inhibitory effect of elevated glucocorticoids on Leydig cells. In adult female sheep, stress disrupts reproductive function via multi-stage mechanisms involving glucocorticoid-mediated suppression of LH secretion, LH action on the ovary and the action of estradiol on its target cells (e.g., uterus). While physiological concentrations of endogenous glucocorticoids are supportive of fetal development, excessive glucocorticoids in utero (i.e., maternal stress) adversely affect mammalian offspring by "programing" abnormalities that are primarily manifest postpartum. The influence of stress on reproduction and development can also be mediated by 11β-hydroxysteroid dehydrogenase (HSD), a bi-directional oxidative:reductive pathway, which governs the balance between biologically active (reduced) endogenous glucocorticoid and inactive (oxidized) metabolites. This pathway is mediated primarily by two isozymes, 11β - HSD1 (reductase) and 11β-HSD2 (oxidase) which act both in an intracrine (intracellular) and endocrine (systemic) fashion. The 11β-HSD pathway appears to play a variety of physiological roles in mammalian reproduction and development and is a target for selected xenobiotics. The effects of the HPA axis on mammalian reproduction and development are potential confounders for in vivo bioassays in rodents employed to identify endocrine disruptive chemicals. Accordingly, consideration of the impact of the HPA axis should be incorporated into the design of bioassays for evaluating endocrine disruptors.

  7. Testing two mechanisms by which rational and irrational beliefs may affect the functionality of inferences.

    PubMed

    Bond, F W; Dryden, W; Briscoe, R

    1999-12-01

    This article describes a role playing experiment that examined the sufficiency hypothesis of Rational Emotive Behaviour Therapy (REBT). This proposition states that it is sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the functionality of inferences (FI). Consistent with the REBT literature (e.g. Dryden, 1994; Dryden & Ellis, 1988; Palmer, Dryden, Ellis & Yapp, 1995) results from this experiment showed that rational and irrational beliefs, as defined by REBT, do affect FI. Specifically, results showed that people who hold a rational belief form inferences that are significantly more functional than those that are formed by people who hold an irrational belief. Contrary to REBT theory, the sufficiency hypothesis was not supported. Thus, results indicated that it is not sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the FI. It appears, then, that preferences and musts are not sufficient mechanisms by which rational and irrational beliefs, respectively, affect the FI. Psychotherapeutic implications of these findings are considered.

  8. Chronobiology in the endocrine system.

    PubMed

    Haus, Erhard

    2007-08-31

    Biological signaling occurs in a complex web with participation and interaction of the central nervous system, the autonomous nervous system, the endocrine glands, peripheral endocrine tissues including the intestinal tract and adipose tissue, and the immune system. All of these show an intricate time structure with rhythms and pulsatile variations in multiple frequencies. Circadian (about 24-hour) and circannual (about 1-year) rhythms are kept in step with the cyclic environmental surrounding by the timing and length of the daily light span. Rhythmicity of many endocrine variables is essential for their efficacy and, even in some instances, for the qualitative nature of their effects. Indeed, the continuous administration of certain hormones and their synthetic analogues may show substantially different effects than expected. In the design of drug-delivery systems and treatment schedules involving directly or indirectly the endocrine system, consideration of the human time organization is essential. A large amount of information on the endocrine time structure has accumulated, some of which is discussed in this review.

  9. Endocrine causes of secondary hypertension.

    PubMed

    Sica, Domenic A

    2008-07-01

    Secondary hypertension is common in clinical practice if a broad definition is applied. Various patterns of hypertension exist in the patient with an endocrine source of their disease, including new-onset hypertension in a previously normotensive individual, a loss of blood pressure control in a patient with previously well-controlled blood pressure, and/or labile blood pressure in the setting of either of these 2 patterns. A thorough history and physical exam, which can rule out concomitant medications, alcohol intake, and over-the-counter medication use, is an important prerequisite to the workup for endocrine causes of hypertension. Endocrine forms of secondary hypertension, such as pheochromocytoma and Cushing's disease, are extremely uncommon. Conversely, primary aldosteronism now occurs with sufficient frequency so as to be considered "top of the list" for secondary endocrine causes in otherwise difficult-to-treat or resistant hypertension. Primary aldosteronism can be insidious in its presentation since a supposed hallmark finding, hypokalemia, may be variable in its presentation. It is important to identify secondary causes of hypertension that are endocrine in nature because surgical intervention may result in correction or substantial improvement of the hypertension.

  10. Risk assessment of 'endocrine substances': guidance on identifying endocrine disruptors.

    PubMed

    Lewis, Richard W

    2013-12-16

    The European regulation on plant protection products (1107/2009) and other related legislation only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. This legislation would appear to make the assumption that endocrine active chemicals should be managed differently from other chemicals presumably due to an assumed lack of a threshold for adverse effects. In the absence of agreed scientific criteria and guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation, a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The first ECETOC technical report and associated workshop, held in 2009, presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. Both sets of data (evidence of the adverse effect in apical studies and conclusive mode of action knowledge) are essential in order to correctly identify endocrine disruption according to accepted definitions. As the legislation seeks to regulate chemicals on a mode of action rather than the more traditional approach of adverse endpoints, then conclusive evidence of the mode of action of concern

  11. Associations between early adrenarche, affective brain function and mental health in children.

    PubMed

    Whittle, Sarah; Simmons, Julian G; Byrne, Michelle L; Strikwerda-Brown, Cherie; Kerestes, Rebecca; Seal, Marc L; Olsson, Craig A; Dudgeon, Paul; Mundy, Lisa K; Patton, George C; Allen, Nicholas B

    2015-09-01

    Early timing of adrenarche, associated with relatively high levels of Dehydroepiandrosterone (DHEA) in children, has been associated with mental health and behavioral problems. However, little is known about effects of adreneracheal timing on brain function. The aim of this study was to investigate the effects of early adrenarche (defined by high DHEA levels independent of age) on affective brain function and symptoms of psychopathology in late childhood (N = 83, 43 females, M age 9.53 years, s.d. 0.34 years). Results showed that higher DHEA levels were associated with decreased affect-related brain activity (i) in the mid-cingulate cortex in the whole sample, and (ii) in a number of cortical and subcortical regions in female but not male children. Higher DHEA levels were also associated with increased externalizing symptoms in females, an association that was partly mediated by posterior insula activation to happy facial expressions. These results suggest that timing of adrenarche is an important moderator of affect-related brain function, and that this may be one mechanism linking early adrenarche to psychopathology.

  12. Associations between early adrenarche, affective brain function and mental health in children

    PubMed Central

    Whittle, Sarah; Simmons, Julian G.; Byrne, Michelle L.; Strikwerda-Brown, Cherie; Kerestes, Rebecca; Seal, Marc L.; Olsson, Craig A.; Dudgeon, Paul; Mundy, Lisa K.; Patton, George C.

    2015-01-01

    Early timing of adrenarche, associated with relatively high levels of Dehydroepiandrosterone (DHEA) in children, has been associated with mental health and behavioral problems. However, little is known about effects of adreneracheal timing on brain function. The aim of this study was to investigate the effects of early adrenarche (defined by high DHEA levels independent of age) on affective brain function and symptoms of psychopathology in late childhood (N = 83, 43 females, M age 9.53 years, s.d. 0.34 years). Results showed that higher DHEA levels were associated with decreased affect-related brain activity (i) in the mid-cingulate cortex in the whole sample, and (ii) in a number of cortical and subcortical regions in female but not male children. Higher DHEA levels were also associated with increased externalizing symptoms in females, an association that was partly mediated by posterior insula activation to happy facial expressions. These results suggest that timing of adrenarche is an important moderator of affect-related brain function, and that this may be one mechanism linking early adrenarche to psychopathology. PMID:25678548

  13. Verbal marking of affect by children with Asperger Syndrome and high functioning autism during spontaneous interactions with family members.

    PubMed

    Müller, Eve; Schuler, Adriana

    2006-11-01

    Verbal marking of affect by older children with Asperger Syndrome (AS) and high functioning autism (HFA) during spontaneous interactions is described. Discourse analysis of AS and HFA and typically developing children included frequency of affective utterances, affective initiations, affective labels and affective explanations, attribution of affective responses to self and others, and positive and negative markers of affect. Findings indicate that children with AS and HFA engaged in a higher proportion of affect marking and provided a higher proportion of affective explanations than typically developing children, yet were less likely to initiate affect marking sequences or talk about the affective responses of others. No significant differences were found between groups in terms of the marking of positive and negative affect.

  14. Endocrine regulation of male fertility by the skeleton

    PubMed Central

    Oury, Franck; Sumara, Grzegorz; Sumara, Olga; Ferron, Mathieu; Chang, Haixin; Smith, Charles E.; Hermo, Louis; Suarez, Susan; Roth, Bryan L.; Ducy, Patricia; Karsenty, Gerard

    2011-01-01

    Although the endocrine capacity of bone is widely recognized, interactions between bone and the reproductive system have until now focused on the gonads as a regulator of bone remodeling. We now show that in males, bone acts as a regulator of fertility. Using co-culture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, while they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function. By binding to a G-protein coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymes required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin, and provides the first evidence that the skeleton is an endocrine regulator of reproduction. PMID:21333348

  15. Single-cell approaches for molecular classification of endocrine tumors

    PubMed Central

    Koh, James; Allbritton, Nancy L.; Sosa, Julie A.

    2015-01-01

    Purpose of review In this review, we summarize recent developments in single-cell technologies that can be employed for the functional and molecular classification of endocrine cells in normal and neoplastic tissue. Recent findings The emergence of new platforms for the isolation, analysis, and dynamic assessment of individual cell identity and reactive behavior enables experimental deconstruction of intratumoral heterogeneity and other contexts, where variability in cell signaling and biochemical responsiveness inform biological function and clinical presentation. These tools are particularly appropriate for examining and classifying endocrine neoplasias, as the clinical sequelae of these tumors are often driven by disrupted hormonal responsiveness secondary to compromised cell signaling. Single-cell methods allow for multidimensional experimental designs incorporating both spatial and temporal parameters with the capacity to probe dynamic cell signaling behaviors and kinetic response patterns dependent upon sequential agonist challenge. Summary Intratumoral heterogeneity in the provenance, composition, and biological activity of different forms of endocrine neoplasia presents a significant challenge for prognostic assessment. Single-cell technologies provide an array of powerful new approaches uniquely well suited for dissecting complex endocrine tumors. Studies examining the relationship between clinical behavior and tumor compositional variations in cellular activity are now possible, providing new opportunities to deconstruct the underlying mechanisms of endocrine neoplasia. PMID:26632769

  16. Endocrine Disorders in Fanconi Anemia: Recommendations for Screening and Treatment

    PubMed Central

    Kanakatti Shankar, Roopa; Giri, Neelam; Hollenberg, Anthony N.; Rutter, Meilan M.; Nathan, Brandon; Lodish, Maya; Alter, Blanche P.; Stratakis, Constantine A.

    2015-01-01

    Context: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention. Evidence Acquisition: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013. Evidence Synthesis: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus. Conclusions: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA. PMID:25575015

  17. Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review)

    PubMed Central

    Del Pup, Lino; Mantovani, Alberto; Cavaliere, Carla; Facchini, Gaetano; Luce, Amalia; Sperlongano, Pasquale; Caraglia, Michele; Berretta, Massimiliano

    2016-01-01

    Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age. PMID:27349723

  18. Endocrine alopecia in a miniature poodle.

    PubMed

    Allan, F J; Jones, B R; Purdie, E C

    1995-06-01

    Hypothyroidism and concurrent sex hormone imbalance associated with alopecia was diagnosed in a 5 year-old entire male Miniature Poodle. The dog had a 3-year history of alopecia, seborrhoea and recurrent superficial pyoderma. Abnormal thyrotropin releasing hormone stimulation test results supported a diagnosis of hypothyroidism. Partial hair regrowth occurred after interstitial cell tumours, which were present in both testicles, were removed by castration. Complete hair regrowth, however, occurred only after thyroid hormone supplementation. This case highlighted difficulties which may be encountered when interpreting serum hormone concentrations and endocrine function tests.

  19. ENDOCRINE DISRUPTORS FROM COMBUSTION AND VEHICULAR EMISSIONS: IDENTIFICATION AND SOURCE NOMINATION

    EPA Science Inventory

    During the last decade, concerns have been raised regarding the possible harmful effects of exposure to certain chemicals that are capable of modulating or disrupting the function of the endocrine system. These chemicals, which are referred to as endocrine disrupting chemicals (E...

  20. Factors Affecting Recovery Time of Pulmonary Function in Hospitalized Patients With Acute Asthma Exacerbations

    PubMed Central

    Kim, Hyo-Jung; Lee, Jaemoon; Kim, Jung-Hyun; Park, So-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom

    2016-01-01

    Purpose Prolonged recovery time of pulmonary function after an asthma exacerbation is a significant burden on asthmatics, and management of these patients needs to be improved. The aim of this study was to evaluate factors associated with a longer recovery time of pulmonary function among asthmatic patients hospitalized due to a severe asthma exacerbation. Methods We retrospectively reviewed the medical records of 89 patients who were admitted for the management of acute asthma exacerbations. The recovery time of pulmonary function was defined as the time from the date each patient initially received treatment for asthma exacerbations to the date the patient reached his or her previous best FEV1% value. We investigated the influence of various clinical and laboratory factors on the recovery time. Results The median recovery time of the patients was 1.7 weeks. Multiple linear regression analysis revealed that using regular inhaled corticosteroids (ICS) before an acute exacerbation of asthma and concurrent with viral infection at admission were associated with the prolonged recovery time of pulmonary function. Conclusions The prolonged recovery time of pulmonary function after a severe asthma exacerbation was not shown to be directly associated with poor adherence to ICS. Therefore the results indicate that an unknown subtype of asthma may be associated with the prolonged recovery of pulmonary function time after an acute exacerbation of asthma despite regular ICS use. Further prospective studies to investigate factors affecting the recovery time of pulmonary function after an asthma exacerbation are warranted. PMID:27582400

  1. Endocrine disrupters and menopausal health.

    PubMed

    Holmes, Philip; Rumsby, Paul; Harrison, Paul T C

    2004-06-01

    Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

  2. EVALUATION OF METHOXYCHLOR AS AN ENDOCRINE DISRUPTOR IN FATHEAD MINNOWS (PIMEPHALES PROMELAS)

    EPA Science Inventory

    Recent concerns over the possible effects of endocrine-disrupting chemicals (EDCs) on humans and wildlife has resulted in considerable interest in environmental contaminants that adversely affect aspects of sexual reproduction and early development. The U.S. Environmental Protect...

  3. Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

    PubMed

    Bechard, Matthew E; Bankaitis, Eric D; Hipkens, Susan B; Ustione, Alessandro; Piston, David W; Yang, Yu-Ping; Magnuson, Mark A; Wright, Christopher V E

    2016-08-15

    The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis.

  4. The protective function of personal growth initiative among a genocide-affected population in Rwanda.

    PubMed

    Blackie, Laura E R; Jayawickreme, Eranda; Forgeard, Marie J C; Jayawickreme, Nuwan

    2015-07-01

    The aim of the current study was to investigate the extent to which individual differences in personal growth initiative (PGI) were associated with lower reports of functional impairment of daily activities among a genocide-affected population in Rwanda. PGI measures an individual's motivation to develop as a person and the extent to which he or she is active in setting goals that work toward achieving self-improvement. We found that PGI was negatively associated with functional impairment when controlling for depression, posttraumatic stress disorder, and other demographic factors. Our results suggest that PGI may constitute an important mindset for facilitating adaptive functioning in the aftermath of adversity and in the midst of psychological distress, and as such they might have practical applications for the development of intervention programs.

  5. Developing fragility functions for the areas affected by the 2009 Samoa earthquake and tsunami

    NASA Astrophysics Data System (ADS)

    Gokon, H.; Koshimura, S.; Imai, K.; Matsuoka, M.; Namegaya, Y.; Nishimura, Y.

    2014-12-01

    Fragility functions in terms of flow depth, flow velocity and hydrodynamic force are developed to evaluate structural vulnerability in the areas affected by the 2009 Samoa earthquake and tsunami. First, numerical simulations of tsunami propagation and inundation are conducted to reproduce the features of tsunami inundation. To validate the results, flow depths measured in field surveys and waveforms measured by Deep-ocean Assessment and Reporting of Tsunamis (DART) gauges are utilized. Next, building damage is investigated by visually interpreting changes between pre- and post-tsunami high-resolution satellite images. Finally, the data related to tsunami features and building damage are integrated using Geographic Information System (GIS), and tsunami fragility functions are developed based on the statistical analyses. From the developed fragility functions, we quantitatively understood the vulnerability of a coastal region in American Samoa characterized by steep terrains and ria coasts.

  6. Metabolic and endocrine modulation of anabolic and catabolic pathways of glucose and fatty acids. I. Chemical anatomy of the major metabolic pathways of the energogenic general function.

    PubMed

    Belloiu, D D; Belloiu, I

    1986-01-01

    This study is an attempt to integrate the intermediary metabolism of energogenic substrates--glucose and fatty acids--within the framework of the energogenic general function (EGF), which is active in two distinct phases: anabolic and catabolic. EGF is a component of the metabolic general function (MGF), which together with the reproductive general function and the adaptation general function may be taken to represent three main "general functions of organisms" common to all beings, whether animal or vegetal. This initial paper presents, descriptively and graphically, the main anabolic functions and pathways of glucose and fatty acids and, separately, the main catabolic ones, in other words, the "chemical anatomy" of EGF. The study begins with the anabolic "digestive" function of the digestive tract, concerning the digestion and absorption of carbohydrates and proteins. Conversion of the non-absorbable macromolecules of ingested carbohydrates into absorbable micromolecules of glucose, is shown to enable the latter, after absorption, to carry out the two characteristic anabolic processes: transmembrane "transport" and "condensation". Absorption and vehiculation of hydrophobic lipids is carried out by means of the major function of intestinal cells: synthesis of chylomicrons. Chylomicrons are hydrophilic special lipoprotein particles which are able to transport fats to the adipose tissue and cholesterol to the liver. In the liver the anabolic aspects of EGF are represented by two main functions: glycogeno-genesis, i.e. "non-reductive" condensation of glucose into glycogen stores, and lipoproteino-genesis, i.e. "reductive" condensation of glucose into lipoproteins or VLDL (very low density lipoproteins). VLDL are hydrophilic (vehiculable) spheric particles (containing triacylglycerols and cholesteryl esters in their core, and phospholipids, cholesterol and apolipoprotein-B at their surface), which are to be released into the general circulation. The anabolic phase in

  7. The Intersection of Neurotoxicology and Endocrine Disruption

    PubMed Central

    Weiss, Bernard

    2012-01-01

    Endocrine disruption, the guiding theme of the 27th International Neurotoxicology Conference, merged into the neurotoxicology agenda largely because hormones help steer the process of brain development. Although the disruption motif first attracted public health attention because of reproductive anomalies in both wildlife and humans, the neurobehavioral implications had been planted decades earlier. They stemmed from the principle that sex differences in behavior are primarily the outcomes of differences in how the brain is sexually differentiated during early development by gonadal hormones (the Organizational Hypothesis). We also now understand that environmental chemicals are capable of altering these underlying events and processes. Among those chemicals, the group labeled as endocrine disrupting chemicals (EDCs) offers the clearest evidence of such selectivity, a consequence of their actions on the endogenous sex steroids, androgens and estrogens. Two EDCs in particular offer useful and intriguing examples. One is phthalate esters. The other is bisphenol A. Both agents are used extensively in plastics manufacture, and are pervasive in the environment. Both are produced in immense quantities. Both are found in almost all humans. Phthalates are considered to function in essence as anti-androgens, while bisphenol A is labeled as an estrogen. Their associations with brain sexual differentiation are reviewed and further questions noted. Both EDCs produce a wider spectrum of health effects, however, than would be extrapolated simply from their properties as anti-androgens and estrogens. Obesity is one example. Further complicating their assessment as health risks are questions about nonmonotonic dose-response functions and about transgenerational effects incurred via epigenetic mechanisms. All these facets of endocrine disruption are pieces of a puzzle that challenge neurotoxicologists for solutions. PMID:22659293

  8. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

  9. Bariatric Surgery and the Endocrine System

    MedlinePlus

    ... Bariatric Surgery and the Endocrine System Fact Sheet Bariatric Surgery and the Endocrine System February, 2012 Download PDFs ... John Morton, MD Marzieh Salehi, MD What is bariatric surgery? Bariatric surgery helps people who are very obese ...

  10. Arrival order among native plant functional groups does not affect invasibility of constructed dune communities.

    PubMed

    Mason, T J; French, K; Jolley, D

    2013-10-01

    Different arrival order scenarios of native functional groups to a site may influence both resource use during development and final community structure. Arrival order may then indirectly influence community resistance to invasion. We present a mesocosm experiment of constructed coastal dune communities that monitored biotic and abiotic responses to different arrival orders of native functional groups. Constructed communities were compared with unplanted mesocosms. We then simulated a single invasion event by bitou (Chrysanthemoides monilifera ssp. rotundata), a dominant exotic shrub of coastal communities. We evaluated the hypothesis that plantings with simultaneous representation of grass, herb and shrub functional groups at the beginning of the experiment would more completely sequester resources and limit invasion than staggered plantings. Staggered plantings in turn would offer greater resource use and invasion resistance than unplanted mesocosms. Contrary to our expectations, there were few effects of arrival order on abiotic variables for the duration of the experiment and arrival order was unimportant in final community invasibility. All planted mesocosms supported significantly more invader germinants and significantly less invader abundance than unplanted mesocosms. Native functional group plantings may have a nurse effect during the invader germination and establishment phase and a competitive function during the invader juvenile and adult phase. Arrival order per se did not affect resource use and community invasibility in our mesocosm experiment. While grass, herb and shrub functional group plantings will not prevent invasion success in restored communities, they may limit final invader biomass.

  11. Does increased physical activity in school affect children's executive function and aerobic fitness?

    PubMed

    Kvalø, S E; Bru, E; Brønnick, K; Dyrstad, S M

    2017-02-16

    This study seeks to explore whether increased PA in school affects children's executive function and aerobic fitness. The "Active school" study was a 10-month randomized controlled trial. The sample included 449 children (10-11 years old) in five intervention and four control schools. The weekly interventions were 2×45 minutes physically active academic lessons, 5×10 minutes physically active breaks, and 5×10 minutes physically active homework. Aerobic fitness was measured using a 10-minute interval running test. Executive function was tested using four cognitive tests (Stroop, verbal fluency, digit span, and Trail Making). A composite score for executive function was computed and used in analyses. Mixed ANCOVA repeated measures were performed to analyze changes in scores for aerobic fitness and executive function. Analysis showed a tendency for a time×group interaction on executive function, but the results were non-significant F(1, 344)=3.64, P=.057. There was no significant time×group interaction for aerobic fitness. Results indicate that increased physical activity in school might improve children's executive function, even without improvement in aerobic fitness, but a longer intervention period may be required to find significant effects.

  12. The association between the body composition and lifestyle affecting pulmonary function in Japanese workers.

    PubMed

    Inomoto, Atsushi; Fukuda, Rika; Deguchi Phn, Junko; Kato, Gohei; Kanzaki Rpt, Ryoko; Hiroshige Rpt, Keiichi; Nakamura, Kouichi; Rpt; Nakano Rpt, Keisuke; Toyonaga, Toshihiro

    2016-10-01

    [Purpose] The purpose of this study was to identify factors related to physical characteristics and lifestyle that affect pulmonary function. [Subjects and Methods] Ninety seven healthy male workers were recruited for this study, and basic information and details about lifestyle were collected. Body composition analyzer and visceral fat measuring device were conducted as measurements. Pulmonary function was measured using spirometer. A multiple stepwise linear regression analysis was performed with pulmonary function as the dependent variable. Variables with a significant association with pulmonary function on univariate analysis were imputed as independent variables. [Results] Height, fat free mass, upper extremity muscle mass, lower extremity muscle mass, and trunk muscle mass had significant positive correlations with FEV1 and FVC. Age, percentage of body fat, and visceral fat area were negatively correlated with FEV1 and FVC. Regarding the association between pulmonary function and lifestyle, a significant difference was found between the smoking index and the presence or absence of metabolic syndrome risk factors and both FEV1 and FVC. The multiple stepwise linear regression analysis with FEV1 as the dependent variable, adjusted for age and height, revealed that visceral fat area and fat free mass were significantly associated with FEV1. A similar analysis, FVC as the dependent variable identified visceral fat area. [Conclusion] FEV1 was independently associated with visceral fat area and fat free mass. FVC was independently associated with visceral fat area. These results may be valuable in preventing the decrease in respiratory function and, hence, in further preventing the onset of COPD.

  13. Incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis

    PubMed Central

    Dang, Wei; Zhang, Wen; Du, Wei-Guo

    2015-01-01

    Identifying how developmental temperature affects the immune system is critical for understanding how ectothermic animals defend against pathogens and their fitness in the changing world. However, reptiles have received little attention regarding this issue. We incubated eggs at three ecologically relevant temperatures to determine how incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis. When exposed to bacterial infections, hatchlings from 24 °C had lower cumulative mortalities (55%, therefore, higher immunocompetence) than those from 28 °C (85%) or 32 °C (100%). Consistent with higher immunocompetence, hatchlings from low incubation temperature had higher IgM, IgD, and CD3γ expressions than their counterparts from the other two higher incubation temperatures. Conversely, the activity of immunity-related enzymes did not match the among-temperature difference in immune function. Specifically, enzyme activity was higher at intermediate temperatures (alkaline phosphatase) or was not affected by incubation temperature (acid phosphatase, lysozyme). Our study is the first to provide unequivocal evidence (at the molecular and organismal level) about the significant effect of incubation temperature on offspring immunity in reptiles. Our results also indicate that the reduced immunity induced by high developmental temperatures might increase the vulnerability of reptiles to the outbreak of diseases under global warming scenarios. PMID:26028216

  14. Incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis.

    PubMed

    Dang, Wei; Zhang, Wen; Du, Wei-Guo

    2015-06-01

    Identifying how developmental temperature affects the immune system is critical for understanding how ectothermic animals defend against pathogens and their fitness in the changing world. However, reptiles have received little attention regarding this issue. We incubated eggs at three ecologically relevant temperatures to determine how incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis. When exposed to bacterial infections, hatchlings from 24 °C had lower cumulative mortalities (55%, therefore, higher immunocompetence) than those from 28 °C (85%) or 32 °C (100%). Consistent with higher immunocompetence, hatchlings from low incubation temperature had higher IgM, IgD, and CD3γ expressions than their counterparts from the other two higher incubation temperatures. Conversely, the activity of immunity-related enzymes did not match the among-temperature difference in immune function. Specifically, enzyme activity was higher at intermediate temperatures (alkaline phosphatase) or was not affected by incubation temperature (acid phosphatase, lysozyme). Our study is the first to provide unequivocal evidence (at the molecular and organismal level) about the significant effect of incubation temperature on offspring immunity in reptiles. Our results also indicate that the reduced immunity induced by high developmental temperatures might increase the vulnerability of reptiles to the outbreak of diseases under global warming scenarios.

  15. Towards Tunable Consensus Clustering for Studying Functional Brain Connectivity During Affective Processing.

    PubMed

    Liu, Chao; Abu-Jamous, Basel; Brattico, Elvira; Nandi, Asoke K

    2017-03-01

    In the past decades, neuroimaging of humans has gained a position of status within neuroscience, and data-driven approaches and functional connectivity analyses of functional magnetic resonance imaging (fMRI) data are increasingly favored to depict the complex architecture of human brains. However, the reliability of these findings is jeopardized by too many analysis methods and sometimes too few samples used, which leads to discord among researchers. We propose a tunable consensus clustering paradigm that aims at overcoming the clustering methods selection problem as well as reliability issues in neuroimaging by means of first applying several analysis methods (three in this study) on multiple datasets and then integrating the clustering results. To validate the method, we applied it to a complex fMRI experiment involving affective processing of hundreds of music clips. We found that brain structures related to visual, reward, and auditory processing have intrinsic spatial patterns of coherent neuroactivity during affective processing. The comparisons between the results obtained from our method and those from each individual clustering algorithm demonstrate that our paradigm has notable advantages over traditional single clustering algorithms in being able to evidence robust connectivity patterns even with complex neuroimaging data involving a variety of stimuli and affective evaluations of them. The consensus clustering method is implemented in the R package "UNCLES" available on http://cran.r-project.org/web/packages/UNCLES/index.html .

  16. Nonruminant Nutrition Symposium: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract.

    PubMed

    Furness, J B; Poole, D P

    2012-04-01

    The functioning of the gastrointestinal tract is under the control of the most extensive system of peripheral neurons in the body, the enteric nervous system, and the largest endocrine system of the body, the GEP endocrine system. The enteric nervous system in large mammals contains 500 million neurons, and the GEP endocrine system produces more than 30 hormones. Numerous enteric neuropathies affecting both humans and animals have been described and digestive disorders affect commercially important species, such as horses and cattle. The most severe enteric neuropathies (e.g., lethal white syndrome in horses or Hirschsprung's disease in humans) can be fatal. Also, horses with ileus or other digestive disorders are commonly euthanized. In this review we discuss examples of enteric neuropathies that affect agricultural animals and humans: prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea. Enteric neurons and glia are a location of prion proteins and are involved in transmission of the infection from gut to brain and brain to gut. Postoperative ileus is a complex disorder involving the local inhibitory effects of sympathetic nervous system activation and the release of opioids, presumably from enteric neurons. Intestinal inflammation, especially of the external muscle that includes enteric ganglia, also occurs in ileus. Congenital distal bowel aganglionosis, responsible for lethal white syndrome in horses, Hirschsprung's disease in humans, and similar conditions in mice and rats, is a fatal condition if untreated. Mutations of the same genes can cause the condition in each of these species. The only effective current treatment is surgical removal of the aganglionic bowel. Infectious diarrheas involve activation of enteric secretomotor neurons by pathogens and the toxins they produce, which causes substantial fluid loss. Strategies to target enteric neurons in the treatment of secretory diarrheas have not been developed. Disorders

  17. Modulation of α power and functional connectivity during facial affect recognition.

    PubMed

    Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

    2013-04-03

    Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

  18. Endocrine and Metabolic Disorders

    MedlinePlus

    ... Human Services, Health Resources and Services Administration Function Navigation Sitemap | Print PDFs | Women's Health USA 2009 Main Navigation Home Preface & Reader's Guide Introduction Population Characteristics Health ...

  19. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity.

    PubMed

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [(3)H](2)O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks.

  20. Multiple Polymorphisms Affect Expression and Function of the Neuropeptide S Receptor (NPSR1)

    PubMed Central

    Anedda, Francesca; Zucchelli, Marco; Schepis, Danika; Hellquist, Anna; Corrado, Lucia; D'Alfonso, Sandra; Achour, Adnane; McInerney, Gerald; Bertorello, Alejandro; Lördal, Mikael; Befrits, Ragnar; Björk, Jan; Bresso, Francesca; Törkvist, Leif; Halfvarson, Jonas

    2011-01-01

    Background neuropeptide S (NPS) and its receptor NPSR1 act along the hypothalamic-pituitary-adrenal axis to modulate anxiety, fear responses, nociception and inflammation. The importance of the NPS-NPSR1 signaling pathway is highlighted by the observation that, in humans, NPSR1 polymorphism associates with asthma, inflammatory bowel disease, rheumatoid arthritis, panic disorders, and intermediate phenotypes of functional gastrointestinal disorders. Because of the genetic complexity at the NPSR1 locus, however, true causative variations remain to be identified, together with their specific effects on receptor expression or function. To gain insight into the mechanisms leading to NPSR1 disease-predisposing effects, we performed a thorough functional characterization of all NPSR1 promoter and coding SNPs commonly occurring in Caucasians (minor allele frequency >0.02). Principal Findings we identified one promoter SNP (rs2530547 [−103]) that significantly affects luciferase expression in gene reporter assays and NPSR1 mRNA levels in human leukocytes. We also detected quantitative differences in NPS-induced genome-wide transcriptional profiles and CRE-dependent luciferase activities associated with three NPSR1 non-synonymous SNPs (rs324981 [Ile107Asn], rs34705969 [Cys197Phe], rs727162 [Arg241Ser]), with a coding variant exhibiting a loss-of-function phenotype (197Phe). Potential mechanistic explanations were sought with molecular modelling and bioinformatics, and a pilot study of 2230 IBD cases and controls provided initial support to the hypothesis that different cis-combinations of these functional SNPs variably affect disease risk. Significance these findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance. PMID:22216302

  1. Acidosis and correction of acidosis does not affect rFVIIa function in swine

    PubMed Central

    Darlington, Daniel N; Kheirabadi, Bijan S; Scherer, Michael R; Martini, Wenjun Z; Cap, Andrew P; Dubick, Michael A

    2012-01-01

    Background: Hemorrhagic shock and trauma are associated with acidosis and altered coagulation. A fall in pH has been reported to attenuate the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by hemorrhagic shock or infusion of HCl attenuates FVIIa activity in vivo. The purpose of this study was to determine if acidosis, induced by two methods, affects recombinant FVIIa (rFVIIa) activity in swine, and if correction of the pH restores rFVIIa activity to normal. Methods: Acidosis was induce in anesthetized swine in two separate models: 1) HCl infusion (n=10) and 2) hemorrhage/hypoventilation (n=8). Three groups per model were used: Control (pH7.4), Acidosis (arterial pH7.1) and Acidosis-Corrected (bicarbonate infusion to return pH from 7.1 to 7.4). Pigs were then injected with rFVIIa (90 μg/kg) or vehicle (saline) at target pH and arterial blood samples were taken for measurement of coagulation function, including Thromboelastography -TEG, Thrombin Generation, Activated Clotting Time, Prothrombin Time, activated Partial Thromboplastin Time, Fibrinogen Concentration and Platelet count before and 5min after injection of rFVIIa. Results: Acidosis led to a hypocoagulation as measured by almost all coagulation parameters in both models. Furthermore, the change in coagulation function produced after infusion of rFVIIa was not different between control, acidosis and acidosis-corrected groups for all coagulation parameters measured. Conclusion: Acidosis associated with hemorrhagic shock or HCl infusion led to a hypocoagulation that was not corrected with bicarbonate infusion. Furthermore, acidosis did not affect rFVIIa function, and correction of the acidosis with bicarbonate had no effect on rFVIIa function in these models. This suggests that in vivo acidosis did not diminish rFVIIa function. PMID:23272296

  2. Drug-induced endocrine disorders in the intensive care unit.

    PubMed

    Thomas, Zachariah; Bandali, Farooq; McCowen, Karen; Malhotra, Atul

    2010-06-01

    The neuroendocrine response to critical illness is key to the maintenance of homeostasis. Many of the drugs administered routinely in the intensive care unit significantly impact the neuroendocrine system. These agents can disrupt the hypothalamic-pituitary-adrenal axis, cause thyroid abnormalities, and result in dysglycemia. Herein, we review major drug-induced endocrine disorders and highlight some of the controversies that remain in this area. We also discuss some of the more rare drug-induced syndromes that have been described in the intensive care unit. Drugs that may result in an intensive care unit admission secondary to an endocrine-related adverse event are also included. Unfortunately, very few studies have systematically addressed drug-induced endocrine disorders in the critically ill. Timely identification and appropriate management of drug-induced endocrine adverse events may potentially improve outcomes in the critically ill. However, more research is needed to fully understand the impact of medications on endocrine function in the intensive care unit.

  3. The Functional Effect of Teacher Positive and Neutral Affect on Task Performance of Students with Significant Disabilities

    ERIC Educational Resources Information Center

    Park, Sungho; Singer, George H. S.; Gibson, Mary

    2005-01-01

    The study uses an alternating treatment design to evaluate the functional effect of teacher's affect on students' task performance. Tradition in special education holds that teachers should engage students using positive and enthusiastic affect for task presentations and praise. To test this assumption, we compared two affective conditions. Three…

  4. Endocrine Responses to Resistance Exercise,

    DTIC Science & Technology

    1987-08-30

    jo- Rfe 681 ENDOCRINE RESPONSES TO RESISTANCE EXERCISE(U) RIRMY RESERRCH INST OF ENYIRWUIENTAL MEDICINE NATICK M N J KRRENER 30 RUG 87 USARIEN-R59-B...factors have been shown to influence GH release including gonadal. thyroid and adrenal hormones (32). Whether it is via a direct or indirect mechanism

  5. The Vitamin D Endocrine System.

    ERIC Educational Resources Information Center

    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)

  6. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

    EPA Science Inventory

    For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

  7. Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.

    PubMed

    Stelzer, I; Kröpfl, J M; Fuchs, R; Pekovits, K; Mangge, H; Raggam, R B; Gruber, H-J; Prüller, F; Hofmann, P; Truschnig-Wilders, M; Obermayer-Pietsch, B; Haushofer, A C; Kessler, H H; Mächler, P

    2015-10-01

    Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration.

  8. Cure Kinetics of Epoxy Nanocomposites Affected by MWCNTs Functionalization: A Review

    PubMed Central

    Saeb, Mohammad Reza; Bakhshandeh, Ehsan; Khonakdar, Hossein Ali; Mäder, Edith; Scheffler, Christina; Heinrich, Gert

    2013-01-01

    The current paper provides an overview to emphasize the role of functionalization of multiwalled carbon nanotubes (MWCNTs) in manipulating cure kinetics of epoxy nanocomposites, which itself determines ultimate properties of the resulting compound. In this regard, the most commonly used functionalization schemes, that is, carboxylation and amidation, are thoroughly surveyed to highlight the role of functionalized nanotubes in controlling the rate of autocatalytic and vitrification kinetics. The current literature elucidates that the mechanism of curing in epoxy/MWCNTs nanocomposites remains almost unaffected by the functionalization of carbon nanotubes. On the other hand, early stage facilitation of autocatalytic reactions in the presence of MWCNTs bearing amine groups has been addressed by several researchers. When carboxylated nanotubes were used to modify MWCNTs, the rate of such reactions diminished as a consequence of heterogeneous dispersion within the epoxy matrix. At later stages of curing, however, the prolonged vitrification was seen to be dominant. Thus, the type of functional groups covalently located on the surface of MWCNTs directly affects the degree of polymer-nanotube interaction followed by enhancement of curing reaction. Our survey demonstrated that most widespread efforts ever made to represent multifarious surface-treated MWCNTs have not been directed towards preparation of epoxy nanocomposites, but they could result in property synergism. PMID:24348181

  9. Exposure to endocrine disrupting chemicals and neurodevelopmental alterations.

    PubMed

    Pinson, A; Bourguignon, J P; Parent, A S

    2016-07-01

    The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling.

  10. Endocrine disruption: fact or urban legend?

    PubMed

    Nohynek, Gerhard J; Borgert, Christopher J; Dietrich, Daniel; Rozman, Karl K

    2013-12-16

    Endocrine disruptors (EDs) are substances that cause adverse health effects via endocrine-mediated mechanisms in an intact organism or its progeny or (sub) populations. Purported EDCs in personal care products include 4-MBC (UV filter) or parabens that showed oestrogenic activity in screening tests, although regulatory toxicity studies showed no adverse effects on reproductive endpoints. Hormonal potency is the key issue of the safety of EDCs. Oestrogen-based drugs, e.g. the contraceptive pill or the synthetic oestrogen DES, possess potencies up to 7 orders of magnitude higher than those of PCP ingredients; yet, in utero exposure to these drugs did not adversely affect fertility or sexual organ development of offspring unless exposed to extreme doses. Additive effects of EDs are unlikely due to the multitude of mechanisms how substances may produce a hormone-like activity; even after uptake of different substances with a similar mode of action, the possibility of additive effects is reduced by different absorption, metabolism and kinetics. This is supported by a number of studies on mixtures of chemical EDCs. Overall, despite of 20 years of research a human health risk from exposure to low concentrations of exogenous chemical substances with weak hormone-like activities remains an unproven and unlikely hypothesis.

  11. Ecosystem structure, function, and composition in rangelands are negatively affected by livestock grazing.

    PubMed

    Eldridge, David J; Poore, Alistair G B; Ruiz-Colmenero, Marta; Letnic, Mike; Soliveres, Santiago

    2016-06-01

    Reports of positive or neutral effects of grazing on plant species richness have prompted calls for livestock grazing to be used as a tool for managing land for conservation. Grazing effects, however, are likely to vary among different response variables, types, and intensity of grazing, and across abiotic conditions. We aimed to examine how grazing affects ecosystem structure, function, and composition. We compiled a database of 7615 records reporting an effect of grazing by sheep and cattle on 278 biotic and abiotic response variables for published studies across Australia. Using these data, we derived three ecosystem measures based on structure, function, and composition, which were compared against six contrasts of grazing pressure, ranging from low to heavy, two different herbivores (sheep, cattle), and across three different climatic zones. Grazing reduced structure (by 35%), function (24%), and composition (10%). Structure and function (but not composition) declined more when grazed by sheep and cattle together than sheep alone. Grazing reduced plant biomass (40%), animal richness (15%), and plant and animal abundance, and plant and litter cover (25%), but had no effect on plant richness nor soil function. The negative effects of grazing on plant biomass, plant cover, and soil function were more pronounced in drier environments. Grazing effects on plant and animal richness and composition were constant, or even declined, with increasing aridity. Our study represents a comprehensive continental assessment of the implications of grazing for managing Australian rangelands. Grazing effects were largely negative, even at very low levels of grazing. Overall, our results suggest that livestock grazing in Australia is unlikely to produce positive outcomes for ecosystem structure, function, and composition or even as a blanket conservation tool unless reduction in specific response variables is an explicit management objective.

  12. Diagnosis and management of endocrine gland neoplasmas. Revision 1

    SciTech Connect

    Weller, R.E.

    1994-03-01

    Functional and nonfunctional neoplasms of the endocrine glands constitute some of the more challenging diagnostic and therapeutic problems in veterinary cancer medicine. This discussion will focus on the clinical signs and syndromes associated with neoplasms of the thyroid, adrenal, and parathyroid glands, and pancreas in companion animals and will concentrate on the mechanisms producing the clinical signs, diagnosis, staging, therapy and prognosis.

  13. Endocrine Disruptor Screening Program: Tier I Screening Battery

    EPA Science Inventory

    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...

  14. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    PubMed

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  15. Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions.

    PubMed

    Levade, Marie; David, Elodie; Garcia, Cédric; Laurent, Pierre-Alexandre; Cadot, Sarah; Michallet, Anne-Sophie; Bordet, Jean-Claude; Tam, Constantine; Sié, Pierre; Ysebaert, Loïc; Payrastre, Bernard

    2014-12-18

    The oral Bruton's tyrosine kinase inhibitor, ibrutinib, has recently demonstrated high efficiency in patients with relapsed B-cell malignancies. Occurrence of bleeding events has been reported in a subgroup of ibrutinib-treated patients. We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow. A longitudinal study of 14 patients indicated a correlation between occurrence of bleeding events and decreased platelet aggregation in response to collagen in platelet-rich plasma and firm adhesion on VWF under arterial flow. The addition of 50% untreated platelets was sufficient to efficiently reverse the effects of ibrutinib, and platelet functions recovered after treatment interruption as physiological platelet renewal occurred. These data have important clinical implications and provide a basis for hemostasis management during ibrutinib treatment.

  16. ENDOCRINE DISRUPTIVE ACTIONS OF INHALED BENZO(a)PYRENE ON OVARIAN FUNCTION AND FETAL SURVIVAL IN FISHER F-344 ADULT RATS

    PubMed Central

    Archibong, Anthony E.; Ramesh, Aramandla; Inyang, Frank; Niaz, Mohammad S.; Hood, Darryl B.; Kopsombut, Prapaporn

    2012-01-01

    This study evaluated the effect of inhaled BaP on female reproductive function. Rats were exposed to 50, or 75 or 100 μg BaP/m3, four hours a day for 14 days via inhalation. Plasma E2, P4, LH and FSH concentrations were determined. Ovarian BaP metabolism and aryl hydrocarbon hydrolase (AHH) activity at proestrus were determined and fertility evaluations were conducted. Ovulation rate and number of pups/litter were reduced in rats exposed to 100 μg BaP/m3 compared with other treatment and control groups. Plasma concentrations of E2, and LH were significantly reduced at proestrus in BaP-exposed versus those of controls whereas those of P4 were significantly reduced at diestrus I. The activity of AHH in ovarian and liver tissues and concentrations of BaP 7,8-diol and BaP 3,6-dione metabolites increased in an exposure concentration-dependent manner. These data suggest that exposure of rats to BaP prior to mating contributes to reduced ovarian function and fetal survival. PMID:23059060

  17. Endocrine involvement in children with beta-thalassaemia major. Transverse and longitudinal studies. I. Pituitary-thyroidal axis function and its correlation with serum ferritin levels.

    PubMed

    Cavallo, L; Licci, D; Acquafredda, A; Marranzini, M; Beccasio, R; Scardino, M L; Altomare, M; Mastro, F; Sisto, L; Schettini, F

    1984-09-01

    Thyroid function was investigated by a TRH test in 24 clinically prepubertal children, 3-15 years old with beta-thalassaemia major; in 7 of them the test was repeated once and in 2 twice at intervals of at least 12 months. Basal T4, T3, TBG and TSH levels and the TSH levels during a TRH test were determined and correlated with age and serum ferritin levels. Basal serum T4, T3 and TBG levels were lower and serum TSH levels were higher during the test and in the basal state in thalassaemia major children than in control children. These results show a compensated sub-clinical primary hypothyroidism. The transversal study did not show any significant correlation between the hormonal parameters studied and chronological age or serum ferritin levels. In contrast, the longitudinal study showed a significant correlation between pituitary-thyroidal axis function and siderosis (positive correlations between the variations of TSH levels as delta, peak, 30 and 45 min values and the variations of serum ferritin levels). The thyroid impairment seems not to be correlated with serum ferritin levels in the transversal study because of the presence of an individual different sensitivity of the gland to the iron overload. The ferritin dependence of this impairment is shown only by longitudinal studies where individual differences in sensitivity of the gland are absent.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth.

    PubMed

    Momoi, Nobuo; Tinney, Joseph P; Liu, Li J; Elshershari, Huda; Hoffmann, Paul J; Ralphe, John C; Keller, Bradley B; Tobita, Kimimasa

    2008-05-01

    Caffeine consumption during pregnancy is reported to increase the risk of in utero growth restriction and spontaneous abortion. In the present study, we tested the hypothesis that modest maternal caffeine exposure affects in utero developing embryonic cardiovascular (CV) function and growth without altering maternal hemodynamics. Caffeine (10 mg.kg(-1).day(-1) subcutaneous) was administered daily to pregnant CD-1 mice from embryonic days (EDs) 9.5 to 18.5 of a 21-day gestation. We assessed maternal and embryonic CV function at baseline and at peak maternal serum caffeine concentration using high-resolution echocardiography on EDs 9.5, 11.5, 13.5, and 18.5. Maternal caffeine exposure did not influence maternal body weight gain, maternal CV function, or embryo resorption. However, crown-rump length and body weight were reduced in maternal caffeine treated embryos by ED 18.5 (P < 0.05). At peak maternal serum caffeine concentration, embryonic carotid artery, dorsal aorta, and umbilical artery flows transiently decreased from baseline at ED 11.5 (P < 0.05). By ED 13.5, embryonic aortic and umbilical artery flows were insensitive to the peak maternal caffeine concentration; however, the carotid artery flow remained affected. By ED 18.5, baseline embryonic carotid artery flow increased and descending aortic flow decreased versus non-caffeine-exposed embryos. Maternal treatment with the adenosine A(2A) receptor inhibitor reproduced the embryonic hemodynamic effects of maternal caffeine exposure. Adenosine A(2A) receptor gene expression levels of ED 11.5 embryo and ED 18.5 uterus were decreased. Results suggest that modest maternal caffeine exposure has adverse effects on developing embryonic CV function and growth, possibly mediated via adenosine A(2A) receptor blockade.

  19. Alcohol Affects Brain Functional Connectivity and its Coupling with Behavior: Greater Effects in Male Heavy Drinkers

    PubMed Central

    Shokri-Kojori, Ehsan; Tomasi, Dardo; Wiers, Corinde E.; Wang, Gene-Jack; Volkow, Nora D.

    2016-01-01

    Acute and chronic alcohol exposure significantly affect behavior but the underlying neurobiological mechanisms are still poorly understood. Here we used functional connectivity density (FCD) mapping to study alcohol-related changes in resting brain activity and their association with behavior. Heavy drinkers (HD; N=16; 16 males) and normal controls (NM; N=24; 14 males) were tested after placebo and after acute alcohol administration. Group comparisons showed that NM had higher FCD in visual and prefrontal cortices, default-mode network regions, and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly increased FCD within the thalamus, impaired cognitive and motor functions, and affected self-reports of mood/drug effects in both groups. Partial least squares regression showed alcohol-induced changes in mood/drug effects were associated with changes in thalamic FCD in both groups. Disruptions in motor function were associated with increases in cerebellar FCD in NM and thalamus FCD in HD. Alcohol-induced declines in cognitive performance were associated with connectivity increases in visual cortex and thalamus in NM, but in HD, increases in precuneus FCD were associated with improved cognitive performance. Acute alcohol reduced “neurocognitive coupling”, the association between behavioral performance and FCD (indexing brain activity), an effect that was accentuated in HD compared to NM. Findings suggest that reduced cortical connectivity in HD contribute to decline in cognitive abilities associated with heavy alcohol consumption, whereas increased cerebellar connectivity in HD may have compensatory effects on behavioral performance. The results reveal how drinking history alters the association between brain functional connectivity density and individual differences in behavioral performance. PMID:27021821

  20. Minimal changes of thyroid axis activity influence brain functions in young females affected by subclinical hypothyroidism.

    PubMed

    Menicucci, D; Sebastiani, L; Comparini, A; Pingitore, A; Ghelarducci, B; L'Abbate, A; Iervasi, G; Gemignani, A

    2013-03-01

    There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.

  1. Factors affecting recovery of postoperative bowel function after pediatric laparoscopic surgery

    PubMed Central

    Michelet, Daphnée; Andreu-Gallien, Juliette; Skhiri, Alia; Bonnard, Arnaud; Nivoche, Yves; Dahmani, Souhayl

    2016-01-01

    Background and Aims: Laparoscopic pediatric surgery allows a rapid postoperative rehabilitation and hospital discharge. However, the optimal postoperative pain management preserving advantages of this surgical technique remains to be determined. This study aimed to identify factors affecting the postoperative recovery of bowel function after laparoscopic surgery in children. Material and Methods: A retrospective analysis of factors affecting recovery of bowel function in children and infants undergoing laparoscopic surgery between January 1, 2009 and September 30, 2009, was performed. Factors included were: Age, weight, extent of surgery (extensive, regional or local), chronic pain (sickle cell disease or chronic intestinal inflammatory disease), American Society of Anaesthesiologists status, postoperative analgesia (ketamine, morphine, nalbuphine, paracetamol, nonsteroidal anti-inflammatory drugs [NSAIDs], nefopam, regional analgesia) both in the Postanesthesia Care Unit and in the surgical ward; and surgical complications. Data analysis used classification and regression tree analysis (CART) with a 10-fold cross validation. Results: One hundred and sixty six patients were included in the analysis. Recovery of bowel function depended upon: The extent of surgery, the occurrence of postoperative surgical complications, the administration of postoperative morphine in the surgical ward, the coadministration of paracetamol and NSAIDs and/or nefopam in the surgical ward and the emergency character of the surgery. The CART method generated a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross validation were 58% and 49%, respectively. Conclusion: Multimodal analgesia using nonopioid analgesia that allows decreasing postoperative morphine consumption should be considered for the speed of bowel function recovery after laparoscopic pediatric surgery. PMID:27625488

  2. Evaluation and management of endocrine dysfunction in fibromyalgia.

    PubMed

    Geenen, Rinie; Jacobs, Johannes W G; Bijlsma, Johannes W J

    2002-05-01

    Fibromyalgia-like symptoms such as muscle pain and tenderness, exhaustion, reduced exercise capacity, and cold intolerance, resemble symptoms associated with endocrine dysfunction like hypothyroidism, and adrenal or growth hormone insufficiency. To investigate the potential of management of endocrine abnormalities for relieve of symptoms of patients with fibromyalgia, we reviewed experimental and clinical studies of endocrine functioning and endocrine treatment. Serum GH, androgen, and 24-hour urinary cortisol levels of patients with fibromyalgia tend to be in the lower part of the normal range, while serum levels of thyroid hormone, female sex hormones, prolactin, and melatonin are normal. With exception of GH, these conclusions are based on studies in small samples. With respect to dynamic responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis, the dexamethasone suppression test and stimulation with ACTH show normal results, while patients show marked ACTH hypersecretion in response to severe acute stressors, perhaps indicative of chronic CRH hyposecretion. This finding and slightly altered responsiveness of growth hormone, thyroid hormone, and prolactin in pharmacologic stimulation tests suggest a central rather than peripheral origin of endocrine deviations. Because hormone level deviations were not severe, occurred in subgroups of patients only, and few controlled clinical trials were performed, there is--unless future research shows otherwise--little support for hormone supplementation as a general therapy in the common patient with fibromyalgia. In patients with clinically overt hormone deficiency, hormonal supplementation is an option. In patients with hormone levels that are in the lower part of the normal range, interventions aimed at pain, fatigue, sleep or mood disturbance, and physical deconditioning may indirectly improve endocrine functioning.

  3. Functional Connectivity under Anticipation of Shock: Correlates of Trait Anxious Affect versus Induced Anxiety.

    PubMed

    Bijsterbosch, Janine; Smith, Stephen; Bishop, Sonia J

    2015-09-01

    Sustained anxiety about potential future negative events is an important feature of anxiety disorders. In this study, we used a novel anticipation of shock paradigm to investigate individual differences in functional connectivity during prolonged threat of shock. We examined the correlates of between-participant differences in trait anxious affect and induced anxiety, where the latter reflects changes in self-reported anxiety resulting from the shock manipulation. Dissociable effects of trait anxious affect and induced anxiety were observed. Participants with high scores on a latent dimension of anxious affect showed less increase in ventromedial pFC-amygdala connectivity between periods of safety and shock anticipation. Meanwhile, lower levels of induced anxiety were linked to greater augmentation of dorsolateral pFC-anterior insula connectivity during shock anticipation. These findings suggest that ventromedial pFC-amygdala and dorsolateral pFC-insula networks might both contribute to regulation of sustained fear responses, with their recruitment varying independently across participants. The former might reflect an evolutionarily old mechanism for reducing fear or anxiety, whereas the latter might reflect a complementary mechanism by which cognitive control can be implemented to diminish fear responses generated due to anticipation of aversive stimuli or events. These two circuits might provide complementary, alternate targets for exploration in future pharmacological and cognitive intervention studies.

  4. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

    PubMed

    Bauer, M; London, E D; Silverman, D H; Rasgon, N; Kirchheiner, J; Whybrow, P C

    2003-11-01

    The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

  5. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    NASA Astrophysics Data System (ADS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (sbnd NH2), carboxyl (sbnd COOH) and methyl (sbnd CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (sbnd COOH and sbnd NH2) can absorb more proteins than these modified with more hydrophobic functional group (sbnd CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the sbnd NH2 modified surfaces encourage osteogenic differentiation; the sbnd COOH modified surfaces promote cell adhesion and spreading and the sbnd CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  6. No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function.

    PubMed

    Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Sadoghi, Patrick; Wiedner, Maria; Haas, Franz; Leithner, Andreas; Windhager, Reinhard; Zwick, Ernst B

    2012-07-01

    The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow-up of 33 months (range, 7-59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0) underwent an instrumented three-dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow-up of 33 months.

  7. Light availability affects stream biofilm bacterial community composition and function, but not diversity

    PubMed Central

    Wagner, Karoline; Besemer, Katharina; Burns, Nancy R.; Battin, Tom J.

    2015-01-01

    Summary Changes in riparian vegetation or water turbidity and browning in streams alter the local light regime with potential implications for stream biofilms and ecosystem functioning. We experimented with biofilms in microcosms grown under a gradient of light intensities (range: 5–152 μmole photons s−1 m−2) and combined 454‐pyrosequencing and enzymatic activity assays to evaluate the effects of light on biofilm structure and function. We observed a shift in bacterial community composition along the light gradient, whereas there was no apparent change in alpha diversity. Multifunctionality, based on extracellular enzymes, was highest under high light conditions and decoupled from bacterial diversity. Phenol oxidase activity, involved in the degradation of polyphenolic compounds, was twice as high on average under the lowest compared with the highest light condition. This suggests a shift in reliance of microbial heterotrophs on biofilm phototroph‐derived organic matter under high light availability to more complex organic matter under low light. Furthermore, extracellular enzyme activities correlated with nutrient cycling and community respiration, supporting the link between biofilm structure–function and biogeochemical fluxes in streams. Our findings demonstrate that changes in light availability are likely to have significant impacts on biofilm structure and function, potentially affecting stream ecosystem processes. PMID:26013911

  8. Dynamic changes in brain activations and functional connectivity during affectively different tactile stimuli.

    PubMed

    Hua, Qing-Ping; Zeng, Xiang-Zhu; Liu, Jian-Yu; Wang, Jin-Yan; Guo, Jian-You; Luo, Fei

    2008-01-01

    In the present study, we compared brain activations produced by pleasant, neutral and unpleasant touch, to the anterior lateral surface of lower leg of human subjects. It was found that several brain regions, including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), as well as contralateral middle and posterior insula cortex were commonly activated under the three touch conditions. In addition, pleasant and unpleasant touch conditions shared a few brain regions including the contralateral posterior parietal cortex (PPC) and bilateral premotor cortex (PMC). Unpleasant touch specifically activated a set of pain-related brain regions such as contralateral supplementary motor area (SMA) and dorsal parts of bilateral anterior cingulated cortex, etc. Brain regions specifically activated by pleasant touch comprised bilateral lateral orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), intraparietal cortex and left dorsal lateral prefrontal cortex (DLPFC). Using a novel functional connectivity model based on graph theory, we showed that a series of brain regions related to affectively different touch had significant functional connectivity during the resting state. Furthermore, it was found that such a network can be modulated between affectively different touch conditions.

  9. Attachment style predicts affect, cognitive appraisals, and social functioning in daily life.

    PubMed

    Sheinbaum, Tamara; Kwapil, Thomas R; Ballespí, Sergi; Mitjavila, Mercè; Chun, Charlotte A; Silvia, Paul J; Barrantes-Vidal, Neus

    2015-01-01

    The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using experience sampling methodology (ESM) in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview (ASI) and received personal digital assistants that signaled them randomly eight times per day for 1 week to complete questionnaires about their current experiences and social context. As hypothesized, participants' momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the ASI and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life.

  10. Catheterization of Intestinal Loops in Ruminants Does Not Adversely Affect Loop Function

    PubMed Central

    Inglis, G Douglas; Kastelic, John P; Uwiera, Richard R E

    2010-01-01

    Catheterized intestinal loops may be a valuable model to elucidate key components of the host response to various treatments within the small intestine of ruminants. We examined whether catheterizing ileal loops in sheep affected the overall health of animals and intestinal function, whether a bacterial treatment could be introduced into the loops through the catheters, and whether broad-spectrum antibiotics could sterilize the loops. Escherichia coli cells transformed to express the GFP gene were introduced readily into the loops through the catheters, and GFP E. coli cells were localized within the injected loops. Catheterized loops, interspaces, and intact ileum exhibited no abnormalities in tissue appearance or electrical resistance. Expression of the IFNγ, IL1α, IL4, IL6, IL12p40, IL18, TGFβ1, and TNFα cytokine genes did not differ significantly among the intact ileum, catheterized loops, and interspaces, nor did the expression of the gene for inducible nitric oxide synthase. Broad-spectrum antibiotics administered during surgery did not sterilize the loops or interspaces and did not substantively change the composition of the microbiota. However, antibiotics reduced the overall number of bacterial cells within the loop and the relative abundance of community constituents. We concluded that catheterization of intestinal loops did not adversely affect health or loop function in sheep. Furthermore, allowing animals to recover fully from surgery and to clear pharmaceuticals will remove any confounding effects due to these factors, making catheterized intestinal loops a feasible model for studying host responses in ruminants. PMID:21262134

  11. Climate change induced rainfall patterns affect wheat productivity and agroecosystem functioning dependent on soil types

    NASA Astrophysics Data System (ADS)

    Tabi Tataw, James; Baier, Fabian; Krottenthaler, Florian; Pachler, Bernadette; Schwaiger, Elisabeth; Whylidal, Stefan; Formayer, Herbert; Hösch, Johannes; Baumgarten, Andreas; Zaller, Johann G.

    2014-05-01

    Wheat is a crop of global importance supplying more than half of the world's population with carbohydrates. We examined, whether climate change induced rainfall patterns towards less frequent but heavier events alter wheat agroecosystem productivity and functioning under three different soil types. Therefore, in a full-factorial experiment Triticum aestivum L. was cultivated in 3 m2 lysimeter plots containing the soil types sandy calcaric phaeozem, gleyic phaeozem or calcic chernozem. Prognosticated rainfall patterns based on regionalised climate change model calculations were compared with current long-term rainfall patterns; each treatment combination was replicated three times. Future rainfall patterns significantly reduced wheat growth and yield, reduced the leaf area index, accelerated crop development, reduced arbuscular mycorrhizal fungi colonisation of roots, increased weed density and the stable carbon isotope signature (δ13C) of both old and young wheat leaves. Different soil types affected wheat growth and yield, ecosystem root production as well as weed abundance and biomass. The interaction between climate and soil type was significant only for the harvest index. Our results suggest that even slight changes in rainfall patterns can significantly affect the functioning of wheat agroecosystems. These rainfall effects seemed to be little influenced by soil types suggesting more general impacts of climate change across different soil types. Wheat production under future conditions will likely become more challenging as further concurrent climate change factors become prevalent.

  12. Attachment style predicts affect, cognitive appraisals, and social functioning in daily life

    PubMed Central

    Sheinbaum, Tamara; Kwapil, Thomas R.; Ballespí, Sergi; Mitjavila, Mercè; Chun, Charlotte A.; Silvia, Paul J.; Barrantes-Vidal, Neus

    2015-01-01

    The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using experience sampling methodology (ESM) in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview (ASI) and received personal digital assistants that signaled them randomly eight times per day for 1 week to complete questionnaires about their current experiences and social context. As hypothesized, participants’ momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the ASI and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life. PMID:25852613

  13. The association between the body composition and lifestyle affecting pulmonary function in Japanese workers

    PubMed Central

    Inomoto, Atsushi; Fukuda, Rika; Deguchi, Junko; Kato, Gohei; Kanzaki, Ryoko; Hiroshige, Keiichi; Nakamura, Kouichi; Nakano, Keisuke; Toyonaga, Toshihiro

    2016-01-01

    [Purpose] The purpose of this study was to identify factors related to physical characteristics and lifestyle that affect pulmonary function. [Subjects and Methods] Ninety seven healthy male workers were recruited for this study, and basic information and details about lifestyle were collected. Body composition analyzer and visceral fat measuring device were conducted as measurements. Pulmonary function was measured using spirometer. A multiple stepwise linear regression analysis was performed with pulmonary function as the dependent variable. Variables with a significant association with pulmonary function on univariate analysis were imputed as independent variables. [Results] Height, fat free mass, upper extremity muscle mass, lower extremity muscle mass, and trunk muscle mass had significant positive correlations with FEV1 and FVC. Age, percentage of body fat, and visceral fat area were negatively correlated with FEV1 and FVC. Regarding the association between pulmonary function and lifestyle, a significant difference was found between the smoking index and the presence or absence of metabolic syndrome risk factors and both FEV1 and FVC. The multiple stepwise linear regression analysis with FEV1 as the dependent variable, adjusted for age and height, revealed that visceral fat area and fat free mass were significantly associated with FEV1. A similar analysis, FVC as the dependent variable identified visceral fat area. [Conclusion] FEV1 was independently associated with visceral fat area and fat free mass. FVC was independently associated with visceral fat area. These results may be valuable in preventing the decrease in respiratory function and, hence, in further preventing the onset of COPD. PMID:27821955

  14. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    PubMed

    Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kawashima, Ryuta

    2010-12-08

    Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  15. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.

    PubMed

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-03-25

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed.

  16. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals

    PubMed Central

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-01-01

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold2 software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. PMID:27023588

  17. Prepubertal endocrine follow-up in subjects with Wilms' tumor

    SciTech Connect

    Perrone, L.; Sinisi, A.A.; Sicuranza, R.; Di Tullio, M.T.; Indolfi, P.; Giuliano, M.G.; Bellastella, A.; Faggiano, M.

    1988-01-01

    Twenty-three prepubertal subjects treated for Wilms' tumor (10 males and 13 females) were endocrinologically evaluated off therapy from 0.5 to 4.08 years. They were divided into two groups: 11 subjects (6M, 5F) who had received chemotherapy only (group 1) and 12 (4M, 8F) who had in addition received abdominal radiation (1,500-3,000 rads) (group 2). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (FT4), free tri-iodo thyronine (FT3), testosterone (T), estradiol-17 beta (E2), and cortisol (F) were measured by radioimmunoassay (RIA). Plasma levels of TSH, PRL, FT4, FT3, and F were normal in both groups, as were FSH, LH, T, and E2 in group 1. In group 2, female subjects showed FSH levels significantly higher than controls, while LH and E2 were normal; male subjects showed significantly higher LH levels, while FSH and T levels were normal. These results indicate that in the treatment protocol used by us for Wilms' tumor (WT), chemotherapy does not affect endocrine function, whereas abdominal radiation seems to damage gonadal function directly. The present findings indicate that gonadal damage may be revealed in WT before puberty not only in females, as has been previously reported, but also in male subjects.

  18. Realistic changes in seaweed biodiversity affect multiple ecosystem functions on a rocky shore.

    PubMed

    Bracken, Matthew E S; Williams, Susan L

    2013-09-01

    Given current threats to biodiversity, understanding the effects of diversity changes on the functions and services associated with intact ecosystems is of paramount importance. However, limited realism in most biodiversity studies makes it difficult to link the large and growing body of evidence for important functional consequences of biodiversity change to real-world losses of biodiversity. Here, we explored two methods of incorporating realism into biodiversity research: (1) the use of two-, five-, and eight-species assemblages that mimicked those that we observed in surveys of seaweed biodiversity patterns on a northern California (USA) rocky shore and the explicit comparison of those assemblages to random assemblages compiled from the same local species pool; and (2) the measurement of two fundamental ecosystem functions, nitrate uptake and photosynthesis, both of which contribute to growth of primary producers. Specifically, we measured nitrate uptake rates of seaweed assemblages as a function of initial nitrate concentrations and photosynthetic rates as a function of irradiance levels for both realistic and random assemblages of seaweeds. We only observed changes in ecosystem functioning along a richness gradient for realistic assemblages, and both maximum nitrate uptake rates (V(max)) and photosynthetic light use efficiency values (alpha(p) = P(max)/I(K)) were higher in realistic assemblages than in random assemblages. Furthermore, the parameter affected by changes in richness depended on the function being measured. Both V(max) and alpha(p) declined with increasing richness in nonrandom assemblages due to a combination of species identity effects (for V(max) and overyielding effects (for both V(max) and alpha(p)). In contrast, neither nitrate uptake efficiency values (alpha(N) = V(max)/K(s)), nor maximum photosynthetic rates (Pmax) changed along the gradient in seaweed species richness. Furthermore, overyielding was only evident in realistic assemblages

  19. Earthworm-mycorrhiza interactions can affect the diversity, structure and functioning of establishing model grassland communities.

    PubMed

    Zaller, Johann G; Heigl, Florian; Grabmaier, Andrea; Lichtenegger, Claudia; Piller, Katja; Allabashi, Roza; Frank, Thomas; Drapela, Thomas

    2011-01-01

    Both earthworms and arbuscular mycorrhizal fungi (AMF) are important ecosystem engineers co-occurring in temperate grasslands. However, their combined impacts during grassland establishment are poorly understood and have never been studied. We used large mesocosms to study the effects of different functional groups of earthworms (i.e., vertically burrowing anecics vs. horizontally burrowing endogeics) and a mix of four AMF taxa on the establishment, diversity and productivity of plant communities after a simulated seed rain of 18 grassland species comprising grasses, non-leguminous forbs and legumes. Moreover, effects of earthworms and/or AMF on water infiltration and leaching of ammonium, nitrate and phosphate were determined after a simulated extreme rainfall event (40 l m(-2)). AMF colonisation of all three plant functional groups was altered by earthworms. Seedling emergence and diversity was reduced by anecic earthworms, however only when AMF were present. Plant density was decreased in AMF-free mesocosms when both anecic and endogeic earthworms were active; with AMF also anecics reduced plant density. Plant shoot and root biomass was only affected by earthworms in AMF-free mesocosms: shoot biomass increased due to the activity of either anecics or endogeics; root biomass increased only when anecics were active. Water infiltration increased when earthworms were present in the mesocosms but remained unaffected by AMF. Ammonium leaching was increased only when anecics or a mixed earthworm community was active but was unaffected by AMF; nitrate and phosphate leaching was neither affected by earthworms nor AMF. Ammonium leaching decreased with increasing plant density, nitrate leaching decreased with increasing plant diversity and density. In order to understand the underlying processes of these interactions further investigations possibly under field conditions using more diverse belowground communities are required. Nevertheless, this study demonstrates that

  20. Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers.

    PubMed

    Shokri-Kojori, E; Tomasi, D; Wiers, C E; Wang, G-J; Volkow, N D

    2016-03-29

    Acute and chronic alcohol exposure significantly affect behavior but the underlying neurobiological mechanisms are still poorly understood. Here, we used functional connectivity density (FCD) mapping to study alcohol-related changes in resting brain activity and their association with behavior. Heavy drinkers (HD, N=16, 16 males) and normal controls (NM, N=24, 14 males) were tested after placebo and after acute alcohol administration. Group comparisons showed that NM had higher FCD in visual and prefrontal cortices, default mode network regions and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly increased FCD within the thalamus, impaired cognitive and motor functions, and affected self-reports of mood/drug effects in both groups. Partial least squares regression showed that alcohol-induced changes in mood/drug effects were associated with changes in thalamic FCD in both groups. Disruptions in motor function were associated with increases in cerebellar FCD in NM and thalamus FCD in HD. Alcohol-induced declines in cognitive performance were associated with connectivity increases in visual cortex and thalamus in NM, but in HD, increases in precuneus FCD were associated with improved cognitive performance. Acute alcohol reduced 'neurocognitive coupling', the association between behavioral performance and FCD (indexing brain activity), an effect that was accentuated in HD compared with NM. Findings suggest that reduced cortical connectivity in HD contribute to decline in cognitive abilities associated with heavy alcohol consumption, whereas increased cerebellar connectivity in HD may have compensatory effects on behavioral performance. The results reveal how drinking history alters the association between brain FCD and individual differences in behavioral performance.Molecular Psychiatry advance online publication, 29 March 2016; doi:10.1038/mp.2016.25.

  1. Tumor-specific mutations in low-frequency genes affect their functional properties.

    PubMed

    Erdem-Eraslan, Lale; Heijsman, Daphne; de Wit, Maurice; Kremer, Andreas; Sacchetti, Andrea; van der Spek, Peter J; Sillevis Smitt, Peter A E; French, Pim J

    2015-05-01

    Causal genetic changes in oligodendrogliomas (OD) with 1p/19q co-deletion include mutations in IDH1, IDH2, CIC, FUBP1, TERT promoter and NOTCH1. However, it is generally assumed that more somatic mutations are required for tumorigenesis. This study aimed to establish whether genes mutated at low frequency can be involved in OD initiation and/or progression. We performed whole-genome sequencing on three anaplastic ODs with 1p/19q co-deletion. To estimate mutation frequency, we performed targeted resequencing on an additional 39 ODs. Whole-genome sequencing identified a total of 55 coding mutations (range 8-32 mutations per tumor), including known abnormalities in IDH1, IDH2, CIC and FUBP1. We also identified mutations in genes, most of which were previously not implicated in ODs. Targeted resequencing on 39 additional ODs confirmed that these genes are mutated at low frequency. Most of the mutations identified were predicted to have a deleterious functional effect. Functional analysis on a subset of these genes (e.g. NTN4 and MAGEH1) showed that the mutation affects the subcellular localization of the protein (n = 2/12). In addition, HOG cells stably expressing mutant GDI1 or XPO7 showed altered cell proliferation compared to those expressing wildtype constructs. Similarly, HOG cells expressing mutant SASH3 or GDI1 showed altered migration. The significantly higher rate of predicted deleterious mutations, the changes in subcellular localization and the effects on proliferation and/or migration indicate that many of these genes functionally may contribute to gliomagenesis and/or progression. These low-frequency genes and their affected pathways may provide new treatment targets for this tumor type.

  2. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

    PubMed Central

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

    2009-01-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

  3. Effect of elevated ambient temperature at parturition on duration of gestation, ruminal temperature, and endocrine function of fall-calving beef cows.

    PubMed

    Wright, E C; Boehmer, B H; Cooper-Prado, M J; Bailey, C L; Wettemann, R P

    2014-10-01

    less (P < 0.05) for late-August compared with cows that calved during the other months. Concentrations of progesterone were greater during 7 d before parturition in October compared with cows that calved in September. Estradiol in plasma of cows during late gestation was not affected by month of calving (P = 0.76). Exposure of beef cows to elevated ambient temperature resulted in shorter gestations. Ruminal temperature in cows decreased ≥ 0.3°C the day before parturition.

  4. The role of magnesium and thyroid function in early pregnancy after in-vitro fertilization (IVF): New aspects in endocrine physiology

    PubMed Central

    Stuefer, Sibilla; Moncayo, Helga; Moncayo, Roy

    2015-01-01

    Background The initiation of a pregnancy is a process that requires adequate energetic support. Recent observations at our Institution suggest a central role of magnesium in this situation. The aim of this study was to evaluate magnesium, zinc, selenium and thyroid function as well as anti-Müllerian hormone in early pregnancy following in-vitro fertilization as compared to spontaneous successful pregnancies. Results A successful outcome of pregnancy after IVF treatment was associated with 2 parameters: higher levels of anti-Müllerian hormone as well as higher levels of magnesium in the pre-stimulation blood sample. These two parameters, however, showed no correlation. Spontaneous pregnancies as well as pregnancies after IVF show a fall of magnesium levels at 2–3 weeks of gestation. This drop of magnesium concentration is larger following IVF as compared to spontaneous pregnancies. Parallel to these changes TSH levels showed an increase in early IVF-pregnancy. At this time point we also observed a positive correlation between fT4 and TSH. This was not observed in spontaneous pregnancies. Thyroid antibodies showed no correlation to outcomes. Conclusions In connection with the initiation of pregnancy following ovarian stimulation dynamic changes of magnesium and TSH levels can be observed. A positive correlation was found between fT4 and TSH in IVF pregnancies. In spontaneous pregnancies smaller increases of TSH levels are related to higher magnesium levels. General significance We propose that magnesium plays a role in early pregnancy as well as in pregnancy success independently from anti-Müllerian hormone. Neither thyroid hormones nor thyroid antibodies were related to outcome. PMID:26675754

  5. Effect of Treatment Modality on the Hypothalamic–Pituitary Function of Patients Treated with Radiation Therapy for Pituitary Adenomas: Hypothalamic Dose and Endocrine Outcomes

    PubMed Central

    Elson, Andrew; Bovi, Joseph; Kaur, Kawaljeet; Maas, Diana; Sinson, Grant; Schultz, Chris

    2014-01-01

    Background: Both fractionated external beam radiotherapy and single fraction radiosurgery for pituitary adenomas are associated with the risk of hypothalamic–pituitary (HP) axis dysfunction. Objective: To analyze the effect of treatment modality (Linac, TomoTherapy, or gamma knife) on hypothalamic dose and correlate these with HP-axis deficits after radiotherapy. Methods: Radiation plans of patients treated post-operatively for pituitary adenomas using Linac-based 3D-conformal radiotherapy (CRT) (n = 11), TomoTherapy-based intensity modulated radiation therapy (IMRT) (n = 10), or gamma knife stereotactic radiosurgery (n = 12) were retrospectively reviewed. Dose to the hypothalamus was analyzed and post-radiotherapy hormone function including growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, and gonadotropins (follicle stimulating hormone/luteinizing hormone) were assessed. Results: Post-radiation, 13 of 27 (48%) patients eligible for analysis developed at least one new hormone deficit, of which 8 of 11 (72%) occurred in the Linac group, 4 of 8 (50%) occurred in the TomoTherapy group, and 1 of 8 (12.5%) occurred in the gamma knife group. Compared with fractionated techniques, gamma knife showed improved hypothalamic sparing for DMax Hypo and V12Gy. For fractionated modalities, TomoTherapy showed improved dosimetric characteristics over Linac-based treatment with hypothalamic DMean (44.8 vs. 26.8 Gy p = 0.02), DMax (49.8 vs. 39.1 Gy p = 0.04), and V12Gy (100 vs. 76% p = 0.004). Conclusion: Maximal dosimetric avoidance of the hypothalamus was achieved using gamma knife-based radiosurgery followed by TomoTherapy-based IMRT, and Linac-based 3D conformal radiation therapy, respectively. PMID:24782984

  6. The osteocyte: an endocrine cell ... and more.

    PubMed

    Dallas, Sarah L; Prideaux, Matthew; Bonewald, Lynda F

    2013-10-01

    Few investigators think of bone as an endocrine gland, even after the discovery that osteocytes produce circulating fibroblast growth factor 23 that targets the kidney and potentially other organs. In fact, until the last few years, osteocytes were perceived by many as passive, metabolically inactive cells. However, exciting recent discoveries have shown that osteocytes encased within mineralized bone matrix are actually multifunctional cells with many key regulatory roles in bone and mineral homeostasis. In addition to serving as endocrine cells and regulators of phosphate homeostasis, these cells control bone remodeling through regulation of both osteoclasts and osteoblasts, are mechanosensory cells that coordinate adaptive responses of the skeleton to mechanical loading, and also serve as a manager of the bone's reservoir of calcium. Osteocytes must survive for decades within the bone matrix, making them one of the longest lived cells in the body. Viability and survival are therefore extremely important to ensure optimal function of the osteocyte network. As we continue to search for new therapeutics, in addition to the osteoclast and the osteoblast, the osteocyte should be considered in new strategies to prevent and treat bone disease.

  7. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.

    PubMed

    D'Amour, Kevin A; Bang, Anne G; Eliazer, Susan; Kelly, Olivia G; Agulnick, Alan D; Smart, Nora G; Moorman, Mark A; Kroon, Evert; Carpenter, Melissa K; Baetge, Emmanuel E

    2006-11-01

    Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, gut-tube endoderm, pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells, they release C-peptide in response to multiple secretory stimuli, but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.

  8. Variation among species in the endocrine control of mammary growth and function: the roles of prolactin, growth hormone, and placental lactogen.

    PubMed

    Forsyth, I A

    1986-03-01

    Prolactin, growth hormone, and placental lactogen form a family of structurally related hormones, which may have evolved from a common ancestral peptide. Prolactin and growth hormone are present in all mammals, but the biological activity associated with placental lactogen has been detected in only some groups. Attempts to detect placental lactogen using bioassay and radioreceptor assay are reported and have been unsuccessful in an insectivore (the shrew), a bat, an edentate (the armadillo), a lagomorph (the rabbit), several carnivores (dog, cat, ferret), perissodactyls (horse, zebra, rhino), and, within the artiodactyls, pigs. Placental lactogenic activity has been detected in primates (chimpanzee, orangutan), rodents (voles, Pinon mouse, guinea-pig, mara), and in numerous artiodactyls (llama, giraffe, several species of deer, antelope, gnu, gazelle, musk ox, cape buffalo, Barbary sheep, several sheep of the genus Ovis, goat, and cow). These results confirm and extend the work of others and are discussed in relation to the evolution of these hormones. In synergism with steroid and thyroid hormones, protein hormones of the prolactin and growth hormone family play a crucial role in stimulating the development of the mammary gland, the differentiation and function of mammary cells to secrete milk, and in the systemic adjustments in maternal metabolism in pregnancy and lactation. Studies in vitro have shown that mammary tissues from several species synthesize milk components in response to insulin plus adrenal corticoid plus prolactin. However, there are also species differences in minimal hormonal requirements for lactogenesis. In vivo, for example, rabbits will initiate or sustain lactation in response to prolactin alone, whereas sheep and goats require prolactin plus growth hormone plus adrenal corticoid plus thyroid hormone. Measurement of hormone concentrations in the plasma of pregnant animals shows considerable differences among species in the pattern of

  9. Effects of endocrine disrupters on the expression of growth hormone and prolactin mRNA in the rainbow trout pituitary.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is now widely accepted that chemical pollutants in the environment can interfere with the endocrine system of animals, thus affecting development and reproduction. Some of these endocrine disrupters (EDs) can have estrogenic or antiestrogenic effects. Most studies to date have focused on the ef...

  10. Soil microbial diversity and soil functioning affect competition among grasses in experimental microcosms.

    PubMed

    Bonkowski, Michael; Roy, Jacques

    2005-03-01

    A gradient of microbial diversity in soil was established by inoculating pasteurized soil with microbial populations of different complexity, which were obtained by a combination of soil fumigation and filtering techniques. Four different soil diversity treatments were planted with six different grass species either in monoculture or in polyculture to test how changes of general microbial functions, such as catabolic diversity and nutrient recycling efficiency would affect the performance of the plant communities. Relatively harsh soil treatments were necessary to elicit visible effects on major soil processes such as decomposition and nitrogen cycling due to the high redundancy and resilience of soil microbial communities. The strongest effects of soil diversity manipulations on plant growth occurred in polycultures where interspecific competition between plants was high. In polycultures, soil diversity reduction led to a gradual, linear decline in biomass production of one subordinate grass species (Bromus hordeaceus), which was compensated by increased growth of two intermediate competitors (Aegilops geniculata, B. madritensis). This negative covariance in growth of competing grass species smoothed the effects of soil diversity manipulations at the plant community level. As a result, total shoot biomass production remained constant. Apparently the effects of soil diversity manipulations were buffered because functional redundancy at both, the microbial and the plant community level complemented each other. The results further suggests that small trade-offs in plant fitness due to general functional shifts at the microbial level can be significant for the outcome of competition in plant communities and thus diversity at much larger scales.

  11. Proliferation of Purple Sulphur Bacteria at the Sediment Surface Affects Intertidal Mat Diversity and Functionality

    PubMed Central

    Hubas, Cédric; Jesus, Bruno; Ruivo, Mickael; Meziane, Tarik; Thiney, Najet; Davoult, Dominique; Spilmont, Nicolas; Paterson, David M.; Jeanthon, Christian

    2013-01-01

    There is a relative absence of studies dealing with mats of purple sulphur bacteria in the intertidal zone. These bacteria display an array of metabolic pathways that allow them to disperse and develop under a wide variety of conditions, making these mats important in terms of ecosystem processes and functions. Mass blooms of purple sulphur bacteria develop during summer on sediments in the intertidal zone especially on macroalgal deposits. The microbial composition of different types of mats differentially affected by the development of purple sulphur bacteria was examined, at low tide, using a set of biochemical markers (fatty acids, pigments) and composition was assessed against their influence on ecosystem functions (sediment cohesiveness, CO2 fixation). We demonstrated that proliferation of purple sulphur bacteria has a major impact on intertidal mats diversity and functions. Indeed, assemblages dominated by purple sulphur bacteria (Chromatiaceae) were efficient exopolymer producers and their biostabilisation potential was significant. In addition, the massive growth of purple sulphur bacteria resulted in a net CO2 degassing whereas diatom dominated biofilms represented a net CO2 sink. PMID:24340018

  12. Functional groups affect physical and biological properties of dextran-based hydrogels.

    PubMed

    Sun, Guoming; Shen, Yu-I; Ho, Chia Chi; Kusuma, Sravanti; Gerecht, Sharon

    2010-06-01

    Modification of dextran backbone allows the development of a hydrogel with specific characteristics. To enhance their functionality for tissue-engineered scaffolds, a series of dextran-based macromers was synthesized by incorporating various functional groups, including allyl isocyanate (Dex-AI), ethylamine (Dex-AE), chloroacetic acid (Dex-AC), or maleic-anhydride (Dex-AM) into dextrans. The dextran-based biodegradable hybrid hydrogels are developed by integrating polyethylene glycol diacrylate (PEGDA). To explore the effect of different derivatives on hydrogel properties, three different ratios of Dex/PEGDA are examined: low (20/80), medium (40/60), and high (60/40). Differences in physical and biological properties of the hydrogels are found, including swelling, degradation rate, mechanics, crosslinking density, biocompatibility (in vitro and in vivo), and vascular endothelial growth factor release. The results also indicate that the incorporation of amine groups into dextran gives rise to hydrogels with better biocompatible and release properties. We, therefore, conclude that the incorporation of different functional groups affects the fundamental properties of a dextran-based hydrogel network, and that amine groups are preferred to generate hydrogels for biomedical use.

  13. Proliferation of purple sulphur bacteria at the sediment surface affects intertidal mat diversity and functionality.

    PubMed

    Hubas, Cédric; Jesus, Bruno; Ruivo, Mickael; Meziane, Tarik; Thiney, Najet; Davoult, Dominique; Spilmont, Nicolas; Paterson, David M; Jeanthon, Christian

    2013-01-01

    There is a relative absence of studies dealing with mats of purple sulphur bacteria in the intertidal zone. These bacteria display an array of metabolic pathways that allow them to disperse and develop under a wide variety of conditions, making these mats important in terms of ecosystem processes and functions. Mass blooms of purple sulphur bacteria develop during summer on sediments in the intertidal zone especially on macroalgal deposits. The microbial composition of different types of mats differentially affected by the development of purple sulphur bacteria was examined, at low tide, using a set of biochemical markers (fatty acids, pigments) and composition was assessed against their influence on ecosystem functions (sediment cohesiveness, CO2 fixation). We demonstrated that proliferation of purple sulphur bacteria has a major impact on intertidal mats diversity and functions. Indeed, assemblages dominated by purple sulphur bacteria (Chromatiaceae) were efficient exopolymer producers and their biostabilisation potential was significant. In addition, the massive growth of purple sulphur bacteria resulted in a net CO2 degassing whereas diatom dominated biofilms represented a net CO2 sink.

  14. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    PubMed Central

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  15. Microbial endocrinology: the interplay between the microbiota and the endocrine system.

    PubMed

    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.

  16. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  17. How can we estimate natural selection on endocrine traits? Lessons from evolutionary biology.

    PubMed

    Bonier, Frances; Martin, Paul R

    2016-11-30

    An evolutionary perspective can enrich almost any endeavour in biology, providing a deeper understanding of the variation we see in nature. To this end, evolutionary endocrinologists seek to describe the fitness consequences of variation in endocrine traits. Much of the recent work in our field, however, follows a flawed approach to the study of how selection shapes endocrine traits. Briefly, this approach relies on among-individual correlations between endocrine phenotypes (often circulating hormone levels) and fitness metrics to estimate selection on those endocrine traits. Adaptive plasticity in both endocrine and fitness-related traits can drive these correlations, generating patterns that do not accurately reflect natural selection. We illustrate why this approach to studying selection on endocrine traits is problematic, referring to work from evolutionary biologists who, decades ago, described this problem as it relates to a variety of other plastic traits. We extend these arguments to evolutionary endocrinology, where the likelihood that this flaw generates bias in estimates of selection is unusually high due to the exceptional responsiveness of hormones to environmental conditions, and their function to induce adaptive life-history responses to environmental variation. We end with a review of productive approaches for investigating the fitness consequences of variation in endocrine traits that we expect will generate exciting advances in our understanding of endocrine system evolution.

  18. How can we estimate natural selection on endocrine traits? Lessons from evolutionary biology

    PubMed Central

    2016-01-01

    An evolutionary perspective can enrich almost any endeavour in biology, providing a deeper understanding of the variation we see in nature. To this end, evolutionary endocrinologists seek to describe the fitness consequences of variation in endocrine traits. Much of the recent work in our field, however, follows a flawed approach to the study of how selection shapes endocrine traits. Briefly, this approach relies on among-individual correlations between endocrine phenotypes (often circulating hormone levels) and fitness metrics to estimate selection on those endocrine traits. Adaptive plasticity in both endocrine and fitness-related traits can drive these correlations, generating patterns that do not accurately reflect natural selection. We illustrate why this approach to studying selection on endocrine traits is problematic, referring to work from evolutionary biologists who, decades ago, described this problem as it relates to a variety of other plastic traits. We extend these arguments to evolutionary endocrinology, where the likelihood that this flaw generates bias in estimates of selection is unusually high due to the exceptional responsiveness of hormones to environmental conditions, and their function to induce adaptive life-history responses to environmental variation. We end with a review of productive approaches for investigating the fitness consequences of variation in endocrine traits that we expect will generate exciting advances in our understanding of endocrine system evolution. PMID:27881753

  19. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) 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% of tumors...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  20. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2006-06-01

    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% of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  1. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder

    PubMed Central

    Henderson, Heather A.; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2015-01-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions. PMID:26496991

  2. RNA INTERFERENCE AGAINST CFTR AFFECTS HL60-DERIVED NEUTROPHIL MICROBICIDAL FUNCTION

    PubMed Central

    Bonvillain, Ryan W.; Painter, Richard G.; Adams, Daniel E.; Viswanathan, Anand; Lanson, Nicholas A.; Wang, Guoshun

    2010-01-01

    Biosynthesis of hypochlorous acid (HOCl), a potent anti-microbial oxidant, in phagosomes is one of the chief mechanisms employed by polymorphonuclear neutrophils (PMNs) to combat infections. This reaction, catalyzed by myeloperoxidase, requires chloride anion (Cl−) as a substrate. Thus, Cl− availability is a rate-limiting factor that affects neutrophil microbicidal function. Our previous research demonstrated that defective CFTR, a cAMP-activated chloride channel, present in cystic fibrosis (CF) patients leads to deficient chloride transport to neutrophil phagosomes and impaired bacterial killing (Painter et al., 2008 & 2010). To confirm this finding, here we used RNA interference against this chloride channel to abate CFTR expression in the neutrophil-like cells derived from HL60 cells, a promyelocytic leukemia cell line, with DMSO. The resultant CFTR deficiency in the phagocytes compromised their bactericidal capability, thereby recapitulating the phenotype seen in CF patient cells. The results provide further evidence suggesting that CFTR plays an important role in phagocytic host defense. PMID:20870018

  3. Stable complex formation between HIV Rev and the nucleosome assembly protein, NAP1, affects Rev function

    SciTech Connect

    Cochrane, Alan; Murley, Laura Lea; Gao Mian; Wong, Raymond; Clayton, Kiera; Brufatto, Nicole; Canadien, Veronica; Mamelak, Daniel; Chen, Tricia; Richards, Dawn; Zeghouf, Mahel; Greenblatt, Jack; Burks, Christian; Frappier, Lori

    2009-05-25

    The Rev protein of HIV-1 is essential for HIV-1 proliferation due to its role in exporting viral RNA from the nucleus. We used a modified version of tandem affinity purification (TAP) tagging to identify proteins interacting with HIV-1 Rev in human cells and discovered a prominent interaction between Rev and nucleosome assembly protein 1 (Nap1). This interaction was also observed by specific retention of Nap1 from human cell lysates on a Rev affinity column. Nap1 was found to bind Rev through the Rev arginine-rich domain and altered the oligomerization state of Rev in vitro. Overexpression of Nap1 stimulated the ability of Rev to export RNA, reduced the nucleolar localization of Rev, and affected Rev nuclear import rates. The results suggest that Nap-1 may influence Rev function by increasing the availability of Rev.

  4. Identification and Functional Characterization of GAA Mutations in Colombian Patients Affected by Pompe Disease.

    PubMed

    Niño, Mónica Yasmín; Mateus, Heidi Eliana; Fonseca, Dora Janeth; Kroos, Marian A; Ospina, Sandra Yaneth; Mejía, Juan Fernando; Uribe, Jesús Alfredo; Reuser, Arnold J J; Laissue, Paul

    2013-01-01

    Pompe disease (PD) is a recessive metabolic disorder characterized by acid α-glucosidase (GAA) deficiency, which results in lysosomal accumulation of glycogen in all tissues, especially in skeletal muscles. PD clinical course is mainly determined by the nature of the GAA mutations. Although ~400 distinct GAA sequence variations have been described, the genotype-phenotype correlation is not always evident.In this study, we describe the first clinical and genetic analysis of Colombian PD patients performed in 11 affected individuals. GAA open reading frame sequencing revealed eight distinct mutations related to PD etiology including two novel missense mutations, c.1106 T > C (p.Leu369Pro) and c.2236 T > C (p.Trp746Arg). In vitro functional studies showed that the structural changes conferred by both mutations did not inhibit the synthesis of the 110 kD GAA precursor form but affected the processing and intracellular transport of GAA. In addition, analysis of previously described variants located at this position (p.Trp746Gly, p.Trp746Cys, p.Trp746Ser, p.Trp746X) revealed new insights in the molecular basis of PD. Notably, we found that p.Trp746Cys mutation, which was previously described as a polymorphism as well as a causal mutation, displayed a mild deleterious effect. Interestingly and by chance, our study argues in favor of a remarkable Afro-American and European ancestry of the Colombian population. Taken together, our report provides valuable information on the PD genotype-phenotype correlation, which is expected to facilitate and improve genetic counseling of affected individuals and their families.

  5. Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model.

    PubMed

    Chaillou, Thomas; Koulmann, Nathalie; Simler, Nadine; Meunier, Adélie; Serrurier, Bernard; Chapot, Rachel; Peinnequin, Andre; Beaudry, Michèle; Bigard, Xavier

    2012-03-01

    Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

  6. Endocrine manifestations in celiac disease

    PubMed Central

    Freeman, Hugh James

    2016-01-01

    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. PMID:27784959

  7. Low-dose irradiation affects the functional behavior of oral microbiota in the context of mucositis.

    PubMed

    Vanhoecke, Barbara W A; De Ryck, Tine R G; De boel, Kevin; Wiles, Siouxsie; Boterberg, Tom; Van de Wiele, Tom; Swift, Simon

    2016-01-01

    The role of host-microbe interactions in the pathobiology of oral mucositis is still unclear; therefore, this study aimed to unravel the effect of irradiation on behavioral characteristics of oral microbial species in the context of mucositis. Using various experimental in vitro setups, the effects of irradiation on growth and biofilm formation of two Candida spp., Streptococcus salivarius and Klebsiella oxytoca in different culture conditions were evaluated. Irradiation did not affect growth of planktonic cells, but reduced the number of K. oxytoca cells in newly formed biofilms cultured in static conditions. Biofilm formation of K. oxytoca and Candida glabrata was affected by irradiation and depended on the culturing conditions. In the presence of mucins, these effects were lost, indicating the protective nature of mucins. Furthermore, the Galleria melonella model was used to study effects on microbial virulence. Irradiated K. oxytoca microbes were more virulent in G. melonella larvae compared to the nonirradiated ones. Our data indicate that low-dose irradiation can have an impact on functional characteristics of microbial species. Screening for pathogens like K. oxytoca in the context of mucosits could be useful to allow early detection and immediate intervention.

  8. Balance between macronutrients affects life span and functional senescence in fruit fly Drosophila melanogaster.

    PubMed

    Lushchak, Oleh V; Gospodaryov, Dmytro V; Rovenko, Bohdana M; Glovyak, Andriy D; Yurkevych, Ihor S; Klyuba, Vira P; Shcherbij, Maria V; Lushchak, Volodymyr I

    2012-02-01

    It has recently been demonstrated that as the ratio of protein to carbohydrate (P:C) in the diet declines, life span increases in Drosophila. Here we explored how extremely low dietary ratios of protein to carbohydrate affected longevity and a selection of variables associated with functional senescence. An increase in P:C ratio from 1:57 to 1:20 shortened life span by increasing age-dependent mortality; whereas a further decline in P:C from 1:57 to 1:95 caused a modest decrease in life span. Female flies consuming the 1:20 and 1:38 diets laid more eggs than those consuming the lower P:C diets. Flies fed diets with higher ratios were more resistant to heat stress. Flies consuming the diets with lowest P:C ratios needed more time to restore activity after paralysis. Our study has therefore extended to very low P:C ratios available data demonstrating that dietary P:C ratio affects life span, fecundity and heat stress resistance, with fecundity and heat stress responses showing the opposite trend to life span.

  9. Spectrum of Endocrine Disorders in Central Ghana

    PubMed Central

    Sarfo, Fred Stephen; Ansah, Eunice Oparebea; Kyei, Ishmael

    2017-01-01

    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. PMID:28326101

  10. Oral health conditions affect functional and social activities of terminally-ill cancer patients

    PubMed Central

    Fischer, D.J.; Epstein, J.B.; Yao, Y.; Wilkie, D.J.

    2013-01-01

    Purpose Oral conditions are established complications in terminally-ill cancer patients. Yet despite significant morbidity, the characteristics and impact of oral conditions in these patients are poorly documented. The study objective was to characterize oral conditions in terminally-ill cancer patients to determine the presence, severity, and the functional and social impact of these oral conditions. Methods This was an observational clinical study including terminally-ill cancer patients (2.5–3 week life expectancy). Data were obtained via the Oral Problems Scale (OPS) that measures the presence of subjective xerostomia, orofacial pain, taste change, and the functional/social impact of oral conditions and a demographic questionnaire. A standardized oral examination was used to assess objective salivary hypofunction, fungal infection, mucosal erythema, and ulceration. Regression analysis and t test investigated the associations between measures. Results Of 104 participants, most were ≥50 years of age, female, and high-school educated; 45% were African American, 43% Caucasian, and 37% married. Oral conditions frequencies were: salivary hypofunction (98%), mucosal erythema (50%), ulceration (20%), fungal infection (36%), and other oral problems (46%). Xerostomia, taste change, and orofacial pain all had significant functional impact; p<.001, p=.042 and p<.001, respectively. Orofacial pain also had a significant social impact (p<.001). Patients with oral ulcerations had significantly more orofacial pain with a social impact than patients without ulcers (p=.003). Erythema was significantly associated with fungal infection and with mucosal ulceration (p<.001). Conclusions Oral conditions significantly affect functional and social activities in terminally-ill cancer patients. Identification and management of oral conditions in these patients should therefore be an important clinical consideration. PMID:24232310

  11. Macrofauna assemblage composition and soil moisture interact to affect soil ecosystem functions

    NASA Astrophysics Data System (ADS)

    Collison, E. J.; Riutta, T.; Slade, E. M.

    2013-02-01

    Changing climatic conditions and habitat fragmentation are predicted to alter the soil moisture conditions of temperate forests. It is not well understood how the soil macrofauna community will respond to changes in soil moisture, and how changes to species diversity and community composition may affect ecosystem functions, such as litter decomposition and soil fluxes. Moreover, few studies have considered the interactions between the abiotic and biotic factors that regulate soil processes. Here we attempt to disentangle the interactive effects of two of the main factors that regulate soil processes at small scales - moisture and macrofauna assemblage composition. The response of assemblages of three common temperate soil invertebrates (Glomeris marginata Villers, Porcellio scaber Latreille and Philoscia muscorum Scopoli) to two contrasting soil moisture levels was examined in a series of laboratory mesocosm experiments. The contribution of the invertebrates to the leaf litter mass loss of two common temperate tree species of contrasting litter quality (easily decomposing Fraxinus excelsior L. and recalcitrant Quercus robur L.) and to soil CO2 fluxes were measured. Both moisture conditions and litter type influenced the functioning of the invertebrate assemblages, which was greater in high moisture conditions compared with low moisture conditions and on good quality vs. recalcitrant litter. In high moisture conditions, all macrofauna assemblages functioned at equal rates, whereas in low moisture conditions there were pronounced differences in litter mass loss among the assemblages. This indicates that species identity and assemblage composition are more important when moisture is limited. We suggest that complementarity between macrofauna species may mitigate the reduced functioning of some species, highlighting the importance of maintaining macrofauna species richness.

  12. Disruption of the melanin-concentrating hormone receptor 1 (MCH1R) affects thyroid function.

    PubMed

    Chung, Shinjae; Liao, Xiao-Hui; Di Cosmo, Caterina; Van Sande, Jacqueline; Wang, Zhiwei; Refetoff, Samuel; Civelli, Olivier

    2012-12-01

    Melanin-concentrating hormone (MCH) is a peptide produced in the hypothalamus and the zona incerta that acts on one receptor, MCH receptor 1 (MCH1R), in rodents. The MCH system has been implicated in the regulation of several centrally directed physiological responses, including the hypothalamus-pituitary-thyroid axis. Yet a possible direct effect of the MCH system on thyroid function has not been explored in detail. We now show that MCH1R mRNA is expressed in thyroid follicular cells and that mice lacking MCH1R [MCH1R-knockout (KO)] exhibit reduced circulating iodothyronine (T(4), free T(4), T(3), and rT(3)) levels and high TRH and TSH when compared with wild-type (WT) mice. Because the TSH of MCH1R-KO mice displays a normal bioactivity, we hypothesize that their hypothyroidism may be caused by defective thyroid function. Yet expression levels of the genes important for thyroid hormones synthesis or secretion are not different between the MCH1R-KO and WT mice. However, the average thyroid follicle size of the MCH1R-KO mice is larger than that of WT mice and contained more free and total T(4) and T(3) than the WT glands, suggesting that they are sequestered in the glands. Indeed, when challenged with TSH, the thyroids of MCH1R-KO mice secrete lower amounts of T(4). Similarly, secretion of iodothyronines in the plasma upon (125)I administration is significantly reduced in MCH1R-KO mice. Therefore, the absence of MCH1R affects thyroid function by disrupting thyroid hormone secretion. To our knowledge, this study is the first to link the activity of the MCH system to the thyroid function.

  13. Behavioral Functions of the Mesolimbic Dopaminergic System: an Affective Neuroethological Perspective

    PubMed Central

    Alcaro, Antonio; Huber, Robert; Panksepp, Jaak

    2008-01-01

    The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors, and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here, views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms. A description of the anatomical framework in which the ML system is embedded is followed by the argument that the SEEKING disposition emerges through functional integration of ventral basal ganglia (BG) into thalamocortical activities. Filtering cortical and limbic input that spread into BG, DA transmission promotes the “release” of neural activity patterns that induce active SEEKING behaviors when expressed at the motor level. Reverberation of these patterns constitutes a neurodynamic process for the inclusion of cognitive and perceptual representations within the extended networks of the SEEKING urge. In this way, the SEEKING disposition influences attention, incentive salience, associative learning, and anticipatory predictions. In our view, the rewarding properties of drugs of abuse are, in part, caused by the activation of the SEEKING disposition, ranging from appetitive drive to persistent craving depending on the intensity of the affect. The implications of such a view for understanding addiction are considered, with particular emphasis on factors predisposing individuals to develop compulsive drug seeking behaviors. PMID:17905440

  14. ADULT EXPOSURE TO PHYTOESTROGEN APIGENIN RESULTS IN CHANGES IN ENDOCRINE PARAMETERS BUT FAILS TO ALTER FECUNDITY

    EPA Science Inventory

    Plant-derived estrogens offer the opportunity to investigate the potential for weakly estrogenic compounds to influence endocrine function and reproduction. The presence of these phytoestrogens in foods, and agricultural and industrial runoff has the potential to increase the tot...

  15. USE OF THE LABORATORY RAT AS A MODEL IN ENDOCRINE DISRUPTOR SCREENING AND TESTING

    EPA Science Inventory

    The screening and testing program the US Environmental Protection Agency is currently developing to detect endocrine-disrupting chemicals (EDCs) is described. EDCs have been shown to alter the following activities: hypothalamic-pituitary-gonadal [HPG] function; estrogen, androge...

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

    EPA Science Inventory

    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...

  17. Exposure to Environmental Endocrine Disruptors and Child Development

    PubMed Central

    Meeker, John D.

    2013-01-01

    Exposure to exogenous chemicals can impact endocrine function at multiple sites and through numerous specific modes of action, which may have far-reaching impacts on human health and development. Widespread human exposure to numerous known or suspected endocrine disrupting chemicals (EDCs) has been documented in the US and worldwide, as have trends for increased rates of endocrine-related diseases and disorders among children. While human epidemiology studies of exposure to EDCs and children’s health remain extremely limited, there is a growing body of evidence showing that exposure to a number of chemicals commonly found in consumer goods, personal care products, food, drinking water, and other sources may adversely impact child development through altered endocrine function. This narrative review provides a brief introduction to several common EDCs (with a specific focus on persistent organic pollutants, phthalates, bisphenol A, and contemporary use pesticides, which only represents a small number of all known or suspected EDCs), an overview of the state of the human evidence for adverse impacts of EDCs on child development (fetal growth, early reproductive tract development, pubertal development, neurodevelopment, and obesity), guidance for health care providers based on current knowledge, and recommendations for future research. PMID:22664748

  18. The eye as a window to rare endocrine disorders

    PubMed Central

    Chopra, Rupali; Chander, Ashish; Jacob, Jubbin J.

    2012-01-01

    The human eye, as an organ, can offer critical clues to the diagnosis of various systemic illnesses. Ocular changes are common in various endocrine disorders such as diabetes mellitus and Graves’ disease. However there exist a large number of lesser known endocrine disorders where ocular involvement is significant. Awareness of these associations is the first step in the diagnosis and management of these complex patients. The rare syndromes involving the pituitary hypothalamic axis with significant ocular involvement include Septo-optic dysplasia, Kallman's syndrome, and Empty Sella syndrome all affecting the optic nerve at the optic chiasa. The syndromes involving the thyroid and parathyroid glands that have ocular manifestations and are rare include Mc Cune Albright syndrome wherein optic nerve decompression may occur due to fibrous dysplasia, primary hyperparathyroidism that may present as red eye due to scleritis and Ascher syndrome wherein ptosis occurs. Allgrove's syndrome, Cushing's disease, and Addison's disease are the rare endocrine syndromes discussed involving the adrenals and eye. Ocular involvement is also seen in gonadal syndromes such as Bardet Biedl, Turner's, Rothmund's, and Klinefelter's syndrome. This review also highlights the ocular manifestation of miscellaneous syndromes such as Werner's, Cockayne's, Wolfram's, Kearns Sayre's, and Autoimmune polyendocrine syndrome. The knowledge of these relatively uncommon endocrine disorders and their ocular manifestations will help an endocrinologist reach a diagnosis and will alert an ophthalmologist to seek specialty consultation of an endocrinologist when encountered with such cases. PMID:22629495

  19. EADB: an estrogenic activity database for assessing potential endocrine activity.

    PubMed

    Shen, Jie; Xu, Lei; Fang, Hong; Richard, Ann M; Bray, Jeffrey D; Judson, Richard S; Zhou, Guangxu; Colatsky, Thomas J; Aungst, Jason L; Teng, Christina; Harris, Steve C; Ge, Weigong; Dai, Susie Y; Su, Zhenqiang; Jacobs, Abigail C; Harrouk, Wafa; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2013-10-01

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.

  20. Endocrine control of epigenetic mechanisms in male reproduction.

    PubMed

    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.

  1. Cosmetics as endocrine disruptors: are they a health risk?

    PubMed

    Nicolopoulou-Stamati, Polyxeni; Hens, Luc; Sasco, Annie J

    2015-12-01

    Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

  2. The hidden life of NAD+-consuming ectoenzymes in the endocrine system.

    PubMed

    Malavasi, Fabio; Deaglio, Silvia; Zaccarello, Gianluca; Horenstein, Alberto L; Chillemi, Antonella; Audrito, Valentina; Serra, Sara; Gandione, Marina; Zitella, Andrea; Tizzani, Alessandro

    2010-10-01

    Ectoenzymes are a family of cell surface molecules whose catalytic domain lies in the extracellular region. A subset of this family, nucleotide-metabolizing ectoenzymes, are key components in the regulation of the extracellular balance between nucleotides (e.g. NAD(+) or ATP) and nucleosides (e.g. adenosine). Their substrates and products are signalling molecules that act by binding to specific receptors, triggering signals that regulate a variety of functions, ranging from the migration of immune cells, to synaptic transmission in the brain, to hormone/receptor interactions in the glands. Almost two decades of accumulated data indicate that these regulatory processes significantly affect the endocrine system, a tightly controlled information signal complex with clear evidence of fine regulation. Functional models discussed in this review include insulin secretion, bone modelling and the association between hormones and behaviour. The emerging pattern is one of a system operating as a scale-free network that hinges around hubs of key molecules, such as NAD(+) or ATP. The underlying natural link between nucleotides, ectoenzymes and the endocrine system is far from being clearly demonstrated. However, the body of evidence supporting the existence of such connection is growing exponentially. This review will try to read the available evidence in a hypothesis-oriented perspective, starting from the description of NAD(+) and of ecto- and endoenzymes involved in its metabolism.

  3. Histopathology of Growth Anomaly Affecting the Coral, Montipora capitata: Implications on Biological Functions and Population Viability

    PubMed Central

    Burns, John H. R.; Takabayashi, Misaki

    2011-01-01

    Growth anomalies (GAs) affect the coral, Montipora capitata, at Wai'ōpae, southeast Hawai'i Island. Our histopathological analysis of this disease revealed that the GA tissue undergoes changes which compromise anatomical machinery for biological functions such as defense, feeding, digestion, and reproduction. GA tissue exhibited significant reductions in density of ova (66.1–93.7%), symbiotic dinoflagellates (38.8–67.5%), mesenterial filaments (11.2–29.0%), and nematocytes (28.8–46.0%). Hyperplasia of the basal body wall but no abnormal levels of necrosis and algal or fungal invasion was found in GA tissue. Skeletal density along the basal body wall was significantly reduced in GAs compared to healthy or unaffected sections. The reductions in density of the above histological features in GA tissue were collated with disease severity data to quantify the impact of this disease at the colony and population level. Resulting calculations showed this disease reduces the fecundity of M. capitata colonies at Wai'ōpae by 0.7–49.6%, depending on GA severity, and the overall population fecundity by 2.41±0.29%. In sum, GA in this M. capitata population reduces the coral's critical biological functions and increases susceptibility to erosion, clearly defining itself as a disease and an ecological threat. PMID:22205976

  4. A systematic review of early life factors which adversely affect subsequent lung function.

    PubMed

    Kouzouna, A; Gilchrist, F J; Ball, V; Kyriacou, T; Henderson, J; Pandyan, A D; Lenney, W

    2016-09-01

    It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies.

  5. Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations.

    PubMed Central

    Léveillard, T; Andera, L; Bissonnette, N; Schaeffer, L; Bracco, L; Egly, J M; Wasylyk, B

    1996-01-01

    The p53 tumour suppressor is mutated in the majority of human tumours. p53's proposed role as the guardian of the genome is reflected in its multiple effects on transcription genome stability, cell growth and survival. We show that p53 interacts both physically and functionally with the TFIIH complex. There are multiple protein-protein contacts, involving two regions of p53 and three subunits of TFIIH, ERCC2 (XPD), ERCC3 (XPB) and p62. p53 and its C-terminus (amino acids 320-393) inhibit both of the TFIIH helicases and in vitro transcription in the absence of TFIIH. Transcription inhibition is overcome by TFIIH. The N-terminal region of p53 (1-320), lacking the C-terminus, is inactive on its own, yet apparently affects the activity of the C-terminus in the native protein. Interestingly, mutant p53s that are frequently found in tumours are less efficient inhibitors of the helicases and transcription. We hypothesize that the interactions provide an immediate and direct link for p53 to the multiple functions of TFIIH in transcription, DNA repair and possibly the cell cycle. Images PMID:8612585

  6. Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

    PubMed

    Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

    2016-01-15

    Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans.

  7. Mutations affecting a putative MutLα endonuclease motif impact multiple mismatch repair functions

    PubMed Central

    Erdeniz, Naz; Nguyen, Megan; Deschênes, Suzanne M.; Liskay, R. Michael

    2008-01-01

    Mutations in DNA mismatch repair (MMR) lead to increased mutation rates and higher recombination between similar, but not identical sequences, as well as resistance to certain DNA methylating agents. Recently, a component of human MMR machinery, MutLα, has been shown to display a latent endonuclease activity. The endonuclease active site appears to include a conserved motif, DQHA(X)2E(X)4E, within the COOH-terminus of human PMS2. Substitution of the glutamic acid residue (E705) abolished the endonuclease activity and mismatch-dependent excision in vitro. Previously, we showed that the PMS2-E705K mutation and the corresponding mutation in Saccharomyces cerevisiae were both recessive loss of function alleles for mutation avoidance in vivo. Here, we show that mutations impacting this endonuclease motif also significantly affect MMR-dependent suppression of homeologous recombination in yeast and responses to Sn1-type methylating agents in both yeast and mammalian cells. Thus, our in vivo results suggest that the endonuclease activity of MutLα is important not only in MMR-dependent mutation avoidance but also for recombination and damage response functions. PMID:17567544

  8. Recognizing menopause in women with amenorrhea induced by cytotoxic chemotherapy for endocrine-responsive early breast cancer.

    PubMed

    Torino, Francesco; Barnabei, Agnese; De Vecchis, Liana; Appetecchia, Marialuisa; Strigari, Lidia; Corsello, Salvatore M

    2012-04-01

    Cytotoxic anticancer treatment may induce amenorrhea or menopause to a variable extent. These side effects may not only impair or impede fertility but also cause sexual dysfunction, bone loss, and menopausal symptoms, with a strikingly negative effect on quality of life in many women. Aromatase inhibitors (AIs) are a recommended adjuvant endocrine treatment option in postmenopausal patients affected by early breast cancer (EBC) but are contraindicated in premenopausal women and in those with residual ovarian function. Women over 40 years of age with chemotherapy-induced amenorrhea (CIA) and routine hormonal levels consistent with menopause may receive an AI as adjuvant endocrine treatment. For these women, the tools available to identify menopause do not appear to be completely reliable. This review focused on the pathophysiology of ovarian toxicity induced by cytotoxic agents and on potentially useful methods to diagnose chemotherapy-induced menopause in patients treated with adjuvant chemotherapy for endocrine-responsive EBC. Moreover, practical approaches are proposed to distinguish true menopausal women, who would benefit from AIs, from those with transient or persistent CIA.

  9. Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormone-related cancer.

    PubMed

    Scsukova, Sona; Rollerova, Eva; Bujnakova Mlynarcikova, Alzbeta

    2016-12-01

    A growing body of evidence suggests that exposure to chemical substances designated as endocrine disrupting chemicals (EDCs) due to their ability to disturb endocrine (hormonal) activity in humans and animals, may contribute to problems with fertility, pregnancy, and other aspects of reproduction. The presence of EDCs has already been associated with reproductive malfunction in wildlife species, but it remains difficult to prove causal relationships between the presence of EDCs and specific reproductive problems in vivo, especially in females. On the other hand, the increasing number of experiments with laboratory animals and in vitro research indicate the ability of different EDCs to influence the normal function of female reproductive system, and even their association with cancer development or progression. Research shows that EDCs may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming. In this review article, we aim to point out a possible contribution of EDCs to the onset and development of female reproductive disorders and endocrine-related cancers with regard to the period of exposure to EDCs and affected endpoints (organs or processes).

  10. Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease

    PubMed Central

    Mills, Nicholas L.; Robinson, Simon D.; Fokkens, Paul H. B.; Leseman, Daan L. A. C.; Miller, Mark R.; Anderson, David; Freney, Evelyn J.; Heal, Mathew R.; Donovan, Robert J.; Blomberg, Anders; Sandström, Thomas; MacNee, William; Boon, Nicholas A.; Donaldson, Ken; Newby, David E.; Cassee, Flemming R.

    2008-01-01

    Background Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans. Objectives We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. Methods Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures. Results Particulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m3) were higher than ambient levels (31 ± 8 μg/m3) and levels in filtered air (0.5 ± 0.4 μg/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. Conclusions Despite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans. PMID:18560524

  11. Key soil functional properties affected by soil organic matter - evidence from published literature

    NASA Astrophysics Data System (ADS)

    Murphy, Brian

    2015-07-01

    The effect of varying the amount of soil organic matter on a range of individual soil properties was investigated using a literature search of published information largely from Australia, but also included relevant information from overseas. Based on published pedotransfer functions, soil organic matter was shown to increase plant available water by 2 to 3 mm per 10 cm for each 1% increase in soil organic carbon, with the largest increases being associated with sandy soils. Aggregate stability increased with increasing soil organic carbon, with aggregate stability decreasing rapidly when soil organic carbon fell below 1.2 to 1.5 5%. Soil compactibility, friability and soil erodibility were favourably improved by increasing the levels of soil organic carbon. Nutrient cycling was a major function of soil organic matter. Substantial amounts of N, P and S become available to plants when the soil organic matter is mineralised. Soil organic matter also provides a food source for the microorganisms involved in the nutrient cycling of N, P, S and K. In soils with lower clay contents, and less active clays such as kaolinites, soil organic matter can supply a significant amount of the cation exchange capacity and buffering capacity against acidification. Soil organic matter can have a cation exchange capacity of 172 to 297 cmol(+)/kg. As the cation exchange capacity of soil organic matter varies with pH, the effectiveness of soil organic matter to contribute to cation exchange capacity below pH 5.5 is often minimal. Overall soil organic matter has the potential to affect a range of functional soil properties.

  12. Susceptible periods during embryogenesis of the heart and endocrine glands.

    PubMed Central

    Sadler, T W

    2000-01-01

    One of the original principles of teratology states that, "Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence" [Wilson JG. Environment and Birth Defects. New York:Academic Press, 1973]. The time of greatest sensitivity encompasses the period of organ formation during weeks 3-8 following fertilization in human gestation. At this time, stem cell populations for each organ's morphogenesis are established and inductive events for the initiation of differentiation occur. Structural defects of the heart and endocrine system are no exception to this axiom and have their origins during this time frame. Although the function and maturation of these organs may be affected at later stages, structural defects and loss of cell types usually occur during these early phases of development. Thus, to determine critical windows for studying mechanisms of teratogenesis, it is essential to understand the developmental processes that establish these organs. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:10852854

  13. Alterations in cognitive performance and affect-arousal state during fluctuations in motor function in Parkinson's disease.

    PubMed Central

    Brown, R G; Marsden, C D; Quinn, N; Wyke, M A

    1984-01-01

    Sixteen patients with idiopathic Parkinson's disease were selected who were all showing severe fluctuations in motor function ("on-off" phenomenon). Measures of cognitive function and of subjective affect/arousal state were taken on two occasions, once when "on" and once when "off". Twenty-five matched normal controls were also assessed on the same measures. Results revealed, on the average, a drop in cognitive function plus an adverse swing in affect/arousal state, in the patient group in the "off" condition, compared to the levels when "on". Analysis of the data suggested that the main factor associated with cognitive function when "off" was not the severity of disability but the level of affect/arousal. The fluctuations in cognitive function found tended to be mild relative to the severe changes in motor ability, and were present in only a proportion of patients. PMID:6736975

  14. Altered mental status and endocrine diseases.

    PubMed

    Park, Elizabeth; Abraham, Michael K

    2014-05-01

    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with