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Sample records for neuroendocrine responses including

  1. Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

    Science.gov (United States)

    Lipiński, Michał; Rydzewska, Grażyna; Foltyn, Wanda; Andrysiak-Mamos, Elżbieta; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Blicharz-Dorniak, Jolanta; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Falconi, Massimo; Handkiewicz-Junak, Daria; Hubalewska-Dydejczyk, Alicja; Jarząb, Barbara; Junik, Roman; Kajdaniuk, Dariusz; Kamiński, Grzegorz; Kolasińska-Ćwikła, Agnieszka; Kowalska, Aldona; Król, Robert; Królicki, Leszek; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Londzin-Olesik, Magdalena; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Poczkaj, Karolina; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; Starzyńska, Teresa; Steinhof-Radwańska, Katarzyna; Strzelczyk, Janusz; Sworczak, Krzysztof; Syrenicz, Anhelli; Szawłowski, Andrzej; Szczepkowski, Marek; Wachuła, Ewa; Zajęcki, Wojciech; Zemczak, Anna; Zgliczyński, Wojciech; Kos-Kudła, Beata

    2017-01-01

    This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.

  2. Neuroendocrine aspects of the response to stress.

    Science.gov (United States)

    Miller, Diane B; O'Callaghan, James P

    2002-06-01

    Disruptions in homeostasis (ie, stress) place demands on the body that are met by the activation of 2 systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Stressor-induced activation of the HPA axis and the SNS results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Here we discuss the key elements of the HPA axis and the neuroendocrine response to stress. A challenge to homeostasis (a stressor) initiates the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which in turn results in release of adrenocortiotropin hormone (ACTH) into general circulation. ACTH then acts on the adrenal cortex resulting in release of a species-specific glucocorticoid into blood. Glucocorticoids act in a negative feedback fashion to terminate the release of CRH. The body strives to maintain glucocorticoid levels within certain boundaries and interference at any level of the axis will influence the other components via feedback loops. Over- or underproduction of cortisol can result in the devastating diseases of Cushing's and Addison's, respectively, but less severe dysregulation of the HPA axis can still have adverse health consequences. These include the deposition of visceral fat as well as cardiovascular disease (eg, atherosclerosis). Thus, chronic stress with its physical and psychological ramifications remains a persistent clinical problem for which new pharmacological treatment strategies are aggressively sought. To date, treatments have been based on the existing knowledge concerning the brain areas and neurobiological substrates that subserve the stress response. Thus, the CRH blocker, antalarmin, is being investigated as a treatment for chronic stress because it prevents CRH from having its

  3. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  4. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part II-specific NE tumour types

    DEFF Research Database (Denmark)

    Oberg, Kjell; Astrup, Lone Bording; Eriksson, Barbro

    2004-01-01

    Part II of the guidelines contains a description of epidemiology, histopathology, clinical presentation, diagnostic procedure, treatment, and survival for each type of neuroendocrine tumour. We are not only including gastroenteropancreatic tumours but also bronchopulmonary and thymic neuroendocrine...... tumours. These guidelines essentially cover basic knowledge in the diagnosis and management of the different forms of neuroendocrine tumour. We have, however, tried to give more updated information about the epidemiology and histopathology, which is essential for the clinical management of these tumours....

  5. A Case of Metastatic Urachal Cancer Including a Neuroendocrine Component Treated with Gemcitabine, Cisplatin and Paclitaxel Combination Chemotherapy.

    Science.gov (United States)

    Ebara, Shin; Kobayashi, Yasuyuki; Sasaki, Katsumi; Araki, Motoo; Sugimoto, Morito; Wada, Koichiro; Fujio, Kei; Takamoto, Atsushi; Watanabe, Toyohiko; Yanai, Hiroyuki; Nasu, Yasutomo

    2016-06-01

    The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/ paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m2) on day 1, 8, cisplatin (70mg/m2) on day 1, and paclitaxel (80mg/m2) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystourethrectomy, and histological examination showed an almost complete pathological response. External beam radiation therapy was also given to the ileac bone metastasis regions. However, PET-CT taken 17 months after the external beam radiation showed multiple lung metastases. He received GCP chemotherapy again, which resulted in a complete response again after three cycles of chemotherapy. This is the first report on GCP chemotherapy used not only as a salvage chemotherapy but also as a rechallenge regimen for metastatic urachal cancer including a neuroendocrine component.

  6. Multiple neuroendocrine responses to chronic social stress: interaction between individual characteristics and situational factors.

    Science.gov (United States)

    Mormède, P; Lemaire, V; Castanon, N; Dulluc, J; Laval, M; Le Moal, M

    1990-06-01

    After four weeks of individual housing, male Wistar rats (selected for high or low spontaneous aggressiveness by multiple round-robin encounters) were housed three per cage and submitted to four weeks of chronic social stress consisting of changing membership in the social groups by daily rotation of the animals among cages every day according to a random permutation procedure. In addition, half the males in each condition were housed with three females. Each environmental condition triggered different neuroendocrine changes. Cohabitation with females increased the hypothalamo-pituitary-adrenocortical axis activity, including enlargement of adrenals and increased circulating corticosterone levels. On the other hand, daily rotation of the rats between different social groups activated part of the sympathetic nervous system, such as increased phenylethanolamine N-methyl transferase (PNMT) activity in the adrenals. The level of aggressiveness, however, had no direct influence but interacted with environmental factors on such neuroendocrine measures as circulating testosterone or plasma renin activity. These results indicate that during chronic stress, there is no single, unique response by the animal, but a highly complex set of neuroendocrine changes, dependent on the interaction between individual characteristics (the level of aggressiveness is an example) and situational factors.

  7. Circadian variation in neuroendocrine response to L-dopa in patients with restless legs syndrome.

    Science.gov (United States)

    Garcia-Borreguero, Diego; Larrosa, Oscar; Granizo, Juan José; de la Llave, Yolanda; Hening, Wayne A

    2004-06-15

    To investigate circadian changes in dopaminergic function by means of a neuroendocrine challenge (growth hormone and prolactin responses to an acute oral administration of L-dopa) in patients with idiopathic restless legs syndrome (RLS) and controls. Randomized administration of the L-dopa neuroendocrine challenge. Sleep disorders laboratory at a 500-bed academic hospital. Twelve patients diagnosed with idiopathic RLS and 12 age- and sex-matched healthy controls. Following a comprehensive evaluation that included nocturnal polysomnographic study, all participants underwent the L-dopa neuroendocrine challenge on 2 occasions (11 am and 11 pm). Subjects were previously randomly assigned to the time of first challenge (11 am or 11 pm). On each occasion, subjects took 200 mg of L-dopa (plus 50 mg carbidopa) by mouth. Blood was drawn 20 minutes and 5 minutes before administration of the drug, as well as 15, 30, 45, 60, 75, 90, 102, and 120 minutes after administration. Prechallenge levels of plasma values of growth hormone or prolactin did not differ in the 2 subject groups. Following only the nighttime administration of L-dopa, RLS patients manifested a more pronounced inhibition of prolactin release and an increase in growth hormone secretion. Prolactin plasma levels were significantly correlated to the periodic limb movement index on the polysomnogram. These findings may reflect enhanced circadian variations in dopaminergic function and support an increased sensitivity at night of dopamine receptors in patients with RLS.

  8. Neuroendocrine and behavioral response to social confrontation: residents versus intruders, active versus passive coping styles.

    Science.gov (United States)

    Ebner, Karl; Wotjak, Carsten T; Landgraf, Rainer; Engelmann, Mario

    2005-01-01

    We investigated in the present study the neuroendocrine correlates in intruder and resident rats of a social confrontation. Adult male Wistar rats (intruders) were introduced into the home cage of a well-trained resident to induce characteristic agonistic interactions including physical attacks prior to separation by a wire mesh. The hypothalamic-pituitary-adrenal (HPA) axis activity and the intrahypothalamic release of arginine vasopressin (AVP) were monitored via chronically implanted jugular venous catheters and microdialysis probes aimed at the hypothalamic paraventricular nucleus (PVN), respectively. Based on the behavioral data collected during the 30-min confrontation, intruders and residents were additionally classified into two different subgroups: intruders which showed almost no freezing behavior (active copers) versus those showing pronounced freezing behavior (passive copers) and residents which were either predominantly aggressive or non-aggressive. The neuroendocrine data show that social confrontation caused a significantly increased secretion of the adrenocorticotropic hormone (ACTH) into plasma in both intruder subgroups, independently of their coping strategy. In contrast, plasma ACTH in residents was increased in response to social confrontation in non-aggressive animals only, whereas aggressive residents failed to mount an ACTH response. Interestingly, plasma AVP decreased in response to social confrontation in active intruders. As measured in microdialysates, the two groups of residents and passive intruders failed to show significant changes of intra-PVN release of AVP. In contrast, an increased release of this neuropeptide within the PVN could be monitored for active intruders. The data of the present study suggest that the different interpretation of an aversive encounter results in differences in the neuroendocrine response and intrahypothalamic vasopressinergic signaling in intruders versus residents.

  9. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model

    OpenAIRE

    Azeredo, Rita; Machado, Marina; Afonso, António; Fierro-Castro, Camino; Reyes-López, Felipe E.; Tort, Lluis; Gesto, Manuel; Conde-Sieira, Marta; Míguez, Jesús M.; José L. Soengas; Kreuz, Eva; Wuertz, Sven; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamin

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 ...

  10. Neuroendocrine and immune responses undertake different fates following tryptophan or methionine dietary treatment: Tales from a teleost model

    OpenAIRE

    Azeredo, Rita; Machado, Marina; Afonso, António; Fierro-Castro, Camino; Reyes-López, Felipe E.; Tort, Lluis; Gesto, Manuel; Conde-Sieira, Marta; Míguez, Jesús M.; José L. Soengas; Kreuz, Eva; Wuertz, Sven; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamin

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 ...

  11. Neuroendocrine and immune responses undertake different fates following tryptophan or methionine dietary treatment: tales from a teleost model

    OpenAIRE

    Rita Azeredo; Marina Machado; António Afonso; Camino Fierro-Castro; Reyes-López, Felipe E.; Lluis Tort; Manuel Gesto; Marta Conde-Sieira; Míguez, Jesús M.; José L. Soengas; Eva Kreuz; Sven Wuertz; Helena Peres; Aires Oliva-Teles; Benjamin Costas

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 ...

  12. Altered Neuroendocrine Immune Responses, a Two-Sword Weapon against Traumatic Inflammation.

    Science.gov (United States)

    Yang, Ce; Gao, Jie; Du, Juan; Yang, Xuetao; Jiang, Jianxin

    2017-01-01

    During the occurrence and development of injury (trauma, hemorrhagic shock, ischemia and hypoxia), the neuroendocrine and immune system act as a prominent navigation leader and possess an inter-system crosstalk between the reciprocal information dissemination. The fundamental reason that neuroendocrinology and immunology could mix each other and permeate toward the field of traumatology is owing to their same biological languages or chemical information molecules (hormones, neurotransmitters, neuropeptides, cytokines and their corresponding receptors) shared by the neuroendocrine and immune systems. The immune system is not only modulated by the neuroendocrine system, but also can modulate the biological functions of the neuroendocrine system. The interactive linkage of these three systems precipitates the complicated space-time patterns for the courses of traumatic inflammation. Recently, compelling evidence indicates that the network linkage pattern that initiating agents of neuroendocrine responses, regulatory elements of immune cells and effecter targets for immune regulatory molecules arouse the resistance mechanism disorders, which supplies the beneficial enlightenment for the diagnosis and therapy of traumatic complications from the view of translational medicine. Here we review the alternative protective and detrimental roles as well as possible mechanisms of the neuroendocrine immune responses in traumatic inflammation.

  13. Central Mechanisms Underlying Variability in the Behavioral and Neuroendocrine Responses to Stress in Fish

    DEFF Research Database (Denmark)

    Moltesen, Maria Møller

    . The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) also plays an important role in the neuroendocrine stress response by controlling CRF release in hypothalamus. The transmission of 5-HT and CRF are under feedback control of glucocorticoids and interact with the stress response by affecting processes...... in the limbic system. In fish, the telencephalon contains regions that are functional homologues to the mammalian limbic system including amygdala and hippocampus. However, the involvement of this brain region in the regulation of the hypothalamicpituitary- interrenal (HPI) axis, the homologue of the mammalian...... glucocorticoid in fish, and if these effects were related to changes in neurochemistry and gene expression in the telencephalon of rainbow trout (Oncorhynchus mykiss). The results showed that chronic stress affected HPI axis reactivity and serotonergic neurochemistry in the telencephalon. Moreover, effects...

  14. Similar cold stress induces sex-specific neuroendocrine and working memory responses.

    Science.gov (United States)

    Solianik, Rima; Skurvydas, Albertas; Urboniene, Daiva; Eimantas, Nerijus; Daniuseviciute, Laura; Brazaitis, Marius

    2015-01-01

    Men have higher cold-induced neuroendocrine response than women; nevertheless, it is not known whether a different stress hormone rise elicits different effects on cognition during whole body cooling. The objective was to compare the effect of cold-induced neuroendocrine responses on the performance of working memory sensitive tasks between men and women. The cold stress continued until rectal temperature reached 35.5 degree C or for a maximum of 170 min. Working memory performance and stress hormone concentrations were monitored. During cold stress, body temperature variables dropped in all subjects (P stress raised plasma epinephrine and serum cortisol levels only in men (P stress adversely affected memory performance in men but not in women (P stress in men and women induces sex-specific neuroendocrine and working memory responses.

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

    Science.gov (United States)

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

    2006-10-01

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

  16. Current Concepts in Neuroendocrine Disruption

    Science.gov (United States)

    2014-01-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  17. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival

    National Research Council Canada - National Science Library

    Gupta, Sanjay; Johnson, Marcella M; Murthy, Ravi; Ahrar, Kamran; Wallace, Michael J; Madoff, David C; McRae, Stephen E; Hicks, Marshall E; Rao, Sujaya; Vauthey, Jean-Nicolas; Ajani, Jaffer A; Yao, James C

    2005-01-01

    The objective of this study was to determine the prognostic variables that influence response and survival in patients with metastatic neuroendocrine tumors who are treated with hepatic arterial embolization (HAE...

  18. Neuroendocrine stress responses predict catecholamine-dependent working memory-related dorsolateral prefrontal cortex activity.

    Science.gov (United States)

    Hernaus, Dennis; Quaedflieg, Conny W E M; Offermann, Jan Stefan; Casales Santa, Marta M; van Amelsvoort, Thérèse

    2018-01-01

    It is generally thought that the effect of acute stress on higher-order functions such as working memory is, for an important part, mediated by central catecholamine activity. However, little is known about the association between neuroendocrine stress responses and catecholamine-dependent working memory-related brain function in the absence of stress. Here, we investigate for the first time in healthy humans (n = 18) how neuroendocrine responses to stress (cortisol and alpha-amylase) relate to fronto-parietal working memory activity changes in response to atomoxetine, a noradrenaline transporter inhibitor that selectively increases extracellular cortical dopamine and noradrenaline. We observed positive correlations between stress-induced cortisol (Pearson's r = 0.75, P working memory-related activity in dorsolateral prefrontal cortex. Stress-induced cortisol increases furthermore correlated with supramarginal gyrus working memory-related activity (r = 0.79, P working memory activity on placebo and greater working memory activity increases following atomoxetine in high stress responders. These results further corroborate the notion that neuroendocrine responses to stress are an informative proxy of catecholamine function relevant to higher order functions and provide novel hints on the complex relationship between acute stress, catecholamine function and working memory. © The Author (2017). Published by Oxford University Press.

  19. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  20. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model

    Directory of Open Access Journals (Sweden)

    Rita Azeredo

    2017-09-01

    Full Text Available Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level or a control diet meeting the amino acids requirement levels (CTRL. Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led to increased levels of plasma cortisol after the inflammatory insult, while brain monoamine content was higher in TRP-fed fish. Peripheral blood respiratory burst was higher in TRP-fed fish injected with the bacteria inoculum but only compared to those fed MET. However, no changes were detected in total antioxidant capacity. Complement factor 3 was upregulated in MET-fed fish but methionine seemed to poorly affect other genes expression patterns. In contrast, fish fed MET showed increased immune cells numbers both before and after immune challenge, suggesting a strong enhancing effect of methionine on immune cells proliferation. Differently, tryptophan effects on inflammatory transcripts suggested an inhibitory mode of action. This, together

  1. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model.

    Science.gov (United States)

    Azeredo, Rita; Machado, Marina; Afonso, António; Fierro-Castro, Camino; Reyes-López, Felipe E; Tort, Lluis; Gesto, Manuel; Conde-Sieira, Marta; Míguez, Jesús M; Soengas, José L; Kreuz, Eva; Wuertz, Sven; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamin

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level) or a control diet meeting the amino acids requirement levels (CTRL). Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led to increased levels of plasma cortisol after the inflammatory insult, while brain monoamine content was higher in TRP-fed fish. Peripheral blood respiratory burst was higher in TRP-fed fish injected with the bacteria inoculum but only compared to those fed MET. However, no changes were detected in total antioxidant capacity. Complement factor 3 was upregulated in MET-fed fish but methionine seemed to poorly affect other genes expression patterns. In contrast, fish fed MET showed increased immune cells numbers both before and after immune challenge, suggesting a strong enhancing effect of methionine on immune cells proliferation. Differently, tryptophan effects on inflammatory transcripts suggested an inhibitory mode of action. This, together with a high

  2. Gender-specific cold responses induce a similar body-cooling rate but different neuroendocrine and immune responses.

    Science.gov (United States)

    Solianik, Rima; Skurvydas, Albertas; Vitkauskienė, Astra; Brazaitis, Marius

    2014-08-01

    This study investigated whether there are any gender differences in body-heating strategies during cold stress and whether the immune and neuroendocrine responses to physiological stress differ between men and women. Thirty-two participants (18 men and 14 women) were exposed to acute cold stress by immersion to the manubrium level in 14 °C water. The cold stress continued until rectal temperature (TRE) reached 35.5 °C or for a maximum of 170 min. The responses to cold stress of various indicators of body temperature, insulation, metabolism, shivering, stress, and endocrine and immune function were compared between men and women. During cold stress, TRE and muscle and mean skin temperatures decreased in all subjects (Pcold strain did not differ between men and women, but men exhibited larger changes in the indicators of neuroendocrine (epinephrine level) and in immune (tumor necrosis factor-α level) responses (both Pcold stress, whereas women exhibited a greater insulative response. Despite the similar experience of cold strain in men and women, the neuroendocrine and immune responses were larger in men. Contrary to our expectations, the cooling rate was similar in men and women. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Effect of yoga on sleep quality and neuroendocrine immune response in metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Raghavendra Mohan Rao

    2017-01-01

    Full Text Available Background: Studies have shown that distress and accompanying neuroendocrine stress responses as important predictor of survival in advanced breast cancer patients. Some psychotherapeutic intervention studies have shown have modulation of neuroendocrine-immune responses in advanced breast cancer patients. In this study, we evaluate the effects of yoga on perceived stress, sleep, diurnal cortisol, and natural killer (NK cell counts in patients with metastatic cancer. Methods: In this study, 91 patients with metastatic breast cancer who satisfied selection criteria and consented to participate were recruited and randomized to receive “integrated yoga based stress reduction program” (n = 45 or standard “education and supportive therapy sessions” (n = 46 over a 3 month period. Psychometric assessments for sleep quality were done before and after intervention. Blood draws for NK cell counts were collected before and after the intervention. Saliva samples were collected for three consecutive days before and after intervention. Data were analyzed using the analysis of covariance on postmeasures using respective baseline measure as a covariate. Results: There was a significant decrease in scales of symptom distress (P < 0.001, sleep parameters (P = 0.02, and improvement in quality of sleep (P = 0.001 and Insomnia Rating Scale sleep score (P = 0.001 following intervention. There was a decrease in morning waking cortisol in yoga group (P = 0.003 alone following intervention. There was a significant improvement in NK cell percent (P = 0.03 following intervention in yoga group compared to control group. Conclusion: The results suggest modulation of neuroendocrine responses and improvement in sleep in patients with advanced breast cancer following yoga intervention.

  4. Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study

    Science.gov (United States)

    2017-01-05

    Poorly Differentiated Malignant Neuroendocrine Carcinoma; Neuroendocrine Carcinoma, Grade 3; Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

  5. Neuroendocrine and behavioral responses and brain pattern of c-fos induction associated with audiogenic stress.

    Science.gov (United States)

    Campeau, S; Watson, S J

    1997-08-01

    The present study determined simultaneously the behavioural, neuroendocrine and regional brain activity, using semi-quantitative analysis of c-fos mRNA induction, produced by 30 min of auditory stimulation at different white noise intensities (background 60 dB, 70, 80, 90 and 105 dBA), in rats. Only the highest noise intensities (90 and 105 dB) significantly increased corticosterone release after 30 min stimulation. Behaviourally, the 105 dB noise condition reliably reduced overall activity, and moderate noise intensities (70 and 80 dB) increased sleeping time. Three distinct patterns of c-fos mRNA induction were observed. First, following exposure to the experimental cages, a wide pattern of brain activation was obtained in experimental animals irrespective of noise intensity presentation, compared to the naive rats. Second, a number of auditory structures (cochlear nuclei, superior olivary complex, nuclei of the lateral lemniscus, inferior colliculus and the medial division of the medial geniculate body) displayed a clear intensity-dependent increase in c-fos induction. Third, compared to all other conditions, the stressed rats (90 and 105 dB conditions) displayed significantly higher c-fos induction in relatively few areas. Particularly intense c-fos induction was observed in the bed nucleus of the stria terminalis, especially its anterior medial and ventral aspects, the septohypothalamic nucleus, the ventral lateral septum, the ventral portion of the dentate gyrus, a number of hypothalamic nuclei including the lateral preoptic area, the medial preoptic nucleus and the paraventricular nucleus, the median raphe and the pedunculopontine tegmental nucleus. The involvement of a number of these structures in a specific audiogenic stress responsive circuit is discussed.

  6. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part I-general overview

    DEFF Research Database (Denmark)

    Oberg, Kjell; Astrup, Lone; Eriksson, Barbro

    2004-01-01

    The incidence of neuroendocrine tumours of the gastroenteropancreatic system seems to have increased during the past decade. New diagnostic and therapeutic procedures have aroused the interest of physicians, though most see very few cases of such diseases. A group of members of the Nordic Neuroen...

  7. The effects of hydrotherapy on anxiety, pain, neuroendocrine responses, and contraction dynamics during labor.

    Science.gov (United States)

    Benfield, Rebecca D; Hortobágyi, Tibor; Tanner, Charles J; Swanson, Melvin; Heitkemper, Margaret M; Newton, Edward R

    2010-07-01

    Hydrotherapy (immersion or bathing) is used worldwide to promote relaxation and decrease parturient anxiety and pain in labor, but the psychophysiological effects of this intervention remain obscure. A pretest-posttest design with repeated measures was used to examine the effects of hydrotherapy on maternal anxiety and pain, neuroendocrine responses, plasma volume shift (PVS), and uterine contractions (CXs) during labor. Correlations among variables were examined at three time points (preimmersion and twice during hydrotherapy). Eleven term women (mean age 24.5 years) in spontaneous labor were immersed to the xiphoid in 37 degrees C water for 1 hr. Blood samples and measures of anxiety and pain were obtained under dry baseline conditions and repeated at 15 and 45 min of hydrotherapy. Uterine contractions were monitored telemetrically. Hydrotherapy was associated with decreases in anxiety, vasopressin (V), and oxytocin (O) levels at 15 and 45 min (all ps hydrotherapy for women with high baseline pain as for those with low baseline pain. beta-endorphin (betaE) levels increased at 15 min but did not differ between baseline and 45 min. During immersion, CX frequency decreased. A positive PVS at 15 min was correlated with contraction duration. Hydrotherapy during labor affects neuroendocrine responses that modify psychophysiological processes.

  8. Serotonergic and dopaminergic neuroendocrine responses of male depressive patients before and after a therapeutic ECT course.

    Science.gov (United States)

    Markianos, Manolis; Hatzimanolis, John; Lykouras, Lefteris

    2002-08-01

    Electroconvulsive therapy (ECT) is an effective treatment for major depressive illness, even for patients who do not respond to antidepressant drugs. According to the prevailing neurophysiological hypotheses for depression, it can be expected that an ECT therapeutic course modulates the responsivity of central neurotransmitter systems, but the results up to now have been inconclusive. To test such hypotheses, we studied possible changes in the serotonergic and in dopaminergic systems' responsivity in 11 male patients with major depression by performing neuroendocrine challenge tests before and after a therapeutic ECT course. Serotonergic responsivity was assessed by measuring the prolactin and cortisol responses to i. v. administration of the serotonin uptake inhibitor clomipramine (CMI test), and dopaminergic responsivity by measuring the prolactin responses to the dopamine receptor blocker haloperidol (HAL test), administered intramuscularly. The prolactin and cortisol responses during the first and the last ECT of the course (8 to 13 sessions) were also assessed. The CMI and HAL tests were also performed in 13 male healthy subjects. The prolactin responses to CMI were significantly blunted in the patient group compared to the control group, and remained unaltered at the end of the ECT course, although the depressive symptomatology was substantially reduced from 27.8 +/- 7.1 to 4.8 +/- 2.3 points in the Hamilton Depression Rating Scale. The cortisol responses to CMI were blunted before the ECT course compared to controls, but not after the course: there was a moderate increase of cortisol at + 30 min in the CMI test after the ECT course compared to that before ECT (p = 0.05). The prolactin and cortisol responses to the electrical stimulus during the first and the last ECT were identical. The strong therapeutic effect of ECT in depression, observed already at the end of the course, is not a result of considerable modifications in central serotonergic or

  9. Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

    Science.gov (United States)

    Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

    2012-01-01

    Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

  10. Effect of maternal restraint stress during gestation on temporal lipopolysaccharide-induced neuroendocrine and immune responses of progeny

    Science.gov (United States)

    The impact of gestational dam restraint stress on progeny immune and neuroendocrine temporal hormone responses to lipopoly-saccharide (LPS) challenge was assessed. Maternal stress (5-min snout snare restraint stress during days 84 to 112 of gestation) increased (P < 0.05) the magnitude of tumor necr...

  11. Trait mindfulness modulates neuroendocrine and affective responses to social evaluative threat.

    Science.gov (United States)

    Brown, Kirk Warren; Weinstein, Netta; Creswell, J David

    2012-12-01

    Individual differences in mindfulness have been associated with numerous self-report indicators of stress, but research has not examined how mindfulness may buffer neuroendocrine and psychological stress responses under controlled laboratory conditions. The present study investigated the role of trait mindfulness in buffering cortisol and affective responses to a social evaluative stress challenge versus a control task. Participants completed measures of trait mindfulness, perceived stress, anxiety, and fear of negative evaluation before being randomized to complete the Trier Social Stress Test (TSST; Kirschbaum et al., 1993) or a control task. At points throughout the session, participants provided five saliva samples to assess cortisol response patterns, and completed four self-report measures of anxiety and negative affect to assess psychological responses. In accord with hypotheses, higher trait mindfulness predicted lower cortisol responses to the TSST, relative to the control task, as well as lower anxiety and negative affect. These relations remained significant when controlling for the role of other variables that predicted cortisol and affective responses. The findings suggest that trait mindfulness modulates cortisol and affective responses to an acute social stressor. Further research is needed to understand the neural pathways through which mindfulness impacts these responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. The medial amygdala modulates body weight but not neuroendocrine responses to chronic stress.

    Science.gov (United States)

    Solomon, M B; Jones, K; Packard, B A; Herman, J P

    2010-01-01

    Stress pathologies such as depression and eating disorders (i.e. anorexia nervosa) are associated with amygdalar dysfunction, which are linked with hypothalamic-pituitary-adrenal axis (HPA) axis hyperactivity. The medial amygdaloid nucleus (MeA), a key output nucleus of the amygdaloid complex, promotes HPA axis activation to acute psychogenic stress and is in a prime position to mediate the deleterious effects of chronic stress on physiology and behaviour. The present study tests the hypothesis that the MeA is necessary for the development of maladaptive physiological changes caused by prolonged stress exposure. Male rats received bilateral ibotenate or sham lesions targeting the MeA and one half underwent 2 weeks of chronic variable stress (CVS) or served as home cage controls. Sixteen hours post CVS, all animals were exposed to an acute restraint challenge. CVS induced thymic involution, adrenal hypertrophy, and attenuated body weight gain and up-regulation of hypothalamic corticotrophin-releasing hormone mRNA expression. Consistent with previous literature, lesions of the MeA dampened stress-induced increases in corticosterone after 30 min of exposure to acute restraint stress. However, this effect was independent of CVS exposure, suggesting that the MeA may not be critical for modulating neuroendocrine responses after chronic HPA axis drive. Interestingly, lesion of the MeA modestly exaggerated the stress-induced attenuation of weight gain. Overall, the data obtained suggest that the MeA modulates the neuroendocrine responses to acute but not chronic stress. In addition, the data suggest that the MeA may be an important neural component for the control of body weight in the face of chronic stress.

  13. A Unique "Angiotensin-Sensitive" Neuronal Population Coordinates Neuroendocrine, Cardiovascular, and Behavioral Responses to Stress.

    Science.gov (United States)

    de Kloet, Annette D; Wang, Lei; Pitra, Soledad; Hiller, Helmut; Smith, Justin A; Tan, Yalun; Nguyen, Dani; Cahill, Karlena M; Sumners, Colin; Stern, Javier E; Krause, Eric G

    2017-03-29

    Stress elicits neuroendocrine, autonomic, and behavioral responses that mitigate homeostatic imbalance and ensure survival. However, chronic engagement of such responses promotes psychological, cardiovascular, and metabolic impairments. In recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses. Initial studies use neuroanatomical techniques to reveal that angiotensin type-1a receptors are localized predominantly to the parvocellular neurosecretory neurons of the paraventricular nucleus of the hypothalamus. These neurons are almost exclusively glutamatergic and send dense projections to the exterior portion of the median eminence. Furthermore, these neurons largely express corticotrophin-releasing hormone or thyrotropin-releasing hormone and do not express arginine vasopressin or oxytocin. Functionally, optogenetic stimulation of these neurons promotes the activation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as well as a rise in systolic blood pressure. When these neurons are optogenetically inhibited, the activity of these neuroendocrine axes are suppressed and anxiety-like behavior in the elevated plus maze is dampened. Collectively, these studies implicate this neuronal population in the integration and coordination of the physiological responses to stress and may therefore serve as a potential target for therapeutic intervention for stress-related pathology.SIGNIFICANCE STATEMENT Chronic stress leads to an array of physiological responses that ultimately

  14. Mediators of compassionate goal intervention effects on human neuroendocrine responses to the Trier Social Stress Test.

    Science.gov (United States)

    Erickson, Thane M; Mayer, Stefanie E; Lopez-Duran, Nestor L; Scarsella, Gina M; McGuire, Adam P; Crocker, Jennifer; Abelson, James L

    2017-11-01

    The hypothalamic-pituitary-adrenal (HPA) axis is thought to mediate the effects of stress on illness. Research has identified a limited number of psychological variables that modulate human HPA responses to stressors (e.g. perceived control and social support). Prosocial goals can reduce subjective stress, but have not been carefully examined in experimental settings where pathways of impact on biological stress markers may be traced. Recent work demonstrated that coaching individuals to strive to help others reduced HPA responses to the Trier Social Stress Test (TSST) relative to other cognitive interventions. However, identification of mediational pathways, which were not examined in the original study, is necessary to determine whether the HPA buffering effects were due to helping motivations (compassionate goals; CGs) rather than via previously identified variables such as control or support. In this new analysis, we combined the original cortisol data with novel observer ratings of interpersonal behavior and psychological variables during the stress task, and conducted new, theory-driven analyses to determine psychological mediators for the intervention's effect on cortisol responses (N = 54; 21 females, 33 males; 486 cortisol samples). Control, support, and task ego-threat failed to account for the effects of the intervention. As hypothesized, self and observer-rated CGs, as well as observer-rated perceptions of participants' interpersonal behavior as morally desirable (but not as dominant or affiliative) were significant mediators of neuroendocrine responses. The findings suggest that stress-reduction interventions based on prosocial behavior should target particular motivational and interpersonal features.

  15. The neuroendocrine response of luteinizing hormone to estrogen administration in heterosexual, homosexual, and transsexual subjects.

    Science.gov (United States)

    Gooren, L

    1986-09-01

    The neuroendocrine response of LH to estrogen administration may be related to sexual dimorphism of the brain, and therefore, homosexual and especially transsexual individuals may differ from heterosexual individuals in their responses. This study failed to find such differences among groups of female heterosexuals, homosexuals, and transsexuals. Specifically, after single dose estrogen administration, all subjects had an initial decline in serum LH levels, followed by a brisk rise of equal magnitude. Among males, the type of response was less uniform. After an initial fall in serum LH levels, the individual responses varied. In 12 of 23 male homosexuals, 10 of 15 male heterosexuals, and all 6 genetic male transsexuals studied, serum LH levels remained below pretreatment levels. In the remaining 11 male homosexuals and 5 of the heterosexuals, serum LH levels increased to values exceeding those before treatment, resembling the response found in the 3 groups of women. Those homosexual and heterosexual men with a rise in serum LH levels to above pretreatment values also had the greatest fall in testosterone levels after estrogen administration, while these same men had the lowest testosterone response to hCG stimulation. I conclude from these results that 1) the similarity of LH responses to estrogen administration in all groups of women studied does not support a theory of brain androgenization as a factor in the establishment of gender identity of sexual orientation; and 2) individual differences in men in the type of LH response to estrogen administration can be satisfactorily explained by endocrine factors, such as Leydig cell function, and need not be related to gender identity, sexual orientation, or other possible causes.

  16. Epigenetic programming of the neuroendocrine stress response by adult life stress

    NARCIS (Netherlands)

    Dirven, B.C.J.; Homberg, J.R.; Kozicz, L.T.; Henckens, M.J.A.G.

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is critically involved in the neuroendocrine regulation of stress adaptation, and the restoration of homeostasis following stress exposure. Dysregulation of this axis is associated with stress-related pathologies like major depressive disorder,

  17. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.

    OpenAIRE

    Bang, Y J; Pirnia, F; Fang, W G; Kang, W K; Sartor, O; Whitesell, L; Ha, M J; Tsokos, M.; Sheahan, M D; Nguyen, P.

    1994-01-01

    Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analog...

  18. Neuroendocrine and immune responses undertake different fates following tryptophan or methionine dietary treatment: tales from a teleost model

    DEFF Research Database (Denmark)

    Azeredo, Rita; Machado, M.; Afonso, A.

    2017-01-01

    the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2x dietary requirement level) or a control...... diet meeting the amino acids requirement levels (CTRL). Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity......, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led...

  19. mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Falletta, Simona; Partelli, Stefano; Rubini, Corrado; Nann, Dominik; Doria, Andrea; Marinoni, Ilaria; Polenta, Vanessa; Di Pasquale, Carmelina; Degli Uberti, Ettore; Perren, Aurel; Falconi, Massimo; Zatelli, Maria Chiara

    2016-11-01

    Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viability and induced apoptosis in primary cultures of 6 P-NET (P-NET-R), where the proliferative and antiapoptotic effects of IGF1 were blocked by Everolimus. On the contrary, 14 P-NET primary cultures (P-NET-NR) were resistant to Everolimus and IGF1, suggesting an involvement of PI3K/AKT/mTOR pathway in the mechanism of resistance. The response to Everolimus in vitro was associated with an active AKT/mTOR pathway and seemed to be associated with a greater clinical aggressiveness. In addition, a patient sensitive to Everolimus in vitro was sensitive to this drug in vivo also and showed a positive p-AKT immunohistochemistry (IHC) at tissue level. Similarly, a patient resistant to Everolimus treatment after surgery was not sensitive to the drug in vitro and had a negative p-AKT IHC staining. Therefore, present data confirm that P-NET primary cultures may be considered a model for testing medical treatment efficacy and that IHC characterization of p-AKT might help in identifying human P-NET who can benefit from Everolimus treatment. These data encourage conducting a prospective multicenter study involving different groups of P-NET patients treated with Everolimus. © 2016 Society for Endocrinology.

  20. Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

    Science.gov (United States)

    D'Orsogna, Maria; Chou, Tom; Kim, Lae

    The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

  1. Adiposity is associated with blunted cardiovascular, neuroendocrine and cognitive responses to acute mental stress.

    Directory of Open Access Journals (Sweden)

    Alexander Jones

    Full Text Available Obesity and mental stress are potent risk factors for cardiovascular disease but their relationship with each other is unclear. Resilience to stress may differ according to adiposity. Early studies that addressed this are difficult to interpret due to conflicting findings and limited methods. Recent advances in assessment of cardiovascular stress responses and of fat distribution allow accurate assessment of associations between adiposity and stress responsiveness. We measured responses to the Montreal Imaging Stress Task in healthy men (N = 43 and women (N = 45 with a wide range of BMIs. Heart rate (HR and blood pressure (BP measures were used with novel magnetic resonance measures of stroke volume (SV, cardiac output (CO, total peripheral resistance (TPR and arterial compliance to assess cardiovascular responses. Salivary cortisol and the number and speed of answers to mathematics problems in the task were used to assess neuroendocrine and cognitive responses, respectively. Visceral and subcutaneous fat was measured using T(2 (*-IDEAL. Greater BMI was associated with generalised blunting of cardiovascular (HR:β = -0.50 bpm x unit(-1, P = 0.009; SV:β = -0.33 mL x unit(-1, P = 0.01; CO:β = -61 mL x min(-1 x unit(-1, P = 0.002; systolic BP:β = -0.41 mmHg x unit(-1, P = 0.01; TPR:β = 0.11 WU x unit(-1, P = 0.02, cognitive (correct answers: r = -0.28, P = 0.01; time to answer: r = 0.26, P = 0.02 and endocrine responses (cortisol: r = -0.25, P = 0.04 to stress. These associations were largely determined by visceral adiposity except for those related to cognitive performance, which were determined by both visceral and subcutaneous adiposity. Our findings suggest that adiposity is associated with centrally reduced stress responsiveness. Although this may mitigate some long-term health risks of stress responsiveness, reduced performance under stress may be a more immediate

  2. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...... of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs...

  3. Impact of the gut microbiota on the neuroendocrine and behavioural responses to stress in rodents

    Directory of Open Access Journals (Sweden)

    Rabot Sylvie

    2016-01-01

    Full Text Available The gastro-intestinal tract hosts a complex microbial ecosystem, the gut microbiota, whose collective genome coding capacity exceeds that of the host genome. The gut microbiota is nowadays regarded as a full organ, likely to contribute to the development of pathologies when its dynamic balance is disrupted (dysbiosis. In the last decade, evidence emerged that the gut microbiota influences brain development and function. In particular, comparisons between germ-free and conventional laboratory rodents showed that the absence of the gut microbiota exacerbates the hypothalamic pituitary adrenal (HPA system reactivity to stress and alters the anxiety-like behaviour. Furthermore, the dysfunctions observed in germ-free animals can be corrected if the gut microbiota is restored in early life but not in adulthood, suggesting a critical period for microbiota imprinting on the responsiveness to stress. The modes of action are still to be deciphered. They may involve transport of neuroactive bacterial metabolites to the brain through the bloodstream, stimulation of the vagus nerve or of entero-endocrine cells, or modulation of the immune system and, consequently, of the inflammatory status. The discovery that the gut microbiota regulates the neuroendocrine and behavioural responses to stress paves the way for the hypothesis that gut microbiota dysbioses could contribute to the pathophysiology of anxiety-related disorders. In this regard, treatments of anxiety-prone rodent strains with probiotics or antibiotics aimed at modifying their gut microbiota have shown an anxiolytic-like activity. Clinical trials are now needed to know if results obtained in preclinical studies can translate to humans.

  4. Effect of a synthetic appeasing pheromone on behavioral, neuroendocrine, immune, and acute-phase perioperative stress responses in dogs.

    Science.gov (United States)

    Siracusa, Carlo; Manteca, Xavier; Cuenca, Rafaela; del Mar Alcalá, Maria; Alba, Aurora; Lavín, Santiago; Pastor, Josep

    2010-09-15

    To study the effects of a synthetic, dog-appeasing pheromone (sDAP) on the behavioral, neuroendocrine, immune, and acute-phase perioperative stress responses in dogs undergoing elective orchiectomy or ovariohysterectomy. Randomized, controlled clinical trial. 46 dogs housed in animal shelters and undergoing elective orchiectomy or ovariohysterectomy. Intensive care unit cages were sprayed with sDAP solution or sham treated with the carrier used in the solution 20 minutes prior to use. Dogs (n = 24 and 22 in the sDAP and sham treatment exposure groups, respectively) were placed in treated cages for 30 minutes before and after surgery. Indicators of stress (ie, alterations in behavioral, neuroendocrine, immune, and acute-phase responses) were evaluated perioperatively. Behavioral response variables, salivary cortisol concentration, WBC count, and serum concentrations of glucose, prolactin, haptoglobin, and C-reactive protein were analyzed. Behavioral response variables and serum prolactin concentration were influenced by sDAP exposure. Dogs exposed to sDAP were more likely to have alertness and visual exploration behaviors after surgery than were dogs exposed to sham treatment. Decreases in serum prolactin concentrations in response to perioperative stress were significantly smaller in dogs exposed to sDAP, compared with findings in dogs exposed to the sham treatment. Variables examined to evaluate the hypothalamic-pituitary-adrenal axis, immune system, and acute-phase responses were unaffected by treatment. sDAP appeared to affect behavioral and neuroendocrine perioperative stress responses by modification of lactotropic axis activity. Use of sDAP in a clinical setting may improve the recovery and welfare of dogs undergoing surgery.

  5. Brief mindfulness meditation training alters psychological and neuroendocrine responses to social evaluative stress.

    Science.gov (United States)

    Creswell, J David; Pacilio, Laura E; Lindsay, Emily K; Brown, Kirk Warren

    2014-06-01

    To test whether a brief mindfulness meditation training intervention buffers self-reported psychological and neuroendocrine responses to the Trier Social Stress Test (TSST) in young adult volunteers. A second objective evaluates whether pre-existing levels of dispositional mindfulness moderate the effects of brief mindfulness meditation training on stress reactivity. Sixty-six (N=66) participants were randomly assigned to either a brief 3-day (25-min per day) mindfulness meditation training or an analytic cognitive training control program. All participants completed a standardized laboratory social-evaluative stress challenge task (the TSST) following the third mindfulness meditation or cognitive training session. Measures of psychological (stress perceptions) and biological (salivary cortisol, blood pressure) stress reactivity were collected during the social evaluative stress-challenge session. Brief mindfulness meditation training reduced self-reported psychological stress reactivity but increased salivary cortisol reactivity to the TSST, relative to the cognitive training comparison program. Participants who were low in pre-existing levels of dispositional mindfulness and then received mindfulness meditation training had the greatest cortisol reactivity to the TSST. No significant main or interactive effects were observed for systolic or diastolic blood pressure reactivity to the TSST. The present study provides an initial indication that brief mindfulness meditation training buffers self-reported psychological stress reactivity, but also increases cortisol reactivity to social evaluative stress. This pattern may indicate that initially brief mindfulness meditation training fosters greater active coping efforts, resulting in reduced psychological stress appraisals and greater cortisol reactivity during social evaluative stressors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Short- and long-term effects of dietary l-tryptophan supplementation on the neuroendocrine stress response in seawater-reared Atlantic salmon (Salmo salar)

    DEFF Research Database (Denmark)

    Basic, D.; Krogdahl, T.; Scholden, J.

    2013-01-01

    The essential amino acid l-tryptophan (Trp) is the immediate precursor of the neurotransmitter serotonin (5-HT). Supplementing Trp through diet has been shown to suppress the neuroendocrine stress response in vertebrates including teleosts. In salmonid fish, adjusting to the social environment...... for aquaculture. Fish were given feed containing 1, 2, 3 or 4 times the Trp content in normal feed for one week. Subsequently, the fish were reintroduced to feed containing the lowest Trp level, corresponding to standard commercial feed for a number of days prior to exposure to an acute confinement stressor....... Basal plasma cortisol levels were lower among non-stressed fish at 1 and 10. days post dietary Trp supplementation. By comparison, stressed fish displayed stimulatory post-stress plasma cortisol responses at 1 and 2. days after the Trp regimen was terminated. However, a reversed pattern was observed...

  7. Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress.

    Science.gov (United States)

    Cruz, Fábio C; Engi, Sheila A; Leão, Rodrigo M; Planeta, Cleopatra S; Crestani, Carlos C

    2012-10-01

    Abuse of cocaine and androgenic-anabolic steroids (AASs) has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous abuse of these substances, potential toxic interactions between cocaine and AASs are poorly known. In the present study, we investigated the effects of either single or combined administration of testosterone and cocaine for one or 10 consecutive days on autonomic (arterial pressure, heart rate and tail cutaneous temperature) and neuroendocrine (plasma corticosterone) responses induced by acute restraint stress in rats. Combined administration of testosterone and cocaine for 10 days reduced the increase in heart rate and plasma corticosterone level, as well as the fall in tail skin temperature induced by restraint stress. Furthermore, repeated administration of cocaine inhibited the increase in arterial pressure observed during restraint, and this effect was not affected by coadministration of testosterone. Ten-day combined administration of testosterone and cocaine increased basal values of arterial pressure. Moreover, chronic administration of testosterone induced rest bradycardia and elevated basal level of plasma corticosterone. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present study demonstrated that combined administration of testosterone and cocaine changed the autonomic and neuroendocrine responses to acute restraint stress. These findings suggest that interaction between AASs and cocaine may affect the ability to cope with stressful events.

  8. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rinke, Anja, E-mail: sprengea@staff.uni-marburg.de; Michl, Patrick; Gress, Thomas [Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, Marburg D-35043 (Germany)

    2012-02-08

    Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-α, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  9. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Thomas Gress

    2012-02-01

    Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  10. Spouses’ Attachment Pairings Predict Neuroendocrine, Behavioral, and Psychological Responses to Marital Conflict

    Science.gov (United States)

    Beck, Lindsey A.; Pietromonaco, Paula R.; DeBuse, Casey J.; Powers, Sally I.; Sayer, Aline G.

    2014-01-01

    This research investigated how spouses’ attachment styles jointly contributed to their stress responses. Newlywed couples discussed relationship conflicts. Salivary cortisol indexed physiological stress; observer-rated behaviors indexed behavioral stress; self-reported distress indexed psychological stress. Multilevel modeling tested predictions that couples including one anxious and one avoidant partner or two anxious partners would show distinctive stress responses. As predicted, couples with anxious wives and avoidant husbands showed physiological reactivity in anticipation of conflict: Both spouses showed sharp increases in cortisol, followed by rapid declines. These couples also showed distinctive behaviors during conflict: Anxious wives had difficulty recognizing avoidant husbands’ distress, and avoidant husbands had difficulty approaching anxious wives for support. Contrary to predictions, couples including two anxious partners did not show distinctive stress responses. Findings suggest that the fit between partners’ attachment styles can improve understanding of relationships by specifying conditions under which partners’ attachment characteristics jointly influence individual and relationship outcomes. PMID:23773048

  11. Neuroendocrine response to CRF stimulation in veterans with and without PTSD in consideration of war zone era.

    Science.gov (United States)

    Golier, Julia A; Caramanica, Kimberly; Yehuda, Rachel

    2012-03-01

    Alterations in hypothalamic-pituitary-adrenal (HPA) axis activity have been observed in Gulf War veterans with posttraumatic stress disorder (PTSD) which differ from those observed in other veteran groups, raising the possibility that there is a unique neuroendocrine profile in this group of veterans. This study seeks to further characterize the effects of PTSD, military cohort (Vietnam, 1991 Gulf War, Operations Enduring Freedom/Iraqi Freedom (OEF/OIF)), and their interaction on the neuroendocrine response to synthetic corticotrophin-releasing factor (CRF) stimulation. 51 male veterans were studied consisting of 21 from the Vietnam era, 16 from the Gulf War era, and 14 from the OEF/OIF era. 16 of these veterans were deployed to a war zone and had chronic PTSD (PTSD+), 25 were deployed to a war zone and did not have chronic PTSD (PTSD-), and 10 were not deployed to a war zone and did not have PTSD (non-exposed). The participants underwent the CRF stimulation test in the afternoon (approximately 2:00 p.m.), which measures the integrity and sensitivity of the pituitary-adrenal axis. Plasma cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline and at intervals over a 2h period following intravenous administration of 1 μg/kg of ovine CRF (o-CRF, max 100 μg). In a small subset of participants, dehydroepiandrosterone (DHEA) and cortisol binding globulin (CBG) were also assessed. There was a significant group by era interaction in the response of ACTH to CRF, in addition to a main effect of group (PTSD+, PTSD-, non-exposed). The interaction reflected that group differences were only evident in the Gulf War cohort; among Gulf War era veterans, the PTSD+ group had higher elevations in ACTH levels following CRF than the PTSD- group and the non-exposed group. Additionally, the peak change in ACTH was associated with a self-reported environmental exposure (pyridostigmine bromide ingestion) which has been found to be linked to the excess morbidity found in

  12. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  13. Perioperative stress in dogs undergoing elective surgery: evaluation of the Dog Appeasing Pheromone (DAP) for the control of behavioural, neuroendocrine, immune and acute phase stress responses

    OpenAIRE

    Siracusa, Carlo

    2009-01-01

    Descripció del recurs: el 7 de gener de 2011 This clinical study is composed of two different trials. In the first we investigated and described the perioperative stress response in dogs undergoing elective orchiectomy and ovariohysterectomy. In the second trial we evaluated the efficacy of a commercial dog synthetic appeasing pheromone for the control of the perioperative stress response. The aim of this trial is to describe the behavioural, neuroendocrine, immune and acute phase stress r...

  14. [EGFR-expression in pulmonary neuroendocrine cell hyperplasia].

    Science.gov (United States)

    Kuhnen, C; Winter, B U

    2006-03-01

    15 cases of pulmonary neuroendocrine cell hyperplasia (carcinoid-tumorlets, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia/DIPNECH) and 20 neuroendocrine pulmonary tumors (10 carcinoid tumors, 5 large cell neuroendocrine, and 5 small cell neuroendocrine lung carcinomas) were immunohistochemically analyzed for the expression of epidermal growth factor receptor (EGFR, = HER-1). All cases of neuroendocrine cell hyperplasia exhibited a maximum EGFR expression (score 3 in 100% of cells) showing predominantly membranous, partly cytoplasmic staining. 4 ot the 10 carcinoid tumors were strongly positive for EGFR, whereas the other 6 were EGFR-negative. A total of 90% of large cell neuroendocrine and small cell neuroendocrine carcinomas were negative for EGFR. Overexpression of EGFR in pulmonary neuroendocrine cell hyperplasia might be significant for the pathogenesis of these lesions. As DIPNECH is characterized by clinical signs and symptoms including mild cough and obstructive functional impairment, a specific antagonistic therapeutic trial could aim at blocking EGFR/HER-1 or its subsequent signal transduction pathway.

  15. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...... occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  16. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    OpenAIRE

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were conside...

  17. A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

    Directory of Open Access Journals (Sweden)

    De Divitiis C

    2015-03-01

    Full Text Available Chiara De Divitiis,1 Claudia von Arx,2 Roberto Carbone,3 Fabiana Tatangelo,4 Elena di Girolamo,5 Giovanni Maria Romano,1 Alessandro Ottaiano,1 Elisabetta de Lutio di Castelguidone,3 Rosario Vincenzo Iaffaioli,1 Salvatore Tafuto1 On behalf of the European Neuroendocrine Tumor Society (ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy 1Department of Abdominal Oncology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy; 2Department of Clinical Medicine and Surgery, “Federico II” University, Naples, Italy; 3Department of Radiology, 4Department of Pathology, 5Department of Endoscopy, National Cancer Institute “Fondazione G Pascale”, Naples, Italy Abstract: Somatostatin analogs (SSAs are typically used to treat the symptoms caused by neuroendocrine tumors (NETs, but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs. Keywords: neuroendocrine tumor, somatostatin analogs, octreotide, metastatic tumor of the ileum, radiological tumor response

  18. Neuroendocrine Role for VGF

    Directory of Open Access Journals (Sweden)

    Jo Edward Lewis

    2015-02-01

    Full Text Available The vgf gene (non-acronymic is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain derived neurotrophic factor, and glial derived growth factor. The VGF gene gives rise to a 68kDa precursor polypeptide which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific pro-hormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly the hypothalamus and hippocampus, and in peripheral tissues including the pituitary gland, the adrenal glands and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles and in this mini-review we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction and cognition.

  19. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

    Energy Technology Data Exchange (ETDEWEB)

    Campana, Davide; Nori, Francesca; Cacciari, Giulia; Tomassetti, Paola [University of Bologna, Department of Medical and Surgical Sciences, Bologna (Italy); Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco [University of Rome, Digestive and Liver Disease Unit, Rome (Italy); Partelli, Stefano [Sacro Cuore Don Calabria Hospital, Department of Surgery, Negrar (Italy); University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy); Tamburrino, Domenico; Falconi, Massimo [University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy)

    2013-08-15

    Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with {sup 90}Y or {sup 177}Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided. (orig.)

  20. CD200 Expression in Neuroendocrine Neoplasms.

    Science.gov (United States)

    Love, Jason E; Thompson, Kimberly; Kilgore, Mark R; Westerhoff, Maria; Murphy, Claire E; Papanicolau-Sengos, Antonios; McCormick, Kinsey A; Shankaran, Veena; Vandeven, Natalie; Miller, Faith; Blom, Astrid; Nghiem, Paul T; Kussick, Steven J

    2017-09-01

    CD200 expression has been well studied in hematopoietic malignancies; however, CD200 expression has not been well-characterized in neuroendocrine neoplasms. We examined CD200 expression in 391 neuroendocrine neoplasms from various anatomic sites. Tissue blocks containing pulmonary small cell carcinoma, pulmonary carcinoid, large cell neuroendocrine carcinoma, pancreatic neuroendocrine tumor, gastrointestinal carcinoid, and Merkel cell carcinoma were evaluated for CD200 expression by immunohistochemistry. A set of nonneuroendocrine carcinomas was stained for comparison. CD200 was expressed in 87% of the neuroendocrine neoplasms studied, including 60 of 72 (83%) pulmonary small cell carcinomas, 15 of 22 (68%) pulmonary carcinoids, three of four (75%) pulmonary large cell neuroendocrine carcinomas, 125 of 146 (86%) Merkel cell carcinomas, 79 of 83 (95%) gastrointestinal luminal carcinoids, and 56 of 60 (93%) pancreatic neuroendocrine tumors. Thirty-two of 157 (20%) nonneuroendocrine carcinomas expressed CD200. In gastrointestinal carcinoid and pancreatic neuroendocrine neoplasms, CD200 negativity correlated with higher grade. CD200 is a relatively sensitive marker of neuroendocrine neoplasms and represents a potential therapeutic target in these difficult-to-treat malignancies.

  1. Development of the Neuroendocrine Hypothalamus.

    Science.gov (United States)

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-03-15

    The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity. Copyright © 2016 John Wiley & Sons, Inc.

  2. Neuroendocrine and immune responses to a cognitive stress challenge in veterans with and without PTSD

    Directory of Open Access Journals (Sweden)

    Carien S. de Kloet

    2012-06-01

    Full Text Available Background: PTSD has been associated with altered hypothalamus–pituitary–adrenal-axis (HPA-axis, immune and sympathetic nervous system (SNS regulation. The purpose of this study was to evaluate the effect of cognitive stress on these systems in PTSD patients and controls. Methods: The subjective units of distress score (SUDS, NK-cell response, plasma levels of noradrenalin and ACTH in response to cognitive stress were assessed in male veterans with PTSD (n=15 and age, region and year of deployment matched veterans without psychopathology (n=15. Results: The challenge induced an increase in SUDS, noradrenalin, ACTH and NK-cell response in both groups. Baseline levels of ACTH were lower in PTSD patients. The test was experienced as more stressful by PTSD patients and resulted in an augmented ACTH response in patients. The noradrenalin and NK-cell responses showed no group differences. The ACTH response correlated with the severity of symptoms in patients, and the noradrenalin response correlated with the ACTH and NK-cell response in controls, but not in patients. Discussion: PTSD patients experience more distress and present with an exaggerated pituitary response to this stressor. In addition, our results suggest an altered interaction between the HPA-axis, SNS and immune system in PTSD.

  3. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  4. PACAP: A master regulator of neuroendocrine stress circuits and the cellular stress response

    OpenAIRE

    Stroth, Nikolas; Holighaus, Yvonne; Ait-Ali, Djida; Eiden, Lee E.

    2011-01-01

    The neuropeptide PACAP is an informational molecule released from stress-transducing neurons. It exerts post-synaptic effects required to complete hypothalamo-pituitary-adrenocortical (HPA) and hypothalamo-splanchnico-adrenomedullary (HSA) circuits activated by psychogenic and metabolic stressors. PACAP-responsive (in cell culture models) and PACAP-dependent (in vivo) transcriptomic responses in the adrenal gland, hypothalamus, and pituitary upon activation of these circuits have been identif...

  5. Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

    Science.gov (United States)

    Castrogiovanni, Daniel; Gaillard, Rolf C; Giovambattista, Andrés; Spinedi, Eduardo

    2008-01-01

    In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity. 2008 S. Karger AG, Basel.

  6. Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression.

    LENUS (Irish Health Repository)

    Dinan, T G

    2012-02-03

    BACKGROUND: In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic-pituitary adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression. METHOD: Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS: The mean +\\/- S.E.M. ACTH response in the depressives was 28.4 +\\/- 4.3 ng\\/l and in the healthy subjects was 18.8 +\\/- 4.9 ng\\/l (P = 0.04). The mean +\\/- S.E.M. cortisol response in the depressives was 261.8 +\\/- 46.5 nmol\\/l and in the healthy subjects was 107.3 +\\/- 26.1 nmol\\/l (P < 0.01). CONCLUSIONS: Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.

  7. Neuroendocrine modulation of the inflammatory response in common carp: adrenaline regulates leukocyte profile and activity

    NARCIS (Netherlands)

    Kepka, M.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

    2013-01-01

    Inflammatory responses have to be carefully controlled, as high concentrations and/or prolonged action of inflammation-related molecules (e.g. reactive oxygen species, nitric oxide and pro-inflammatory cytokines) can be detrimental to host tissue and organs. One of the potential regulators of the

  8. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

    Science.gov (United States)

    Imhof, Anna; Brunner, Philippe; Marincek, Nicolas; Briel, Matthias; Schindler, Christian; Rasch, Helmut; Mäcke, Helmut R; Rochlitz, Christoph; Müller-Brand, Jan; Walter, Martin A

    2011-06-10

    To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.

  9. Response of the nitrergic system to activation of the neuroendocrine stress axis

    Directory of Open Access Journals (Sweden)

    Hsiao-Jou Cortina eChen

    2015-01-01

    Full Text Available Exposure to stressful stimuli causes activation of the hypothalamic-pituitary-adrenal axis which rapidly releases high concentrations of glucocorticoid stress hormones, resulting in increased cellular metabolism and spontaneous oxygen and nitrogen radical formation. High concentrations of nitrogen radicals, including nitric oxide, cause damage to cellular proteins in addition to inhibiting components of the mitochondrial transport chain, leading to cellular energy deficiency. During stress exposure, pharmacological inhibition of nitric oxide production reduces indicators of anxiety- and depressive-like behavior in animal models. Therefore, the purpose of this review is to present an overview of the current literature on stress-evoked changes in the nitrergic system, particularly within neural tissue.

  10. Neuroendocrine Responses and Body Composition Changes Following Resistance Training Under Normobaric Hypoxia

    Directory of Open Access Journals (Sweden)

    Chycki Jakub

    2016-12-01

    Full Text Available The aim of the present study was to evaluate the effects of a 6 week resistance training protocol under hypoxic conditions (FiO2 = 12.9%, 4000 m on muscle hypertrophy. The project included 12 resistance trained male subjects, randomly divided into two experimental groups. Group 1 (n = 6; age 21 ± 2.4 years; body height [BH] 178.8 ± 7.3 cm; body mass [BM] 80.6 ± 12.3 kg and group 2 (n = 6; age 22 ± 1.5 years; BH 177.8 ± 3.7cm; BM 81.1 ± 7.5 kg. Each group performed resistance exercises alternately under normoxic and hypoxic conditions (4000 m for 6 weeks. All subjects followed a training protocol that comprised two training sessions per week at an exercise intensity of 70% of 1RM; each training session consisted of eight sets of 10 repetitions of the bench press and barbell squat, with 3 min rest periods. The results indicated that strength training in normobaric hypoxia caused a significant increase in BM (p < 0.01 and fat free mass (FFM (p < 0.05 in both groups. Additionally, a significant increase (p < 0.05 was observed in IGF-1 concentrations at rest after 6 weeks of hypoxic resistance training in both groups. The results of this study allow to conclude that resistance training (6 weeks under normobaric hypoxic conditions induces greater muscle hypertrophy compared to training in normoxic conditions.

  11. Nuclear Medicine diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract, including carcinoids; Nuklearmedizinische Diagnostik und Therapie neuroendokriner Tumoren des Gastrointestinaltraktes einschliesslich des Karzinoides

    Energy Technology Data Exchange (ETDEWEB)

    Behr, T.M.; Gotthardt, M.; Behe, M. [Klinik fuer Nuklearmedizin der Phillipps-Univ. Marburg (Germany); Kann, P.H. [Bereich fuer Endokrinologie and Diabetologie der Phillipps-Univ. Marburg (Germany); Arnold, R. [Klinik fuer Gastroenterologie, Stoffwechsel, Endokrinologie der Phillipps-Univ. Marburg (Germany)

    2003-06-01

    Neuroendocrine tumors of the gastrointestinal tract are the special domain of Nuclear Medical diagnosis and therapy, especially since they have been recognized as overexpressing receptors for regulatory peptides. Regulatory peptides are small, readily diffusible and potent natural substances with a wide spectrum of receptor-mediated actions. High affinity receptors are reliably (over-) expressed on a variety of tumors, and these receptors represent novel molecular targets for tumor diagnosis and therapy. Whereas the historically more ancient MIBG scintigraphy showed only limited sensitivity and therapeutic efficacy, somatostatin receptor scintigraphy has revolutionized the staging of gastro-enteropancreatic tumors. Physiologically, these peptides bind to G-protein associated receptors in the cell membranes. Historically, somatostatin analogues are the first class of receptor-binding peptides with a broader field of clinical applications. In-111-DTPA-[D-Phe1]-octreotide is the first and only radiopeptide having gained approval by the respective regulatory agencies in Europe and the United States of America. Extensive clinical studies with several thousands of patients were able to show that the main application of somatostatin receptor scintigraphy lies in the detection and the staging of gastroenteropancreatic neuro-endocrine tumors (carcinoids and others). In these, radiolabeled octreotide is superior to all other forms or methods of staging. A variety of novel radiolabeled regulatory peptides is in development, binding to other, novel receptor types. Radiolabeled vasoactive intestinal peptide (VIP), gastrin and cholecystokinin derivatives, gastrin-releasing peptide/bombesin, neurotensin, substance P, glucagon-like peptide-1 (GLP-1) analogues and potentially also pan-somatostatin receptor ligands stay in differently developed stages of their pre-clinical or even clinical testing. Radiolalebeled regulatory peptides have opened new horizons in Nuclear oncology for

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

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

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

  13. Neuroendocrine effects of cytokines in the rat.

    Science.gov (United States)

    Rivier, C

    1993-01-01

    The necessity ot maintain and/or restore homeostasis is an essential feature of mammals. This requires complex interactions between body cells, such as those from the immune and neuroendocrine systems, and in particular implies that the occurrence of immune activation be conveyed to the brain. It is now widely recognized that following infection, injury or inflammation, some immune cells (particularly macrophages) produce polypeptides called cytokines, interleukins or lymphokines /48/. These proteins provide the basis for intercellular communication between leukocytes (hence the name "interleukins") and mediate the immunoinflammatory responses (in particular T and B lymphocyte proliferation) /4,177/. In addition, interleukins (IL) can enter the general circulation and reach cells of the neuroendocrine axes, a phenomenon which represents one arm of the bidirectional communication links between the immune and the endocrine systems /25/. The early events which take place after presentation of an antigen (the so-called "acute-phase response" /89/) include metabolic and endocrine changes, such as changes in the circulating levels of insulin, TSH, GH, LH and ACTH, as well as adrenal and gonadal steroids /7,14/. This article reviews our present state of knowledge with regard to the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes of the rodent in response to interleukins.

  14. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  15. Dissociative symptoms and neuroendocrine dysregulation in depression.

    Science.gov (United States)

    Bob, Petr; Fedor-Freybergh, Peter; Jasova, Denisa; Bizik, Gustav; Susta, Marek; Pavlat, Josef; Zima, Tomas; Benakova, Hana; Raboch, Jiri

    2008-10-01

    Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.

  16. Neuroendocrine-immune interaction: regulation of inflammation via G-protein coupled receptors

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Aa, van der L.M.; Chadzinska, M.K.

    2013-01-01

    Neuroendocrine- and immune systems interact in a bi-directional fashion to communicate the status of pathogen recognition to the brain and the immune response is influenced by physiological changes. The network of ligands and their receptors involved includes cytokines and chemokines,

  17. THE EFFICACY OF PREGABALIN AS A PREMEDICANT IN ATTENUATING NEUROENDOCRINE STRESS RESPONSE DURING GENERAL ANAESTHESIA IN ELECTIVE SURGERIES: A PROSPECTIVE RANDOMISED PLACEBO CONTROLLED STUDY

    Directory of Open Access Journals (Sweden)

    Bhavani Muthukrishnan

    2016-06-01

    Pregabalin in the dose of 150 mg given per orally one hour before elective surgeries can attenuate the neuroendocrine stress response due to induction and intubation. Better surgical skills and techniques have got a major role in attenuating neuroendocrine stress response more than the conventional anaesthetic interventions.

  18. Smart Farming: Including Rights Holders for Responsible Agricultural Innovation

    Directory of Open Access Journals (Sweden)

    Kelly Bronson

    2018-02-01

    Full Text Available This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming innovations. The article is of interest to smart farming’s decision makers (from farmers to governance actors and a broader audience – anyone interested in engendering equity through innovation-led societal transitions.

  19. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

    Directory of Open Access Journals (Sweden)

    Arpad eDobolyi

    2012-10-01

    Full Text Available The G-protein coupled parathyroid hormone 2 receptor (PTH2R is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand,tuberoinfundibular peptide of 39 residues (TIP39, is synthesized in only 2 brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control

  20. A prepared speech in front of a pre-recorded audience: subjective, physiological, and neuroendocrine responses to the Leiden Public Speaking Task.

    Science.gov (United States)

    Westenberg, P Michiel; Bokhorst, Caroline L; Miers, Anne C; Sumter, Sindy R; Kallen, Victor L; van Pelt, Johannes; Blöte, Anke W

    2009-10-01

    This study describes a new public speaking protocol for youth. The main question asked whether a speech prepared at home and given in front of a pre-recorded audience creates a condition of social-evaluative threat. Findings showed that, on average, this task elicits a moderate stress response in a community sample of 83 12- to 15-year-old adolescents. During the speech, participants reported feeling more nervous and having higher heart rate and sweatiness of the hands than at baseline or recovery. Likewise, physiological (heart rate and skin conductance) and neuroendocrine (cortisol) activity were higher during the speech than at baseline or recovery. Additionally, an anticipation effect was observed: baseline levels were higher than recovery levels for most variables. Taking the anticipation and speech response together, a substantial cortisol response was observed for 55% of participants. The findings indicate that the Leiden Public Speaking Task might be particularly suited to investigate individual differences in sensitivity to social-evaluative situations.

  1. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites

  2. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of

  3. PET/CT in Neuroendocrine Tumors.

    Science.gov (United States)

    Castellucci, Paolo; Ambrosini, Valentina; Montini, Giancarlo

    2008-04-01

    Neuroendocrine tumors (NETs) are a rare group of neoplasms that originate from pluripotent stem cells or differentiated neuroendocrine cells, mostly localized in the bronchus, lungs, or gastroenteropancreatic tract. This issue reviews the results achieved with PET. The potential applications of the most commonly used receptor or metabolic positron-emitter radiopharmaceuticals in the field of NET to stage or restage disease, to detect unknown primary tumor, and to assess and monitor therapy response to different kind of treatments are analyzed. Copyright © 2008 Elsevier Inc. All rights reserved.

  4. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  5. Neuroendocrine Tumor, diagnostic difficulties

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  6. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    INTRODUCTION. Neuroendocrine tumors comprise heterogeneous group of neoplasms which originate from endocrine cells, both within endocrine organs and within the cells of diffuse endocrine system. These tumors have vari- able clinical behavior ranging from well-differentiated, slow growing tumors to ...

  7. Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system.

    Science.gov (United States)

    Morale, M C; Gallo, F; Tirolo, C; Testa, N; Caniglia, S; Marletta, N; Spina-Purrello, V; Avola, R; Caucci, F; Tomasi, P; Delitala, G; Barden, N; Marchetti, B

    2001-08-01

    Bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life. Signals generated by the hypothalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the development of immune system function. Conversely, products generated by immune system activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to preperinatal experiences, including hormonal manipulations and immune challenges, which may influence the future predisposition to several disease entities. We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the central nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate major changes in response to hormonal manipulations and pro-inflammatory triggers. The interplay between LHRH, sex steroids, GC and pro-inflammatory mediators in some physiological and pathological states, together with the potential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmacological targeting with drugs acting at the neuroendocrine-immune interface.

  8. Neuroendocrine tumor presenting like lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Vincenzi Bruno

    2011-10-01

    Full Text Available Abstract Introduction Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. Case presentation We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. Conclusion The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor.

  9. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT)

    Energy Technology Data Exchange (ETDEWEB)

    Kong, G.; Thompson, M.; Johnston, V.; Eu, P. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); Collins, M.; Herschtal, A. [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne, VIC (Australia); Hofman, M.S.; Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Michael, M. [The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia)

    2014-10-15

    To review the response and outcomes of {sup 177}Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was

  10. Neuroendocrine breast cancer.

    Science.gov (United States)

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-08-13

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast lump. Physical examination, mammography and ultrasonography showed a 2.4 cm nodule, probably a benign lesion (BI-RADS 3). A fine needle aspiration biopsy was performed and revealed proliferative epithelial papillary lesion. She was submitted to excisional biopsy and histology showed endocrine breast cancer well differentiated (G1). Immunohistochemically, tumour cells were positive for synaptophysin. These breast cancers are characterised for their excellent prognosis and conservative treatment is almost always enough to obtain patient cure.

  11. Conditioned Neuroendocrine and Cardiovascular Stress Responsiveness Accompanying Behavioral Passivity and Activity in Aged and in Young Rats

    NARCIS (Netherlands)

    Korte, S.M.; Buwalda, B.; Bouws, G.A.H.; Koolhaas, J.M.; Maes, F.W.; Bohus, B.

    1992-01-01

    Mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E), plasma norepinephrine (NE), and plasma corticosterone (CORT) were measured in 3-month- and 24-month-old male Wistar rats exposed to a conditioned emotional stress response (CER) paradigm and a conditioned defensive burying (CDB)

  12. Primary neuroendocrine carcinoma of the breast: report of 2 cases and literature review

    Directory of Open Access Journals (Sweden)

    Fernando Collado-Mesa, MD

    2017-03-01

    Full Text Available Neuroendocrine tumors of the breast are very rare accounting for less than 0.1% of all breast cancers and less than 1% of all neuroendocrine tumors. Focal neuroendocrine differentiation can be found in different histologic types of breast carcinoma including in situ and invasive ductal or invasive lobular. However, primary neuroendocrine carcinoma of the breast requires the expression of neuroendocrine markers in more than 50% of the cell population, the presence of ductal carcinoma in situ, and the absence of clinical evidence of concurrent primary neuroendocrine carcinoma of any other organ. Reports discussing the imaging characteristics of this rare carcinoma in different breast imaging modalities are scarce. We present 2 cases of primary neuroendocrine carcinoma of the breast for which mammography, ultrasound, and magnetic resonance imaging findings and pathology findings are described. A review of the medical literature on this particular topic was performed, and the results are presented.

  13. Differential Diagnosis in Neuroendocrine Neoplasms of the Larynx

    NARCIS (Netherlands)

    Hunt, Jennifer L; Ferlito, Alfio; Hellquist, Henrik; Rinaldo, Alessandra; Skálová, Alena; Slootweg, Pieter J; Willems, Stefan M; Cardesa, Antonio

    2017-01-01

    The differential diagnosis of neuroendocrine neoplasms of the larynx is broad and includes lesions of epithelial, mesenchymal, and neuroectodermal origin. These lesions have overlapping clinical and pathologic aspects and must be carefully considered in the differential diagnosis of laryngeal

  14. Mixed adenocarcinoma and neuroendocrine prostate cancer: a case report

    Directory of Open Access Journals (Sweden)

    Rittu Hingorani

    2014-11-01

    Full Text Available Background: Neuroendocrine prostate cancer is rare but lethal. It is one of the most common extra pulmonary manifestations of small cell cancer. Case presentation: Here we present a case report of a 53-year-old male who presents with a mixed adenocarcinoma and neuroendocrine prostate tumor on a background of previously normal prostate-specific antigen (PSA. His initial symptoms prior to diagnosis included decreased urine output and acute kidney injury (AKI. Conclusion: Neuroendocrine tumor does not elevate the PSA level and hence is often a late finding with a poor prognosis. Special staining on histopathogy is required to reveal this diagnosis.

  15. Molecular neuroendocrine targets for obesity therapy.

    Science.gov (United States)

    de Kloet, Annette D; Woods, Stephen C

    2010-10-01

    Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy. During the review period, considerable progress occurred in the understanding of previously described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of the neuroendocrine regulation of energy homeostasis has been expanded. Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical-weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging.

  16. Molecular neuroendocrine targets for obesity therapy

    Science.gov (United States)

    de Kloet, Annette D.; Woods, Stephen C.

    2013-01-01

    Purpose of review Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy. Recent findings During the review period, considerable progress occurred in the understanding of previously-described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of neuroendocrine regulators of energy homeostasis has been expanded. Summary Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging. PMID:20585249

  17. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial

    DEFF Research Database (Denmark)

    Knorr, Ulla; Vinberg, Maj; Hansen, Allan

    2011-01-01

    -term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD). Methods Eighty healthy first-degree relatives to patients with MDD were randomized...... to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUCtotal) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. Results Change in CorAUCtotal showed...... no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in Cor...

  18. Escitalopram and Neuroendocrine Response in Healthy First-Degree Relatives to epressed Patients – A Randomized Placebo-Controlled Trial

    DEFF Research Database (Denmark)

    Knorr, Ulla Benedichte Søsted; Vinberg, Maj; Hansen, Allan

    2011-01-01

    long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD). Methods: Eighty healthy first-degree relatives to patients with MDD were...... randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUCtotal) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. Results: Change in Cor......AUCtotal showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration...

  19. Escitalopram and Neuroendocrine Response in Healthy First-Degree Relatives to Depressed Patients – A Randomized Placebo-Controlled Trial

    Science.gov (United States)

    Knorr, Ulla; Vinberg, Maj; Hansen, Allan; Klose, Marianne; Feldt-Rasmussen, Ulla; Hilsted, Linda; Hasselstrøm, Jørgen; Gether, Ulrik; Winkel, Per; Gluud, Christian; Wetterslev, Jørn; Kessing, Lars Vedel

    2011-01-01

    Introduction The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD). Methods Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUCtotal) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. Results Change in CorAUCtotal showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUCtotal, rho = −0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUCtotal. Conclusion The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age. Trial Registration ClinicalTrials.gov [NCT00386841 PMID:21738622

  20. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Ulla Knorr

    Full Text Available INTRODUCTION: The mechanisms by which selective serotonin re-uptake inhibitors (SSRI act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH test in healthy first-degree relatives to patients with major depressive disorder (MDD. METHODS: Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC(total for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. RESULTS: Change in CorAUC(total showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC(total, rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC(total. CONCLUSION: The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age. TRIAL REGISTRATION: ClinicalTrials.gov NCT00386841.

  1. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  2. Psychological and neuroendocrine reactivity to ostracism.

    Science.gov (United States)

    Zwolinski, Jennifer

    2012-01-01

    This study used the ostracism detection theory to investigate how ostracism impacts individuals in two ways: (1) immediate poststressor needs, mood, ruminative thoughts, and desire to affiliate, and (2) short-term affective and cortisol reactivity. A total of 58 college students were randomly assigned to the inclusion or ostracism conditions of Cyberball, a virtual ball-tossing game. Immediately following the experimental manipulation, ostracized participants reported more thwarted psychological need states, more negative mood, and fewer positive ruminative thoughts, relative to their included counterparts. Ostracized participants reported a greater interest in affiliating with others in online or in-person settings. In the short-term, ostracized males reported more hostility than included males, although the scores were within expected norms for most males. There was no relation between Cyberball condition and gender across time for depression, anxiety, or positive affect. Approximately 20 min after the onset of the stressor, women in the luteal phase and women taking oral contraceptives in the ostracized group displayed higher cortisol than their counterparts in the included group. Relative to baseline, however, cortisol did not reliably increase after the onset of the stressor. Ostracized females taking oral contraceptives showed the greatest decline in cortisol, compared to included oral contraceptive users. Overall, results suggest that most of the negative effects of ostracism are immediate and limited to psychological, not neuroendocrine, responses. © 2012 Wiley Periodicals, Inc.

  3. Protocol for an experimental investigation of the roles of oxytocin and social support in neuroendocrine, cardiovascular, and subjective responses to stress across age and gender

    Directory of Open Access Journals (Sweden)

    Block Jason

    2009-12-01

    Full Text Available Abstract Background Substantial empirical evidence has demonstrated that individuals who are socially isolated or have few positive social connections seem to age at a faster rate and have more chronic diseases. Oxytocin is a neurohypophyseal hormone hypothesized to coordinate both the causes and effects of positive social interactions, and may be involved in positive physiological adaptations such as buffering the deleterious effects of stress and promoting resilience. The proposed research will examine whether and how oxytocin influences responses to stress in humans and will consider effects in relation to those of social support. Methods/Design Experimental research will be used to determine whether exogenously administered oxytocin (intranasal influences psychological and physiological outcomes under conditions of stress across gender and age in adulthood. Hypotheses to be tested are: 1 Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress; 2 Oxytocin and social support have similar and additive stress-buffering effects; 3 Oxytocin effects are stronger in women versus men; and 4 Oxytocin effects are similar across a range of adult ages. Hypotheses will be tested with a placebo-controlled, double-blind study using a sample of healthy men and women recruited from the community. Participants are randomly assigned to receive either oxytocin or placebo. They undergo a social stress manipulation with and without social support (randomly assigned, and outcome measures are obtained at multiple times during the procedure. Discussion Understanding the determinants of healthy aging is a major public health priority and identifying effective measures to prevent or delay the onset of chronic diseases is an important goal. Experimental research on oxytocin, social relationships, and health in adulthood will contribute to the scientific knowledge base for maximizing active life and health expectancy. At

  4. Metabolic and neuroendocrine responses to Roux-en-Y gastric bypass. I: energy balance, metabolic changes, and fat loss.

    Science.gov (United States)

    Liu, X; Lagoy, A; Discenza, I; Papineau, G; Lewis, E; Braden, G; Romanelli, J; Braun, B; Silva, J E

    2012-08-01

    Obesity is a major health problem. Effective treatment requires understanding the homeostatic responses to caloric restriction. The aim was to study Roux-en-Y gastric bypass patients longitudinally for 6 months after surgery to identify major factors modulating fat loss. We studied 13 patients (11 females and two males) aged 41.2 ± 2 yr. Mean body mass index was 44.6 ± 1.2 kg/m(2), with 50 ± 1% body fat (58.3 kg). Selection excluded patients with confounding comorbidities or treatments. Caloric intake was reduced 742 ± 82 kcal/d by 1 month and 450 kcal/d between 2 and 4 months postoperatively. By 6 months, relative to baseline, body mass index decreased 24.8 ± 1.1%; percentage body fat, 37.3 ± 3.2% (21.7 kg); fat free mass (FFM), 9.7 ± 1.2%; and resting metabolic rate (RMR), 18.1 ± 4.3%. RMR correlated with FFM at all times (r = 0.71; P Fat loss did not correlate with the aggregate energy deficit or its individual components. Resting or postexercise respiratory exchange ratio (RER) was lowest, whereas plasma β-OH-butyrate and glycerol were highest, between 1 and 2 months after surgery. RER increased linearly with mild exercise, and fat loss correlated positively with physical activity level and RER. Although the ultimate cause for weight loss is the energy deficit, the variance in fat loss correlated with glucose oxidation, suggesting that glucose partition between oxidation (muscle) and storage (adipose tissue) is an important factor affecting fat loss in individuals submitted to Roux-en-Y gastric bypass.

  5. Neuroendocrine, immune and oxidative stress in shift workers.

    Science.gov (United States)

    Faraut, Brice; Bayon, Virginie; Léger, Damien

    2013-12-01

    Shift work is commonly associated with disturbed life rhythms, resulting in chronic exposure to circadian desynchronization and sleep restriction. Epidemiological data have shown that shift workers are at an increased risk of cardiovascular disease and breast cancer. In this review, we will explore how observed increases in neuroendocrine stress, non-specific immune responses and pro-oxidative status could act as biological mediators for these damaging health risks in shift workers. To explain these risks, compelling evidence from laboratory studies links circadian misalignment but also sleep restriction to disruptions in the neuroendocrine, immune and oxidative stress systems. Assessment of neuroendocrine, oxidative and immune stress in the shift worker population is still a limited and novel field, which may have considerable clinical relevance. Finally, we will consider the potential benefits of a countermeasure, such as napping, in minimizing the neuroendocrine and immune stress and cardiovascular risk imposed by shift work. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Benign gastric neuroendocrine tumors in three snow leopards (Panthera uncia).

    Science.gov (United States)

    Dobson, Elizabeth C; Naydan, Dianne K; Raphael, Bonnie L; McAloose, Denise

    2013-06-01

    Neuroendocrine tumors are relatively rare neoplasms arising from neuroendocrine cells that are distributed throughout the body and are predominant in the gastrointestinal tract. This report describes benign, well-differentiated gastric neuroendocrine tumors in three captive snow leopards (Panthera uncia). All tumors were well circumscribed, were within the gastric mucosa or submucosa, and had histologic and immunohistochemical features of neuroendocrine tumors. Histologic features included packeted cuboidal to columnar epithelial cells that were arranged in palisades or pseudorosettes and contained finely granular cellular cytoplasm with centrally placed, round nuclei. Cytoplasmic granules of neoplastic cells strongly expressed chromogranin A, variably expressed neuron-specific enolase, and did not express synaptophysin or gastrin. Each leopard died or was euthanatized for reasons unrelated to its tumor.

  7. Interventional treatment of neuroendocrine liver metastases

    DEFF Research Database (Denmark)

    Knigge, U.; Hansen, C.P.; Stadil, F.

    2008-01-01

    Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases s....... The symptomatic response rate is 90% with a mean duration of two years. Liver transplantation should be restricted to very few and highly selected patients without extrahepatic disease. Recurrence is inevitable in nearly all patients Udgivelsesdato: 2008/8......Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases...

  8. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity

    Science.gov (United States)

    Geenen, Vincent; Bodart, Gwennaëlle; Henry, Séverine; Michaux, Hélène; Dardenne, Olivier; Charlet-Renard, Chantal; Martens, Henri; Hober, Didier

    2013-01-01

    For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of “neuroendocrine self-peptides” has been proposed, together with the definition of “neuroendocrine self.” Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). At the same time, self-antigen presentation in the thymus generates regulatory T (Treg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic

  9. Performance of 177Lu-DOTATATE-based peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumor: a multiparametric response evaluation correlating with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics.

    Science.gov (United States)

    Thapa, Pradeep; Ranade, Rohit; Ostwal, Vikas; Shrikhande, Shailesh V; Goel, Mahesh; Basu, Sandip

    2016-10-01

    To assess the performance of Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in metastatic gastroenteropancreatic neuroendocrine tumor (GEP-NET) and correlate it with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics. Fifty patients (M : F 33 : 17, age: 26-71 years) with histopathologically confirmed metastatic/inoperable NETs who had undergone at least three cycles of PRRT with Lu-DOTATATE were included in the analysis. As part of the pretreatment evaluation, they underwent either Tc-HYNIC TOC (n=40)/Ga-DOTATATE PET (n=10) or fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT). Response was assessed after three and five cycles PRRT on the basis of three parameters: (a) symptomatic and subjective scale, (b) biochemical tumor marker level, and (c) objective imaging (F-FDG/Ga DOTATATE PET/CT, Tc-HYNIC TOC, ceCT), and was categorized using predefined criteria (detailed in methods). Stable disease on imaging assessment with response on symptomatic or biochemical tumor marker scales or both were included in the responder group. The study population was broadly classified into (a) metastatic GEP-NET with known primary (n=43 i.e. 86%), which was further subclassified according to the site of primary and (b) those with unknown primary (n=7 i.e. 14%). Symptomatic response: 96% of patients showed a symptomatic response or improvement in health-related quality of life, irrespective of tumor proliferation index, dual tracer imaging characteristics, and response or progression of disease in the scan. Biochemical tumor marker response: 83% of scan responders showed a decrease, 10% showed a stable value, and 7% showed an increase in tumor marker levels. Among the scan nonresponders, 67% patients showed a corresponding increase in the tumor marker level, 22% patient showed a decrease, whereas 11% showed stable values. Scan response: 31 out of total 50 patients (62%) showed a partial scan response with either a

  10. Neuroendocrine regulation of feminine sexual behavior: lessons from rodent models and thoughts about humans.

    Science.gov (United States)

    Blaustein, Jeffrey D

    2008-01-01

    Much has been learned concerning the neuroendocrine processes and cellular mechanisms by which steroid hormones influence reproductive behaviors in rodents and other animals. In this review, a short discussion of hormones and feminine sexual behavior in some rodent species is followed by an outline of the main principles that have been learned from these studies. Examples are given of the importance of considering the timing of hormone treatments, dosage of hormone, use of a specific hormone, particular class of hormones, or form of hormone, interactions between hormones, route of administration, peripheral factors that influence hormonal response, and the possible mechanisms of action by which hormones and other factors influence sexual behaviors. Although cellular studies in humans are presently impossible to perform, mechanistic studies in rodents may provide clues about the neuroendocrine mechanisms by which hormones act and interact in the brain to influence behavior in all species, including humans.

  11. Reproductive disturbances in multiple neuroendocrine tumor syndromes.

    Science.gov (United States)

    Lytras, Aristides; Tolis, George

    2009-12-01

    In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

  12. Studies in neuroendocrine pharmacology

    Science.gov (United States)

    Maickel, R. P.

    1976-01-01

    The expertise and facilities available within the Medical Sciences Program section on Pharmacology were used along with informational input from various NASA sources to study areas relevant to the manned space effort. Topics discussed include effects of drugs on deprivation-induced fluid consumption, brain biogenic amines, biochemical responses to stressful stimuli, biochemical and behavioral pharmacology of amphetamines, biochemical and pharmacological studies of analogues to biologically active indole compounds, chemical pharmacology: drug metabolism and disposition, toxicology, and chemical methodology. Appendices include a bibliography, and papers submitted for publication or already published.

  13. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  14. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Wu, Yin; Pfeifer, Andreas Klaus; Myschetzky, Rebecca

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising...... clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following...... treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy....

  15. Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty.

    Science.gov (United States)

    Avendaño, M S; Vazquez, M J; Tena-Sempere, M

    2017-11-01

    Puberty is a complex developmental event, controlled by sophisticated regulatory networks that integrate peripheral and internal cues and impinge at the brain centers driving the reproductive axis. The tempo of puberty is genetically determined but is also sensitive to numerous modifiers, from metabolic and sex steroid signals to environmental factors. Recent epidemiological evidence suggests that the onset of puberty is advancing in humans, through as yet unknown mechanisms. In fact, while much knowledge has been gleaned recently on the mechanisms responsible for the control of mammalian puberty, fundamental questions regarding the intimate molecular and neuroendocrine pathways responsible for the precise timing of puberty and its deviations remain unsolved. By combining data from suitable model species and humans, we aim to provide a comprehensive summary of our current understanding of the neuroendocrine mechanisms governing puberty, with particular focus on its central regulatory pathways, underlying molecular basis and mechanisms for metabolic control. A comprehensive MEDLINE search of articles published mostly from 2003 to 2017 has been carried out. Data from cellular and animal models (including our own results) as well as clinical studies focusing on the pathophysiology of puberty in mammals were considered and cross-referenced with terms related with central neuroendocrine mechanisms, metabolic control and epigenetic/miRNA regulation. Studies conducted during the last decade have revealed the essential role of novel central neuroendocrine pathways in the control of puberty, with a prominent role of kisspeptins in the precise regulation of the pubertal activation of GnRH neurosecretory activity. In addition, different transmitters, including neurokinin-B (NKB) and, possibly, melanocortins, have been shown to interplay with kisspeptins in tuning puberty onset. Alike, recent studies have documented the role of epigenetic mechanisms, involving mainly

  16. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Pasupuleti Prathima

    2016-11-01

    Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

  17. Immune-Neuroendocrine Interactions: Evolution, Ecology, and Susceptibility to Illness.

    Science.gov (United States)

    Blom, Johanna M C; Ottaviani, Enzo

    2017-11-16

    The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latter, the principle player is the lymphocyte. Immunocytes are characterized by the presence of pro-opiomelanocortin (POMC) peptides, CRH, and other molecules that display a significant similarity to their mammalian counterparts regarding their functions, as both are mainly involved in fundamental functions such as immune (chemotaxis, phagocytosis, cytotoxicity, etc.) and neuroendocrine (stress) responses. Furthermore, the immune-neuroendocrine system provides vital answers to ecological and immunological demands in terms of economy and efficiency. Finally, susceptibility to disease emerges as the result of a continuous dynamic interaction between the world within and the world outside. New fields such as ecological immunology study the susceptibility to pathogens in an evolutionary perspective while the field of neuro-endocrine-immunology studies the susceptibility from a more immediate perspective.

  18. Relaxin-3/RXFP3 signaling and neuroendocrine function – A perspective on extrinsic hypothalamic control

    Directory of Open Access Journals (Sweden)

    Despina E Ganella

    2013-09-01

    Full Text Available Complex neural circuits within the hypothalamus that govern essential autonomic processes and associated behaviors signal using amino acid and monoamine transmitters and a variety of neuropeptide (hormone modulators, often via G-protein coupled receptors (GPCRs and associated cellular pathways. Relaxin-3 is a recently identified neuropeptide that is highly conserved throughout evolution. Neurons expressing relaxin-3 are located in the brainstem, but broadly innervate the entire limbic system including the hypothalamus. Extensive anatomical data in rodents and non-human primate, and recent regulatory and functional data, suggest relaxin-3 signaling via its cognate GPCR, RXFP3, has a broad range of effects on neuroendocrine function associated with stress responses, feeding and metabolism, motivation and reward, and possibly sexual behavior and reproduction. Therefore, this article aims to highlight the growing appreciation of the relaxin-3/RXFP3 system as an important ‘extrinsic’ regulator of the neuroendocrine axis by reviewing its neuroanatomy and its putative roles in arousal-, stress- and feeding-related behaviors and links to associated neural substrates and signaling networks. Current evidence identifies RXFP3 as a potential therapeutic target for treatment of neuroendocrine disorders and related behavioral dysfunction.

  19. Wavelet-based evolutionary response of multi-span structures including wave-passage and site-response effects

    NARCIS (Netherlands)

    Dinh, V.N.; Basu, B.; Brinkgreve, R.B.J.

    2013-01-01

    Stochastic seismic wavelet-based evolutionary response of multispan structures including wave-passage and site-response effects is formulated in this paper. A procedure to estimate site-compatible parameters of surface-to-bedrock frequency response function (FRF) by using finite-element analysis of

  20. Compensatory activation of Akt in response to mTOR and Raf inhibitors - a rationale for dual-targeted therapy approaches in neuroendocrine tumor disease.

    Science.gov (United States)

    Zitzmann, Kathrin; Rüden, Janina von; Brand, Stephan; Göke, Burkhard; Lichtl, Jennifer; Spöttl, Gerald; Auernhammer, Christoph J

    2010-09-01

    Several studies have established a link between aberrant PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling and neuroendocrine tumor disease. In this study, we comparatively investigate the antitumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antitumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K-Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling in NET disease. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

  2. [Role of somatostatin analogs in the treatment of neuroendocrine tumours].

    Science.gov (United States)

    Cuccurullo, V; Cascini, G L; Rambaldi, P F; Mansi, L

    2001-09-01

    Current therapeutic approaches in neuroendocrine tumours include surgery, radiotherapy and polychemotherapy. Different metabolic patterns of neuroendocrine tumours allow the use of a wide range of diagnostic options in nuclear medicine, due to the presence of a wide spectrum of radiotracers electively concentrating in these neoplasms. Nuclear medicine, and in particular 111In Octreotide (OCT) scintigraphy, 123I Methaiodobenzylguanidine (MIBG) and pentavalent 99mTc-DMSA (V-DMSA), together with biohumoral markers, are currently able to locate tumours also not detectable using traditional diagnostic techniques. Somatostatin analogs, such as octreotide have become increasingly important over the years in the treatment of patients with neuroendocrine tumours. At present the therapeutic use of somatostatin analogs can be schematised as 1) pharmacological treatment (with cold octreotide); 2) surgical treatment (radioguided surgery); 3) radiometabolic treatment (with marked octreotide). The development of new synthetic molecules and new radiocompounds will probably open up interesting scenarios in the near future.

  3. [Neuroendocrine neoplasms of the breast].

    Science.gov (United States)

    Anlauf, M; Neumann, M; Bomberg, S; Luczak, K; Heikaus, S; Gustmann, C; Antke, C; Ezziddin, S; Fottner, C; Pavel, M; Pape, U-F; Rinke, A; Lahner, H; Schott, M; Cremer, B; Hörsch, D; Baum, R P; Groh, U; Alkatout, I; Rudlowski, C; Scheler, P; Zirbes, T K; Hoffmann, J; Fehm, T; Gabbert, H E; Baldus, S E

    2015-05-01

    Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

  4. Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes.

    Science.gov (United States)

    Memon, Khairuddin; Lewandowski, Robert J; Mulcahy, Mary F; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Gates, Vanessa L; Atassi, Bassel; Newman, Steven; Omary, Reed A; Benson, Al B; Salem, Riad

    2012-07-01

    To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with (90)Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden ≤25% (p = 0.0019), albumin ≥3.5 g/dL (p = 0.017), and bilirubin ≤1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin ≤1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival with low toxicity, in line with published national guidelines

  5. Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Memon, Khairuddin; Lewandowski, Robert J. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Mulcahy, Mary F. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Newman, Steven [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Omary, Reed A. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Benson, Al B. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States)

    2012-07-01

    Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival

  6. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    Science.gov (United States)

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

  7. Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Federspiel, Birgitte

    2017-01-01

    BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreac...

  8. Endocrine and neuroendocrine regulation of fathering behavior in birds.

    Science.gov (United States)

    Lynn, Sharon E

    2016-01-01

    This article is part of a Special Issue "Parental Care". Although paternal care is generally rare among vertebrates, care of eggs and young by male birds is extremely common and may take on a variety of forms across species. Thus, birds provide ample opportunities for investigating both the evolution of and the proximate mechanisms underpinning diverse aspects of fathering behavior. However, significant gaps remain in our understanding of the endocrine and neuroendocrine influences on paternal care in this vertebrate group. In this review, I focus on proximate mechanisms of paternal care in birds. I place an emphasis on specific hormones that vary predictably and/or unpredictably during the parental phase in both captive and wild birds: prolactin and progesterone are generally assumed to enhance paternal care, whereas testosterone and corticosterone are commonly-though not always correctly-assumed to inhibit paternal care. In addition, because endocrine secretions are not the sole mechanistic influence on paternal behavior, I also explore potential roles for certain neuropeptide systems (specifically the oxytocin-vasopressin nonapeptides and gonadotropin inhibitory hormone) and social and experiential factors in influencing paternal behavior in birds. Ultimately, mechanistic control of fathering behavior in birds is complex, and I suggest specific avenues for future research with the goal of narrowing gaps in our understanding of this complexity. Such avenues include (1) experimental studies that carefully consider not only endocrine and neuroendocrine mechanisms of paternal behavior, but also the ecology, phylogenetic history, and social context of focal species; (2) investigations that focus on individual variation in both hormonal and behavioral responses during the parental phase; (3) studies that investigate mechanisms of maternal and paternal care independently, rather than assuming that the mechanistic foundations of care are similar between the sexes; (4

  9. Short-term antioxidative responses of 15 microalgae exposed to excessive irradiance including ultraviolet radiation

    NARCIS (Netherlands)

    Janknegt, Paul J.; De Graaff, C. Marco; Van De Poll, Willem H.; Visser, Ronald J. W.; Rijstenbil, Jan W.; Buma, Anita G. J.

    2009-01-01

    Short-term photosensitivity and oxidative stress responses were compared for three groups of marine microalgae: Antarctic microalgae, temperate diatoms and temperate flagellates. In total, 15 low-light-acclimated species were exposed to simulated surface irradiance including ultraviolet radiation

  10. Neuroendocrine control of ionic balance in zebrafish.

    Science.gov (United States)

    Kwong, Raymond W M; Kumai, Yusuke; Perry, Steve F

    2016-08-01

    Zebrafish (Danio rerio) is an emerging model for integrative physiological research. In this mini-review, we discuss recent advances in the neuroendocrine control of ionic balance in this species, and identify current knowledge gaps and issues that would benefit from further investigation. Zebrafish inhabit a hypo-ionic environment and therefore are challenged by a continual loss of ions to the water. To maintain ionic homeostasis, they must actively take up ions from the water and reduce passive ion loss. The adult gill or the skin of larvae are the primary sites of ionic regulation. Current models for the uptake of major ions in zebrafish incorporate at least three types of ion transporting cells (also called ionocytes); H(+)-ATPase-rich cells for Na(+) uptake, Na(+)/K(+)-ATPase-rich cells for Ca(2+) uptake, and Na(+)/Cl(-)-cotransporter expressing cells for both Na(+) and Cl(-) uptake. The precise molecular mechanisms regulating the paracellular loss of ions remain largely unknown. However, epithelial tight junction proteins, including claudins, are thought to play a critical role in reducing ion losses to the surrounding water. Using the zebrafish model, several key neuroendocrine factors were identified as regulators of epithelial ion movement, including the catecholamines (adrenaline and noradrenaline), cortisol, the renin-angiotensin system, parathyroid hormone and prolactin. Increasing evidence also suggests that gasotransmitters, such as H2S, are involved in regulating ion uptake. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Drug effects on neuroendocrine regulation; Proceedings of the International Symposium, Snowmass-at-Aspen, Colo., July 17-19, 1972

    Science.gov (United States)

    Zimmermann, E. (Editor); Gispen, W. H.; Marks, B. H.; De Wied, D.

    1973-01-01

    Subjects related to the characterization of neuroendocrine systems are discussed, taking into account the need for the precise identification and rigorous description of their operations. Steroid effects on neuroendocrine system performance are considered along with biogenic amine effects on neuroendocrine systems and the influence of drugs of abuse on neuroendocrine behavior. Other topics explored include pituitary-adrenal influences on avoidance and approach behavior of the rat, the adrenocortical mediation of the effects of early life experiences, and the implication of noradrenaline in avoidance learning in the rat. Individual items are announced in this issue.

  12. Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

    Science.gov (United States)

    Ottinger, M.A.; Abdelnabi, M.A.; Henry, P.; McGary, S.; Thompson, N.; Wu, J.M.

    2001-01-01

    Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in

  13. Functional imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Loft, Annika

    2010-01-01

    UNLABELLED: Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In......-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), and (18)F-FDG PET. METHODS: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET on average within 40 d. The functional images were fused with low......-positive, of which 3 were also (123)I-MIBG scintigraphy-positive, giving a combined overall sensitivity of 96%. SRS also exceeded (123)I-MIBG scintigraphy and (18)F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. (123)I-MIBG scintigraphy was superior to (18)F...

  14. Cognitive Performance and the Alteration of Neuroendocrine Hormones in Chronic Tension-Type Headache.

    Science.gov (United States)

    Qu, Ping; Yu, Jin-Xia; Xia, Lan; Chen, Gui-Hai

    2017-03-24

    Tension-type headache (TTH) is the most prevalent primary headache. Chronic TTH (CTTH), the most serious form of TTH, is refractory, with a high socio-economic burden. Research studies have shown patients with migraine often had cognitive impairment, but few studies have focused on the cognition in patients with CTTH. In this study, we assumed that patients with CTTH also have cognitive impairments, which are modulated by the neuroendocrine state. Participants were recruited, including patients with CTTH and healthy controls. Cognitive ability was evaluated using the Montreal Cognitive Assessment and the Nine Box Maze Test. The administration of neuroendocrine hormones has been established to be associated with cognitive performance, and we detected the hormonal changes in the hypothalamus-pituitary-adrenal axis, the hypothalamus-pituitary-thyroid axis, and gonadotropin-releasing hormone. These results showed that compared to the controls, significant cognitive impairment and neuroendocrine dysfunction were present in the patients with CTTH. We also assessed the correlations between the neuroendocrine hormones and Pittsburgh Sleep Quality Index score, 17-term Hamilton's Depression Scale score, pain intensity, and duration of pain to determine whether the neuroendocrine hormones had any associations with these symptoms of CTTH. These results showed that changes in neuroendocrine hormones were involved in these symptoms of CTTH. Intervention with the neuroendocrine state may be a strategy for CTTH treatment. © 2017 World Institute of Pain.

  15. The frequency of neuroendocrine cell hyperplasia in patients with pulmonary neuroendocrine tumours and non-neuroendocrine cell carcinomas.

    Science.gov (United States)

    Rizvi, Selim M H; Goodwill, Joseph; Lim, Eric; Yap, Yoong K; Wells, Athol U; Hansell, David M; Davis, Peter; Selim, Abdel-Ghani; Abdel-Ghani, Syed; Goldstraw, Peter; Nicholson, Andrew G

    2009-09-01

    To evaluate the frequency of neuroendocrine cell hyperplasia (NEH) in resected neuroendocrine tumours and non-neuroendocrine cell carcinomas and to study its relationship to selected clinical parameters. Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) (P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) (P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) (P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH. NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential.

  16. The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold and heat

    Directory of Open Access Journals (Sweden)

    Kazuo eNakashima

    2014-05-01

    Full Text Available Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs are master regulators of gene expression. ABRE-binding protein (AREB and ABRE-binding factor (ABF TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein (DREB TFs and NAC TFs are also involved in stress responses including drought, heat and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these transcription factors in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.

  17. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress

    Directory of Open Access Journals (Sweden)

    Sarah J Spencer

    2013-06-01

    Full Text Available Feeding behavior is closely regulated by neuroendocrine mechanisms that can be influenced by stressful life events. However, the feeding response to stress varies among individuals with some increasing and others decreasing food intake after stress. In addition to the impact of acute lifestyle and genetic backgrounds, the early life environment can have a life-long influence on neuroendocrine mechanisms connecting stress to feeding behavior and may partially explain these opposing feeding responses to stress. In this review I will discuss the perinatal programming of adult hypothalamic stress and feeding circuitry. Specifically I will address how early life (prenatal and postnatal nutrition, early life stress, and the early life hormonal profile can program the hypothalamic-pituitary-adrenal (HPA axis, the endocrine arm of the body’s response to stress long-term and how these changes can, in turn, influence the hypothalamic circuitry responsible for regulating feeding behavior. Thus, over- or under-feeding and / or stressful events during critical windows of early development can alter glucocorticoid (GC regulation of the HPA axis, leading to changes in the GC influence on energy storage and changes in GC negative feedback on HPA axis-derived satiety signals such as corticotropin-releasing-hormone. Furthermore, peripheral hormones controlling satiety, such as leptin and insulin are altered by early life events, and can be influenced, in early life and adulthood, by stress. Importantly, these neuroendocrine signals act as trophic factors during development to stimulate connectivity throughout the hypothalamus. The interplay between these neuroendocrine signals, the perinatal environment, and activation of the stress circuitry in adulthood thus strongly influences feeding behavior and may explain why individuals have unique feeding responses to similar stressors.

  18. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

    Science.gov (United States)

    Kos-Kudła, Beata; Blicharz-Dorniak, Jolanta; Strzelczyk, Janusz; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Falconi, Massimo; Foltyn, Wanda; Handkiewicz-Junak, Daria; Hubalewska-Dydejczyk, Alicja; Jarząb, Barbara; Junik, Roman; Kajdaniuk, Dariusz; Kamiński, Grzegorz; Kolasińska-Ćwikła, Agnieszka; Kowalska, Aldona; Król, Robert; Królicki, Leszek; Krzakowski, Maciej; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Lipiński, Michał; Londzin-Olesik, Magdalena; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nawrocki, Sergiusz; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; Starzyńska, Teresa; Steinhof-Radwańska, Katarzyna; Sworczak, Krzysztof; Syrenicz, Anhelli; Szawłowski, Andrzej; Szczepkowski, Marek; Wachuła, Ewa; Zajęcki, Wojciech; Zemczak, Anna; Zgliczyński, Wojciech; Zieniewicz, Krzysztof

    2017-01-01

    Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

  19. Gastrointestinal Surgery of Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Olsen, Ingrid Marie Holst; Knigge, Ulrich

    2015-01-01

    Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may...... be performed to reduce local or hormone-induced symptoms and to improve quality of life. The surgical procedures for GEP-NENs are accordingly described below. In most patients life-long follow-up is required, even following radical surgery, as recurrence may occur several years later....

  20. Active control of environmental noise, VIII: increasing the response to primary source changes including unpredictable noise

    Science.gov (United States)

    Wright, S. E.; Atmoko, H.; Vuksanovic, B.

    2004-07-01

    Conventional adaptive cancellation systems using traditional transverse finite impulse response (FIR) filters, together with least mean square (LMS) adaptive algorithms, well known in active noise control, are slow to adapt to primary source changes. This makes them inappropriate for cancelling rapidly changing noise, including unpredictable noise such as speech and music. Secondly, the cancelling structures require considerable computational processing effort to adapt to primary source and plant changes, particularly for multi-channel systems. This paper describes methods to increase the adaptive speed to primary source changes in large enclosed spaces and outdoor environments. A method is described that increases the response to time varying periodic noise using traditional transverse FIR filters. Here a multi-passband filter, with individual variable adaptive step sizes for each passband is automatically adjusted according to the signal level in each band. This creates a similar adaptive response for all frequencies within the total pass-band, irrespective of amplitude, minimizing the signal distortion and increasing the combined adaptive speed. Unfortunately, there is a limit to the adaptive speed using the above method as classical transverse FIR filters have a finite adaptive speed given by the stability band zero bandwidth. For rapidly changing periodic noise and unpredictable non-stationary noise, a rapid to instantaneous response is required. In this case the on-line adaptive FIR filters are dispensed with and replaced by a time domain solution that gives virtually instantaneous cancellation response (infinite adaptive speed) to primary source changes, and is computationally efficient.

  1. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Kim, Ji Hoon; Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2015-05-01

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  2. Central gene expression changes associated with enhanced neuroendocrine and autonomic response habituation to repeated noise stress after voluntary wheel running in rats

    Directory of Open Access Journals (Sweden)

    Sarah K eSasse

    2013-11-01

    Full Text Available Accumulating evidence indicates that regular physical exercise benefits health in part by counteracting some of the negative physiological impacts of stress. While some studies identified reductions in some measures of acute stress responses with prior exercise, limited data were available concerning effects on cardiovascular function, and reported effects on HPA axis responses were largely inconsistent. Given that exposure to repeated or prolonged stress is strongly implicated in the precipitation and exacerbation of illness, we proposed the novel hypothesis that physical exercise might facilitate adaptation to repeated stress, and subsequently demonstrated significant enhancement of both HPA axis (glucocorticoid and cardiovascular (tachycardia response habituation to repeated noise stress in rats with long-term access to running wheels compared to sedentary controls. Stress habituation has been attributed to modifications of brain circuits, but the specific sites of adaptation and the molecular changes driving its expression remain unclear. Here, in situ hybridization histochemistry was used to examine regulation of select stress-associated signaling systems in brain regions representing likely candidates to underlie exercise-enhanced stress habituation. Analyzed brains were collected from active (6 weeks of wheel running and sedentary rats following control, acute, or repeated noise exposures that induced a significantly faster rate of glucocorticoid response habituation in active animals but preserved acute noise responsiveness. Nearly identical experimental manipulations also induce a faster rate of cardiovascular response habituation in exercised, repeatedly stressed rats. The observed regulation of the corticotropin-releasing factor and brain-derived neurotrophic factor systems across several brain regions suggests widespread effects of voluntary exercise on central functions and related adaptations to stress across multiple response

  3. Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives.

    Science.gov (United States)

    Spencer, Karen A

    2017-08-19

    The social world is filled with different types of interactions, and social experience interacts with stress on several different levels. Activation of the neuroendocrine axis that regulates the response to stress can have consequences for innumerable behavioural responses, including social decision-making and aspects of sociality, such as gregariousness and aggression. This is especially true for stress experienced during early life, when physiological systems are developing and highly sensitive to perturbation. Stress at this time can have persistent effects on social behaviours into adulthood. One important question remaining is to what extent these effects are adaptive. This paper initially reviews the current literature investigating the complex relationships between the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems and several aspects of social behaviour in vertebrates. In addition, the review explores the evidence surrounding the potential for 'social programming' via differential development and activation of the HPA axis, providing an insight into the potential for positive effects on fitness following early life stress. Finally, the paper provides a framework from which novel investigations could work to fully understand the adaptive significance of early life effects on social behaviours.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

  4. Child Maltreatment and Gender Interactions as Predictors of Differential Neuroendocrine Profiles

    Science.gov (United States)

    Doom, Jenalee R.; Cicchetti, Dante; Rogosch, Fred A.; Dackis, Melissa N.

    2013-01-01

    Summary Child maltreatment is a potent stressor associated with neuroendocrine dysregulation and increased risk for mental and physical disorders throughout the lifespan. Gender differences in stress reactivity and adult psychopathology prevalence may be related to sex-specific responsivity to stress. The purpose of this study is to examine whether gender interacts with the stress of maltreatment to produce differential neuroendocrine profiles in children. Participants included 137 maltreated and 110 nonmaltreated low-income, racially and ethnically diverse children (range: 7.9–10.9 years; M= 9.42 years; 52% male) who attended a summer research day camp. Saliva was collected 3 times across the day for 5 days for cortisol and dehydroepiandosterone (DHEA) analysis. Department of Human Services records were examined to determine the type, severity, chronicity, onset, and recency of maltreatment for children in the maltreated group. Significant interactions between gender and maltreatment pervasiveness predicted diurnal cortisol, DHEA, and cortisol/DHEA ratio levels. Elevated daily cortisol levels were reported for boys compared to girls in the group with more pervasive maltreatment. Boys with less pervasive maltreatment had lower DHEA and higher cortisol/DHEA ratio levels than girls with similar experiences, nonmaltreated boys, and boys with more pervasive maltreatment. Further results are consistent with down-regulation of cortisol production in girls with more pervasive maltreatment and girls who experienced maltreatment that was early onset and not recent. The effectiveness of interventions for maltreated children may be improved with greater knowledge of how maltreatment differentially affects neuroendocrine regulation by gender. PMID:23333253

  5. Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Spinelli C

    2013-09-01

    Full Text Available Primary neuroendocrine carcinomas of the breast are extremely rare. Neuroendocrine tumors mainly occur in the broncopolmonary system and gastrointestinal tract. The diagnosis of small cell neuroendocrine carcinoma (SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. We are going to describe two cases and to discuss their clinical, radiological and pathological manifestations. Introduction: Neuroendocrine tumors are rare and slow-growing neoplasias derived from neuroendocrine cells. We describe two cases of small cell neuroendocrine carcinoma of the breast and discuss their clinical, radiological and pathological manifestations. Case report: Our patients are two Italian females (38 and 36 year-old with no family history of breast disease. In both cases the diagnosis was confirmed after surgery, when immunohistochemistry revealed a neuroendocrine differentiation of the tumor. The patients are alive and disease free after more than ten years of follow-up. Conclusion: Primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. After surgery, a strict follow-up including octreotide scan should be performed and this doesn’t differ from the one of the usual breast carcinoma.

  6. [Surgical treatment of gastroentero-pancreatic neuroendocrine tumor].

    Science.gov (United States)

    Ohtsuka, Takao; Takahata, Shunichi; Ueda, Junji; Ueki, Takashi; Nagai, Eishi; Mizumoto, Kazuhiro; Shimizu, Shuji; Tanaka, Masao

    2013-07-01

    The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is resection. Because it is difficult to determine the histological grade of NET before operation, the treatment strategy is usually made based on an imaging study including the tumor's size. Some selected gastrointestinal NETs are indicated for endoscopic resection, while others are resected surgically with lymph node dissection. The types of resections for pancreatic NETs vary from enucleation to pancreatectomy with or without regional lymph node dissection, based on the type of excessive hormone, tumor size, distance from the main pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic metastases are also resected, if indicated, and even in patients having unresectable metastatic lesions, multidisciplinary therapy including reduction surgery of over 90% of tumor volume might lead to a favorable prognosis. Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while there is no evidence to support adjuvant therapy for curatively resected well-differentiated NET.

  7. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas

    DEFF Research Database (Denmark)

    Christensen, Lene Svendstrup; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    , a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers...... are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas....

  8. Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women.

    Science.gov (United States)

    Ronaldson, Amy; Gazali, Ahmad M; Zalli, Argita; Kaiser, Frank; Thompson, Stephen J; Henderson, Brian; Steptoe, Andrew; Carvalho, Livia

    2016-05-01

    The percentage of regulatory T cells (TRegs)-a subtype of T lymphocyte that suppresses the immune response-appears to be reduced in a number of stress-related diseases. The role of the TReg in stress-disease pathways has not yet been investigated. The aim of the study was to investigate the association between biological responsivity to acute psychosocial stress and the percentage of TRegs in healthy older adults. The secondary purpose was to measure the associations between TReg percentage and psychological and physical well-being in the participants. Salivary cortisol and plasma interleukin (IL)-6 samples were obtained from 121 healthy older men and women from the Whitehall II cohort following acute psychophysiological stress testing. Three years later at a follow-up visit, we measured TReg percentages and psychological and physical well-being were recorded using the Short Form 36 Health Survey and the Center for Epidemiologic Studies Depression Scale. Blunted cortisol responses (p = 0.004) and elevated IL-6 responses (p = 0.027) to acute psychophysiological stress were associated with greater TReg percentage independently of age, sex, BMI, smoking status, employment grade, time of testing, and baseline measures of cortisol and IL-6, respectively. Percentage of TRegs was associated cross-sectionally with lower physical (p = 0.043) and mental health status (p = 0.008), and higher levels of depressive symptoms (p = 0.002), independently of covariates. Increased levels of TRegs may act as a defence against increased inflammation and may be a pre-indication for chronically stressed individuals on the cusp of clinical illness.

  9. Brief cognitive intervention can modulate neuroendocrine stress responses to the Trier Social Stress Test: buffering effects of a compassionate goal orientation.

    Science.gov (United States)

    Abelson, James L; Erickson, Thane M; Mayer, Stefanie E; Crocker, Jennifer; Briggs, Hedieh; Lopez-Duran, Nestor L; Liberzon, Israel

    2014-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a critical mediator linking stress to health. Understanding how to modulate its reactivity could potentially help reduce the detrimental health effects of HPA axis activation. Social evaluative threat is a potent activator of this system. Access to control and coping responses can reduce its reactivity to pharmacological activation. Compassionate or affiliative behaviors may also moderate stress reactivity. Impact of these moderators on social evaluative threat is unknown. Here, we tested the hypotheses that interventions to increase control, coping, or compassionate (versus competitive) goals could reduce HPA-axis response to social evaluative threat. Healthy participants (n=54) were exposed to social evaluative threat using the Trier Social Stress Test (TSST). They were randomly assigned to receive one of four different instructions prior to the stressor: Standard TSST instructions (SI), standard instructions with access to "control" (SI Control), or one of two cognitive interventions (CI) that (1) increased familiarity and helped participants prepare coping strategies (CI Coping), or (2) shifted goal orientation from self-promotion to helping others (CI Compassionate Goals). ACTH and cortisol were obtained before and after stress exposure via intravenous catheter. Control alone had no effect. CI Compassionate Goals significantly reduced ACTH and cortisol responses to the TSST; CI Coping raised baseline levels. Compassionate Goals reduced hormonal responses without reducing subjective anxiety, stress or fear, while increasing expression of pro-social intentions and focus on helping others. Brief intervention to shift focus from competitive self-promotion to a goal orientation of helping-others can reduce HPA-axis activation to a potent psychosocial stressor. This supports the potential for developing brief interventions as inoculation tools to reduce the impact of predictable stressors and lends support to growing

  10. Investigation on plasmonic responses in multilayered nanospheres including asymmetry and spatial nonlocal effects

    Science.gov (United States)

    Dong, Tianyu; Shi, Yi; Liu, Hui; Chen, Feng; Ma, Xikui; Mittra, Raj

    2017-12-01

    In this work, we present a rigorous approach for analyzing the optical response of multilayered spherical nano-particles comprised of either plasmonic metal or dielectric, when there is no longer radial symmetry and when nonlocality is included. The Lorenz–Mie theory is applied, and a linearized hydrodynamic Drude model as well as the general nonlocal optical response model for the metals are employed. Additional boundary conditions, viz., the continuity of normal components of polarization current density and the continuity of first-order pressure of free electron density, respectively, are incorporated when handling interfaces involving metals. The application of spherical addition theorems, enables us to express a spherical harmonic about one origin to spherical harmonics about a different origin, and leads to a linear system of equations for the inward- and outward-field modal coefficients for all the layers in the nanoparticle. Scattering matrices at interfaces are obtained and cascaded to obtain the expansion coefficients, to yield the final solution. Through extensive modelling of stratified concentric and eccentric metal-involved spherical nanoshells illuminating by a plane wave, we show that, within a nonlocal description, significant modifications of plasmonic response appear, e.g. a blue-shift in the extinction / scattering spectrum and a broadening spectrum of the resonance. In addition, it has been demonstrated that core–shell nanostructures provide an option for tunable Fano-resonance generators. The proposed method shows its capability and flexibility to analyze the nonlocal response of eccentric hybrid metal–dielectric multilayer structures as well as adjoined metal-involved nanoparticles, even when the number of layers is large.

  11. NOAA Atmospheric, Marine and Arctic Monitoring Using UASs (including Rapid Response)

    Science.gov (United States)

    Coffey, J. J.; Jacobs, T.

    2015-12-01

    Unmanned systems have the potential to efficiently, effectively, economically, and safely bridge critical observation requirements in an environmentally friendly manner. As the United States' Atmospheric, Marine and Arctic areas of interest expand and include hard-to-reach regions of the Earth (such as the Arctic and remote oceanic areas) optimizing unmanned capabilities will be needed to advance the United States' science, technology and security efforts. Through increased multi-mission and multi-agency operations using improved inter-operable and autonomous unmanned systems, the research and operations communities will better collect environmental intelligence and better protect our Country against hazardous weather, environmental, marine and polar hazards. This presentation will examine NOAA's Atmospheric, Marine and Arctic Monitoring Unmanned Aircraft System (UAS) strategies which includes developing a coordinated effort to maximize the efficiency and capabilities of unmanned systems across the federal government and research partners. Numerous intra- and inter-agency operational demonstrations and assessments have been made to verify and validated these strategies. This includes the introduction of the Targeted Autonomous Insitu Sensing and Rapid Response (TAISRR) with UAS concept of operations. The presentation will also discuss the requisite UAS capabilities and our experience in using them.

  12. Mid-term effects of serial sleep deprivation therapy implemented in cognitive-behavioral treatment on the neuroendocrine response to clomipramine in patients with major depression.

    Science.gov (United States)

    Kundermann, Bernd; Strate, Peter; Hemmeter-Spernal, Julia; Huber, Martin Tobias; Krieg, Jürgen-Christian; Lautenbacher, Stefan

    2009-04-01

    While data dealing with neurobiological effects of sleep deprivation (SD) are mainly restricted to the acute effects of a single night, only few studies have investigated mid-term effects after repeated SD. We therefore examined the clinical and hormonal characteristics of depressive patients before and after serial SD to determine potential sustained effects, focusing especially on serotoninergic functions. One tool to investigate serotoninergic dysfunction in depression is the use of serotoninergic agents to stimulate hormonal secretion, which is assumed to normalize during a clinically effective therapy. Eighteen drug-free inpatients with unipolar major depression received cognitive-behavioral treatment for three weeks and - according to a randomized control design - additional SD therapy (six nights of total SD within three weeks, separated by nights of recovery sleep) or no SD therapy (control group). Serotoninergic function was assessed by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg) before and after the treatment period. The post-treatment challenge test was performed three days after the last SD night. Apart from of a transient overnight improvement of mood induced by SD, both groups showed a comparable clinical course during the three-week treatment period. Compared to the control group, the SD-treated patients exhibited significantly decreased pre-stimulation cortisol levels and significantly increased cortisol responses to clomipramine, whereas no treatment effects were observed for prolactin. In conclusion, our findings suggest that the mid-term effects of serial SD therapy lead to a normalization of serotoninergic dysfunction, although an obvious impact on clinical symptoms was not detected.

  13. The Structure of the Neuroendocrine Hypothalamus: The Neuroanatomical Legacy of Geoffrey Harris

    Science.gov (United States)

    Watts, Alan G.

    2015-01-01

    In November 1955 Geoffrey Harris published a paper based on the Christian A. Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing this Harris introduced a set of properties that would help define the neuroendocrine hypothalamus. They included: a) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; b) an analogy between the representation of body parts in sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and c) the idea that neuroendocrine neurons were motor neurons, with the pituitary stalk functioning as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons had to pass to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries being made in the early 1950s were beginning to influence neuroendocrinology? The present article discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and within this framework, how novel and powerful techniques are taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. PMID:25994006

  14. Optimization of Gluten-Free Tulumba Dessert Formulation Including Corn Flour: Response Surface Methodology Approach

    Directory of Open Access Journals (Sweden)

    Yildiz Önder

    2017-03-01

    Full Text Available Tulumba dessert is widely preferred in Turkey; however, it cannot be consumed by celiac patients because it includes gluten. The diversity of gluten-free products should be expanded so that celiac patients may meet their daily needs regularly. In this study, corn flour (CF / potato starch (PS blend to be used in the gluten-free tulumba dessert formulation was optimized using the Response Surface Methodology (RSM. Increasing ratio of PS in the CF-PS led to a decrease in hardness of the dessert and to an increase in expansion, viscosity, adhesiveness, yield of dessert both with and without syrup (P0.05, additionally these desserts had a much higher sensory score compared to the control sample in terms of the overall quality and pore structure (P<0.05.

  15. Day-ahead resource scheduling including demand response for electric vehicles

    DEFF Research Database (Denmark)

    Soares, Joao; Morais, Hugo; Sousa, Tiago

    2014-01-01

    Summary form only given. The energy resource scheduling is becoming increasingly important, as the use of distributed resources is intensified and massive gridable vehicle (V2G) use is envisaged. This paper presents a methodology for day-ahead energy resource scheduling for smart grids considering...... the intensive use of distributed generation and V2G. The main focus is the comparison of different EV management approaches in the day-ahead energy resources management, namely uncontrolled charging, smart charging, V2G and Demand Response (DR) programs in the V2G approach. Three different DR programs....... Mixed integer non-linear programming is also used for comparison purposes. Full ac power flow calculation is included to allow taking into account the network constraints. A case study with a 33-bus distribution network and 2000 V2G resources is used to illustrate the performance of the proposed method....

  16. Neuroendocrine and immune characteristics of aging in avian species.

    Science.gov (United States)

    Ottinger, M A; Lavoie, E

    2007-01-01

    Avian species show a remarkable diversity in lifespan. The differing lifespan patterns are found across a number of birds, in spite of higher body temperature and apparent increased metabolic rate. These characteristics make study of age-related changes of great interest, especially for understanding the biology of aging associated with surprisingly long lifespan in some birds. Our studies have focused on a short-lived avian model, the Japanese quail in order to describe reproductive aging and the neuroendocrine characteristics leading to reproductive senescence. Biomarkers of aging used in mammalian species include telomere length, oxidative damage, and selected metabolic indicators. These markers provide confirming evidence that the long-lived birds appear to age more slowly. A corollary area of interest is that of immune function and aging. Immune responses have been studied in selected wild birds and there has been a range of studies that have considered the effects of stress in wild and domestic species. Our laboratory studies have specifically tested response to immune challenge relative to aging in the quail model and these studies indicate that there is an age-related change in the qualitative aspects of the response. However, there are also intriguing differences in the ability of the aging quail to respond that differ from mammalian data. Finally, another approach to understanding aging is to attempt to develop or test strategies that may extend lifespan and presumably health. One area of great interest has been to consider the effect of calorie restriction, which is a treatment shown to extend lifespan in a variety of species. This approach is routinely used in domestic poultry as a means for extending reproductive function and enhancing health. Our data indicate that moderate calorie restriction has beneficial effects, and that physiological and endocrine responses reflect these benefits. Copyright 2007 S. Karger AG, Basel.

  17. Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

    Directory of Open Access Journals (Sweden)

    Helga Bertani

    2011-01-01

    Full Text Available Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10% (1. Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2 cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2. Myasthenia gravis (MG is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR. MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3. No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour.

  18. Neuroendocrine brake for the treatment of morbid obesity. Preliminary report

    Directory of Open Access Journals (Sweden)

    Aureo Ludovico de Paula

    2005-06-01

    Full Text Available Objectives: To demonstrate the preliminary results of a newtechnique named neuroendocrine brake, for surgical treatment ofmorbid obesity. Methods: In November 2003, three patientsunderwent the neuroendocrine brake operation performed by thelaparoscopic approach. The mean age was 46.4 years; all patientswere female. Mean BMI was 42.3 kg/m2. The patients selectedpresented some relative or absolute contraindications to the useof gastrointestinal bypass techniques, including gastric ulcer anda family history of gastric malignancy(1 and chronic anemia (2.All patients had associated diseases, including type II diabetesmellitus (2, hypertension (2, obstructive sleep apnea (1,dyslipidemia (3, cholecystolithiasis (1, gastric ulcer (1 andchronic anemia (2. The laparoscopic technique consisted of anileal interposition at the proximal jejunum and longitudinalgastrectomy. Results: There was no conversion to open surgery orpostoperative complications. Sixteen months later, the meanpercentage of initial body weight loss was 44.6% and the meanBMI was 24.3 kg/m2. Glucose, triglyceride and cholesterol levelswere normalized, and sleep apnea showed remission. Conclusion:In spite of the reduced number of patients and short term followup, the good results suggest that the neuroendocrine brake maybecome an option for surgical treatment of morbid obesity in thenear future.

  19. Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Engelund Luna, Iben; Monrad, Nina; Binderup, Tina

    2016-01-01

    OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological, and bio......OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological...

  20. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    OpenAIRE

    Todorović-Tirnanić Mila; Artiko Vera; Pavlović Smiljana; Šobić-Šaranović Dragana; Obradović Vladimir

    2015-01-01

    The new positron emission tomography (PET/CT) methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In-pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline a...

  1. Neuroendocrine Function After Hypothalamic Depletion of Glucocorticoid Receptors in Male and Female Mice.

    Science.gov (United States)

    Solomon, Matia B; Loftspring, Matthew; de Kloet, Annette D; Ghosal, Sriparna; Jankord, Ryan; Flak, Jonathan N; Wulsin, Aynara C; Krause, Eric G; Zhang, Rong; Rice, Taylor; McKlveen, Jessica; Myers, Brent; Tasker, Jeffrey G; Herman, James P

    2015-08-01

    Glucocorticoids act rapidly at the paraventricular nucleus (PVN) to inhibit stress-excitatory neurons and limit excessive glucocorticoid secretion. The signaling mechanism underlying rapid feedback inhibition remains to be determined. The present study was designed to test the hypothesis that the canonical glucocorticoid receptors (GRs) is required for appropriate hypothalamic-pituitary-adrenal (HPA) axis regulation. Local PVN GR knockdown (KD) was achieved by breeding homozygous floxed GR mice with Sim1-cre recombinase transgenic mice. This genetic approach created mice with a KD of GR primarily confined to hypothalamic cell groups, including the PVN, sparing GR expression in other HPA axis limbic regulatory regions, and the pituitary. There were no differences in circadian nadir and peak corticosterone concentrations between male PVN GR KD mice and male littermate controls. However, reduction of PVN GR increased ACTH and corticosterone responses to acute, but not chronic stress, indicating that PVN GR is critical for limiting neuroendocrine responses to acute stress in males. Loss of PVN GR induced an opposite neuroendocrine phenotype in females, characterized by increased circadian nadir corticosterone levels and suppressed ACTH responses to acute restraint stress, without a concomitant change in corticosterone responses under acute or chronic stress conditions. PVN GR deletion had no effect on depression-like behavior in either sex in the forced swim test. Overall, these findings reveal pronounced sex differences in the PVN GR dependence of acute stress feedback regulation of HPA axis function. In addition, these data further indicate that glucocorticoid control of HPA axis responses after chronic stress operates via a PVN-independent mechanism.

  2. A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

    Directory of Open Access Journals (Sweden)

    Godwin Ofikwu

    2015-01-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linear proliferation. It is usually seen in middle-aged, nonsmoking women with symptoms of cough, dyspnea, and wheezing. We present a 45-year-old, nonsmoking woman who presented with symptoms of DIPNECH associated with bilateral pulmonary nodules and left hilar adenopathy. Of interest, DIPNECH in our patient was associated with metastatic pulmonary carcinoids, papillary carcinoma of the left breast, oncocytoma and angiomyolipoma of her left kidney, and cortical nodules suggestive of tuberous sclerosis. She had video assisted thoracoscopic surgery (VATS, modified radical mastectomy with reconstruction, and radical nephrectomy. She is currently symptom-free most of the time with over two years of follow-up.

  3. Management of neuroendocrine tumors of unknown primary.

    Science.gov (United States)

    Alexandraki, Krystallenia; Angelousi, Anna; Boutzios, Georgios; Kyriakopoulos, Georgios; Rontogianni, Dimitra; Kaltsas, Gregory

    2017-12-04

    Neuroendocrine neoplams (NENs) are mostly relatively indolent malignancies but a significant number have metastatic disease at diagnosis mainly to the liver. Although in the majority of such cases the primary origin of the tumor can be identified, in approximately 11-22% no primary tumor is found and such cases are designated as NENs of unknown primary origin (UPO). This has significant therapeutic implications with respect to potentially resectable hepatic disease and/or application of appropriate medical therapy, either chemotherapeutic agents or targeted treatment, as the response to various treatments varies according to the origin of the primary tumor. This lack of tumor specific orientated treatment may also account for the relatively poorer prognosis of NENs of UPO compared to metastatic NENs with a known primary site. In the majority of cases the primary tumors are located in the small bowel and the lung, but a number may still elude detection. Occasionally the presence of a functional syndrome may direct to the specific tissue of origin but in the majority of cases a number of biochemical, imaging, histopathological and molecular modalities are utilized to help identify the primary origin of the tumor and direct treatment accordingly. Several diagnostic algorithms have recently been developed to help localize an occult primary tumor; however, in a number of cases no lesion is identified even after prolonged follow-up. It is expected that the delineation of the molecular signature of the different NENs may help identify such cases and provide appropriate treatment.

  4. Primary Neuroendocrine Carcinoma of Ocular Adnexa

    Directory of Open Access Journals (Sweden)

    Daisuke Yamanouchi

    2013-01-01

    Full Text Available We present our findings in a case of primary neuroendocrine carcinoma (NEC of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

  5. Diagnosis and Treatment of Gastroenteropancreatic Neuroendocrine Tumors: Current Data on a Prospectively Collected, Retrospectively Analyzed Clinical Multicenter Investigation

    OpenAIRE

    Niederle, Martin B.; Niederle, Bruno

    2011-01-01

    Clinical information concerning diagnosis, symptoms, and treatment of 277 patients with gastrointestinal neuroendocrine tumors (including pancreatic tumors) diagnosed prospectively within 1 year were analyzed. Endoscopic and surgical techniques are the key to both correct diagnosis and effective treatment.

  6. How to include the variability of TMS responses in simulations: a speech mapping case study

    Science.gov (United States)

    De Geeter, N.; Lioumis, P.; Laakso, A.; Crevecoeur, G.; Dupré, L.

    2016-11-01

    When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca’s with Wernicke’s area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case- and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.

  7. The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma.

    Science.gov (United States)

    Miyasaka, Tomomitsu; Dobashi-Okuyama, Kaori; Takahashi, Tomoko; Takayanagi, Motoaki; Ohno, Isao

    2018-01-01

    Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2)-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17)-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg) cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a "neuropsychiatry phenotype" in asthma. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  8. Role of Neuropeptide FF (NPFF in central cardiovascular and neuroendocrine regulation.

    Directory of Open Access Journals (Sweden)

    Jack H. Jhamandas

    2013-02-01

    Full Text Available Neuropeptide FF (NPFF is an octapeptide belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain including central cardiovascular and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1and NPFF2 receptors that are abundantly expressed in the rat and human brain. Herein, we review evidence for the role of NPFF in central regulation of blood pressure particularly within the brainstem and the hypothalamic paraventricular nucleus (PVN. At a cellular level, NPFF demonstrates distinct responses in magnocellular and parvocellular neurons of the PVN, which regulate the secretion of neurohypohyseal hormones, and sympathetic ouflow, respectively. Finally, the presence of NPFF system in the human brain and its alterations within the hypertensive brain are discussed.

  9. DIABETES MELLITUS IN NEUROENDOCRINE DISEASES

    Directory of Open Access Journals (Sweden)

    I. V. Trigolosova

    2014-01-01

    early disability and death of patients with neuroendocrine diseases.

  10. Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Richter, Catherine A.; Martyniuk, Christopher J.; Annis, Mandy L.; Brumbaugh, William G.; Chasar, Lia C.; Denslow, Nancy D.; Tillitt, Donald E.

    2014-01-01

    Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.

  11. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Wagner, Ludwig; Brandt Sørensen, Flemming

    2005-01-01

    , synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas...

  12. Incidental neuroendocrine tumor of the appendiceal base less ...

    African Journals Online (AJOL)

    Incidental neuroendocrine tumor of the appendiceal base less than20 mm in diameter: is appendectomy enough? Landolsi Sana, Mannai Saber. Abstract. The appendixis the second primary site for neuroendocrine tumors. The management of incidentelly discovered neuroendocrine tumor of the appendiceal base less ...

  13. Hybridising Sport Education and Teaching for Personal and Social Responsibility to Include Students with Disabilities

    Science.gov (United States)

    Menendez, Jose Ignacio; Fernandez-Rio, Javier

    2017-01-01

    The present study aimed to explore the impact of the combination of two pedagogical models, Sport Education and Teaching for Personal and Social Responsibility, for learners with disabilities experiencing a contactless kickboxing learning unit. Twelve secondary education students agreed to participate. Five had disabilities (intellectual and…

  14. Subjective response to foot-fall noise, including localization of the source position

    DEFF Research Database (Denmark)

    Brunskog, Jonas; Hwang, Ha Dong; Jeong, Cheol-Ho

    2011-01-01

    annoyance, using simulated binaural room impulse responses, with sources being a moving point source or a non-moving surface source, and rooms being a room with a reverberation time of 0.5 s or an anechoic room. The paper concludes that no strong effect of the source localization on the annoyance can...

  15. The Assessment of Real Estate Initiatives to Be Included in the Socially-Responsible Funds

    Directory of Open Access Journals (Sweden)

    Fabrizio Battisti

    2017-06-01

    Full Text Available The acknowledgment of the ongoing economic and financial crisis involving real estate, creates the need to formulate proposals and scenarios (in real estate with the characteristics of socially responsible investments. These kind of investments aim towards “sustainable” development both environmentally (safeguarding the shortage of resources such as land, energy, and natural elements, and socially (protecting the population and raising its level of well-being according to so-called “ethical finance”, instead of a mere “speculative” investment. Effectively, real estate is still an investment sector only marginally explored by the socially-responsible funds. Based on these premises, this paper will: (i briefly analyze the nature of socially-responsible investments, setting their characteristics apart from “traditional investments”; and (ii propose a possible procedure (of the multi-criteria type which aims to assess socially-responsible investments in real estate. This will be applied to a case study regarding a social housing initiative in the municipality of Anguillara Sabazia (Rome, Italy.

  16. Simulated selection responses for breeding programs including resistance and resilience to parasites in Creole goats

    NARCIS (Netherlands)

    Gunia, M.; Phocas, F.; Gourdine, J.L.; Bijma, P.; Mandonnet, N.

    2013-01-01

    The Creole goat is a local breed used for meat production in Guadeloupe (French West Indies). As in other tropical countries, improvement of parasite resistance is needed. In this study, we compared predicted selection responses for alternative breeding programs with or without parasites resistance

  17. CORPORATE SOCIAL RESPONSIBILITY AS CONDITION OF INCLUDING UKRAINE IN EUROPE AND WORLD ECONOMIC SPACE

    Directory of Open Access Journals (Sweden)

    T. Lytvynenko

    2013-09-01

    Full Text Available The thesis that companies’ activities for introduction of corporate social responsibility stimulates the speed of to the processes of the technical upgrade, modernization of company’s activity and increase of its profitability is proved within the article. Those Ukrainian companies, which have high index of activities transparency, are also the most profitable. However, we can’t observe any significant increment of number of companies joining the Global agreement. One of the explanations we could name is the unproved idea supported by some politicians and economists about a shadow (‘black’ market that allegedly allows creating workplaces and taking off social tension in society on the certain stage. Insignificant values of index of citizens’ trust to activity of industries holds on the development socially of responsible business. Trust considered as a part of the general social capital. The Government of Ukraine must support initiative of companies to introduce social responsibility of business, as many European governments do it. It is also important to inform society of advantages of CSR.

  18. Large cell neuroendocrine carcinoma of the kidney with cardiac metastasis: a case report

    Directory of Open Access Journals (Sweden)

    Moeka Shimbori

    2017-10-01

    Full Text Available Abstract Background Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis. Case presentation A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart. A cardiac biopsy under transesophageal echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple lung lesions were detected, and a right nephrectomy was performed after these metastases were suspected to have originated from renal carcinoma. Large cell neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic metastasis was detected on computed tomography postoperatively. Three courses of chemotherapy with carboplatin and irinotecan were administered, and were temporarily effective against the metastatic lesions in the lungs and pancreas. However, our patient’s general condition deteriorated with the progression of the lesions, and he died 9 months after his initial examination. Conclusions Multi-agent chemotherapy, including platinum-based drugs was effective against large cell neuroendocrine carcinoma metastases, albeit only temporarily. This is the first reported case of large cell neuroendocrine carcinoma with cardiac metastasis.

  19. Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling.

    Science.gov (United States)

    O'Neill, Casey E; Newsom, Ryan J; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C; Spencer, Robert L; Campeau, Serge; Bachtell, Ryan K

    2016-05-01

    basal Crf mRNA in the central nucleus of the amygdala, but no additional effects of stress or caffeine consumption were observed in other brain regions. Together these findings suggest that adolescent caffeine consumption may increase vulnerability to psychiatric disorders including anxiety-related disorders, and this vulnerability may result from dysregulation of the neuroendocrine stress response system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. GERD assessment including pH metry predicts a high response rate to PPI standard therapy

    Directory of Open Access Journals (Sweden)

    Kandulski Arne

    2013-01-01

    Full Text Available Abstract Background Inadequate response to proton pump inhibitor (PPI therapy in patients with gastroesophageal reflux disease (GERD is reported in up to 40%. Patients with non erosive reflux disease (NERD have lower response rates compared to patients with erosive reflux disease (ERD; pH metry contributes to GERD diagnosis and is critical for proper diagnosis of NERD. Aim of the study was to assess the need for doubling esomeprazole standard dose (40 mg for 4 weeks in PPI naive patients with typical reflux symptoms and diagnosis of GERD based on endoscopy and 48 hours, wireless pH metry. Methods All patients underwent upper GI endoscopy. Symptoms were recorded with a structured questionnaire (RDQ and acid exposure was determined by 48 hours, wireless pH monitoring (BRAVO. In case of abnormal acid exposure, patients received a short term treatment with esomeprazole 40 mg q.d. for 4 weeks. If symptoms persisted, patients underwent a second pH metry on PPI and the dose was increased to 40 mg b.i.d. Results 31 consecutive patients with typical reflux symptoms underwent 48 hours pH monitoring. 22 patients (71% had abnormal acid exposure, 9 patients had normal pH metry (29%. Of the 9 patients with normal pH metry, 2 were found with erosive esophagitis and 7 without endoscopic abnormalities. 24 patients with documented GERD received esomeprazole treatment. 21 patients achieved complete symptom resolution with 40 mg q.d. after 4 weeks (88%. Only 2 patients required doubling the dose of esomeprazole for complete symptom resolution, 1 patient remained with symptoms. Conclusions Patients with typical reflux symptoms and abnormal acid exposure have a high response rate to standard dose esomeprazole regardless of whether they have ERD or NERD.

  1. Update on the management of neuroendocrine hepatic metastases.

    Science.gov (United States)

    Madoff, David C; Gupta, Sanjay; Ahrar, Kamran; Murthy, Ravi; Yao, James C

    2006-08-01

    Neuroendocrine tumors (NETs) are rare and represent a diverse collection of malignancies that occur in many organ systems throughout the body, including the gastrointestinal and respiratory tracts. Unfortunately, the majority of patients with NETs have hepatic metastases at the time of diagnosis. Although some patients may be asymptomatic, others have unusual clinical presentations and variable tumor growth patterns. Although many patients have long indolent courses, without treatment, most patients die within 5 years of diagnosis. This article reviews the care of patients with NETs and hepatic metastases, with emphasis on the increasingly important role of oncologic image-guided interventions.

  2. Integrated outage management: Leveraging utility system assets including GIS and AMR for optimum outage response

    Energy Technology Data Exchange (ETDEWEB)

    Finamore, E. P.

    2004-02-01

    The control of electrical system outages is discussed. The principal argument advanced is that traditional stand-alone methods of outage response will no longer get the job done without utility companies integrating their outage management systems with other system assets such as GIS (geographic information system) and AMR (advanced metering systems). Many meter reading systems, while primarily supporting customer billing, can also provide outage alarm and some are also capable of service restoration notification, which is an invaluable benefit to service operators since it obviates the need for verifying system restoration by labour-intensive on-site visits or customer call-backs. If successfully leveraged, optimization of all utility assets and improvements in labour productivity can results in improved outage management performance gains without affecting performance in other areas.

  3. Predicting Mountainous Watershed Biogeochemical Dynamics, Including Response to Droughts and Early Snowmelt

    Science.gov (United States)

    Hubbard, S. S.; Williams, K. H.; Long, P.; Agarwal, D.; Banfield, J. F.; Beller, H. R.; Bouskill, N.; Brodie, E.; Maxwell, R. M.; Nico, P. S.; Steefel, C. I.; Steltzer, H.; Tokunaga, T. K.; Wainwright, H. M.

    2016-12-01

    Climate change, extreme weather, land-use change, and other perturbations are significantly reshaping interactions with in watersheds throughout the world. While mountainous watersheds are recognized as the water towers for the world, hydrological processes in watersheds also mediate biogeochemical processes that support all terrestrial life. Developing predictive understanding of watershed hydrological and biogeochemical functioning is challenging, as complex interactions occurring within a heterogeneous watershed can lead to a cascade of effects on downstream water availability and quality. Although these interactions can have significant implications for energy production, agriculture, water quality, and other benefits valued by society, uncertainty associated with predicting watershed function is high. The Watershed Function project aims to substantially reduce this uncertainty through developing a predictive understanding of how mountainous watersheds retain and release downgradient water, nutrients, carbon, and metals. In particular, the project is exploring how early snowmelt, drought, and other disturbances will influence mountainous watershed dynamics at seasonal to decadal timescales. The Watershed Function project is being carried out in a headwater mountainous catchment of the Upper Colorado River Basin, within a watershed characterized by significant gradients in elevation, vegetation and hydrogeology. A system-within system project perspective posits that the integrated watershed response to disturbances can be adequately predicted through consideration of interactions and feedbacks occurring within a limited number of subsystems, each having distinct vegetation-subsurface biogeochemical-hydrological characteristics. A key technological goal is the development of scale-adaptive simulation capabilities that can incorporate genomic information where and when it is useful for predicting the overall watershed response to disturbance. Through developing

  4. Standardisation of imaging in neuroendocrine tumours: results of a European delphi process

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, J. E-mail: jens@charite.de; Klose, K.-J.; Mignon, M.; Oeberg, K.; Wiedenmann, B

    2001-01-01

    In 1998 and 1999, a delphi consensus procedure was performed to establish guidelines for standardised diagnostic imaging of neuroendocrine tumours. The procedure included four consecutive workshops of a European group of experts in neuroendocrine tumours as well as feedback given by specialists from the departments of radiology, nuclear medicine, surgery and internal medicine of the according home institutions. Diverging approaches among the centres, which became apparent during the discussion, reflect a lack of controlled studies specifically for rare subgroups of neuroendocrine tumours. This paper summarises the standards for diagnostic imaging as developed during the delphi process. In particular, the diagnostic workflows as well as the technical properties of different imaging modalities are described in detail.

  5. Midgut neuroendocrine tumor presenting with acute intestinal ischemia.

    Science.gov (United States)

    Mantzoros, Ioannis; Savvala, Natalia Antigoni; Ioannidis, Orestis; Parpoudi, Styliani; Loutzidou, Lydia; Kyriakidou, Despoina; Cheva, Angeliki; Intzos, Vasileios; Tsalis, Konstantinos

    2017-12-07

    Neuroendocrine tumors represent a heterogeneous group of neoplasms that arise from neuroendocrine cells and secrete various peptides and bioamines. While gastrointestinal neuroendocrine tumors, commonly called carcinoids, account for about 2/3 of all neuroendocrine tumors, they are relatively rare. Small intestine neuroendocrine tumors originate from intestinal enterochromaffin cells and represent about 1/4 of small intestine neoplasms. They can be asymptomatic or cause nonspecific symptoms, which usually leads to a delayed diagnosis. Imaging modalities can aid diagnosis and surgery remains the mainstay of treatment. We present a case of a jejunal neuroendocrine tumor that caused nonspecific symptoms for about 1 year before manifesting with acute mesenteric ischemia. Abdominal X-rays revealed pneumatosis intestinalis and an abdominal ultrasound and computed tomography confirmed the diagnosis. The patient was submitted to segmental enterectomy. Histopathological study demonstrated a neuroendocrine tumor with perineural and arterial infiltration and lymph node metastasis. The postoperative course was uneventful and the patient denied any adjuvant treatment.

  6. 'Including health in systems responsible for urban planning': a realist policy analysis research programme.

    Science.gov (United States)

    Harris, Patrick; Friel, Sharon; Wilson, Andrew

    2015-07-23

    Realist methods are increasingly being used to investigate complex public health problems. Despite the extensive evidence base clarifying the built environment as a determinant of health, there is limited knowledge about how and why land-use planning systems take on health concerns. Further, the body of research related to the wider determinants of health suffers from not using political science knowledge to understand how to influence health policy development and systems. This 4-year funded programme of research investigates how the land-use planning system in New South Wales, Australia, incorporates health and health equity at multiple levels. The programme uses multiple qualitative methods to develop up to 15 case studies of different activities of the New South Wales land-use planning system. Comparison cases from other jurisdictions will be included where possible and useful. Data collection includes publicly available documentation and purposively sampled stakeholder interviews and focus groups of up to 100 participants across the cases. The units of analysis in each case are institutional structures (rules and mandates constraining and enabling actors), actors (the stakeholders, organisations and networks involved, including health-focused agencies), and ideas (policy content, information, and framing). Data analysis will focus on and develop propositions concerning the mechanisms and conditions within and across each case leading to inclusion or non-inclusion of health. Data will be refined using additional political science and sociological theory. Qualitative comparative analysis will compare cases to develop policy-relevant propositions about the necessary and sufficient conditions needed to include health issues. Ethics has been approved by Sydney University Human Research Ethics Committee (2014/802 and 2015/178). Given the nature of this research we will incorporate stakeholders, often as collaborators, throughout. We outline our research translation

  7. FDA Approves Lutathera for Neuroendocrine Tumors

    Science.gov (United States)

    FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

  8. A pancreatic neuroendocrine tumor diagnosed during the ...

    African Journals Online (AJOL)

    Pancreatic neuroendocrine tumors (PNET) are increasingly being discovered. A case of PNET diagnosed and treated during the management of acute appendicitis is presented and discussed. The importance of imaging modalities in patients with acute abdominal pain is emphasized. To the best our knowledge, this is the ...

  9. Nuclear Medicine Imaging of Neuroendocrine Tumors

    NARCIS (Netherlands)

    Brabander, Tessa; Kwekkeboom, Dik J.; Feelders, Richard A.; Brouwers, Adrienne H.; Teunissen, Jaap J. M.; Papotti, M; DeHerder, WW

    2015-01-01

    An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with In-111-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy

  10. Other PET tracers for neuroendocrine tumors

    NARCIS (Netherlands)

    Koopmans, Klaas Pieter; Glaudemans, Andor W J M

    In this article the applicability of (124)I-MIBG and (11)C-5-HTP PET for the detection of abdominal gastro-enteropancreatic neuroendocrine tumors is discussed. (124)I-MIBG is a positron-emitting variant of (123)I-MIBG and therefore suited for PET imaging. Due to the better intrinsic characteristics

  11. A detector response function design in pinhole SPECT including geometrical calibration.

    Science.gov (United States)

    El Bitar, Z; Huesman, R H; Boutchko, R; Bekaert, Virgile; Brasse, David; Gullberg, G T

    2013-04-07

    Clinical single photon emission computed tomography (SPECT) equipped with pinhole collimators have a magnification factor that results in high spatial resolution images for small animal imaging. Using Monte Carlo simulations to model the acquisition process and the propagation of the photons from their point of emission to their detection point then integrating the model into an iterative reconstruction algorithm improves the signal-to-noise ratio, the contrast and the spatial resolution in the reconstructed images. However, pinhole SPECT systems are known to be very sensitive to geometrical misalignments. Geometrical misalignments are defined as the radial or axial shift of the collimator pinhole and/or twist and tilt of the detector heads and are introduced in the system each time the collimation device is changed (pinhole to parallel holes or vice versa). In this work, we present a flexible detector response function table (DRFT) design that takes into account the geometrical misalignments and avoids performing new Monte Carlo simulations for each exam in order to calculate a geometrical study-dependent system matrix. The utilization of the DRFT for the calculation of the system matrix speeds up its computation time by two orders of magnitude making it acceptable for preclinical and clinical applications.

  12. Impact of Prenatal Stress on Neuroendocrine Programming

    Directory of Open Access Journals (Sweden)

    Odile Viltart

    2007-01-01

    programming strongly, notably when hormonal surges occur during sensitive periods of development, so-called developmental windows of vulnerability. Stressful events occurring during the perinatal period may impinge on various aspects of the neuroendocrine programming, subsequently amending the offspring's growth, metabolism, sexual maturation, stress responses, and immune system. Such prenatal stress-induced modifications of the phenotypic plasticity of the progeny might ultimately result in the development of long-term diseases, from metabolic syndromes to psychiatric disorders. Yet, we would like to consider the outcome of this neuroendocrine programming from an evolutionary perspective. Early stressful events during gestation might indeed shape internal parameters of the developing organisms in order to adapt the progeny to its everyday environment and thus contribute to an increased reproductive success, or fitness, of the species. Moreover, parental care, adoption, or enriched environments after birth have been shown to reverse negative long-term consequences of a disturbed gestational environment. In this view, considering the higher potential for neonatal plasticity within the brain in human beings as compared to other species, long-term consequences of prenatal stress might not be as inexorable as suggested in animal-based studies published to date.

  13. [Small cell neuroendocrine tumour of the bladder: with reference to a case and bibliographical revision].

    Science.gov (United States)

    Lahoz Tornos, A; Marrón Penón, Maria C; Pardo López, Maria L; Nogueras Gimeno, M A; Pujol Obis, E; Del Villar Sordo, V

    2006-09-01

    The small cell neuroendocrine tumour is an infrecuent neoplasia, with inmunohistochemistry being the key to diagnosis. We present a new case making reference to treatment and its evolution there after. The clinic, diagnosis and treatment of this tumour is described. Bibliographical revision follours. The neuroendocrine tumour of small cell is an infrecuent neoplasia, in which the inmunohistochemistry study is key in the diagnosis. The differential diagnosis includes the high degree diferentiation transitionals cells carcinoma and primary and secondary linfoma. The standard treatment is based on chemotherapy plus surgery.

  14. Differential expression of the PTEN tumor suppressor protein in fetal and adult neuroendocrine tissues and tumors: progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms.

    Science.gov (United States)

    Wang, Luoquan; Ignat, Ana; Axiotis, Constantine A

    2002-06-01

    Genetic alteration and loss of expression of tumor suppressor gene PTEN has been found in carcinomas of the breast, prostate, and endometrium, as well as in gliomas. PTEN expression in neural crest/neuroendocrine (NC/NE) tissues and in neoplasms has not been reported. This study examines PTEN expression in embryonal, fetal, and adult tissues by immunohistochemistry. The authors found high PTEN expression in embryonal, fetal, and adult NC/NE tissues. The authors also study the PTEN expression in NC/NE neoplasms (N = 37), including 5 melanocytic nevi, 2 melanomas, 9 carcinoids, 2 moderately differentiated neuroendocrine carcinomas, 13 poorly differentiated neuroendocrine carcinomas, 2 paragangliomas, 2 pheochromocytomas, 2 medullary thyroid carcinomas, and 1 neuroblastoma. All carcinoid tumors and melanocytic nevi showed moderate or strong immunostaining for PTEN. In contrast, the majority of poorly differentiated neuroendocrine carcinomas (7 of 13) were negative for PTEN (54%); the remainder showed diminished reactivity. The two melanomas studied were also negative for PTEN immunostaining. The paragangliomas, pheochromocytomas, medullary thyroid carcinomas, and neuroblastoma all showed a strong PTEN stain. The authors postulate that PTEN is a differentiation marker for NC/NE tissue and tumors and that loss of PTEN expression may represent an important step in the progression of NE tumors.

  15. Minichromosome Maintenance Expression Defines Slow-Growing Gastroenteropancreatic Neuroendocrine Neoplasms

    Directory of Open Access Journals (Sweden)

    Simon Schimmack

    2016-10-01

    Full Text Available BACKGROUND: Small intestinal neuroendocrine neoplasm (SI-NEN proliferation is quantified by Ki67 measurements which capture G1-G2M phases of the cell cycle. G0 and early G1 phases, typical of slow-growing cells, can be detected by minichromosome maintenance protein (MCM expression. We hypothesized that these replication licensing markers may provide clinically relevant information to augment Ki67 in low-grade neuroendocrine neoplasia. METHODS: Immunohistochemical staining (IHC, Western blot analysis, quantitative polymerase chain reaction, and copy number variations of MCM2, MCM3, and Ki67 were undertaken in SI-NENs (n = 22. MCM and Ki67 expression was compared by Kaplan-Meier survival analysis (tissue microarray, independent set [n = 55]. Forty-three pancreatic NENs and 14 normal tissues were included as controls. RESULTS: In SI-NENs, MCM2 (mean: 21.2%: range: 16%-25% and MCM3 (28.7%: 22%-34% were detected in significantly more cells than Ki67 (2.3%: 0%-7%, P < .01. MCM2 mRNA correlated with Ki67 IHC (P < .05. MCM3 protein expression was higher in metastases (38-fold than in normal small intestine (P = .06 and was largely absent in normal neuroendocrine cells. There was considerable variation at the MCM copy number level (0-4 copies. MCM3 expression in proliferating cells significantly predicted overall survival (P < .002. Combinations of Ki67 and MCM2/3 in algorithms differentiated low and higher proliferative lesions (overall survival: 12 vs 6.1 years, P = .06. MCM expression was not informative in pancreatic NENs. CONCLUSION: MCMs are expressed in a higher proportion of NEN cells than Ki67 in slow-growing small intestinal lesions and correlate with survival. Assessment can be used to augment Ki67 to improve prognostic classification in these low-grade tumors.

  16. 99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

    Science.gov (United States)

    Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

    2015-05-01

    The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

  17. Neuroendocrine Tumours : From Radiomolecular Imaging to Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    GEORGIOS eLIMOURIS

    2012-02-01

    Full Text Available Transhepatic radionuclide infusion (THRI has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan. Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabelled somatostatin analogues, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3±0.3 GBq (~ 160-180 mCi of In-111-DTPA-Phe1- Pentetreotide, 10-12 fold in total, administered monthly or of 4.1± 0.2 GBq (~105-116 mCi of Y-90 DOTA TOC, 3 fold in total or of 7.0 ± 0.4 GBq (~178-200 mCi of Lu-177 DOTA TATE, 4-6 fold in total (the choice of which being based on the tumor size, assessed by CT or MRI . Follow-up at monthly intervals has to be performed by means of ultrasonography (US. Treat- ment response has to be assessed according to the WHO criteria (RECIST or SWOG.

  18. Rare neuroendocrine tumours : Results of the surveillance of rare cancers in Europe project

    NARCIS (Netherlands)

    van der Zwan, Jan Maarten; Trama, Annalisa; Otter, Renee; Larranaga, Nerea; Tavilla, Andrea; Marcos-Gragera, Rafael; Dei Tos, Angelo Paolo; Baudin, Eric; Poston, Graeme; Links, Thera

    Because of the low incidence, and limited opportunities for large patient volume experiences, there are very few relevant studies of neuroendocrine tumours (NETs). A large population-based database (including cancer patients diagnosed from 1978 to 2002 and registered in 76 population-based cancer

  19. Niacin (Vitamin B-3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor

    NARCIS (Netherlands)

    Bouma, Grietje; van Faassen, Martijn; Kats-Ugurlu, Gursah; Vries, de Elisabeth G. E.; Kema, Ido P.; Walenkamp, Annemiek M. E.

    2016-01-01

    BACKGROUND/AIMS: Tryptophan is the precursor of serotonin and niacin (vitamin B3). The latter is critical for normal cellular metabolism. Tryptophan and niacin can be deficient in patients with serotonin producing neuroendocrine tumors (NETs). Niacin deficiency can lead to severe symptoms including

  20. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Todorović-Tirnanić Mila

    2015-01-01

    Full Text Available The new positron emission tomography (PET/CT methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1 somatostatin analogues labeled with indium-111 (111In-pentetreotide or technetium-99m (99mTc-EDDA/HYNIC-TOC; 2 noradrenaline analogue labeled with iodine-131 or -123 (131I/123I-MIBG; or 3 99mTc(V-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F, galium-68 (68Ga, or carbon-11 (11C]: 1 glucose analogue (18FDG; 2 somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC; 3 aminoacid precursors of bioamines: [a dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine, b serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan]; or 4 dopamine analogue 18F-DA (6-18F-fluorodopamine. Conventional and contemporary (PET/ CT somatostatin receptor detection showed identical high specificity (92%, but conventional had very low sensitivity (52% compared to PET/CT (97%. It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic method. In metastatic pheochromocytoma detection contemporary (PET/ CT methods (18F-DOPA and 18F-DA have higher sensitivity than conventional (131I/123I-MIBG. In medullary thyroid carcinoma diagnostics contemporary method (18F-DOPA is more sensitive than conventional 99mTc(V-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET/CT methods for

  1. Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001

    Directory of Open Access Journals (Sweden)

    Corey A. Carter

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903; serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration.

  2. Colonic neuroendocrine carcinoma in a child

    Energy Technology Data Exchange (ETDEWEB)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes [King Faisal Specialist Hospital and Research Centre, Department of Radiology, MBC 28, Riyadh (Saudi Arabia); Sathiapalan, Rajeev; Kofide, Amani [King Faisal Specialist Hospital and Research Centre, Department of Paediatric Haematology and Oncology, Riyadh (Saudi Arabia); Tulbah, Asthma Mahmoud Mohamed [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia); Al-Mehaidib, Ali [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia)

    2005-03-01

    A 10-year-old boy with congenital immunodeficiency (X-linked agammaglobulinaemia) presented with loss of appetite and weight, right-sided abdominal pain, diarrhoea and low-grade fever. Radiological investigations with barium follow-through, CT, PET and octreotide scans revealed a primary caecal/ascending proximal colonic mass with liver and bony metastases. Urine screen for 5HIAA was positive. Percutaneous liver biopsy confirmed the diagnosis of neuroendocrine carcinoma. The radiological work-up and the usefulness of various imaging modalities in the diagnosis of this rare paediatric tumour are discussed. The PET scan demonstrated the primary tumour and the metastatic locations more vividly than the octreotide scan, which is currently considered to be the most specific imaging modality for neuroendocrine masses. (orig.)

  3. Nuclear Image Analysis Study of Neuroendocrine Tumors

    OpenAIRE

    Park, Meeja; Baek, Taehwa; Baek, Jongho; Son, Hyunjin; Kang, Dongwook; Kim, Jooheon; Lee, Hyekyung

    2012-01-01

    Background There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images. Methods We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells a...

  4. Taurine, energy drinks, and neuroendocrine effects.

    Science.gov (United States)

    Caine, Jonathan J; Geracioti, Thomas D

    2016-12-01

    Taurine is an amino acid found abundantly in brain, retina, heart, and reproductive organ cells, as well as in meat and seafood. But it is also a major ingredient in popular "energy drinks," which thus constitute a major source of taurine supplementation. Unfortunately, little is known about taurine's neuroendocrine effects. The authors review the sparse data and provide a basic background on the structure, synthesis, distribution, metabolism, mechanisms, effects, safety, and currently proposed therapeutic targets of taurine. Copyright © 2016 Cleveland Clinic.

  5. Acute Disseminated Intravascular Coagulation in Neuroendocrine Carcinoma

    OpenAIRE

    Ru-Wen Teh; Tsoi, Daphne T.

    2012-01-01

    Malignancy is a common cause of disseminated intravascular coagulation and usually presents as a chronic disorder in solid organ tumours. We present a rare case of recurrent acute disseminated intravascular coagulation in neuroendocrine carcinoma after manipulation, firstly, by core biopsy and, later, by cytotoxic therapy causing a release of procoagulants and cytokines from lysed tumour cells. This is reminiscent of tumour lysis syndrome where massive quantities of intracellular electrolytes...

  6. Neuroendocrine carcinoma of the prostate gland.

    Science.gov (United States)

    Hoof, Pamela; Tsai-Nguyen, Ginger; Paulson, Scott; Syed, Almas; Mora, Adam

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease.

  7. Octreotide long-acting repeatable in the treatment of neuroendocrine tumors: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Yau H

    2017-12-01

    Full Text Available Hanford Yau,1 Mustafa Kinaan,2 Suzanne L Quinn,3 Andreas G Moraitis3 1Division of Endocrinology, Diabetes, and Metabolism, University of California, San Francisco (Fresno Division, Fresno, CA, USA; 2Division of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA; 3Division of Endocrinology, Diabetes, and Metabolism, Orlando VA Medical Center, Orlando, FL, USA Abstract: Over the past three decades, the incidence and prevalence of neuroendocrine tumors have gradually increased. Due to the slow-growing nature of these tumors, most cases are diagnosed at advanced stages. Prognosis and survival are associated with location of primary lesion, biochemical functional status, differentiation, initial staging, and response to therapy. Octreotide, the first synthetic somatostatin analog, was initially used for the management of gastrointestinal symptoms associated with functional carcinoid tumors. Its commercial development over time led to long-acting repeatable octreotide acetate, a long-acting version that provided greater administration convenience. Recent research demonstrates that octreotide’s efficacy has evolved beyond symptomatic management to targeted therapy with antitumoral effects. This review examines the history and development of octreotide, provides a synopsis on the classification, grading, and staging of neuroendocrine tumors, and reviews the evidence of long-acting repeatable octreotide acetate as monotherapy and in combination with other treatment modalities in the management of non-pituitary neuroendocrine tumors with special attention to recent high-quality Phase III trials. Keywords: carcinoid, everolimus, neuroendocrine tumor, octreotide LAR, somatostatin analog, ITMO, NETTER-1, PROMID, RADIANT-2

  8. [Surgical approach of gastroduodenal neuroendocrine neoplasms].

    Science.gov (United States)

    Fendrich, V; Bartsch, D K

    2016-04-01

    Gastroduodenal neuroendocrine tumors are rare but an increase in incidence has been recognized worldwide over the past 35 years. At the same time the prognosis of patients has substantially improved because the majority of these tumors can now be detected at an early stage. Neuroendocrine neoplasms (NENs) of the stomach are the most frequent neoplasms of neuroendocrine origin in the gastrointestinal tract. The therapeutic management of these tumors is complicated by the fact that they must be classified not only by staging and grading but also according to their pathophysiological background (types). These types differ in biological behavior and therefore have an influence on the therapeutic concept. Because more than 90 % of duodenal NENs are often asymptomatic and are as a rule identified at a curable stage, resection of the tumor should always be the first line of therapy. The therapeutic strategies vary from local endoscopic resection (duodenotomy with excision) up to pancreas retaining duodenectomy and pylorus retaining or classical Whipple procedures. This article presents the various surgical approaches to gastric and duodenal NENs.

  9. Risk factors of type 1 gastric neuroendocrine neoplasia in patients with chronic atrophic gastritis. A retrospective, multicentre study.

    Science.gov (United States)

    Campana, Davide; Ravizza, Davide; Ferolla, Piero; Faggiano, Antongiulio; Grimaldi, Franco; Albertelli, Manuela; Ricci, Claudio; Santini, Donatella; Brighi, Nicole; Fazio, Nicola; Colao, Annamaria; Ferone, Diego; Tomassetti, Paola

    2017-06-01

    The aim of this retrospective study was to evaluate the presence of risk factors for a type 1 gastric neuroendocrine neoplasia in a large cohort of patients with chronic atrophic gastritis. The study design consisted of an Italian multicentre, retrospective analysis. The study included all consecutive patients with chronic atrophic gastritis with or without type 1 gastric neuroendocrine neoplasias followed at the participating centres. Two hundred and twenty-nine patients with chronic atrophic gastritis were enroled at the participating centres. A total of 207 patients (154 female, 53 males, median age: 56.0 years) were included in the final analysis. One hundred and twenty-six patients had chronic atrophic gastritis without a gastric neuroendocrine neoplasia and 81 had a chronic atrophic gastritis with type 1 gastric neuroendocrine neoplasia. The median Chromogranin A level, evaluated in 141 patients, was 52.0 U/L. At upper gastrointestinal endoscopy, atrophy of the gastric mucosa was mild/moderate in 137 patients and severe in 68. Intestinal metaplasia of the corpus was present in 168 patients. At histological examination, 81 patients had a gastric neuroendocrine neoplasia (42 patients had a NET G1 and 33 a NET G2). The median Ki67 index was 2.0 %. At univariate and multivariate analysis, the risk factors for a gastric neuroendocrine neoplasia were: male gender, chromogranin A greater than 61 U/L, presence of intestinal metaplasia and age equal to or greater than 59 years. Chromogranin A greater than 61 U/L, the presence of intestinal metaplasia and male gender were independent risk factors for a type 1 gastric neuroendocrine neoplasia in patients with chronic atrophic gastritis.

  10. Meta-type analysis of dopaminergic effects on gene expression in the neuroendocrine brain of female goldfish

    Directory of Open Access Journals (Sweden)

    Jason T Popesku

    2012-11-01

    Full Text Available Dopamine (DA is a major neurotransmitter important for neuroendocrine control and recent studies have described genomic signalling pathways activated and inhibited by DA agonists and antagonists in the goldfish brain. Here we perform a meta-type analysis using microarray datasets from experiments conducted with female goldfish to characterize the gene expression responses that underlie dopaminergic signalling. Sexually mature, pre-spawning (GSI 4.5 ± 1.3% or sexually regressing ( GSI 3 ± 0.4% female goldfish (15-40 g injected intraperitoneally with either SKF 38393, LY 171555, SCH 23390, sulpiride, or a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and α-methyl-p-tyrosine. Microarray meta-type analysis identified 268 genes in the telencephalon and hypothalamus as having reciprocal (i.e. opposite between agonism and antagonism/depletion fold change responses, suggesting that these transcripts are likely targets for DA-mediated regulation. Noteworthy genes included ependymin, vimentin, and aromatase, genes that support the significance of DA in neuronal plasticity and tissue remodelling. Sub-network enrichment analysis (SNEA was used to identify common gene regulators and binding proteins associated with the differentially expressed genes mediated by DA. SNEA analysis identified gene expression targets that were related to three major categories that included cell signalling (STAT3, SP1, SMAD, Jun/Fos, immune response (IL6, IL1β, TNFs, cytokine, NF-κB, and cell proliferation and growth (IGF1, TGFβ1. These gene networks are also known to be associated with neurodegenerative disorders such as Parkinsons’ disease, well-known to be associated with loss of dopaminergic neurons. This study identifies genes and networks that underlie DA signalling in the vertebrate CNS and provides targets that may be key neuroendocrine regulators. The results provide a foundation for future work on dopaminergic regulation of gene expression in fish

  11. A randomised controlled trial to determine the effect on response of including a lottery incentive in health surveys [ISRCTN32203485

    Science.gov (United States)

    Roberts, LM; Wilson, S; Roalfe, A; Bridge, P

    2004-01-01

    Background Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey. Methods Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices). Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for £100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire. Results 5,209 individuals responded with identical rates in both groups (62.1%). Practice, patient age, sex and Townsend score (a postcode based deprivation measure) were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived). Conclusion This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for £100 of High Street vouchers has no effect on response rates to a postal health questionnaire. PMID:15533256

  12. A randomised controlled trial to determine the effect on response of including a lottery incentive in health surveys [ISRCTN32203485

    Directory of Open Access Journals (Sweden)

    Bridge P

    2004-11-01

    Full Text Available Abstract Background Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey. Methods Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices. Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for £100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire. Results 5,209 individuals responded with identical rates in both groups (62.1%. Practice, patient age, sex and Townsend score (a postcode based deprivation measure were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived. Conclusion This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for £100 of High Street vouchers has no effect on response rates to a postal health questionnaire.

  13. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research.

    Science.gov (United States)

    Kockel, Lutz; Huq, Lutfi M; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E S; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E; Chisholm, Townley W; Kim, Seung K

    2016-10-13

    Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. Copyright © 2016 Kockel et al.

  15. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research

    Science.gov (United States)

    Kockel, Lutz; Huq, Lutfi M.; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E. S.; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M.; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E.; Chisholm, Townley W.; Kim, Seung K.

    2016-01-01

    Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila. However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. PMID:27527793

  16. The Role of the Pulmonary Embolism Response Team: How to Build One, Who to Include, Scenarios, Organization, and Algorithms.

    Science.gov (United States)

    Galmer, Andrew; Weinberg, Ido; Giri, Jay; Jaff, Michael; Weinberg, Mitchell

    2017-09-01

    Pulmonary embolism response teams (PERTs) are multidisciplinary response teams aimed at delivering a range of diagnostic and therapeutic modalities to patients with pulmonary embolism. These teams have gained traction on a national scale. However, despite sharing a common goal, individual PERT programs are quite individualized-varying in their methods of operation, team structures, and practice patterns. The tendency of such response teams is to become intensely structured, algorithmic, and inflexible. However, in their current form, PERT programs are quite the opposite. They are being creatively customized to meet the needs of the individual institution based on available resources, skills, personnel, and institutional goals. After a review of the essential core elements needed to create and operate a PERT team in any form, this article will discuss the more flexible feature development of the nascent PERT team. These include team planning, member composition, operational structure, benchmarking, market analysis, and rudimentary financial operations. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. VGF: an inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers.

    Science.gov (United States)

    Ferri, Gian-Luca; Noli, Barbara; Brancia, Carla; D'Amato, Filomena; Cocco, Cristina

    2011-12-01

    The vgf gene (non-acronymic) is induced in vivo by neurotrophins including Nerve Growth Factor (NGF), Brain Derived Growth Factor (BDNF) and Glial Derived Growth Factor (GDNF), by synaptic activity and by homeostatic and other stimuli. Post-translational processing of a single VGF precursor gives raise to a varied multiplicity of neuro-endocrine peptides, some of which are secreted upon stimulation both in vitro and in vivo. Several VGF peptides, accounting for ∼20% of the VGF precursor sequence, have shown biological roles including regulation of food intake, energy balance, reproductive and homeostatic mechanisms, synaptic strengthening, long-term potentiation (LTP) and anti-depressant activity. From a further ∼50% of VGF derive multiple "fragments", largely identified in the human cerebro-spinal fluid by proteomic studies searching for disease biomarkers. These represent an important starting point for discovery of further VGF products relevant to neuronal brain functions, as well as to neurodegenerative and psychiatric disease conditions. A distinct feature of VGF peptides is their cell type specific diversity in all neuroendocrine organs studied so far. Selective differential profiles are found across the cell populations of pituitary, adrenal medulla and pancreatic islets, and in gastric neuroendocrine as well as some further mucosal cells, and are yet to be investigated in neuronal systems. At the same time, specific VGF peptide/s undergo selective modulation in response to organ or cell population relevant stimuli. Such pattern argues for a multiplicity of roles for VGF peptides, including endocrine functions, local intercellular communication, as well as the possible mediation of intracellular mechanisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. [Advances of circulating biomarkers in gastroenteropancreatic neuroendocrine neoplasms].

    Science.gov (United States)

    Chen, Luohai; Chen, Minhu; Chen, Jie

    2017-03-25

    Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.

  19. Mixed Neuroendocrine-Nonneuroendocrine Neoplasms (MiNENs): Unifying the Concept of a Heterogeneous Group of Neoplasms.

    Science.gov (United States)

    La Rosa, Stefano; Sessa, Fausto; Uccella, Silvia

    2016-12-01

    The wide application of immunohistochemistry to the study of tumors has led to the recognition that epithelial neoplasms composed of both a neuroendocrine and nonneuroendocrine component are not as rare as traditionally believed. It has been recommended that mixed neuroendocrine-nonneuroendocrine epithelial neoplasms are classified as only those in which either component represents at least 30 % of the lesion but this cutoff has not been universally accepted. Moreover, since their pathogenetic and clinical features are still unclear, mixed neuroendocrine-nonneuroendocrine epithelial neoplasms are not included as a separate clinicopathological entity in most WHO classifications, although they have been observed in virtually all organs. In the WHO classification of digestive tumors, mixed neuroendocrine-nonneuroendocrine neoplasm is considered a specific type and is defined as mixed adenoneuroendocrine carcinoma, a definition that has not been accepted for other organs. In fact, this term does not adequately convey the morphological and biological heterogeneity of digestive mixed neoplasms and has created some misunderstanding among both pathologists and clinicians. In the present study, we have reviewed the literature on mixed neuroendocrine-nonneuroendocrine epithelial neoplasms reported in the pituitary, thyroid, nasal cavity, larynx, lung, digestive system, urinary system, male and female genital organs, and skin to give the reader an overview of the most important clinicopathological features and morphological criteria for diagnosing each entity. We also propose to use the term "mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN)" to define and to unify the concept of this heterogeneous group of neoplasms, which show different characteristics mainly depending on the type of neuroendocrine and nonneuroendocrine components.

  20. Neuroendocrine and Cardiac Metabolic Dysfunction and NLRP3 Inflammasome Activation in Adipose Tissue and Pancreas following Chronic Spinal Cord Injury in the Mouse

    Directory of Open Access Journals (Sweden)

    Gregory E. Bigford

    2013-08-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immunohistochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  1. Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET-CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion.

    Science.gov (United States)

    Ranade, Rohit; Basu, Sandip

    2017-01-01

    Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET.

  2. Neuroendocrine tumour in a patient with neurofibromatosis type 1 ...

    African Journals Online (AJOL)

    2015-06-26

    Jun 26, 2015 ... concomitant gastrin-producing neuroendocrine tumour was found. Neuroendocrine tumours. (NETs) are very rare neoplasms originating from a wide variety of endocrine and nervous system tissue with the ability to produce different hormones. A somatostatin- and gastrin- secreting NET in a patient with HIV ...

  3. Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Cevriye Cansız Ersöz

    2016-01-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors.

  4. A short history of neuroendocrine tumours and their peptide hormones

    DEFF Research Database (Denmark)

    de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark

    2016-01-01

    The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The panc...

  5. Recognition memory tasks in neuroendocrine research.

    Science.gov (United States)

    Luine, Victoria

    2015-05-15

    The recognition memory tasks, novel object and novel object location, have been beneficial to neuroendocrine research concerning the effects of gonadal and adrenal hormones on cognitive function. This review discusses the advantages of these tasks in comparison with other learning and memory tasks. Experiments conducted across a number of laboratories show that gonadal hormones, both estradiol and testosterone, promote memory while the adrenal hormone, corticosterone, impairs memory. The effects of these steroid hormones on spine density in the prefrontal cortex and hippocampus are also briefly presented. Overall, results show that these steroid hormones are potent modulators of memory consolidation in rodent models. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Posintro™-HBsAg, a modified ISCOM including HBsAg, induces strong cellular and humoral responses

    DEFF Research Database (Denmark)

    Schiött, Asa; Larsson, Kristina; Manniche, Søren

    2011-01-01

    To improve the hepatitis B vaccines on the market new adjuvant systems have to substitute aluminium. In this study the hepatitis B surface antigen (HBsAg) was incorporated into a novel adjuvant system, the Posintro™, a modification of the traditional immune stimulatory complexes (ISCOMs). This new...... HBsAg vaccine formulation, Posintro™-HBsAg, was compared to two commercial hepatitis B vaccines including aluminium or monophosphoryl lipid A (MPL) and the two adjuvant systems MF59 and QS21 in their efficiency to prime both cellular and humoral immune responses. The Posintro™-HBsAg induced....... The results demonstrate that this novel experimental vaccine formulation, the Posintro™-HBsAg, is strongly immunogenic and can induce both class I and class II responses in experimental animals. This shows promise both for the protection against hepatitis B virus infection and as a potential therapeutic...

  7. Social stress contagion in rats: Behavioural, autonomic and neuroendocrine correlates.

    Science.gov (United States)

    Carnevali, Luca; Montano, Nicola; Statello, Rosario; Coudé, Gino; Vacondio, Federica; Rivara, Silvia; Ferrari, Pier Francesco; Sgoifo, Andrea

    2017-08-01

    The negative emotional consequences associated with life stress exposure in an individual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as "demonstrator" (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined "observer" (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between

  8. Solitary pulmonary metastasis from prostate cancer with neuroendocrine differentiation: a case report and review of relevant cases from the literature.

    Science.gov (United States)

    Maebayashi, Toshiya; Abe, Katsumi; Aizawa, Takuya; Sakaguchi, Masakuni; Ishibash, Naoya; Fukushima, Shoko; Honma, Taku; Kusumi, Yoshiaki; Matsui, Tsuyoshi; Kawata, Nozomu

    2015-05-07

    Solitary lung metastasis from prostate cancer is rare. There are few reports of such cases with neuroendocrine differentiation. A 50-year-old man presented to our hospital with a chief complaint of dysuria. Histological examination revealed prostate cancer, which was classified as cT4 N0 M0, stage IV adenocarcinoma. Since the patient was at high risk, endocrine and radiation therapies were started. One year after starting radiation therapy, the patient developed bloody sputum. Chest radiography revealed a nodular shadow in his left lung (S5). Although 18-fluoro-2-deoxyglucose positron emission tomography revealed abnormal accumulation in the lesion, the cytological diagnosis was class IIIa, which did not yield a definitive diagnosis. Given that prostate specific antigen (PSA) was not elevated, a primary lung tumor was suspected, and thoracoscopic segmental resection of the lung was performed with lymph node dissection. The final pathological diagnosis was solitary lung metastasis from prostate cancer with neuroendocrine differentiation and mediastinal lymph node metastasis. The specimen showed a mixed pattern of conventional prostatic and neuroendocrine carcinomas. We herein report a case with neuroendocrine differentiation (NED), along with a review of the relevant literature, including histopathological findings. According to previous case reports, some patients with solitary lung metastasis from prostate cancer achieved relatively good long-term survival. We consider establishing the correct diagnosis and implementing an appropriate treatment plan to be essential in prostate cancer patients with oligometastases that have the potential to be neuroendocrine (NE) tumors.

  9. A review of regression procedures for randomized response data, including univariate and multivariate logistic regression, the proportional odds model and item response model, and self-protective responses

    NARCIS (Netherlands)

    Cruyff, M.; Böckenholt, U.; van der Heijden, P.G.M.; Frank, L.E.

    2016-01-01

    In survey research, it is often problematic to ask people sensitive questions because they may refuse to answer or they may provide a socially desirable answer that does not reveal their true status on the sensitive question. To solve this problem Warner (1965) proposed randomized response (RR).

  10. The efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong-Jang; Pak, Kyoungjune [Pusan National University Hospital, Department of Nuclear Medicine and Biomedical Research Institute, Busan (Korea, Republic of); Koo, Phillip J.; Kwak, Jennifer J.; Chang, Samuel [University of Colorado School of Medicine, Department of Radiology, Aurora, CO (United States)

    2015-12-15

    This study was performed to evaluate the efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of ''neuroendocrine'', ''{sup 177}Lu'' and ''prognosis''. All published studies of neuroendocrine tumours treated with {sup 177}Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8 % with a pooled effect of 29 % [95 % confidence interval (CI) 24-34 %]. Disease control rates ranged from 71.8 to 100 %. The random-effects model showed an average disease control rate of 81 % (95 % CI 71-91 %). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5 % with a pooled effect of 23 % (95 % CI 11-38 %). Disease control rates ranged from 73.9 to 89.1 %. The random-effects model showed an average disease control rate of 82 % (95 % CI 71-91 %). {sup 177}Lu-labelled PRRT is an effective treatment

  11. Developing an explicit strategy towards social responsibility in the NHS: a case for including NHS managers in this strategy.

    Science.gov (United States)

    Merali, Faruk

    2006-01-01

    To explore the concept of corporate social responsibility (CSR) within the UK National Health Service (NHS) and to examine how it may be developed to positively influence the psyche, behaviour and performance of NHS managers. Primary research based upon semi-structured individual face to face interviews with 20 NHS managers. Theoretical frameworks and concepts relating to organisational culture and CSR are drawn upon to discuss the findings. The NHS managers see themselves as being driven by altruistic core values. However, they feel that the public does not believe that they share the altruistic NHS value system. The study is based on a relatively small sample of NHS managers working exclusively in London and may not necessarily represent the views of managers either London-wide or nation-wide. It is suggested that an explicit recognition by the NHS of the socially responsible commitment of its managers within its CSR strategy would help challenge the existing negative public image of NHS managers and in turn improve the managers' self esteem and morale. This paper addresses the relative lacunae in research relating to public sector organisations (such as the NHS) explicitly including the role and commitment of its staff within the way it publicises its CSR strategy. This paper would be of interest to a wide readership including public sector and NHS policy formulators, NHS practitioners, academics and students.

  12. Inclusive Education Reform in Bangladesh: Pre-Service Teachers’ Responses to Include Students with Special Educational Needs in Regular Classrooms

    Directory of Open Access Journals (Sweden)

    Md. Saiful Malak

    2013-01-01

    Full Text Available Inclusive education (IE has been recognized as a key strategy to ensure education for all in the developing world for the last two decades. As a developing country, Bangladesh is striving to address IE by undergoing various initiatives such as policy reform, awareness creation and teacher development. This paper based on a qualitative approach attempts to explore pre-service teachers’ responses to include students with special educational needs (SEN in regular classrooms in primary schools. A one-on-one interview was conducted with 20 pre-service teachers who were enrolled in a teacher education program of one public university in Bangladesh. The findings revealed from the study indicate that majority of the pre-service teachers have unfavourable attitudes to include students with SEN in regular classrooms. Misconception and lack of knowledge about disabilities are revealed from most of the pre-service teachers’ responses. Further large class size, high workloads, inflexible curriculum policy of primary education and inadequate experiential learning facilities of teacher education program are identified as barriers to IE reform. Several issues are discussed as implications in order to promote better inclusive practices in regular primary education.

  13. Blunted neuroendocrine stress reactivity in young women with eating disorders.

    Science.gov (United States)

    Het, Serkan; Vocks, Silja; Wolf, Jutta M; Hammelstein, Philipp; Herpertz, Stephan; Wolf, Oliver T

    2015-03-01

    Stress is known to influence risk and progression of eating disorders (EDs). However, studies investigating physiological and psychological stress responses under laboratory conditions in patients with Anorexia nervosa or Bulimia nervosa are scarce and often produce conflicting findings. We therefore aimed to compare the neuroendocrine and affective stress response in ED inpatients and healthy controls. Twenty-eight female inpatients with Anorexia or Bulimia nervosa and 26 healthy women were exposed to the Trier Social Stress Test (TSST). Salivary cortisol and alpha-amylase (sAA) levels were assessed before as well as repeatedly after stress exposure, while heart rate and heart rate variability were determined before and during the TSST. Negative affective state was assessed at baseline and post-TSST. Compared to healthy controls, ED patients showed blunted cortisol stress responses combined with overall attenuated sAA levels. The latter was reflected in generally enhanced parasympathetic activity indicated by lower heart rate and stronger high-frequency heart rate variability throughout the TSST. Although patients reported more negative affect overall, they did not differ in their affective stress response. In summary, patients suffering from eating disorders show a blunted HPA axis reactivity to stress exposure and a generally reduced sympathetic/exaggerated parasympathetic nervous system activity. This combination may contribute to elevated health risks seen in eating disorder patients, such as enhanced inflammatory activity, and thus provide insight into the underlying stress-related mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. High clinical and morphologic response using {sup 90}Y-DOTA-octreotate sequenced with {sup 177}Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Grace; Callahan, Jason; Pattison, David A.; Akhurst, Tim; Eu, Peter [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); Hofman, Michael S. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Parkville (Australia); Michael, Michael [Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia)

    2017-03-15

    Bulky disease is an adverse prognostic factor for {sup 177}Lu-DOTA-octreotate ({sup 177}Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). {sup 90}Y-DOTA-octreotate ({sup 90}Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than {sup 177}Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of {sup 90}Y-DOTATATE followed by 2-3 cycles of {sup 177}Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq {sup 90}Y-DOTATATE, and 21 GBq {sup 177}Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with {sup 90}Y -DOTATATE followed by {sup 177}Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either

  15. Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia.

    Science.gov (United States)

    Maasberg, Sebastian; Knappe-Drzikova, Barbora; Vonderbeck, Dorothée; Jann, Henning; Weylandt, Karsten H; Grieser, Christian; Pascher, Andreas; Schefold, Jörg C; Pavel, Marianne; Wiedenmann, Bertram; Sturm, Andreas; Pape, Ulrich-Frank

    2017-01-01

    Malnutrition is a common problem in oncological diseases, influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet been studied systematically in neuroendocrine neoplasms (NEN), which, due to their growing prevalence and additional therapeutic options, provide an increasing clinical challenge to diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches, and to analyse the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. When applying malnutrition screening scores, 21-25% of the NEN patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, by determination of serum surrogate parameters such as albumin as well as by bioelectrical impedance analysis (BIA), particularly phase angle α. The length of hospital stay was significantly longer in malnourished NEN patients, while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk of malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3 NEC). Malnutrition is therefore an underrecognized problem in NEN patients which should systematically be diagnosed by widely available standard methods such as Nutritional Risk Screening (NRS), serum albumin assessment and BIA, and treated to improve both short- and long-term outcomes. © 2015 S. Karger AG, Basel.

  16. Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E

    Science.gov (United States)

    Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam

    2011-01-01

    Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094

  17. The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

    Science.gov (United States)

    Wolfe, Andrew; Divall, Sara; Wu, Sheng

    2014-01-01

    The mammalian reproductive hormone axis regulates gonadal steroid hormone levels and gonadal function essential for reproduction. The neuroendocrine control of the axis integrates signals from a wide array of inputs. The regulatory pathways important for mediating these inputs have been the subject of numerous studies. One class of proteins that have been shown to mediate metabolic and growth signals to the CNS includes Insulin and IGF-1. These proteins are structurally related and can exert endocrine and growth factor like action via related receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction has been studied extensively. This review summarizes the in vitro and in vivo models that have been used to study these neuroendocrine structures and the influence of these growth factors on neuroendocrine control of reproduction. PMID:24929098

  18. A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism

    Science.gov (United States)

    Palamiuc, Lavinia; Noble, Tallie; Witham, Emily; Ratanpal, Harkaranveer; Vaughan, Megan; Srinivasan, Supriya

    2017-01-01

    Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity. PMID:28128367

  19. Neuroendocrine differentiation in prostate cancer – a review

    Directory of Open Access Journals (Sweden)

    R. Popescu

    2015-12-01

    Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

  20. ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs

    Directory of Open Access Journals (Sweden)

    Mark D. Borromeo

    2016-08-01

    Full Text Available Small cell lung carcinoma (SCLC is a high-grade pulmonary neuroendocrine tumor. The transcription factors ASCL1 and NEUROD1 play crucial roles in promoting malignant behavior and survival of human SCLC cell lines. Here, we find that ASCL1 and NEUROD1 identify heterogeneity in SCLC, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, and NFIB while NEUROD1 targets MYC. ASCL1 and NEUROD1 regulate different genes that commonly contribute to neuronal function. ASCL1 also regulates multiple genes in the NOTCH pathway including DLL3. Together, ASCL1 and NEUROD1 distinguish heterogeneity in SCLC with distinct genomic landscapes and distinct gene expression programs.

  1. Finite Element Modeling and Analysis of Nonlinear Impact and Frictional Motion Responses Including Fluid—Structure Coupling Effects

    Directory of Open Access Journals (Sweden)

    Yong Zhao

    1997-01-01

    Full Text Available A nonlinear three dimensional (3D single rack model and a nonlinear 3D whole pool multi-rack model are developed for the spent fuel storage racks of a nuclear power plant (NPP to determine impacts and frictional motion responses when subjected to 3D excitations from the supporting building floor. The submerged free standing rack system and surrounding water are coupled due to hydrodynamic fluid-structure interaction (FSI using potential theory. The models developed have features that allow consideration of geometric and material nonlinearities including (1 the impacts of fuel assemblies to rack cells, a rack to adjacent racks or pool walls, and rack support legs to the pool floor; (2 the hydrodynamic coupling of fuel assemblies with their storing racks, and of a rack with adjacent racks, pool walls, and the pool floor; and (3 the dynamic motion behavior of rocking, twisting, and frictional sliding of rack modules. Using these models 3D nonlinear time history dynamic analyses are performed per the U.S. Nuclear Regulatory Commission (USNRC criteria. Since few such modeling, analyses, and results using both the 3D single and whole pool multiple rack models are available in the literature, this paper emphasizes description of modeling and analysis techniques using the SOLVIA general purpose nonlinear finite element code. Typical response results with different Coulomb friction coefficients are presented and discussed.

  2. Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation

    Directory of Open Access Journals (Sweden)

    Watson Andrew J

    2007-01-01

    Full Text Available Abstract Background Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2. The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments. Results Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4 are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels. Conclusion These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.

  3. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... for the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3-octreotide...

  4. Neuroendocrine tumor of the inguinal node: A very rare presentation

    Directory of Open Access Journals (Sweden)

    Niharika Bisht

    2017-12-01

    Full Text Available Neuroendocrine tumors are a broad family of tumors arising most commonly in the gastrointestinal tract and the bronchus pulmonary tree. The other common sounds are the parathyroid, pituitary and adrenal gland. Inguinal node as a primary presentation of a neuroendocrine tumor is an extremely rare presentation. We present the case of a 43-year-old-male who presented with the complaints of an inguinal node swelling without any other symptoms and on further evaluation was diagnosed to have a non-metastatic neuroendocrine tumor of the inguinal node. He was treated with a combination of chemotherapy and surgery and is presently awaiting completion chemotherapy.

  5. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia diagnosed by tranbronchoscopic cryoprobe biopsy technique

    OpenAIRE

    Patel, Ravi; Collazo‐Gonzalez, Carolina; Andrews, Arthur; Johnson, Jean; Rumbak, Mark; Smith, Maxwell

    2017-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) remains a poorly understood clinical entity. It is currently classified as a premalignant condition by the World Health Organization (WHO). Symptoms are similar to those associated with obstructive lung disease, including breathlessness and cough. The presentation is often initially ascribed to other diseases such as asthma or chronic obstructive pulmonary disease. Here, we present what we believe is the first described ca...

  6. Including total EGFR staining in scoring improves EGFR mutations detection by mutation-specific antibodies and EGFR TKIs response prediction.

    Directory of Open Access Journals (Sweden)

    Shang-Gin Wu

    Full Text Available Epidermal growth factor receptor (EGFR is a novel target for therapy in subsets of non-small cell lung cancer, especially adenocarcinoma. Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs. We aimed to identify the discriminating capacity of immunohistochemical (IHC scoring to detect L858R and E746-A750 deletion mutation in lung adenocarcinoma patients and predict EGFR TKIs response. Patients with surgically resected lung adenocarcinoma were enrolled. EGFR mutation status was genotyped by PCR and direct sequencing. Mutation-specific antibodies for L858R and E746-A750 deletion were used for IHC staining. Receiver operating characteristic (ROC curves were used to determine the capacity of IHC, including intensity and/or quickscore (Q score, in differentiating L858R and E746-A750 deletion. We enrolled 143 patients during September 2000 to May 2009. Logistic-regression-model-based scoring containing both L858R Q score and total EGFR expression Q score was able to obtain a maximal area under the curve (AUC: 0.891 to differentiate the patients with L858R. Predictive model based on IHC Q score of E746-A750 deletion and IHC intensity of total EGFR expression reached an AUC of 0.969. The predictive model of L858R had a significantly higher AUC than L858R intensity only (p = 0.036. Of the six patients harboring complex EGFR mutations with classical mutation patterns, five had positive IHC staining. For EGFR TKI treated cancer recurrence patients, those with positive mutation-specific antibody IHC staining had better EGFR TKI response (p = 0.008 and longer progression-free survival (p = 0.012 than those without. In conclusion, total EGFR expression should be included in the IHC interpretation of L858R. After adjusting for total EGFR expression, the scoring method decreased the false positive rate and increased diagnostic power. According to the scoring method, the IHC method is useful to predict the

  7. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  8. Anxiety sensitivity, the menstrual cycle, and panic disorder: a putative neuroendocrine and psychological interaction.

    Science.gov (United States)

    Nillni, Yael I; Toufexis, Donna J; Rohan, Kelly J

    2011-11-01

    The 2:1 female-to-male sex difference in the prevalence of panic disorder (PD) suggests that there is a sex-specific vulnerability involved in the etiology and/or maintenance of this disorder. The purpose of this paper is to present a new conceptual model, which emphasizes the interaction between a cognitive vulnerability for PD, anxiety sensitivity, and the effects of progesterone and its metabolite, allopregnanolone, on behavioral and physiological responses to stress during the premenstrual phase. This interaction is proposed to be a potential sex-specific pathway that may initiate and/or maintain panic and anxiety symptoms in women. This review paper presents preliminary evidence from both the human and animal literatures to support this new model. Specific topics reviewed include: psychopathology related to the menstrual cycle, anxiety sensitivity and its relationship to the menstrual cycle, PMS, and PMDD, anxiety-modulating effects of progesterone and its neuroactive metabolite, allopregnanolone, and how results from the neuroendocrine literature relate to psychopathology or symptoms associated with the menstrual cycle. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Glucocorticoids as cytokine inhibitors: role in neuroendocrine control and therapy of inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Giamila Fantuzzi

    1993-01-01

    Full Text Available Glucocorticoids are potent inhibitors of inflammation and endotoxic shock. This probably occurs through an inhibition of the synthesis of pro-inflammatory cytokines as well as of many of their toxic activities. Therefore, endogenous glucocorticoids (GC might represent a major mechanism in the control of cytokine mediated pathologies. GC inhibit the synthesis of cytokines in various experimental models. Adrenalectomy or GC antagonists potentiate TNF, IL-1 and IL-6 production in LPS treated mice. GC inhibit the formation of arachidonic acid metabolites and the induction of NO synthase. They also inhibit various activities of cytokines including toxicity, haemodynamic shock and fever. Adrenalectomy sensitizes to the toxic effects of LPS, TNF and IL-1. On the other hand, GC potentiate the synthesis of several cytokine induced APP by the liver. Since many of these proteins have anti-toxic activities (antioxidant, antiprotease etc. or bind cytokines, this might well represent a GC mediated protective feedback mechanism involving the liver. Not only do GC inhibit cytokines, but in vivo LPS and various cytokines (TNF, IL-1, IL-6 increase blood GC levels through a central mechanism involving the activation of the HPA. Thus, this neuroendocrine response to cytokines constitutes an important immunoregulatory feedback involving the brain.

  10. A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA.

    Directory of Open Access Journals (Sweden)

    Christoph Coch

    Full Text Available Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR or RIG-I like helicases (RLH are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4 was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.

  11. A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA.

    Science.gov (United States)

    Coch, Christoph; Lück, Christian; Schwickart, Anna; Putschli, Bastian; Renn, Marcel; Höller, Tobias; Barchet, Winfried; Hartmann, Gunther; Schlee, Martin

    2013-01-01

    Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR) or RIG-I like helicases (RLH) are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA) that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4) was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC) based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand) in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.

  12. Vegetation response to invasive Tamarix control in southwestern U.S. rivers: A collaborative study including 416 sites

    Science.gov (United States)

    González, Eduardo; Sher, Anna A; Anderson, Robert M.; Bay, Robin F.; Bean, Daniel W.; Bissonnete, Gabriel J.; Bourgeois, Bérenger; Cooper, David J.; Dohrenwend, Kara; Eichhorst, Kim D.; El Waer, Hisham; Kennard, Deborah K.; Harms-Weissinger, Rebecca; Henry, Annie L.; Makarick, Lori J.; Ostoja, Steven M.; Reynolds, Lindsay V.; Robinson, W. Wright; Shafroth, Patrick B.

    2017-01-01

    Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species.

  13. A NEW INCOME IN PEDIATRIC PATHOLOGY: GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS. PART I: PANCREATIC TUMORS

    Directory of Open Access Journals (Sweden)

    Smaranda DIACONESCU

    2013-03-01

    Full Text Available Gastroenteropancreatic neuroendocrine tumors (GEP NET represent a heterogenous group of neoplasms: carcinoids (serotoninomas and gastroenteropancreatic (insulinomas, gastrinomas, VIPomas, glucagonomas, somatostatinomas respectively, unified by their origin (neuroendocrine cells, histology and immunohistochemical profile. Unlike their frequency in adults, the rarity of these lesions in childhood makes difficult their early diagnosis. Many tumors can be asymptomatic or may show non-specific features, the diagnosis being nevertheless based on clinical signs, dosage of hormonal specific peptides, nuclear medicine imaging and pathology confirmation. Baseline tests should also include chromogranine A and sinaptophysine. Localising studies comprise CT, MRI, somatostatine receptor scintigraphy and ultrasonography completed by endoscopy. Surgery is the mainstay therapy of GEP NET, as a complete removal can potentially cure the disease; debulking and metastasis surgery, together with adjuvant medical therapy can alleviate some symptoms, sometimes for a long period. Survival is variable, depending on tumour’s type, stage, histology and also on the completeness of the treatment.

  14. Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC.

    Science.gov (United States)

    Artiko, Vera; Afgan, Aida; Petrović, Jelena; Radović, Branislava; Petrović, Nebojša; Vlajković, Marina; Šobić-Šaranović, Dragana; Obradović, Vladimir

    2016-01-01

    This paper is the short review of our preliminary results obtained with 99mTc-EDDA/HYNIC-TOC. The total of 495 patients with different neuroendocrine tumors were investigated during last few years. There have been 334 true positive (TP), 73 true negative (TN), 6 false positive (FP) and 82 false negative findings (FN). Diagnosis was made according to SPECT findings in 122 patients (25%). The mean T/NT ratio for TP cases was significantly higher (p Tektrotyd is a useful method for diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors. SPECT had important role in diagnosis. It is also helpful in the appropriate choice of the therapy, including the peptide receptor radionuclide therapy. In the absence of 68Ga-labeled peptides and PET/CT, the special emphasize should be given to application of SPECT/CT as well as to the radioguided surgery.

  15. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

    DEFF Research Database (Denmark)

    Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L

    2009-01-01

    in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

  16. The special relationship: glia-neuron interactions in the neuroendocrine hypothalamus.

    Science.gov (United States)

    Clasadonte, Jerome; Prevot, Vincent

    2018-01-01

    Natural fluctuations in physiological conditions require adaptive responses involving rapid and reversible structural and functional changes in the hypothalamic neuroendocrine circuits that control homeostasis. Here, we discuss the data that implicate hypothalamic glia in the control of hypothalamic neuroendocrine circuits, specifically neuron-glia interactions in the regulation of neurosecretion as well as neuronal excitability. Mechanistically, the morphological plasticity displayed by distal processes of astrocytes, pituicytes and tanycytes modifies the geometry and diffusion properties of the extracellular space. These changes alter the relationship between glial cells of the hypothalamus and adjacent neuronal elements, especially at specialized intersections such as synapses and neurohaemal junctions. The structural alterations in turn lead to functional plasticity that alters the release and spread of neurotransmitters, neuromodulators and gliotransmitters, as well as the activity of discrete glial signalling pathways that mediate feedback by peripheral signals to the hypothalamus. An understanding of the contributions of these and other non-neuronal cell types to hypothalamic neuroendocrine function is thus critical both to understand physiological processes such as puberty, the maintenance of bodily homeostasis and ageing and to develop novel therapeutic strategies for dysfunctions of these processes, such as infertility and metabolic disorders.

  17. Targeted Therapies Improve Survival for Patients with Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and everolimus for patients with pancreatic neuroendocrine tumors. Updated results from the everolimus trial were published in September 2016.

  18. Neuroendocrine tumors in the urinary bladder: a literature review

    Directory of Open Access Journals (Sweden)

    Monika Ulamec

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs can be found in most organs, as well as in the urinary bladder. Some of the clinical and pathologic features of these tumors may be characteristic of the organ of origin, but most of the properties are shared by neuroendocrine neoplasms regardless of their anatomic site. In the bladder, NETs comprise less than 1% of all bladder tumors and can be found in a pure form or intermixed with urothelial carcinoma and its variants. Bladder NETs are classified into 2 subtypes: carcinoid tumor and neuroendocrine carcinoma, which is further subdivided into small cell and large cell neuroendocrine carcinoma. Characteristics of bladder NETs and its differential diagnosis are discussed herein.

  19. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Energy Technology Data Exchange (ETDEWEB)

    Tonelli, Francesco, E-mail: f.tonelli@dfc.unifi.it; Giudici, Francesco [Department of Clinical Physiopathology, Surgical Unit, Medical School, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy); Giusti, Francesca; Brandi, Maria Luisa [Department of Internal Medicine, Medical School and Regional Centre for Hereditary Endocrine Tumors, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy)

    2012-05-07

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

  20. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    Department of Pathology, ESIC Medical College and PGIMSR, Rajajinagar, Bangalore, India. Abstract. Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic entity till recently due ... whole body computed tomography and magnetic resonance imaging revealed no extra mammary primary tumor.

  1. [The role of endoscopy in gastroenteropancreatic neuroendocrine tumors].

    Science.gov (United States)

    Magno, L; Sivero, L; Napolitano, V; Ruggiero, S; Fontanarosa, G; Massa, S

    2010-01-01

    Versione italiana Riassunto: Il ruolo dell'endoscopia nei tumori neuroendocrini gastroenteropancreatici. L. Magno, L. Sivero, V. Napolitano, S. Ruggiero, G. Fontanarosa, S. Massa I tumori neuroendocrini (NET) gastro-entero-pancreatici (GEP) sono neoplasie rare che originano dalle cellule neuroendocrine del tubo digerente e del pancreas. L'endoscopia digestiva e l'ecoendoscopia rivestono un ruolo importante nella diagnosi, stadiazione e sorveglianza dei pazienti con NET. Inoltre, in casi selezionati, le tecniche endoscopiche operative consentono il trattamento di queste neoplasie in fase precoce. English version Summary: The role of endoscopy in gastroenteropancreatic neuroendocrine tumors. L. Magno, L. Sivero, V. Napolitano, S. Ruggiero, G. Fontanarosa, S. Massa Gastroenteropancreatic (GEP) neuroendocrine tumors (NET) are rare neoplasia arisen from neuroendocrine cells present in the gut mucosa and pancreas. Digestive endoscopy and endoscopic ultrasonography play a relevant role in NET diagnosis, stadiation and surveillance. Moreover, in selected patients, surgical endoscopy allows the tratment of these cancers at an early stage.

  2. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  3. Anxiety, Family Functioning and Neuroendocrine Biomarkers in Obese Children

    Directory of Open Access Journals (Sweden)

    Inês Pinto

    2017-04-01

    Conclusion: These results highlight the importance of taking into account family functioning, parental mental state and gender, when investigating neuroendocrine biomarkers in obese children associated with symptoms of anxiety and depression.

  4. Involvement of dopamine beta-hydroxylase in the neuroendocrine-immune regulatory network of white shrimp, Litopenaeus vannamei.

    Science.gov (United States)

    Cheng, Winton; Ka, Ya-Wen; Chang, Chin-Chyuan

    2017-09-01

    In shrimp, the biosynthesis of catecholamines, including dopamine and norepinephrine, is required for physiological and immunological responses against stress. Dopamine beta-hydroxylase (DBH), a copper-containing monooxygenase enzyme that plays an important role in catecholamine synthesis of the neuroendocrine regulatory network, was identified in Litopenaeus vannamei. In the present study, the potential role of DBH in the immunocompetence of L. vannamei was further estimated by depleting DBH by pharmaceutical inhibition of disulfiram and a gene silencing technique of L. vannamei DBH-double-stranded (ds)RNA (LvDBH-dsRNA). Immunocompetence was evaluated following the determination of the total hemocyte count, differential hemocyte count, phenoloxidase activity, respiratory bursts, superoxide dismutase activity, phagocytic activity, and the clearance efficiency as well as the susceptibility against Vibrio alginolyticus infection. At 30-120 min after shrimp had received disulfiram, they exhibited significantly reduced total hemocyte count, phenoloxidase activity of hemocytes in hemolymph, respiratory bursts of hemocytes in hemolymph and per hemocyte, phagocytic activity, clearance efficiency, and survival ratio against V. alginolyticus infection, compared to those injected with saline. In addition, the significantly lower total hemocyte count, phagocytic activity, clearance efficiency, and resistance to V. alginolyticus infection were observed in shrimp that received LvDBH-dsRNA at 3 days post injection compared to those injected with diethyl pyrocarbonate-water or non-targeting gene-dsRNA. The DBH depleted L. vannamei revealed immunosuppression and decreased the survival ratio to V. alginolyticus infection, which indicated that DBH played a crucial role in the neuroendocrine-immune regulatory network. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Neuroendocrine Merkel cell carcinoma is associated with mutations in key DNA repair, epigenetic and apoptosis pathways: a case-based study using targeted massively parallel sequencing.

    Science.gov (United States)

    Graves, Christian A; Jones, Ashley; Reynolds, Justin; Stuart, Jeremy; Pirisi, Lucia; Botrous, Peter; Wells, James

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma with a poorly understood molecular etiology. We implemented a comprehensive deep sequencing approach to identify mutations in the tumor DNA from a cohort of patients treated at our institution over the past 15 years. Our results indicate mutations that may constitute therapeutic targets in MCC. Five patients were treated for MCC within the study interval. Patients with adequate tissue (n = 4), positive neuroendocrine differentiation (chromogranin, synaptophysin, and cytokeratin 20), and histopathological confirmation of MCC were included in the study. DNA was extracted from archival tumor tissue samples and analyzed by massively parallel sequencing using a targeted, multiplex PCR approach followed by semiconductor sequencing. We demonstrate high-penetrance nonsense mutations in PDE4DIP (n = 4) as well as various missense mutations in the DNA damage response (PRKDC, AURKB, ERCC5, ATR, and ATRX) and epigenetic modulating enzymes (MLL3). We describe several mutations in potential disease-relevant genes and pathways. These targets should be evaluated in a larger cohort to determine their role in the molecular pathogenesis of MCC. © 2015 S. Karger AG, Basel.

  6. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

    Directory of Open Access Journals (Sweden)

    Akihiro Ohmoto

    2017-01-01

    Full Text Available Pancreatic neuroendocrine neoplasms (pNENs are rare tumors accounting for only 1%–2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC, will be needed to improve the prognosis.

  7. Neuroendocrine regulation of long-term pair maintenance in the monogamous zebra finch.

    Science.gov (United States)

    Prior, Nora H; Soma, Kiran K

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Understanding affiliative behavior is critical to understanding social organisms. While affiliative behaviors are present across a wide range of taxa and contexts, much of what is known about the neuroendocrine regulation of affiliation comes from studies of pair-bond formation in prairie voles. This leaves at least three gaps in our current knowledge. First, little is known about long-term pair-bond maintenance. Second, few studies have examined non-mammalian systems, even though monogamy is much more common in birds than in mammals. Third, the influence of breeding condition on affiliation is largely unknown. The zebra finch (Taeniopygia guttata) is an excellent model system for examining the neuroendocrine regulation of affiliative behaviors, including the formation and maintenance of a long-term pair bond. Zebra finches form genetically monogamous pair bonds, which they actively maintain throughout the year. The genomic and neuroanatomical resources, combined with the wealth of knowledge on the ecology and ethology of wild zebra finches, give this model system unique advantages to study the neuroendocrine regulation of pair bonding. Here, we review the endocrinology of opportunistic breeding in zebra finches, the sex steroid profiles of breeding and non-breeding zebra finches (domesticated and wild), and the roles of sex steroids and other signaling molecules in pair-maintenance behaviors in the zebra finch and other monogamous species. Studies of zebra finches and other songbirds will be useful for broadly understanding the neuroendocrine regulation of affiliative behaviors, including pair bonding and monogamy. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome.

    Science.gov (United States)

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

    2017-08-01

    Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.

  9. Characterization of Genotoxic Response to 15 Multiwalled Carbon Nanotubes with Variable Physicochemical Properties Including Surface Functionalizations in the FE1-Muta(TM) Mouse Lung Epithelial Cell Line

    DEFF Research Database (Denmark)

    Jackson, Petra; Kling, Kirsten; Jensen, Keld Alstrup

    2015-01-01

    Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured Nanoma...

  10. Molecular Imaging Radiotherapy: Theranostics for Personalized Patient Management of Neuroendocrine Tumors (NETs).

    Science.gov (United States)

    Oberg, Kjell

    2012-01-01

    Neuroendocrine tumors (NETs) possess unique features including expression of peptide hormone receptors as well as the capacity to concentrate and take up precursor forms of amines and peptides making hormones that are stored in secretory granules within the tumor cells (APUD). The expression of somatostatin receptors on tumor cells have been widely explored during the last two decades starting with (111)In-DTPA-Octreotide as an imaging agent followed by (68)Ga-DOTATOC/TATE positron emission tomography scanning. The new generation of treatment includes (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE/DOTANOC treatment of various subtypes of NETs. The objective response rate by these types of PRRT is in the range of 30-45% objective responses with 5-10% grade 3/4 toxicity mainly hematologic and renal toxicity. The APUD mechanism is another unique feature of NETs which have generated an interest over the last two decades to develop specific tracers including (11)C-5HTP, (18)F-DOPA and (11)C-hydroxyefedrin. These radioactive tracers have been developed in centres with specific interest in NETs and are not available everywhere. (111)In-DTPA-Octreotide is still the working horse in diagnosis and staging of metastatic NETs, but will in the future be replaced by (68)Ga-DOTATOC/DOTATATE PET/CT scanning which provide higher sensitivity and specificity and is also more convenient for the patient because it is a one-stop-procedure. Both (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE are important new therapies for malignant metastatic NETs. However, the precise role in the treatment algorithm has to be determined in forthcoming randomized trials.

  11. High grade neuroendocrine neoplasm of the antrum and orbit.

    Science.gov (United States)

    MacIntosh, Peter W; Jakobiec, Frederick A; Stagner, Anna M; Gilani, Sapideh; Fay, Aaron

    2015-01-01

    Neuroendocrine malignancies-tumors characterized by the production of dense-core secretory granules-are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient's tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV-hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Quality and Timing of Stressors Differentially Impact on Brain Plasticity and Neuroendocrine-Immune Function in Mice

    Directory of Open Access Journals (Sweden)

    Sara Capoccia

    2013-01-01

    Full Text Available A growing body of evidence suggests that psychological stress is a major risk factor for psychiatric disorders. The basic mechanisms are still under investigation but involve changes in neuroendocrine-immune interactions, ultimately affecting brain plasticity. In this study we characterized central and peripheral effects of different stressors, applied for different time lengths, in adult male C57BL/6J mice. We compared the effects of repeated (7 versus 21 days restraint stress (RS and chronic disruption of social hierarchy (SS on neuroendocrine (corticosterone and immune function (cytokines and splenic apoptosis and on a marker of brain plasticity (brain-derived neurotrophic factor, BDNF . Neuroendocrine activation did not differ between SS and control subjects; by contrast, the RS group showed a strong neuroendocrine response characterized by a specific time-dependent profile. Immune function and hippocampal BDNF levels were inversely related to hypothalamic-pituitary-adrenal axis activation. These data show a fine modulation of the crosstalk between central and peripheral pathways of adaptation and plasticity and suggest that the length of stress exposure is crucial to determine its final outcome on health or disease.

  13. Late neuro endocrinological sequelae of radiation therapy; Effets tardifs de la radiotherapie sur la sphere neuroendocrine

    Energy Technology Data Exchange (ETDEWEB)

    Bieri, S.; Bernier, J. [Ospedale San Giovanni (Switzerland); Sklar, C. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Constine, L. [Rochester Univ., NY (United States)

    1997-12-01

    When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common than has been appreciated in the past. Clinical damage to the pituitary and thyroid glands usually occurs months to years after treatment, and is preceded by a long subclinical phase. Primary brain tumors represent the largest group of malignant solid tumors in children. The survival rates of 50 reported in the literature are achieved at the expense of late occurring effects. Radiation-induced abnormalities are generally dose-dependent. Growth hormone deficiency and premature sexual development can occur at doses as low as 18 Gy in conventional fractionation, and is the most common neuroendocrine problem in children. In patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid stimulation hormone, and adrenocorticotropin (> 50 Gy), hyperprolactinemia can be seen, especially among young women. Most neuroendocrine disturbances that develop as a result of HPA can be treated efficiently, provided that an early detection of these endocrine dysfunctions abnormalities is done. (authors)

  14. Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Morgan, Rosemary E; Pommier, SuEllen J; Pommier, Rodney F

    2017-11-02

    Recently, there has been a move toward decreasing the threshold for liver debulking for metastatic carcinoid tumors from 90% to 70%. The debulking threshold and factors that predict outcomes of liver debulking operations specifically among pancreatic neuroendocrine tumors are not well defined. Records of patients with pancreatic neuroendocrine tumors undergoing liver debulking with a threshold of 70% from 2006 to 2016 were reviewed. Extrahepatic metastases and positive margins by enucleation were allowed. Liver progression-free survival and overall survival were calculated by the Kaplan-Meier method for various factors and compared by log-rank. Factors also were correlated with liver progression-free survival and overall survival by multivariate regression analyses. Forty-two patients underwent 44 operations, of which 24 resulted in 100% debulking, 12 resulted in ≥90% debulking, and 8 resulted in ≥70% debulking. Median liver progression-free survival was 11 months. The 5-year overall survival rate was 81%. There were no significant differences in outcome based on percent debulked. Only liver metastasis ≥5 cm correlated with liver progression-free survival and overall survival. Consideration should be given to expanding the criteria for liver debulking in pancreatic neuroendocrine tumors to include a new threshold of >70% debulking, intermediate grade tumors, positive margins, and extrahepatic metastases; these criteria yield results indistinguishable from complete resection. Using these expanded criteria will increase the number of patients eligible for an operation and maintain high survival rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram

    Directory of Open Access Journals (Sweden)

    Fabiana Policeni

    2016-01-01

    Full Text Available Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient′s left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI.

  16. Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence.

    Science.gov (United States)

    Shahanoor, Ziasmin; Sultana, Razia; Baker, Madelyn R; Romeo, Russell D

    2017-12-01

    Adolescence is associated with the maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress response. Adolescence is also a period in development marked by a variety of stress-related vulnerabilities, including psychological and physiological dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA axis. In adult mice, a model of disrupted HPA function has been developed using oral chronic corticosterone administration via the drinking water, which results in various physiological and neurobehavioral abnormalities, including changes in stress reactivity and anxiety-like behaviors. In an effort to further complement and extend this model, we tested the impact of HPA disruption in adolescent mice. We also examined whether this disruption led to different outcomes depending on whether the treatment happened during adolescence or adulthood. In the current set of experiments, we exposed adult (70days of age) or adolescent (30days of age) male C57BL/6N mice to 4 weeks of either 0 or 25μg/ml oral corticosterone via their drinking water. We measured body weight during treatment and plasma corticosterone levels and activation of the paraventricular nucleus (PVN), as indexed by FOS immunohistochemistry, before and after a 30min session of restraint stress. Our data indicate that adolescent animals exposed to chronic corticosterone showed weight loss during treatment, an effect not observed in adults. Further, we found stress failed to elevate plasma corticosterone levels in treated mice, regardless of whether exposure occurred in adulthood or adolescence. Despite this reduced hormonal responsiveness, we found significant neural activation in the PVN of both adult- and adolescent-treated mice, indicating a dissociation between stress-induced peripheral and central stress responses following chronic corticosterone exposure. Moreover, stress-induced neural activation in the PVN was unaffected

  17. Predicting species distribution and abundance responses to climate change: why it is essential to include biotic interactions across trophic levels

    NARCIS (Netherlands)

    Van der Putten, W.H.; Macel, M.; Visser, M.E.

    2010-01-01

    Current predictions on species responses to climate change strongly rely on projecting altered environmental conditions on species distributions. However, it is increasingly acknowledged that climate change also influences species interactions. We review and synthesize literature information on

  18. Neuroendocrine Carcinoma: Immunohistochemistry Department Of Cancer Institute 1996 - 2000

    Directory of Open Access Journals (Sweden)

    Yazdani F

    2003-07-01

    Full Text Available Dispersed neuroendocrine system (D.N.S consists of a wide variety of cells that are present in the central and peripheral nervous system and in many classic endocrine organs and different tissues such as respiratory and gastrointestinal tracts, skin, prostate, breast and also their neoplasm show neuroendocrine differentiation by electron microscopy, immunohistochemistry or biochemical techniques:"nMaterials and Methods: The present study has been carried out by case-series method in order to evaluating the characteristics of all types of neuroendocrine carcinoma: different anatomical locations during 5 years period in immunohistochemistry department of cancer institute."nResults: The diagnosis of 109 cases of neuroendocrine carcinoma consisting of neuroendocrine carcinoma, small cell carcinoma, medullary carcinoma of thyroid, carcinoid tumor and merkel cell carcinoma are confirmed that among them the most common diagnosis was related to neuroendocrine carcinoma (50.5 percent. The most prevalent age group was 40-49 years and male to female distribution were 56 percent and 44 percent respectively. Anatomical distribution of tumor show that about 30 percent of cases were metastatic carcinoma, 30 percent in thyroid, respiratory tract and head and neck region and remainder in a variety of tissues. In over 50 percent of cases one of endocrinoid patterns as trabecular, organoid or mixed of them were seen."nConclusion: Immunohistochemically N.S.E (Neuron Specific Enolase show high sensitivity with 96 percent positive reaction and more specific endocrine markers as chromogranin A in 80 percent and synaptophysin only in 24 percent because of lesser application of the latter. Also epithelial markers such as cytokeratin and E.M.A."n(Epithelial Membrane Antigen were positive in 69 percent and 74 percent respectively. Mean survival rate of all neuroendocrine carcinoma reached to 4.8 years with lowest survival of 4.3 years among small cell carcinoma and

  19. [Neuroendocrine factors in hypertension during pregnancy].

    Science.gov (United States)

    Diaconu, Minodora; Ghiciuc, Cristina-Mihaela; Tarţău, Liliana; Lupuşoru, Cătălina-Elena

    2011-01-01

    Pregnancy induced hypertension is a condition of high blood pressure during early and mid-pregnancy. This type of hypertension is much like the chronic type, but it occurs only when the woman is pregnant and resolves completely after delivery. to evaluate some stress hormones in both normotensive and hypertensive pregnant women. The study investigated the correlation between pregnancy induced hypertension and different immune/inflammatory and other markers. This exploratory investigation was performed on pregnant women diagnosed with pregnancy-induced hypertension, admitted to the lasi Cuza Voda Hospital. The psychometric assessment was performed by using the daily stress test, daily hassle scale, blood pressure measurements, and determination of anthropometrical parameters. Some parameters, such as the neuroendocrine and immune/inflammatory ones, and specific parameters for pregnancy hypertension were determined. Our study revealed that blood pressure values presented significant differences between systolic, but not diastolic blood pressure values (p < 0.05). In 75% of subjects blood cortisol levels were not changed. Daily stress level assessment proved that low potential factors and an annoying environment had a high influence on both normotensive and hypertensive pregnant women. Hypertensive women also presented leukocytosis and thrombocytopenia. The research results showed that plasma cortisol level was higher in hypertensive pregnant women, compared with normotensives.

  20. Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)

    2016-04-15

    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

  1. Spectrum of malignant somatostatin-producing neuroendocrine tumors.

    Science.gov (United States)

    Moayedoddin, Baback; Booya, Fargol; Wermers, Robert A; Lloyd, Ricardo V; Rubin, Joseph; Thompson, Geoffrey B; Fatourechi, Vahab

    2006-01-01

    To evaluate the clinical manifestations and outcome of patients with somatostatinomas--rare neuroendocrine tumors of pancreaticoduodenal origin. We searched the medical archives and tumor registry of our institution for somatostatinomas or somatostatin-staining tumors for the 12-year period from January 1990 to February 2002. In addition, we reviewed laboratory databases for patients who had an elevated serum somatostatin level. Patients with a neuroendocrine tumor and an elevated serum somatostatin level or somatostatin-positive tumor immunostaining were included in this study. Eleven patients qualified (9 men and 2 women; median age at diagnosis, 45 years; age range, 22 to 73). The diagnosis of a somatostatinoma was made by immunostaining of the tumor in 9 patients and by finding elevated serum somatostatin levels in 2. Five primary tumors were of duodenal and 6 of pancreatic origin. Psammoma body formation and association with neurofibromatosis were seen only in the duodenal tumors. The known primary tumor sizes varied from 2 to 6 cm. Liver metastatic lesions were present in 6 patients, abdominal lymph node involvement was found in 10 patients, and lung, spleen, and ovarian metastatic involvement was noted in 1 patient each. Diabetes was present in 4 patients (36%) and cholelithiasis in 7 (64%). The presence of a mass led to the diagnosis in most patients with primary duodenal tumors, whereas patients with pancreatic tumors were more likely to have endocrine manifestations. A Whipple procedure was performed in 6 patients, distal pancreatectomy in 3, hepatic artery embolization or ligation in 3, and partial hepatectomy in 1. Cancer-related death occurred in 4 patients, 1 to 8 years after diagnosis (median, 4.5 years). At last follow-up, 2 patients were alive without evidence of disease (8 and 10 years after diagnosis), and 3 were alive with liver metastatic lesions. The status of 2 patients was unclear. Somatostatinomas occurred with approximately equal frequency

  2. An Assessment on Reports of Institutional Social Responsibility in Turkey: Companies Included In BİST -30 Index

    Directory of Open Access Journals (Sweden)

    Ender Guler

    2014-04-01

    Full Text Available As a consequence of the technological and economic developments experienced in line with globalization, the competition between companies and dependency of societies to one another increased. This burdened the companies the responsibility of developing their knowledge and interest in the society in which they live and operate. Within this framework, the concept of “Institutional Social Responsibility” came into prominence as well. Companies prepare reports for the purpose of publicizing the projects they fulfill with respect to institutional social responsibility in addition to explaining their financial situations. In this study, the companies operating in BIST-30 Index in Turkey were classified on sector basis and reports indicating the projects they fulfill in accordance with the concept of institutional social responsibility were discussed and assessed. Normal 0 21 false false false TR X-NONE X-NONE

  3. Benign Endometrial Polyp and Primary Endometrial Small Cell Neuroendocrine Carcinoma Confined to the Polyp: A Rare Association

    Directory of Open Access Journals (Sweden)

    Pembe Oltulu

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs are a heterogeneous group of tumoral lesions originating from diffuse endo­crine system cells. They occur mostly in the gastrointes­tinal system and the lung. Primary NETs of the female reproductive tract are rare. In a widely used classification, primary small cell neuroendocrine carcinomas (SCNECs and large cell neuroendocrine carcinomas (LCNECs of the endometrium were included in a subgroup of poorly differentiated neuroendocrine carcinomas. SCNECs of the endometrium are very rare and they are often com­bined with other epithelial neoplasms. Their myometrial and extrauterine invasions are common during the initial diagnosis due to their aggressive behaviors. In this ar­ticle, we present a rare case of primary endometrial SC­NEC detected within the benign endometrial polyp and without invasion of myometrium and extrauterine tissues in a 70-year-old female patient presenting with post­menopausal bleeding. Histopathologically, the tumor cells showed positive staining with Synaptophysin, the Ki-67 labeling index was 80-90%, the mitotic index was 15/10 per HPF and there was no necrosis and lymphovascular invasion. J Clin Exp Invest 2016; 7 (1: 107-110

  4. Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours.

    Science.gov (United States)

    Rodríguez-Zarco, E; Vallejo-Benítez, A; Umbría-Jiménez, S; Pereira-Gallardo, S; Pabón-Carrasco, S; Azueta, A; González-Cámpora, R; Espinal, P S; García-Escudero, A

    2017-10-01

    Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets. Copyright © 2017 AEU. All rights reserved.

  5. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  6. Epidemiology of neuroendocrine cancers in an Australian population.

    Science.gov (United States)

    Luke, Colin; Price, Timothy; Townsend, Amanda; Karapetis, Christos; Kotasek, Dusan; Singhal, Nimit; Tracey, Elizabeth; Roder, David

    2010-06-01

    The aim was to explore incidence, mortality and case survivals for invasive neuroendocrine cancers in an Australian population and consider cancer control implications. Directly age-standardised incidence and mortality rates were investigated from 1980 to 2006, plus disease-specific survivals. Annual incidence per 100,000 increased from 1.7 in 1980-1989 to 3.3 in 2000-2006. A corresponding mortality increase was not observed, although numbers of deaths were low, reducing statistical power. Increases in incidence affected both sexes and were more evident for female lung, large bowel (excluding appendix), and unknown primary site. Common sites were lung (25.9%), large bowel (23.3%) (40.9% were appendix), small intestine (20.6%), unknown primary (15.0%), pancreas (6.5%), and stomach (3.7%). Site distribution did not vary by sex (p = 0.260). Younger ages at diagnosis applied for lung (p = 0.002) and appendix (p colon (excluding appendix). Incidence rates are increasing. Research is needed into possible aetiological factors for lung and large-bowel sites, including tobacco smoking, and excess body weight and lack of exercise, respectively; and Crohn's disease as a possible precursor condition.

  7. Genetic and epigenetic drivers of neuroendocrine tumours (NET).

    Science.gov (United States)

    Di Domenico, Annunziata; Wiedmer, Tabea; Marinoni, Ilaria; Perren, Aurel

    2017-09-01

    Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging. Indeed, mutations in genes encoding for proteins directly involved in chromatin remodelling, such as DAXX and ATRX are a frequent event in NET. Epigenetic changes are reversible and targetable; therefore, an attractive target for treatment. The discovery of the mechanisms underlying the epigenetic changes and the implication on gene and miRNA expression in the different subgroups of NET may represent a crucial change in the diagnosis of this disease, reveal new therapy targets and identify predictive markers. Molecular profiles derived from omics data including DNA mutation, methylation, gene and miRNA expression have already shown promising results in distinguishing clinically and molecularly different subtypes of NET. In this review, we recapitulate the major genetic and epigenetic characteristics of pancreatic, lung and small intestinal NET and the affected pathways. We also discuss potential epigenetic mechanisms leading to NET development. © 2017 Society for Endocrinology.

  8. Simulation of spatially varying ground motions including incoherence, wave‐passage and differential site‐response effects

    DEFF Research Database (Denmark)

    Konakli, Katerina; Der Kiureghian, Armen

    2012-01-01

    A method is presented for simulating arrays of spatially varying ground motions, incorporating the effects of incoherence, wave passage, and differential site response. Non‐stationarity is accounted for by considering the motions as consisting of stationary segments. Two approaches are developed....... In the first, simulated motions are consistent with the power spectral densities of a segmented recorded motion and are characterized by uniform variability at all locations. Uniform variability in the array of ground motions is essential when synthetic motions are used for statistical analysis of the response...... of multiply‐supported structures. In the second approach, simulated motions are conditioned on the segmented record itself and exhibit increasing variance with distance from the site of the observation. For both approaches, example simulated motions are presented for an existing bridge model employing two...

  9. Treatment responses in five patients with Ribbing disease including two with 466C>T missense mutations in TGFβ1.

    Science.gov (United States)

    Savoie, Anne; Gouin, François; Maugars, Yves; Isidor, Bertrand; Larrose, Catherine; Berthelot, Jean-Marie

    2013-12-01

    To assess 5-year treatment responses and TGFB1 gene abnormalities in five patients with ribbing disease. PCR analysis and bidirectional sequencing of TGFβ1 exons 1 through 7 were performed in all five patients. The five patients, four women and one man with a mean age of 34 years at symptom onset, shared the following features: severe diaphyseal pain predominating in the lower limbs with diaphyseal hyperostosis; increased radionuclide uptake at sites of pain and, in some cases at other cortical sites; asymmetric or asynchronous lesions; long symptom duration (5-18 years) despite a variety of treatments; and a delay of several years (2-15) between symptom onset and the diagnosis. Of our five patients, two had a heterozygous missense mutation in exon 2 of TGFβ1 (c.466C>T, p.Arg156Cys, previously described in Camurati-Engelmann syndrome) and three had commonly found TGFβ1 polymorphisms. Intravenous bisphosphonate therapy was used in all five patients but induced substantial improvements in a single patient. Of the three patients given bolus methylprednisolone therapy, two experienced a lasting response; the exception was one of the two women with a TGFβ1 mutation. Considerable heterogeneity in the clinical presentations, genetic abnormalities, and treatment responses contribute to the diagnostic challenges raised by ribbing disease. Detailed genetic studies are needed. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  10. The controlled-source electromagnetic response of two buried plates, including mutual inductance and interaction with the host medium

    Science.gov (United States)

    Stalnaker, J. L.; Everett, M. E.

    2002-12-01

    A solution for the response of multiple buried plates in a host medium to controlled-source electromagnetic (CSEM) stimulation has been found. This solution accounts for the interaction between the plates and the host medium. The solution for a plate in free space is well-known and analytic. However, adding a second plate or a conducting host medium increases the complexity of the solution. Time-varying currents induced by the source in the plates and the host medium introduce new magnetic flux to the system that in turn modify the currents via mutual inductance. This solution is obtained by solving the (A,φ ) potential formulation of Maxwell's equations using the finite element method. The finite element mesh generator allows for local refinement of the mesh in regions where greater resolution is desirable. This allows finer meshing in the region of the plates, which allows for more accurate modeling of the nuances in the induced currents caused by the interaction between the plates and the host medium. The effect of mutual induction and the efficacy of the locally refined finite element solution are demonstrated. The response of a model containing two plates within a host medium is compared to the sum of the responses of the two plates modeled separately. The plates are 2 m by 2 m, with a separation distance of 1 m, buried at a depth of 1 m. The plates have a conductivity of 100 S/m, and are within a host medium of conductivity 0.01 S/m. The system is excited by a source with a frequency between 1 and 100 kHz. It is shown that the model response of a two-plate system differs from the sum of the responses of two one-plate systems. The interaction between the two plates and the host medium must be properly modeled. An accurate model of the interaction of buried conductors excited by a controlled source is necessary to properly discriminate and classify buried targets. This is particularly true in the near-surface region of the earth where complex heterogeneity is

  11. Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Herrera-Martínez, Aura D; Gahete, Manuel D; Pedraza-Arevalo, Sergio; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Serrano-Blanch, Raquel; Luque, Raúl M; Gálvez-Moreno, María A; Castaño, Justo P

    2018-02-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of malignancies often presenting with metastasis at diagnosis and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and control progression in some NETs. However, many patients do not respond to SSAs or develop resistance, and there are many uncertainties regarding pathophysiology of SST and its receptors (sst1-sst5) in GEP-NETs. The expression of SST system components in GEP-NETs was determined, compared with that of non-tumor adjacent and normal tissues and correlated with clinical and histological characteristics. Specifically, 58 patients with GEP-NETs and 14 normal samples were included. Cell viability in NET cell lines was determined in response to specific SSAs. Normal samples and non-tumor adjacent tissues presented a similar expression profile, with appreciable expression of sst2 and sst3, and a lower expression of the other receptors. In contrast, cortistatin, sst1, sst4, and sst5 were overexpressed in tumors, while sst3 and sst4 seemed overexpressed in less differentiated tumors. Some SST system components were related to vascular/nerve invasion and metastasis. In vitro, sst1 and sst3 agonists reduced viability in BON-1 cells, while they, similar to octreotide and pasireotide, increased viability in QGP-1 cells. These results provide novel information on SST system pathophysiology in GEP-NETs, including relevant associations with clinical-histological parameters, which might help to better understand the intrinsic heterogeneity of NETs and to identify novel biomarkers and/or targets with potential prognostic and/or therapeutic value for GEP-NETs patients.

  12. Seismic response of a deep continental basin including velocity inversion: the Sulmona intramontane basin (Central Apennines, Italy)

    Science.gov (United States)

    Di Giulio, Giuseppe; de Nardis, Rita; Boncio, Paolo; Milana, Giuliano; Rosatelli, Gianluigi; Stoppa, Francesco; Lavecchia, Giusy

    2016-01-01

    The Sulmona plain (central Italy) is an intramontane basin of the Abruzzi Apennines that is known in the literature for its high seismic hazard. We use extensive measurements of ambient noise to map the fundamental frequency and to detect the presence of geological heterogeneities in the basin. We perform noise measurements along two basin-scale orthogonal transects, in conjunction with 2-D array experiments in specific key areas. The key areas are located in different positions with respect to the basin margins: one at the eastern boundary (fault-controlled basin margin) and one in the deepest part of the basin. We also collect independent data by using active seismic experiments (MASW), down-hole and geological surveys to characterize the near-surface geology of the investigated sites. In detail, the H/V noise spectral ratios and 2-D array techniques indicate a fundamental resonance (f0) in the low-frequency range (0.35-0.4 Hz) in the Sulmona Basin. Additionally, our results highlight the important role that is played by the alluvial fans near the edge-sectors of the basin, which are responsible for a velocity inversion in the uppermost layering of the soil profile. The H/V ratios and the dispersion curves of adjacent measurements strongly vary over a few dozens of meters in the alluvial fan area. Furthermore, we perform 1-D numerical simulations that are based on a linear-equivalent approach to estimate the site response in the key areas, using realistic seismic inputs. Finally, we perform a 2-D simulation that is based on the spectral element method to propagate surface waves in a simple model with an uppermost stiff layer, which is responsible for the velocity inversion. The results from the 2-D modelling agree with the experimental curves, showing deamplified H/V curves and typical shapes of dispersion curves of a not normally dispersive site.

  13. HER2-Positive Neuroendocrine Breast Cancer: Case Report and Review of Literature.

    Science.gov (United States)

    Gevorgyan, Arpine; Bregni, Giacomo; Galli, Giulia; Zanardi, Elisa; de Braud, Filippo; Di Cosimo, Serena

    2016-12-01

    Neuroendocrine carcinoma is an uncommon histology for breast cancer. Our patient underwent right quadrantectomy for a neuroendocrine carcinoma in 1984 and had a bone relapse 30 years later. After thorough pathological and immunohistochemical analysis the diagnosis was confirmed and HER2 amplification was observed. Here we discuss the management, rationale and results of HER2-targeted therapy in advanced neuroendocrine breast carcinoma.

  14. CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Ho; Kim, Se Hyung; Shin, Cheong-il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Kim, Min-A [Seoul National University Hospital, Department of Pathology, Jongno-gu, Seoul (Korea, Republic of)

    2015-07-15

    To evaluate the differential CT features of gastric poorly-differentiated neuroendocrine tumours (PD-NETs) from well-differentiated NETs (WD-NETs) and gastric adenocarcinomas (ADCs) and to suggest differential features of hepatic metastases from gastric NETs and ADCs. Our study population was comprised of 36 patients with gastric NETs (18 WD-NETs, 18 PD-NETs) and 38 patients with gastric ADCs who served as our control group. Multiple CT features were assessed to identify significant differential CT findings of PD-NETs from WD-NETs and ADCs. In addition, CT features of hepatic metastases including the metastasis-to-liver ratio were analyzed to differentiate metastatic NETs from ADCs. The presence of metastatic lymph nodes was the sole differentiator of PD-NETs from WD-NETs (P =.001, odds ratio = 56.67), while the presence of intact overlying mucosa with mucosal tenting was the sole significant CT feature differentiating PD-NETs from ADCs (P =.047, odds ratio = 15.3) For hepatic metastases, metastases from NETs were more hyper-attenuated than those from ADCs. The presence of metastatic LNs and intact overlying mucosa with mucosal tenting are useful CT discriminators of PD-NETs from WD-NETs and ADCs, respectively. In addition, a higher metastasis-to-liver ratio may help differentiate hepatic metastases of gastric NETs from those of gastric ADCs with high accuracy. (orig.)

  15. Post-traumatic intrahepatic splenosis mimicking a neuroendocrine tumour.

    Science.gov (United States)

    Leong, Chee Weng; Menon, Tulsi; Rao, Sudhakar

    2013-03-06

    A 52-year-old man presented with abdominal pain with a background of splenectomy 25 years previously. Initial investigations lead to suspicion of a neuroendocrine tumour. Positron emission tomography octreotide scanning and chromogranin were raised. He subsequently underwent a lateral segmentectomy. The histopathology was consistent with splenosis. 1. Splenosis must be considered as differential in any patient with abdominal symptoms post-traumatic splenectomy. 2. Positron emission tomography (PET) octreotide scanning can detect splenosis giving false positives for a neuroendocrine tumour. This is the first case to describe such an association.

  16. Metastatic breast cancer presenting as a primary hindgut neuroendocrine tumour.

    Science.gov (United States)

    Okines, Alicia F C; Hawkes, Eliza A; Rao, Sheela; VAN As, Nicholas; Marsh, Henry; Riddell, Angela; Wilson, Philip O G; Osin, Peter; Wotherspoon, Andrew C; Wetherspoon, Andrew C

    2010-07-01

    The examination of limited, potentially non-representative fragments of tumour tissue from a core biopsy can be misleading and misdirect subsequent treatment, especially in cases where a primary tumour has not been identified. This case report is of a 65-year-old woman presenting with a destructive sacral mass, diagnosed on radiological imaging and core biopsy as a hindgut neuroendocrine tumour, which on histopathological review of the subsequently resected tumour was found instead to represent a metastasis from an occult hormone-positive breast cancer with neuroendocrine features.

  17. Unusual apocrine carcinoma with neuroendocrine differentiation: a cutaneous neoplasm may be analogous to neuroendocrine carcinoma with apocrine differentiation of breast.

    Science.gov (United States)

    Li, Yang; Chen, Li-li; Li, Bin; Tian, Xiao-ying; Li, Zhi

    2015-06-10

    Cutaneous apocrine carcinoma (AC) is a rare adnexal neoplasm that histologically can mimic breast carcinoma metastatic to the skin or apocrine carcinoma arising in ectopic breast tissue. As extremely rare condition, neuroendocrine differentiation may be observed in AC although its etiology and pathogenesis is still unclear. We report here a case of unusual AC with neuroendocrine differentiation in right labium majus pudenda. A 43-year-old woman presented with a 6-month history of an asymptomatic pea-sized brownish nodule in right labium majus pudenda without enlargement of inguinal lymph nodes and bilateral breast nodules. The mass was totally resected. Microscopically, the tumor was solitary and located in the deep dermis without epidermal connection. Tumor cells were arranged in a micronodular or formed massive solid nests separated by densely fibroblastic stroma. Scattered glandular or rosette-like structures were identified within the tumor nodules. Immunohistochemically, the tumor cells were diffusely positive to CK7, CEA, GCDFP-15, synaptophysin, estrogen and progesterone receptors. Part of tumor cells expressed androgen receptor, but they were negative to CK20, CK5/6, p63 and S-100. Because of its rarity and histogenesis complexity, there exist diagnostic challenges for pathologists to differentiate cutaneous AC with neuroendocrine differentiation from other carcinomas with apocrine or neuroendocrine features. Our case demonstrates that the tumor shares some features with mammary carcinoma and might originate from mammary-like sweat gland in anogenital region. The results suggest that, for the first time, primary cutaneous AC with neuroendocrine differentiation may be analogous to the mammary neuroendocrine carcinoma with apocrine differentiation in histological feature and biological behavior. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7732276716685708.

  18. Safety and efficacy of doxorubicin-eluting superabsorbent polymer microspheres for the treatment of liver metastases from neuroendocrine tumours: preliminary results

    Directory of Open Access Journals (Sweden)

    Bonne Lawrence

    2017-02-01

    Full Text Available The aim of the study was to retrospectively evaluate the symptom control, tumour response, and complication rate in patients with liver-predominant metastatic neuroendocrine tumours treated with transarterial chemoembolization using doxorubicin-eluting superabsorbent polymer (SAP microspheres.

  19. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

    Science.gov (United States)

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-02-16

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

  20. Comparative Analysis of Clinical, Hormonal and Morphological Studies in Patients with Neuroendocrine ACTH-Producing Tumours

    Directory of Open Access Journals (Sweden)

    G. S. Kolesnikova

    2013-01-01

    Full Text Available This paper highlights the problem of neuroendocrine tumours (NETs with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH by tumour cells. In most cases (85%, the tumours were localized in the pituitary gland (Cushing's disease; 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS. Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS. Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2 ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67 was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas.

  1. A constitutive model for the compressive response of metallic closed-cell foams including micro-inertia effects

    Directory of Open Access Journals (Sweden)

    Barthélémy Romain

    2015-01-01

    Full Text Available Metallic foams have known a keen interest in the last decades. Their ability to undergo very large deformations while transmitting low stress levels make them capable of performing functions of protective layers against intense loadings and of energy absorbers, for instance. The behaviour of metal foams varies considerably between quasi-static and dynamic regimes. Those differences can be linked to the strain-rate sensitivity of the skeleton material and to micro-inertial effects (induced by the crushing of the foam cells. In the present work, a micromechanical model has been developed to take into account micro-inertia effects on the macroscopic behaviour of closed-cell foams under dynamic loading conditions. The proposed modelling is based on the dynamic homogenisation procedure introduced by Molinari and Mercier (J. Mech. Phys. Solids 49 (2001 1497–1516. Within this framework, the macrostress is the sum of two terms. The first one is a static stress, that can be described with any existing model of metal foam. The second contribution is a dynamic stress related to micro-inertia effects. Considering an initially spherical shell as a Representative Volume Element (RVE of the foam material, a closed-form expression of the dynamic stress was obtained. The proposed modelling was applied to shock propagation in aluminium foams (it should however be noted that the present theory is not restricted to uniaxial deformation but can be applied to arbitrary loadings. From experimental data of the literature, it is observed that incorporating micro-inertia effects allows one to achieve a better description of the foam shock response. This indicates that micro-inertia may have a significant influence on the dynamic behaviour of metallic foams.

  2. Biological responses of three-dimensional cultured fibroblasts by sustained compressive loading include apoptosis and survival activity.

    Directory of Open Access Journals (Sweden)

    Toshiki Kanazawa

    Full Text Available Pressure ulcers are characterized by chronicity, which results in delayed wound healing due to pressure. Early intervention for preventing delayed healing due to pressure requires a prediction method. However, no study has reported the prediction of delayed healing due to pressure. Therefore, this study focused on biological response-based molecular markers for the establishment of an assessment technology to predict delayed healing due to pressure. We tested the hypothesis that sustained compressive loading applied to three dimensional cultured fibroblasts leads to upregulation of heat shock proteins (HSPs, CD44, hyaluronan synthase 2 (HAS2, and cyclooxygenase 2 (COX2 along with apoptosis via disruption of adhesion. First, sustained compressive loading was applied to fibroblast-seeded collagen sponges. Following this, collagen sponge samples and culture supernatants were collected for apoptosis and proliferation assays, gene expression analysis, immunocytochemistry, and quantification of secreted substances induced by upregulation of mRNA and protein level. Compared to the control, the compressed samples demonstrated that apoptosis was induced in a time- and load- dependent manner; vinculin and stress fiber were scarce; HSP90α, CD44, HAS2, and COX2 expression was upregulated; and the concentrations of HSP90α, hyaluronan (HA, and prostaglandin E2 (PGE2 were increased. In addition, the gene expression of antiapoptotic Bcl2 was significantly increased in the compressed samples compared to the control. These results suggest that compressive loading induces not only apoptosis but also survival activity. These observations support that HSP90α, HA, and, PGE2 could be potential molecular markers for prediction of delayed wound healing due to pressure.

  3. Exercise intensity-dependent changes in the inflammatory response in sedentary women: role of neuroendocrine parameters in the neutrophil phagocytic process and the pro-/anti-inflammatory cytokine balance.

    Science.gov (United States)

    Giraldo, E; Garcia, J J; Hinchado, M D; Ortega, E

    2009-01-01

    It is still not really known what is the optimal level of exercise that improves, but does not impair or overstimulate the innate immune function. This is especially the case in women, who have higher basal levels of 'inflammatory markers' than men. The aim of this work was to evaluate differences in the magnitude of the stimulation of the innate/inflammatory response following a single bout of moderate or intense exercise in sedentary women, all of them in the follicular phase of their menstrual cycle. Changes in stress and sexual hormones were also evaluated. Changes induced by exercise (45 min at 55% VO(2) max vs. 1 h at 70% VO(2) max on a cycle ergometer) in the phagocytic process (chemotaxis, phagocytosis, and microbicide capacity against Candida albicans) and in serum concentrations of IL-1beta, IL-2, IFN-gamma, IL-12, IL-6, and IL-4 (ELISA) were evaluated. Parallel determinations were also made of serum or plasma concentrations of catecholamines (HPLC) and cortisol, oestradiol, and progesterone (electrochemiluminescence immunoassay). Both exercise intensities increased chemotaxis, phagocytosis, and microbicide capacity of the neutrophils. However, the increase in chemotaxis was greater after moderate exercise. All the cytokines assayed were affected by exercise intensity. IFN-gamma increased significantly only immediately after the intense exercise; IL-1beta increased following both exercise intensities, although at 24 h it only remained elevated after the intense exercise; IL-12 only increased 24 h after the intense exercise, and IL-2 only showed a significant decrease following the moderate exercise. IL-6 increased immediately after both exercise intensities, but more so after moderate exercise. While IL-4 (an anti-inflammatory cytokine) increased following the moderate exercise, it decreased after the intense exercise. Both moderate and intense exercise increased norepinephrine and decreased cortisol, both of which returned to basal levels after 24 h

  4. Dietary l-tryptophan leaves a lasting impression on the brain and the stress response

    DEFF Research Database (Denmark)

    Höglund, Erik; Øverli, Øyvind; Åberg Andersson, Madelene

    2017-01-01

    Comparative models suggest that effects of dietary tryptophan (Trp) on brain serotonin (5-hydroxytryptamine; 5-HT) neurochemistry and stress responsiveness are present throughout the vertebrate lineage. Moreover, hypothalamic 5-HT seems to play a central role in control of the neuroendocrine stre......, they indicate that trophic/structural effects in the brain underlie the effects of dietary Trp treatment on stress reactivity.......Comparative models suggest that effects of dietary tryptophan (Trp) on brain serotonin (5-hydroxytryptamine; 5-HT) neurochemistry and stress responsiveness are present throughout the vertebrate lineage. Moreover, hypothalamic 5-HT seems to play a central role in control of the neuroendocrine stress...... axis in all vertebrates. Still, recent fish studies suggest long-term effects of dietary Trp on stress responsiveness, which are independent of hypothalamic 5-HT. Here, we investigated if dietary Trp treatment may result in long-lasting effects on stress responsiveness, including changes in plasma...

  5. Neuroendocrine disruption of organizational and activational hormone programming in poikilothermic vertebrates.

    Science.gov (United States)

    Rosenfeld, Cheryl S; Denslow, Nancy D; Orlando, Edward F; Gutierrez-Villagomez, Juan Manuel; Trudeau, Vance L

    2017-01-01

    In vertebrates, sexual differentiation of the reproductive system and brain is tightly orchestrated by organizational and activational effects of endogenous hormones. In mammals and birds, the organizational period is typified by a surge of sex hormones during differentiation of specific neural circuits; whereas activational effects are dependent upon later increases in these same hormones at sexual maturation. Depending on the reproductive organ or brain region, initial programming events may be modulated by androgens or require conversion of androgens to estrogens. The prevailing notion based upon findings in mammalian models is that male brain is sculpted to undergo masculinization and defeminization. In absence of these responses, the female brain develops. While timing of organizational and activational events vary across taxa, there are shared features. Further, exposure of different animal models to environmental chemicals such as xenoestrogens such as bisphenol A-BPA and ethinylestradiol-EE2, gestagens, and thyroid hormone disruptors, broadly classified as neuroendocrine disrupting chemicals (NED), during these critical periods may result in similar alterations in brain structure, function, and consequently, behaviors. Organizational effects of neuroendocrine systems in mammals and birds appear to be permanent, whereas teleost fish neuroendocrine systems exhibit plasticity. While there are fewer NED studies in amphibians and reptiles, data suggest that NED disrupt normal organizational-activational effects of endogenous hormones, although it remains to be determined if these disturbances are reversible. The aim of this review is to examine how various environmental chemicals may interrupt normal organizational and activational events in poikilothermic vertebrates. By altering such processes, these chemicals may affect reproductive health of an animal and result in compromised populations and ecosystem-level effects.

  6. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

    This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

  7. The value of 68Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature

    Science.gov (United States)

    Mojtahedi, Alireza; Thamake, Sanjay; Tworowska, Izabela; Ranganathan, David; Delpassand, Ebrahim S

    2014-01-01

    Neuroendocrine tumors (NETs) are rare group of neoplasms arising from nervous and endocrine systems. Somatostatin analogue imaging is a functional imaging modality of choice for evaluating the NETs. Recent availability of positron emitting radioisotope labeled somatostatin analogues to image neuroendocrine cancers, has raised the interests to use this new imaging modality in management of patients with NETs. 68Ga-DOTATATE PET/CT has demonstrated superiority in lesion detection compared to Octreoscan, MIBG scintigraphy and MRI. In this article, we reviewed the published studies evaluating the role of 68Ga-DOTATATE PET in diagnosis and management of patients with neuroendocrine tumors and comparing it to current FDA approved imaging modalities including Octreoscan, MIBG scintigraphy, 18F FDG PET/CT, CT and MRI. PMID:25143861

  8. The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature.

    Science.gov (United States)

    Mojtahedi, Alireza; Thamake, Sanjay; Tworowska, Izabela; Ranganathan, David; Delpassand, Ebrahim S

    2014-01-01

    Neuroendocrine tumors (NETs) are rare group of neoplasms arising from nervous and endocrine systems. Somatostatin analogue imaging is a functional imaging modality of choice for evaluating the NETs. Recent availability of positron emitting radioisotope labeled somatostatin analogues to image neuroendocrine cancers, has raised the interests to use this new imaging modality in management of patients with NETs. (68)Ga-DOTATATE PET/CT has demonstrated superiority in lesion detection compared to Octreoscan, MIBG scintigraphy and MRI. In this article, we reviewed the published studies evaluating the role of (68)Ga-DOTATATE PET in diagnosis and management of patients with neuroendocrine tumors and comparing it to current FDA approved imaging modalities including Octreoscan, MIBG scintigraphy, (18)F FDG PET/CT, CT and MRI.

  9. Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Jacob Ø; von Holstein, Sarah L; Prause, Jan U

    2014-01-01

    hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.......A 71-year-old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological...... and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary...

  10. Neuroendocrine differentiation in a case of cervical cancer | Rashed ...

    African Journals Online (AJOL)

    tumor; that further showed neuroendocrine differentiation, as demonstrated by chromogranin-A positivity. It is important to differentiate small cell carcinoma from other malignant tumors of the uterine cervix. Morphological features play an important role in making a diagnosis and the immunohistochemistry study can offer an ...

  11. Large-cell neuroendocrine carcinoma of the uterine cervix- a ...

    African Journals Online (AJOL)

    Objective. The present study describes 5 cases of large-cell neuroendocrine carcinoma (LCNEC) of the uterine cervix, evaluating their clinical features and pathological profiles. Methods. Clinical data were obtained from the patients' clinical files at the combined gynaecological-oncology unit of Johannesburg Hospital and ...

  12. Everolimus Effect on Gastrin and Glucagon in Pancreatic Neuroendocrine Tumors

    NARCIS (Netherlands)

    Pavel, Marianne E.; Chen, David; He, Wei; Cushman, Stephanie; Voi, Maurizio; de Vries, Elisabeth G. E.; Baudin, Eric; Yao, James C.

    Objectives: The pharmacodynamic effects of everolimus on gastrointestinal hormone levels have not been described in patients with pancreatic neuroendocrine tumors (pNETs). We report the effects of everolimus on gastrin and glucagon levels in patients with progressive pNETin RADIANT-1 (a single-arm

  13. Towards a unified model of neuroendocrine-immune interaction.

    Science.gov (United States)

    Petrovsky, N

    2001-08-01

    Although the neuroendocrine system has immunomodulating potential, studies examining the relationship between stress, immunity and infection have, until recently, largely been the preserve of behavioural psychologists. Over the last decade, however, immunologists have begun to increasingly appreciate that neuroendocrine-immune interactions hold the key to understanding the complex behaviour of the immune system in vivo. The nervous, endocrine and immune systems communicate bidirectionally via shared messenger molecules variously called neurotransmitters, cytokines or hormones. Their classification as neurotransmitters, cytokines or hormones is more serendipity than a true reflection of their sphere of influence. Rather than these systems being discrete entities we would propose that they constitute, in reality, a single higher-order entity. This paper reviews current knowledge of neuroendocrine-immune interaction and uses the example of T-cell subset differentiation to show the previously under-appreciated importance of neuroendocrine influences in the regulation of immune function and, in particular, Th1/Th2 balance and diurnal variation there of.

  14. Surgical Treatment of an Isolated Metastatic Myocardial Neuroendocrine Tumor.

    Science.gov (United States)

    Caldeira, Christiano C B; Sayad, Dany; Strosberg, Jonathan; Faber, Cristiano; Saouma, Samer; Michaud, Tabitha

    2016-02-01

    We describe a patient diagnosed with a neuroendocrine tumor of the small intestine metastatic to the heart who underwent successful cardiac metastasectomy. The tumor was located on the right ventricle free wall, obstructing the right ventricular outflow tract. There was no valvular involvement. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

    NARCIS (Netherlands)

    Halmos, Gyorgy B; van der Laan, Tom P; van Hemel, Bettien M; Dikkers, Frederik G; Slagter-Menkema, Lorian; van der Laan, Bernard F A M; Schuuring, Ed

    The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were

  16. Neuroendocrine Tumour in a Patient with Neurofibromatosis Type 1 ...

    African Journals Online (AJOL)

    We report the case of an HIV-positive female patient with neurofibromatosis type 1 who was treated for recurrent peptic ulcer disease and later developed diabetes mellitus and chronic diarrhoea. A metastasising somatostatinoma was histologically proven and evidence of a concomitant gastrin-producing neuroendocrine ...

  17. Pulmonary response to surface‐coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew

    2011-01-01

    Titanium dioxide nanoparticles (nanoTiO2) are used in various applications including in paints. NanoTiO2 inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface‐coated nanoTiO2...

  18. Tumor thrombosis: a peculiar finding associated with pancreatic neuroendocrine neoplasms. A pictorial essay.

    Science.gov (United States)

    De Robertis, Riccardo; Paiella, Salvatore; Cardobi, Nicolò; Landoni, Luca; Tinazzi Martini, Paolo; Ortolani, Silvia; De Marchi, Giulia; Gobbo, Stefano; Giardino, Alessandro; Butturini, Giovanni; Tortora, Giampaolo; Bassi, Claudio; D'Onofrio, Mirko

    2017-07-04

    While abutment, encasement or vessel occlusion are identified in most patients with a pancreatic tumor, tumor thrombosis is an uncommon finding. In particular, there are no description in the literature of tumor thrombosis associated with ductal adenocarcinoma, the most common pancreatic tumor. On the other hand, surgical series reveal that tumor thrombosis is associated with about 5% of pancreatic neuroendocrine neoplasms (PanNENs), and literature data suggest that this finding is frequently underreported on pre-operative imaging examinations. Tumor thrombosis may be clinically relevant, causing splenoportomesenteric hypertension, possibly responsible for life-threatening upper gastrointestinal bleeding. Bland thrombosis caused by direct infiltration of peri-pancreatic vessels frequently determines surgical unresectability, even in neuroendocrine tumors; on the opposite, tumor thrombosis associated with PanNENs do not exclude surgery per se, even though both morbidity and mortality can be increased by such condition. Considering the favorable prognosis of PanNENs and the frequent need to treat tumor thrombosis in order to prevent complications or to relieve symptoms, it is of paramount importance for radiologists the knowledge of the variety of findings associated with tumor thrombosis in PanNENs.

  19. Effect of salinity on regulation mechanism of neuroendocrine-immunoregulatory network in Litopenaeus vannamei.

    Science.gov (United States)

    Zhao, Qun; Pan, Luqing; Ren, Qin; Wang, Lin; Miao, Jingjing

    2016-02-01

    The effects of low salinity (transferred from 31‰ to 26‰, 21‰, and 16‰) on the regulation pathways of neuroendocrine-immunoregulatory network were investigated in Litopenaeus vannamei. The results showed that the hormones (corticotrophin-releasing hormone, adrenocorticotropic hormone) and biogenic amines (dopamine, noradrenaline, 5-hydroxytryptamine) concentrations in lower salinity groups increased significantly within 12 h. The gene expression of biogenic amine receptors showed that dopamine receptor D4 and α2 adrenergic receptor in lower salinity groups decreased significantly within 12 h, whereas the 5-HT7 receptor significantly increased within 1d. The second messenger synthetases (adenylyl cyclase, phospholipase C) and the second messengers (cyclic adenosine monophosphate, cyclic guanosine monophosphate) of lower salinity groups shared a similar trend in which adenylyl cyclase and cyclic adenosine monophosphate reached the maximum at 12 h, whereas phospholipase C and cyclic guanosine monophosphate reached the minimum. The immune parameters (total hemocyte count, phenoloxidase activity, phagocytic activity, crustin expression, antibacterial activity, C-type lectin expression, hemagglutinating activity) in lower salinity groups decreased significantly within 12 h. Except for the total hemocyte count, all the parameters recovered to the control levels afterwards. Therefore, it may be concluded that the neuroendocrine-immunoregulatory network plays a principal role in adapting to salinity changes as the main center for sensing the stress and causes immune response in L. vannamei. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Risk-averse personalities have a systemically potentiated neuroendocrine stress axis: A multilevel experiment in Parus major.

    Science.gov (United States)

    Baugh, Alexander T; Senft, Rebecca A; Firke, Marian; Lauder, Abigail; Schroeder, Julia; Meddle, Simone L; van Oers, Kees; Hau, Michaela

    2017-07-01

    Hormonal pleiotropy-the simultaneous influence of a single hormone on multiple traits-has been hypothesized as an important mechanism underlying personality, and circulating glucocorticoids are central to this idea. A major gap in our understanding is the neural basis for this link. Here we examine the stability and structure of behavioral, endocrine and neuroendocrine traits in a population of songbirds (Parus major). Upon identifying stable and covarying behavioral and endocrine traits, we test the hypothesis that risk-averse personalities exhibit a neuroendocrine stress axis that is systemically potentiated-characterized by stronger glucocorticoid reactivity and weaker negative feedback. We show high among-individual variation and covariation (i.e. personality) in risk-taking behaviors and demonstrate that four aspects of glucocorticoid physiology (baseline, stress response, negative feedback strength and adrenal sensitivity) are also repeatable and covary. Further, we establish that high expression of mineralocorticoid and low expression of glucocorticoid receptor in the brain are linked with systemically elevated plasma glucocorticoid levels and more risk-averse personalities. Our findings support the hypothesis that steroid hormones can exert pleiotropic effects that organize behavioral phenotypes and provide novel evidence that neuroendocrine factors robustly explain a large fraction of endocrine and personality variation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1 : Results from the DutchMEN1 Study Group

    NARCIS (Netherlands)

    Conemans, Elfi B.; Brosens, Lodewijk A. A.; Raicu-Ionita, Gabriela M.; Pieterman, Carolina R. C.; de Herder, Wouter W.; Dekkers, Olaf M.; Hermus, Ad R.; van der Horst-Schrivers, Anouk N.; Bisschop, Peter H.; Havekes, Bas; Drent, Madeleine L.; Timmers, H. Th Marc; Offerhaus, G. Johan; Valk, Gerlof D.; Vriens, Menno R.

    2017-01-01

    Background: The prognostic value of WHO grade in pancreatic neuroendocrine tumors (PanNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1) is unknown. Methods: We performed a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population with data

  2. Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases

    Directory of Open Access Journals (Sweden)

    Jonathan M. Loree

    2016-01-01

    Full Text Available Background: Management options for pancreatic neuroendocrine tumors (pNETs metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 (90Y microspheres. 90Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with 90Y and chemoembolization; however, the long-term sequelae of 90Y treatment are poorly understood. Case Presentation: We present the case of a 65-year-old Caucasian woman who suffered biliary damage following 90Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of 90Y therapy. Conclusion: This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of 90Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment.

  3. Single-institution experience of radioembolization with yttrium-90 microspheres for unresectable metastatic neuroendocrine liver tumors.

    Science.gov (United States)

    Jia, Zhongzhi; Paz-Fumagalli, Ricardo; Frey, Gregory; Sella, David M; McKinney, J Mark; Wang, Weiping

    2017-09-01

    The aim of this study was to assess the effectiveness of yttrium-90 ((90) Y) microspheres for the treatment of unresectable metastatic liver neuroendocrine tumors (NET). From February 2006 to September 2015, 36 patients (19 male and 17 female, age 63.6 ± 9.4 years) who underwent (90) Y therapy for unresectable liver metastases of NET were included and analyzed retrospectively. All patients received a variety of treatments before (90) Y therapy. The radiological response, symptoms improvement of carcinoid syndrome, tumor marker changes, complications, side effects/toxicity, survival, and factors related to survival were evaluated and analyzed. Of the 36 patients, the mean delivered dose of (90) Y was 1.8 ± 0.7 GBq with a total of 40 treatments. Overall disease control rate was 88.9% (32/36) at 3 months following therapy. In 16 patients with carcinoid syndrome, 15 (93.8%) patients had symptomatic improvement. Tumor marker response (5-hydroxyindoleacetic acid [n = 7] and chromogranin A [n = 13]) at 3 months after treatment were as follows: none (n = 0, 4), partial (n = 6, 7), and complete (n = 1, 2). Radiation-induced gastrointestinal ulcers (n = 2, 5.6%) were identified. Side effects included fatigue (n = 31, 86.1%), anorexia (n = 26, 72.2%), nausea (n = 15, 41.7%), vomiting (n = 14, 38.9%), abdominal pain (n = 10, 27.8%), and fever (n = 8, 22.2%). The mean follow-up was 27.0 ± 16.4 months, with a median survival of 41.0 months. Child-Pugh classification (P = 0.008) and lymph node metastases (P = 0.045) had statistically significant influence on overall survival. Yttrium-90 radioembolization can be effective in the treatment of unresectable liver metastases of NET who failed to respond to other treatments. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  4. Relationship between response to induction chemotherapy and disease control in patients with advanced laryngeal carcinoma included in an organ preservation protocol.

    Science.gov (United States)

    León, Xavier; Valero, Cristina; Rovira, Carlota; Rodriguez, Camilo; López, Montserrat; García-Lorenzo, Jacinto; Quer, Miquel

    2017-06-01

    The aim of the study is to analyze the relationship between the degree of response to induction chemotherapy and the disease control in patients with locally advanced laryngeal carcinomas candidates to total laryngectomy. This retrospective study includes 389 patients with T3-T4 laryngeal tumors candidates to total laryngectomy, diagnosed between 1985 and 2013, treated with induction chemotherapy in an organ preservation protocol. Five-year local recurrence-free survival for patients receiving conservative treatment with radiotherapy after a complete response to induction chemotherapy was 75.4%; for patients with partial response greater than 50%, it was 62.0%; and for patients with the absence of response, it was 32.7%. There were significant differences in local recurrence-free survival and laryngeal dysfunction-free survival according to the response to induction chemotherapy (P = 0.0001) at the expense of patients with absence of response to induction chemotherapy. Patients with partial response greater than 50% treated with radiotherapy had a tendency to have worse local recurrence-free survival and laryngeal dysfunction-free survival than patients with complete response, but the differences did not reach statistical significance. Patients with the absence of response after induction chemotherapy had significant differences in disease-specific survival according to the second treatment: for patients treated with surgery it was 70.2%, whereas for patients treated with radiotherapy, it was 28.2% (P = 0.0001). In patients with the absence of response to induction chemotherapy, conservative treatment with radiotherapy implies a significant decrease in survival.

  5. Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness

    DEFF Research Database (Denmark)

    Eskesen, T G; Wetterslev, M; Perner, A

    2016-01-01

    PURPOSE: Central venous pressure (CVP) has been shown to have poor predictive value for fluid responsiveness in critically ill patients. We aimed to re-evaluate this in a larger sample subgrouped by baseline CVP values. METHODS: In April 2015, we systematically searched and included all clinical...

  6. Pulmonary Neuroendocrine Cell Hyperplasia in Hemoglobin Bart-induced Hydrops Fetalis: A model for Chronic Intrauterine Hypoxia.

    Science.gov (United States)

    Taweevisit, Mana; Theerasantipong, Boochit; Taothong, Kanlaya; Thorner, Paul Scott

    2017-01-01

    The pulmonary neuroendocrine system includes pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) that are distributed throughout respiratory epithelium and regulate lung growth and maturation antenatally. Abnormalities in this system have been linked to many hypoxia-associated pediatric pulmonary disorders. Hemoglobin (Hb) Bart disease is a severe form of α-thalassemia resulting in marked intrauterine hypoxia with hydrops fetalis (HF) and usually death in utero. Affected fetuses can serve as a naturally occurring human model for the effects of intrauterine hypoxia, and we postulated that these effects should include changes in the pulmonary neuroendocrine system. Bombesin immunostaining was used to assess PNECs and NEBs in stillborn fetuses with Hb Bart HF ( n = 16) and with HF from other causes ( n = 14) in comparison to non-HF controls. Hb Bart HF showed a significant increase in the proportion of PNECs in respiratory epithelium ( P = .002), mean number of NEB nuclei ( P = .03), and mean size of NEBs ( P = .002), compared to normal non-HF controls. Significant differences were not observed between HF due to other causes and non-HF controls with normal lungs. Non-HF controls with pulmonary hypoplasia showed significant increases in PNECs compared to HF cases not due to Hb Bart HF, implying HF alone does not cause such increases. In contrast, no significant differences were noted between non-HF controls with pulmonary hypoplasia and Hb Bart cases. Hb Bart HF may provide a useful model for studying the pulmonary neuroendocrine system under chronic intrauterine hypoxia.

  7. Insulinoma and gastrinoma syndromes from a single intrapancreatic neuroendocrine tumor.

    Science.gov (United States)

    Lodish, Maya B; Powell, Anathea C; Abu-Asab, Mones; Cochran, Craig; Lenz, Petra; Libutti, Steven K; Pingpank, James F; Tsokos, Maria; Gorden, Phillip

    2008-04-01

    The insulinoma syndrome is marked by fasting hypoglycemia and inappropriate elevations of insulin. The gastrinoma syndrome is characterized by hypergastrinemia, ulcer disease, and/or diarrhea. Rarely, insulinoma and gastrinoma coexist in the same patient simultaneously. Our objective was to determine the cause of a patient's hypoglycemic episodes and peptic ulcer disease. This is a clinical case report from the Clinical Research Center of the National Institutes of Health. One patient with hypoglycemic episodes and peptic ulcer disease had a surgical resection of neuroendocrine tumor. The patient was found to have a single tumor cosecreting both insulin and gastrin. Resection of this single tumor was curative. A single pancreatic neuroendocrine tumor may lead to the expression of both the hyperinsulinemic and hypergastrinemic syndromes.

  8. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Josef Zihl

    2015-05-01

    Full Text Available Endocrine dysfunction is a common effect of traumatic brain injury (TBI. In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

  9. Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment.

  10. Contemporary Incidence and Mortality Rates of Neuroendocrine Prostate Cancer.

    Science.gov (United States)

    Alanee, Shaheen; Moore, Aaron; Nutt, Max; Holland, Bradley; Dynda, Danuta; El-Zawahry, Ahmed; McVary, Kevin T

    2015-07-01

    The purpose of the study was to provide an update ever the incidence and mortality for neuroendocrine prostate cancer (NEPC) in the United States. Using a large national database, we examined changes in age-adjusted incidence (AAIR), mortality rates (MR) and 5-year cancer-specific survival (CSS) for 378 patients diagnosed with NEPC between 1992 and 2011. Analysis was performed for all NEPC and for its two major sub-groups [small cell carcinoma (SCC) and neuroendocrine carcinoma (NEC)]. AAIR of NEPC continues to rise in recent years (2004-2011:+6.8%/year, p>0.05). AAIR of SCC has been increasing significantly by 6.94%/year since 2001 (from 0.470 to 0.582/1,000,000 person years, pAAIR of SCC is increasing with no change in the MR of NEPC over the past 20 years. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Effects in dogs with behavioural disorders of a commercial nutraceutical diet on stress and neuroendocrine parameters.

    Science.gov (United States)

    Sechi, S; Di Cerbo, A; Canello, S; Guidetti, G; Chiavolelli, F; Fiore, F; Cocco, R

    2017-01-07

    The well-being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioural disorders including fear, hyperactivity and anxiety, followed by negative affective moods and poor welfare. This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioural disorders related to anxiety and chronic stress. They were fed a control diet or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, β-endorphins, noradrenaline and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP)) parameters related to behavioural disorders were evaluated at the beginning and end of the study period. Results showed a significant increase in serotonin, dopamine and β-endorphins plasma concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neuroendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and nutraceuticals in the treatment of behavioural disorders. British Veterinary Association.

  12. Neuroendocrine Disturbances after Brain Damage: An Important and Often Undiagnosed Disorder

    Directory of Open Access Journals (Sweden)

    Fatih Tanriverdi

    2015-04-01

    Full Text Available Traumatic brain injury (TBI is a common and significant public health problem all over the world. Until recently, TBI has been recognized as an uncommon cause of hypopituitarism. The studies conducted during the last 15 years revealed that TBI is a serious cause of hypopituitarism. Although the underlying pathophysiology has not yet been fully clarified, new data indicate that genetic predisposition, autoimmunity and neuroinflammatory changes may play a role in the development of hypopituitarism. Combative sports, including boxing and kickboxing, both of which are characterized by chronic repetitive head trauma, have been shown as new causes of neuroendocrine abnormalities, mainly hypopituitarism, for the first time during the last 10 years. Most patients with TBI-induced pituitary dysfunction remain undiagnosed and untreated because of the non-specific and subtle clinical manifestations of hypopituitarism. Replacement of the deficient hormones, of which GH is the commonest hormone lost, may not only reverse the clinical manifestations and neurocognitive dysfunction, but may also help posttraumatic disabled patients resistant to classical treatment who have undiagnosed hypopituitarism and GH deficiency in particular. Therefore, early diagnosis, which depends on the awareness of TBI as a cause of neuroendocrine abnormalities among the medical community, is crucially important.

  13. Neuroendocrine differentiated breast carcinoma: imaging features correlated with clinical and histopathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Guenhan-Bilgen, Isil; Ustuen, Esin Emin; Memis, Aysenur [Department of Radiology, Ege University Hospital, Bornova, 35100 Izmir (Turkey); Zekioglu, Osman; Erhan, Yildiz [Department of Pathology, Ege University Hospital, Bornova, 35100 Izmir (Turkey)

    2003-04-01

    The aim of this study was to describe the imaging features of neuroendocrine differentiated breast carcinoma (NEDBC) and to correlate the radiological findings with the clinical and histopathological findings. A retrospective review of the mammograms of 1845 histopathologically proven breast cancer cases revealed five NEDBC. The clinical, imaging, and histopathological findings were analyzed. On mammography, a high-density mass was seen in all patients. The shape of the mass was round in 4 and irregular in 1 patient. The margins were spiculated in 2, indistinct in 1, microlobulated in 1, and partially obscured in 1 patient. On sonography, 4 patients had homogeneously hypoechoic masses with normal sound transmission. In 1 patient the mass was heterogeneously hypoechoic with mild posterior acoustic enhancement. The margins were microlobulated in 2, irregular in 2, and well-circumscribed in 1 patient. Neuroendocrine differentiated breast carcinoma should be included in the differential diagnosis of mammographically dense, round masses with predominantly spiculated or lobulated margins. Sonographically, they mostly present as irregular or microlobulated, homogeneously hypoechoic masses with normal sound transmission. (orig.)

  14. Massive gastrointestinal bleed due to multiple gastric neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Vishal Sharma

    2015-01-01

    Full Text Available Gastric neuroendocrine tumors (G-NETs are uncommon lesions which are usually diagnosed on histological evaluation of gastric polyps. These may occur sporadically or due to hypergastrinemia in the setting of atrophic gastritis or Zollinger-Ellison Syndrome. Large lesions may ulcerate and result in gastrointestinal bleeding. However, massive gastrointestinal bleeding is rare in patients with NETs. We report a 60-year-old lady who presented with massive gastrointestinal bleeding due to multiple G-NETs.

  15. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed M Ragab Shalaby

    2016-01-01

    Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

  16. A Neuroendocrine Carcinoma of Undetermined Origin in a Dog

    OpenAIRE

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-01-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-l...

  17. Improved Benefit of SPECT/CT Compared to SPECT Alone for the Accurate Localization of Endocrine and Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Gonca G. Bural

    2012-12-01

    Full Text Available Objective: To assess the clinical utility of SPECT/ CT in subjects with endocrine and neuroendocrine tumors compared to SPECT alone. Material and Methods: 48 subjects (31 women;17 men; mean age 54±11 with clinical suspicion or diagnosis of endocrine and neuroendocrine tumor had 50 SPECT/CT scans (32 Tc-99m MIBI, 5 post treatment I-131, 8 In-111 Pentetreotide, and 5 I-123 MIBG. SPECT alone findings were compared to SPECT/CT and to pathology or radiological follow up. Results: From the 32 Tc-99m MIBI scans, SPECT accurately localized the lesion in 22 positive subjects while SPECT/CT did in 31 subjects. Parathyroid lesions not seen on SPECT alone were smaller than 10 mm. In five post treatment I-131 scans, SPECT alone neither characterized, nor localized any lesions accurately. SPECT/CT revealed 3 benign etiologies, a metastatic lymph node, and one equivocal lesion. In 8 In-111 Pentetreotide scans, SPECT alone could not localize primary or metastatic lesions in 6 subjects all of which were localized with SPECT/CT. In five I-123 MIBG scans, SPECT alone could not detect a 1.1 cm adrenal lesion or correctly characterize normal physiologic adrenal uptake in consecutive scans of the same patient with prior history of adrenelectomy, all of which were correctly localized and characterized with SPECT/CT. Conclusion: SPECT/CT is superior to SPECT alone in the assessment of endocrine and neuroendocrine tumors. It is better in lesion localization and lesion characterization leading to a decrease in the number of equivocal findings. SPECT/CT should be included in the clinical work up of all patients with diagnosis or suspicion of endocrine and neuroendocrine tumors. (MIRT 2012;21:91-96

  18. Neuroendocrine stimulatory tests of hypothalamus-pituitary-adrenal axis in psoriasis and correlative implications with psychopathological and immune parameters.

    Science.gov (United States)

    Karanikas, Evangelos; Harsoulis, Faidon; Giouzepas, Ioannis; Griveas, Ioannis; Chrisomallis, Fotios

    2009-01-01

    Psoriasis constitutes one of the most representative examples of psychosomatic disorders. The published work investigating the psychological parameters and the way they interact during the course of the disease is extensive, whereas only a few studies have focused on the neuroendocrine framework of psoriasis. In the present study, the objective was to investigate the neuroendocrine parameters of psoriasis and the way they interact with psychopathological and immune variables. Patients with psoriasis (n=24) and the same number of matched healthy controls underwent psychiatric evaluation with interviews and psychometric questionnaires. Both of the groups underwent the corticotropin-releasing hormone (CRH) test and the dexamethasone suppression test (DST) to investigate functional parameters of the hypothalamus-pituitary-adrenal (HPA) axis. The evaluation of immune variables included the estimation of the distribution of T-cell and natural killer lymphocytes. Levels of depressive and anxiety features were increased within subjects with psoriasis and they were significantly correlated with stressful life events and the extent of the disease. The adrenocorticotrophic hormone and cortisol levels increased after CRH infusion without significant differences between the two groups and the psoriatic subjects' cortisol suppression after DST was within normal range, though relatively blunted. No significant correlations were identified among neuroendocrine, psychopathological and immune parameters. No particular neuroendocrine profile has been identified among psoriatic patients and the hypothesized interaction with psychopathological and immune parameters was not replicated. Nevertheless, it is still premature to exclude the possibility that a subtle latent alteration of the HPA axis function might exist, in psoriasis, either stemming from the psychopathology or from the disease per se.

  19. Small neuroendocrine tumor of the duodenal bulb: Endoscopic submucosal dissection, laparoscopic and endoscopic cooperative surgery or surgery?

    Directory of Open Access Journals (Sweden)

    Nikolaos V Chrysanthos

    2016-01-01

    Full Text Available Neuroendocrine neoplasms of the gastric tube are less common than adenocarcinomas. Topography includes stomach, small intestine, Vater ampulla, and gross intestine. They are graded as neuroendocrine tumors grade I and II (NETs GI and GII and neuroendocrine carcinomas GIII based on Ki-67 index and mitotic count. [1] Endoscopic treatment for GI NETs ≤1 cm that does not extend beyond the submucosal layer and does not demonstrate lymph node metastasis is recommended. Tumors ≥2 cm, with lymph node metastasis, are indicated for surgical treatment. The treatment strategy for tumors between 10 and 20 mm in size remains controversial. [2] We present a rare case of a 60-year-old male patient with end-stage renal failure who underwent a screening pretransplantation endoscopic control. Colonoscopy had no pathological findings. Gastroscopy reveals an abnormal mucosa in the anterior upper part of the duodenal bulb that was described as a micronodular mucosa and a central nodule of 6 mm with erythematous mucosa. Histology of the micronodular mucosa reveals a heterotopic gastric mucosa and a small hyperplastic polyp. Biopsies from the nodule reveal a carcinoid tumor (NET GI. Immunohistochemistry: Positive chromogranin levels, low mitotic index (1/10 HPF, and Ki-67 index 2 cm and those of the duodenal bulb with histological extensions and the lack of assessing depth invasion.

  20. Endoscopic treatment of sporadic small duodenal and ampullary neuroendocrine tumors.

    Science.gov (United States)

    Gincul, Rodica; Ponchon, Thierry; Napoleon, Bertrand; Scoazec, Jean-Yves; Guillaud, Olivier; Saurin, Jean-Christophe; Ciocirlan, Mihai; Lepilliez, Vincent; Pioche, Mathieu; Lefort, Christine; Adham, Mustapha; Pialat, Jean; Chayvialle, Jean-Alain; Walter, Thomas

    2016-11-01

    Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment of duodenal NETs. Patients and methods: We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs < 20 mm were included. Treatment consisted of endoscopic mucosal resection in 19 cases, and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15 cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All NETs were well differentiated. A total of 27 lesions were classified as grade 1 and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions, respectively. Three R1 patients underwent additional surgical treatment, with no residual tumor on the surgical specimen but with positive metastatic lymph nodes in two cases. One patient was lost to follow-up. Finally, 24 patients were included in the follow-up analysis. The median follow-up period was 56 months (range 6 - 175 months). Two patients presented a tumor recurrence during the follow-up period. Conclusions: Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk. © Georg Thieme Verlag KG Stuttgart · New York.

  1. A neuroendocrine carcinoma of undetermined origin in a dog.

    Science.gov (United States)

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-09-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-like structures. Scattered small necrotic foci and invasion to fibrous septa were typically observed. Neoplastic cells showed round to oval-shaped nuclei with prominent nucleoli and abundant eosinophilic cytoplasm that were positive for Grimelius' silver impregnation staining and immunostaining with cytokeratin, synaptophysin, vasoactive intestinal peptide and chromogranin A, indicative of the development of a neuroendocrine carcinoma. However, judging from the distribution of tumors lacking the portion suggestive of the primary site in any organ examined, as well as no further indication of differentiation potential of neoplastic cells, this tumor has so far been diagnosed as neuroendocrine carcinoma of undetermined origin.

  2. Mucinous Carcinoma with Neuroendocrine Differentiation of Salivary Gland Origin.

    Science.gov (United States)

    Wong, Frankie K; Zumsteg, Zachary S; Langevin, Claude-Jean; Ali, Nabilah; Maclary, Shawn; Balzer, Bonnie L; Ho, Allen S

    2017-06-01

    Primary mucinous adenocarcinomas of the salivary gland are rare malignancies defined by aggregates of epithelial cells suspended in large pools of extracellular mucin. We report a case of a giant mucinous adenocarcinoma of salivary gland origin, with low-grade cytoarchitectural features and neuroendocrine differentiation arising in the submental region. Grossly, the tumor measured 12.5 × 13.4 × 8.2 cm and replaced the bone and soft tissues of the anterior oral cavity. Microscopically, the neoplasm was composed of large extracellular pools of mucin, which contained papillary and acinar aggregates, and small nodules of ductal type epithelium with minimal nuclear enlargement, powdery chromatin and little pleomorphism. The nodules comprised 20 % of the tumor and showed morphologic and immunohistochemical evidence of neuroendocrine differentiation. Examination revealed histologic features comparable to mammary gland analogues in mucin predominance, ductal type morphology, expression of estrogen and progesterone receptors, and GATA-3 positivity. This is the first case reported of mucin-rich carcinoma of salivary gland origin exhibiting neuroendocrine differentiation.

  3. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

  4. Genetic strain differences in learned fear inhibition associated with variation in neuroendocrine, autonomic, and amygdala dendritic phenotypes.

    Science.gov (United States)

    Camp, Marguerite C; Macpherson, Kathryn P; Lederle, Lauren; Graybeal, Carolyn; Gaburro, Stefano; Debrouse, Lauren M; Ihne, Jessica L; Bravo, Javier A; O'Connor, Richard M; Ciocchi, Stephane; Wellman, Cara L; Lüthi, Andreas; Cryan, John F; Singewald, Nicolas; Holmes, Andrew

    2012-05-01

    Mood and anxiety disorders develop in some but not all individuals following exposure to stress and psychological trauma. However, the factors underlying individual differences in risk and resilience for these disorders, including genetic variation, remain to be determined. Isogenic inbred mouse strains provide a valuable approach to elucidating these factors. Here, we performed a comprehensive examination of the extinction-impaired 129S1/SvImJ (S1) inbred mouse strain for multiple behavioral, autonomic, neuroendocrine, and corticolimbic neuronal morphology phenotypes. We found that S1 exhibited fear overgeneralization to ambiguous contexts and cues, impaired context extinction and impaired safety learning, relative to the (good-extinguishing) C57BL/6J (B6) strain. Fear overgeneralization and impaired extinction was rescued by treatment with the front-line anxiety medication fluoxetine. Telemetric measurement of electrocardiogram signals demonstrated autonomic disturbances in S1 including poor recovery of fear-induced suppression of heart rate variability. S1 with a history of chronic restraint stress displayed an attenuated corticosterone (CORT) response to a novel, swim stressor. Conversely, previously stress-naive S1 showed exaggerated CORT responses to acute restraint stress or extinction training, insensitivity to dexamethasone challenge, and reduced hippocampal CA3 glucocorticoid receptor mRNA, suggesting downregulation of negative feedback control of the hypothalamic-pituitary-adrenal axis. Analysis of neuronal morphology in key neural nodes within the fear and extinction circuit revealed enlarged dendritic arbors in basolateral amygdala neurons in S1, but normal infralimbic cortex and prelimbic cortex dendritic arborization. Collectively, these data provide convergent support for the utility of the S1 strain as a tractable model for elucidating the neural, molecular and genetic basis of persistent, excessive fear.

  5. Temozolomide as second or third line treatment of patients with neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Sørensen, Jens B; Federspiel, Birgitte

    2012-01-01

    Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results....

  6. Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13.

    Directory of Open Access Journals (Sweden)

    Amy B Hart

    Full Text Available Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943 in the 8(th intron of cadherin 13 (CDH13; P = 4.58×10(-8, a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402 in the 1(st intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10(-7, a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses.

  7. Effect of antidepressants on neuroendocrine axis in humans.

    Science.gov (United States)

    Meltzer, H Y; Fang, V S; Tricou, B J; Robertson, A

    1982-01-01

    Unlike neuroleptic drugs, the effect of antidepressant drugs on the neuroendocrine axis in man is highly variable and may or may not be intimately related to their antidepressant action. However, the limited neuroendocrine data available does shed some light on the mechanism of action of these agents and raises some important questions, particularly about the regulation of PRL secretion and the interaction between various neurotransmitter systems. At one end of the spectrum, the ability of nomifensine and buproprion to lower serum PRL levels, presumably due to their ability to block the reuptake of DA by tuberoinfundibular DA neurons, suggests that it may be necessary to reconsider the conclusion that these neurons lack a DA reuptake mechanism or that these two agents are antidepressant by virtue of their ability to block DA uptake. Similarly, the inability of amphetamine or methylphenidate to decrease serum PRL levels in man suggests important differences between the tuberoinfundibular DA neurons in man and the rat. These findings also call into question the ability of these agents to block DA uptake or increase DA release in the tuberoinfundibular DA neurons. The finding that fluoxetine raises serum PRL levels, even in one subject, whereas zimelidine has not yet been shown to do so, and that fluoxetine does not potentiate the ability of 5-HTP to stimulate PRL secretion, has raised important questions about the role of 5-HT in PRL and GH regulation in man and the relationship between 5-HT and DA neurons in man. The occasional increase in serum PRL levels found in patients treated with lithium or the MAO inhibitor phenelzine are suggestive of important interindividual differences which may be revealed by neuroendocrine studies, differences which could be valuable in understanding the mechanism of action of these agents - e.g., does lithium decrease DA receptor sensitivity? - and fundamental aspects of neuroendocrine regulation - e.g., do the MAO inhibitors

  8. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    Directory of Open Access Journals (Sweden)

    Ciuffreda Libero

    2009-11-01

    Full Text Available Abstract Background Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU infusion plus long-acting release (LAR octreotide in patients with neuroendocrine carcinoma. Methods Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily plus LAR octreotide (20 mg monthly. Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Results Assessment by Response Evaluation Criteria in Solid Tumors (RECIST criteria showed partial response in 7 (24.1%, stable disease in 20 (69.0%, and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A response was observed in 12/25 assessable patients (48.0%; symptom relief was obtained in 9/15 symptomatic patients (60.0%. There was non significant decrease in circulating vascular epithelial growth factor (VEGF over time. Median time to progression was 22.6 months (range, 2.7-68.5; median overall survival was not reached yet. Toxicity was mild and manageable. Conclusion Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. Trial registration NCT00953394

  9. Exercise improves physical and psychological quality of life in people with depression: A meta-analysis including the evaluation of control group response.

    Science.gov (United States)

    Schuch, Felipe B; Vancampfort, Davy; Rosenbaum, Simon; Richards, Justin; Ward, Philip B; Stubbs, Brendon

    2016-07-30

    Exercise has established efficacy as an antidepressant in people with depression. However, few meta-analyses have assessed the effects of exercise across different domains of Quality of Life (QoL) in people with depression. Furthermore, there has been no previous meta-analysis of control group response in relation to QoL in exercise trials for depression. Randomized Clinical Trials(RCTs) were initially identified from a Cochrane review, and those including QoL assessments were included in the analysis. Search of major electronic databases were conducted to identify RCTs that compared the exercise effects on QoL versus control condition in people with depression. A random effects meta-analysis was employed to evaluate the Standardized Mean Difference (SMD). Six RCTs were included. Exercise significantly improved physical and psychological domains and overall QoL. Effects on social relationship and environment domains were not significant. No significant control group response was found for any domain or overall QoL. Exercise can be considered as a therapeutic strategy to improve physical and psychological domains and overall QoL of people with depression, with no effect evident across the social and environmental domains. The lack of improvement among control groups reinforces the role of exercise as a treatment for depression with benefits to QoL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3)

    DEFF Research Database (Denmark)

    Sorbye, H; Welin, S; Langer, S W

    2013-01-01

    Background As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Patients and methods Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively ...... registered at 12 Nordic hospitals. Results The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67 ...

  11. A water-based training program that include perturbation exercises to improve stepping responses in older adults: study protocol for a randomized controlled cross-over trial

    Directory of Open Access Journals (Sweden)

    Tsedek Irit

    2008-08-01

    Full Text Available Abstract Background Gait and balance impairments may increase the risk of falls, the leading cause of accidental death in the elderly population. Fall-related injuries constitute a serious public health problem associated with high costs for society as well as human suffering. A rapid step is the most important protective postural strategy, acting to recover equilibrium and prevent a fall from initiating. It can arise from large perturbations, but also frequently as a consequence of volitional movements. We propose to use a novel water-based training program which includes specific perturbation exercises that will target the stepping responses that could potentially have a profound effect in reducing risk of falling. We describe the water-based balance training program and a study protocol to evaluate its efficacy (Trial registration number #NCT00708136. Methods/Design The proposed water-based training program involves use of unpredictable, multi-directional perturbations in a group setting to evoke compensatory and volitional stepping responses. Perturbations are made by pushing slightly the subjects and by water turbulence, in 24 training sessions conducted over 12 weeks. Concurrent cognitive tasks during movement tasks are included. Principles of physical training and exercise including awareness, continuity, motivation, overload, periodicity, progression and specificity were used in the development of this novel program. Specific goals are to increase the speed of stepping responses and improve the postural control mechanism and physical functioning. A prospective, randomized, cross-over trial with concealed allocation, assessor blinding and intention-to-treat analysis will be performed to evaluate the efficacy of the water-based training program. A total of 36 community-dwelling adults (age 65–88 with no recent history of instability or falling will be assigned to either the perturbation-based training or a control group (no training

  12. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    Science.gov (United States)

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  13. Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism.

    Science.gov (United States)

    Silverman, J L; Yang, M; Turner, S M; Katz, A M; Bell, D B; Koenig, J I; Crawley, J N

    2010-12-29

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and

  14. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

    DEFF Research Database (Denmark)

    Janson, Eva Tiensuu; Sorbye, Halfdan; Welin, Staffan

    2014-01-01

    BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine...

  15. Neuroendocrine dysregulations in sexually abused children and adolescents: a systematic review

    NARCIS (Netherlands)

    Bicanic, I. A. E.; Meijer, M.; Sinnema, G.; van de Putte, E. M.; Olff, M.

    2008-01-01

    Several studies provided evidence for neuroendocrine dysregulations in adults with a history of child sexual abuse. This review focuses on neuroendocrine studies in sexually abused children and adolescents, dating from January 1, 1990 to January 1, 2007 and obtained from a systematic Medline Indexed

  16. Tracer development for detection and characterization of neuroendocrine tumors with PET

    NARCIS (Netherlands)

    Neels, Olivier Christiaan

    2008-01-01

    Neuroendocrine tumors are slowly growing tumors which originate from neuroendocrine cells. These tumors can secrete several products. In case of overproduction of serotonin, symptoms such as flushing, diarrhea and right-sided heart disease can occur. Next to serotonin, other well known products are

  17. Neuroendocrine reactivity and recovery from work with different physical and mental demands

    NARCIS (Netherlands)

    Sluiter, JK; Frings-Dresen, MHW; van der Beek, AJ; Meijman, TF; Heisterkamp, SH

    Objectives The purpose of this study was to examine the extent to which the type or nature (physical, mental or mixed mental and physical) of work and work characteristics is related to the course of neuroendocrine reactivity and recovery from work. Methods Neuroendocrine reactivity and recovery

  18. Nrf2 regulates the inflammatory response, including heme oxygenase-1 induction, by mycoplasma pneumoniae lipid-associated membrane proteins in THP-1 cells.

    Science.gov (United States)

    Hu, Jihong; Chen, Chunyan; Ou, Guangli; You, Xiaoxing; Tan, Tianping; Hu, Xinnian; Zeng, Yihua; Yu, Minjun; Zhu, Cuiming

    2017-06-01

    A series of inflammatory responses caused by Mycoplasma pneumoniae largely depend on the lipid-associated membrane proteins (LAMPs). Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, is considered to be a critical modulator of inflammatory responses and cellular redox homeostasis. Monocytes play an important role in the invasion and immunity to resist pathogens. Here, we investigated the role of Nrf2 in the anti-inflammatory response stimulated by LAMPs using the human monocyte cell line THP-1. LAMPs were shown to affect the localization of Nrf2, and the levels of reactive oxygen species and inflammatory reactants, including nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines (IL-6, IL-8), were highly elevated in LAMP-stimulated Nrf2-silenced THP-1 cells. Moreover, LAMPs induced the levels of mRNA and the expression of heme oxygenase-1 (HO-1). In summary, our results demonstrated that LAMPs cause nuclear translocation of Nrf2, which further suppresses the expression of inflammatory reactants in THP-1 cells. © Crown copyright 2017.

  19. Neuroendocrine regulation of salt and water metabolism

    Directory of Open Access Journals (Sweden)

    S.M. McCann

    1997-04-01

    Full Text Available Neurons which release atrial natriuretic peptide (ANPergic neurons have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stress-induced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypothalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart to slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume

  20. Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2015-11-15

    Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

  1. Treatment of pancreatic neuroendocrine tumor with liver metastases

    Directory of Open Access Journals (Sweden)

    LI Zhao

    2015-05-01

    Full Text Available Pancreatic neuroendocrine tumor (pNET is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is still the optimal treatment for resectable, well-differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis.

  2. Mucinous Carcinoma with Neuroendocrine Differentiation of Salivary Gland Origin

    OpenAIRE

    Wong, Frankie K.; Zumsteg, Zachary S.; Langevin, Claude-Jean; Ali, Nabilah; Maclary, Shawn; Balzer, Bonnie L.; Ho, Allen S.

    2016-01-01

    Primary mucinous adenocarcinomas of the salivary gland are rare malignancies defined by aggregates of epithelial cells suspended in large pools of extracellular mucin. We report a case of a giant mucinous adenocarcinoma of salivary gland origin, with low-grade cytoarchitectural features and neuroendocrine differentiation arising in the submental region. Grossly, the tumor measured 12.5 × 13.4 × 8.2 cm and replaced the bone and soft tissues of the anterior oral cavity. Microscopically, the neo...

  3. Role of brainstem TRH/TRH-R1 receptors in the vagal gastric cholinergic response to various stimuli including sham-feeding.

    Science.gov (United States)

    Taché, Y; Yang, H; Miampamba, M; Martinez, V; Yuan, P Q

    2006-04-30

    Pavlov's pioneering work established that sham-feeding induced by sight or smell of food or feeding in dogs with permanent esophagostomy stimulates gastric acid secretion through vagal pathways. Brain circuitries and transmitters involved in the central vagal regulation of gastric function have recently been unraveled. Neurons in the dorsal vagal complex including the dorsal motor nucleus of the vagus (DMN) express thyrotropin-releasing hormone (TRH) receptor and are innervated by TRH fibers originating from TRH synthesizing neurons in the raphe pallidus, raphe obscurus and the parapyramidal regions. TRH injected into the DMN or cisterna magna increases the firing of DMN neurons and gastric vagal efferent discharge, activates cholinergic neurons in gastric submucosal and myenteric plexuses, and induces a vagal-dependent, atropine-sensitive stimulation of gastric secretory (acid, pepsin) and motor functions. TRH antibody or TRH-R1 receptor oligodeoxynucleotide antisense pretreatment in the cisterna magna or DMN abolished vagal-dependent gastric secretory and motor responses to sham-feeding, 2-deoxy-D-glucose, cold exposure and chemical activation of cell bodies in medullary raphe nuclei. TRH excitatory action in the DMN is potentiated by co-released prepro-TRH-(160-169) flanking peptide, Ps4 and 5-HT, and inhibited by a number of peptides involved in the stress/immune response and inhibition of food-intake. These neuroanatomical, electrophysiological and neuropharmacological data are consistent with a physiological role of brainstem TRH in the central vagal stimulation of gastric myenteric cholinergic neurons in response to several vagal dependent stimuli including sham-feeding.

  4. Neuro-endocrine disruption in molluscs

    DEFF Research Database (Denmark)

    Holbech, Henrik; Bech Sanderhoff, Lene; Waller, Stine P.

    The Mollusca phylum is the second largest animal phylum with around 85,000 registered mollusc species and increasing attention to effects of chemicals on the molluscan endocrine system have been given during the last years. This includes initiation of the development of OECD test guidelines (TG......) to assess the effect of chemicals in molluscs. To date no endocrine specific mollusc biomarkers have though been validated and included in draft test guidelines due to lack of knowledge of the endocrine system. Here we investigate effects of pharmaceuticals targeting serotonin and dopamine in a cost...... efficient and fast in vivo system using embryos of the freshwater pulmonate gastropod Lymnaea stagnalis (the great pond snail). It is known that serotonin and dopamine are involved in many reproductive processes in molluscs Incl. egg maturation and spawning and that pedal ciliary activity causing L...

  5. Neuroendocrine regulation of somatic growth in fishes.

    Science.gov (United States)

    Dai, XiangYan; Zhang, Wei; Zhuo, ZiJian; He, JiangYan; Yin, Zhan

    2015-02-01

    Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

  6. Psychoneuroendocrine research in depression. I. Hormone levels of different neuroendocrine axes and the dexamethasone suppression test.

    Science.gov (United States)

    Rupprecht, R; Lesch, K P

    1989-01-01

    Psychoneuroendocrinology is of major importance in the biological research of depression. Most studies have focussed on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis but other endocrine systems such as the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-somatotropic (HPS), and the hypothalamic-pituitary-gonadal (HPG) axis have also been shown to be involved in the psychobiology of depression. There are close interrelations between various endocrine axes which possibly are affected during depressive illness. A variety of neuroendocrine abnormalities has been detected in depressive disorder but the pathophysiology of these derangements remains still unclear. Although the currently used neuroendocrine tests are not of diagnostic validity they may help to clarify the pathophysiological significance of the complex regulatory mechanisms of different neuroendocrine axes in affective disorders. Neuroendocrine regulation is determined both by peripheral and central mechanisms which both have to be adequately considered as well as potent interactions between various endocrine systems in further neuroendocrine depression research.

  7. Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome

    OpenAIRE

    Naik, Chinna; Basu, Sandip

    2017-01-01

    Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also gi...

  8. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia diagnosed by tranbronchoscopic cryoprobe biopsy technique

    Science.gov (United States)

    Patel, Ravi; Collazo‐Gonzalez, Carolina; Johnson, Jean; Rumbak, Mark; Smith, Maxwell

    2017-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) remains a poorly understood clinical entity. It is currently classified as a premalignant condition by the World Health Organization (WHO). Symptoms are similar to those associated with obstructive lung disease, including breathlessness and cough. The presentation is often initially ascribed to other diseases such as asthma or chronic obstructive pulmonary disease. Here, we present what we believe is the first described case of DIPNECH diagnosed by transbronchoscopic cryoprobe biopsy. The patient presented with chronic cough, dyspnoea, pulmonary function tests consistent with obstruction, and a computed tomography (CT) scan of chest with multiple nodules. The patient went on to have transbronchoscopic cryoprobe biopsies of the lung, which confirmed the diagnosis of DIPNECH. PMID:29026608

  9. Neuroendocrine Cell Carcinoma of Unknown Primary Arising in Long Standing History of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stergios Boussios

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease that targets myelinated axons in the central nervous system (CNS. Cancer of unknown primary site (CUP is a well-recognised clinical disorder, accounting for 3–5% of all malignant epithelial tumors. CUP is clinically characterised as an aggressive disease with early dissemination. Studies of cancer risk in MS patients have shown inconsistent findings. An increased risk of malignancy in patients with MS has been suggested, but recently serious questions have been raised regarding this association. Use of disease-modifying therapies might contribute to an increased cancer risk in selected MS patients. The concurrence of MS and CUP is exceptionally rare. Here we describe the case of a neuroendocrine carcinoma of unknown primary diagnosed in a male patient with a nine-year history of MS. The discussion includes data from all available population-based register studies with estimates of certain malignancies in patients with MS.

  10. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

    DEFF Research Database (Denmark)

    Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S

    2015-01-01

    Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery...... to the post-bariatric surgery hypoglycemia patient. LEARNING POINTS: pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric...... (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach...

  11. Subordination stress: behavioral, brain, and neuroendocrine correlates.

    Science.gov (United States)

    Blanchard, D C; Sakai, R R; McEwen, B; Weiss, S M; Blanchard, R J

    1993-12-20

    In mixed-sex rat groups consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males can be differentiated from dominants on the basis of both agonistic and non-agonistic behaviors, wound patterns, weight changes. Their behavior changes suggest chronic defensiveness and are also broadly isomorphic to many of the symptoms of depression; their voluntary alcohol consumption increases, and their life-spans are shortened. Both subordinate and dominant males tend to show organ change compared to non-grouped controls, with adrenal and spleen enlargement and thymus reduction. However, these changes appear to be more marked in subordinates, and only subordinates show reduced testes weights. Basal corticosterone (CORT) levels were sharply higher, and plasma testosterone (T) sharply lower, in subordinates compared to both dominants and controls, and reduced corticosterone binding globulin further enhanced free CORT for subordinates particularly. Many subordinates failed to show a normal CORT response to restraint stress. Subordinates also appear to show widespread changes in serotonin systems, with increased 5-HIAA/5-HT ratios in a number of brain areas, and alterations of 5-HT1A receptor binding at some sites. These changes suggest that subordination, a common and consistent feature of life for many animals living in social groups, may be a particularly relevant model for investigating the behavioral, neural and endocrine correlates of chronic stress.

  12. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. © 2016 Society for Endocrinology.

  13. Meta-iodobenzyl guanidine for detection and staging of neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pryma, Daniel [Nuclear Medicine and Clinical Molecular Imaging Division, University of Pennsylvania, Philadelphia, PA 19105 (United States); Divgi, Chaitanya [Nuclear Medicine and Clinical Molecular Imaging Division, University of Pennsylvania, Philadelphia, PA 19105 (United States)], E-mail: chaitanya.divgi@uphs.upenn.edu

    2008-08-15

    Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are slow-growing neoplasms that arise from the neuroendocrine system of the gastrointestinal tract and pancreas. These may be classified based on location into the following: pheochromocytomas and parangangliomas; carcinoids; and pancreatic endocrine tumors. The majority of these tumors are nonfunctional, and thus, molecular imaging methods are critical in detection and staging of disease. Meta-iodobenzyl guanidine (MIBG) is a norepinephrine analog taken up by norepinephrine transporters that are overexpressed in the majority of GEP-NET. Radioactive MIBG can be used to image GEP-NET. The isotopes suitable for imaging include iodine-123 and iodine-131, using single-photon cameras, and iodine-124, using positron emission tomography (PET). Imaging is usually carried out a day or more after administration of the radiotracer, and serial and tomographic imaging may be necessary for optimal delineation. MIBG imaging is more useful for detecting pheochromocytoma, with reported accuracies greater than 80%, than for detecting carcinoid tumors, where the accuracy has been {approx}70% and is reportedly higher in mid-gut tumors. MIBG imaging has been invaluable in the accurate staging of children with neuroblastoma, a lethal childhood tumor of the sympathetic nervous system. An important application of MIBG imaging is to demonstrate targeting of therapeutic I-131 MIBG. Imaging is thus useful in the detection of disease as well as in the demonstration of adequate targeting for therapy - either qualitatively or quantitatively with dosimetry. The latter will probably be feasible with PET using isotopes like iodine-124, and perhaps with single photon emission computed tomography/computed tomography. Imaging with MIBG will continue to be the mainstay for detection and staging of GEP-NET. More importantly, perhaps, imaging with MIBG will form part of an imaging continuum, including assessment of glycolytic rate and somatostatin

  14. Reproductive neuroendocrine pathways of social behavior

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    Ishwar eParhar

    2016-03-01

    Full Text Available Social behaviors are key components of reproduction because they are essential for successful fertilization. Social behaviors such as courtship, mating, and aggression are strongly associated with sex steroids, such as testosterone, estradiol and progesterone. Secretion of sex steroids from the gonads is regulated by the hypothalamus-pituitary-gonadal (HPG axis in vertebrates. Gonadotropin-releasing hormone (GnRH is a pivotal hypothalamic neuropeptide that stimulates gonadotropin release from the pituitary. In recent years, the role of neuropeptides containing the C-terminal Arg-Phe-NH2 (RFamide peptides has been emphasized in vertebrate reproduction. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH, emerged as critical accelerator and suppressor of gonadotropin secretion. Kisspeptin stimulates GnRH release by directly acting on GnRH neurons, whereas GnIH inhibits gonadotropin release by inhibiting kisspeptin or GnRH neurons or pituitary gonadotropes. These neuropeptides can regulate social behavior by regulating the HPG axis. However, distribution of neuronal fibers of GnRH, kisspeptin and GnIH neurons are not limited within the hypothalamus, and the existence of extra-hypothalamic neuronal fibers suggests direct control of social behavior within the brain. It has traditionally been shown that central administration of GnRH can stimulate female sexual behavior in rats. Recently, it was shown that Kiss1, one of the paralogs of kisspeptin peptide family, regulates fear responses in zebrafish and GnIH inhibits socio-sexual behavior in birds. Here we highlight recent findings regarding the role of GnRH, kisspeptin and GnIH in the regulation of social behaviors in fish, birds and mammals and discuss their importance in future biological and biomedical research.

  15. {sup 177}Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India

    Energy Technology Data Exchange (ETDEWEB)

    Danthala, Madhav; Raghavendra Rao, M. [HCG Oncology Hospitals, Bangalore, Karnataka (India); Kallur, K.G.; Prashant, G.R.; Rajkumar, K. [HCG Oncology Hospitals, Department of Nuclear Medicine, Bangalore, Karnataka (India)

    2014-07-15

    The choice of an appropriate treatment option in patients with inoperable or metastatic neuroendocrine tumours (NETs) is limited, and approximately 50 % of patients have advanced NET at diagnosis, and 65 % die within 5 years. Treatment with {sup 177}Lu-DOTATATE ({sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}] octreotate) is a promising new option in the treatment of metastatic NETs. Patients with metastatic NET who underwent {sup 177}Lu-DOTATATE during the period 2009 to 2013 were included in this retrospective study. Follow-up imaging studies including a {sup 68}Ga-DOTANOC PET/CT scan and a posttherapy {sup 177}Lu-DOTATATE scan were compared with baseline imaging to determine response to treatment. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and Cox regression analysis was also done. Ten patients (25 %) had a minimal response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease. Progressive disease was seen in 8 patients (20 %), including 6 patients who died during or after the treatment period. The estimated mean PFS in those who received one or two cycles of {sup 177}Lu-DOTATATE was 8.3 months (95 % CI 6.2 to 10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to 50.2 months) in those who received more than two cycles of {sup 177}Lu-DOTATATE (log-rank Mantel-Cox Χ {sup 2} = 8.01, p = 0.005). Our study showed that treatment with {sup 177}Lu-DOTATATE should be considered in the management of NETs, considering the limited success of alternative treatment modalities. Treatment response and PFS is determined primarily by the dose delivered and best results are obtained when more than two cycles of {sup 177}Lu-DOTATATE are given, with careful monitoring for possible side effects. (orig.)

  16. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  17. Current Status of Radiopharmaceuticals for the Theranostics of Neuroendocrine Neoplasms

    Directory of Open Access Journals (Sweden)

    Melpomeni Fani

    2017-03-01

    Full Text Available Abstract: Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs. Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr, other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them. The Glucagon-Like Peptide-1 Receptor (GLP-1R is highly expressed in benign insulinomas, the Cholecystokinin 2 (CCK2/Gastrin receptor is expressed in different NENs, in particular medullary thyroid cancer, and the Glucose-dependent Insulinotropic Polypeptide (GIP receptor was found to be expressed in gastrointestinal and bronchial NENs, where interestingly, it is present in most of the sstr-negative and GLP-1R-negative NENs. Also in the field of sstr targeting new discoveries brought into light an alternative approach with the use of radiolabeled somatostatin receptor antagonists, instead of the clinically used agonists. The purpose of this review is to present the current status and the most innovative strategies for the diagnosis and treatment (theranostics of neuroendocrine neoplasms using a cadre of radiolabeled regulatory peptides targeting their receptors.

  18. Irritable bowel syndrome: the role of gut neuroendocrine peptides.

    Science.gov (United States)

    El-Salhy, Magdy; Seim, Inge; Chopin, Lisa; Gundersen, Doris; Hatlebakk, Jan Gunnar; Hausken, Trygve

    2012-06-01

    Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 percent of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity.

  19. Circadian adaptations to meal timing: Neuroendocrine mechanisms

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    Danica F Patton

    2013-10-01

    Full Text Available Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus is directly entrained by daily light-dark cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this

  20. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia in a patient with multiple pulmonary nodules: case report and literature review

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    Yamin HS

    2017-12-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare pulmonary disease, where carcinoid tumorlets invade the pulmonary parenchyma and bronchioles. These nests of cells release a variety of mediators including bombesin and gastrin releasing peptide that cause heterogeneous bronchoconstriction, creating a mosaic appearance on chest imaging studies, especially on expiratory scans. Clinically patients usually have long standing symptoms of shortness of breath (SOB and cough that are difficult to distinguish from asthma. In this article we describe a case of DIPNECH in a patient with several years’ history of SOB and cough, and review 179 cases of DIPNECH reported in the literature since 1992.

  1. Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum.

    Science.gov (United States)

    Niemeijer, Nicolasine D; Papathomas, Thomas G; Korpershoek, Esther; de Krijger, Ronald R; Oudijk, Lindsey; Morreau, Hans; Bayley, Jean-Pierre; Hes, Frederik J; Jansen, Jeroen C; Dinjens, Winand N M; Corssmit, Eleonora P M

    2015-10-01

    Mutations in genes encoding the subunits of succinate dehydrogenase (SDH) can lead to pheochromocytoma/paraganglioma formation. However, SDH mutations have also been linked to nonparaganglionic tumors. The objective was to investigate which nonparaganglionic tumors belong to the SDH-associated tumor spectrum. This was a retrospective cohort study. The setting was a tertiary referral center. Patients included all consecutive SDHA/SDHB/SDHC and SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center who were affected by non-pheochromocytoma/paraganglioma solid tumors. Main outcome measures were SDHA/SDHB immunohistochemistry, mutation analysis, and loss of heterozygosity analysis of the involved SDH-encoding genes. Twenty-five of 35 tumors (from 26 patients) showed positive staining on SDHB and SDHA immunohistochemistry. Eight tumors showed negative staining for SDHB and positive staining for SDHA: a pancreatic neuroendocrine tumor, a macroprolactinoma, two gastric gastrointestinal stromal tumors, an abdominal ganglioneuroma, and three renal cell carcinomas. With the exception of the abdominal ganglioneuroma, loss of heterozygosity was detected in all tumors. A prolactinoma in a patient with a germline SDHA mutation was the only tumor immunonegative for both SDHA and SDHB. Sanger sequencing of this tumor revealed a somatic mutation (p.D38V) as a likely second hit leading to biallelic inactivation of SDHA. One tumor (breast cancer) showed heterogeneous SDHB staining, positive SDHA staining, and retention of heterozygosity. This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal stromal tumors. Furthermore, our results indicate that pancreatic neuroendocrine tumor also falls within the SDH-related tumor spectrum.

  2. Association between ABO blood types and sporadic pancreatic neuroendocrine tumors in the Chinese Han population.

    Science.gov (United States)

    Ben, Qiwen; Liu, Jun; Wang, Weiyi; Guo, Fang; Yao, Weiyan; Zhong, Jie; Yuan, Yaozong

    2017-08-15

    Although the relationship between non-O blood types and the risk of exocrine pancreatic cancer has been demonstrated, the association between ABO blood types and sporadic pancreatic neuroendocrine tumor (PNET) has not been reported thus far. This hospital-based, case-control study included 387 patients with PNET and 542 age- and sex-matched controls. Unconditional multivariable logistic regression analysis was performed to estimate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs). The relationship between ABO blood types and clinicopathologic features was also analyzed. After adjusting for age, sex, smoking status, alcohol drinking, and first-degree family history of any cancer, the AORs (95% CI) of functional PNET were 0.87 (0.59-1.28) for blood type A, 0.86 (0.58-1.28) for blood type B, and 0.71 (0.39-1.26) for blood type AB compared with subjects with blood type O. A similar ABO blood-type distribution was observed among cases with non-functional PNETs compared with controls. On comparing blood type B with non-B blood type, cases with non-functional PNETs had marginally higher rates of lymph node invasion (P = 0.047), distant metastasis (P = 0.044), and advanced European Neuroendocrine Tumor Society Stage (P = 0.040). There is no association between the ABO blood group and the development of functional and non-functional PNETs. The ABO blood types are not associated with the clinicopathologic features in patients with functional and non-functional PNETs.

  3. Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

    Science.gov (United States)

    Sergieva, Sonya; Robev, Bozhil; Dimcheva, Milena; Fakirova, Albena; Hristoskova, Radka

    2016-01-01

    Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

  4. Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.

    Science.gov (United States)

    Tenenbaum-Rakover, Yardena; Commenges-Ducos, Monique; Iovane, André; Aumas, Chantal; Admoni, Osnat; de Roux, Nicolas

    2007-03-01

    Loss of function of the G protein-coupled receptor of kisspeptins (GPR54) was recently described as a new cause of isolated hypogonadotropic hypogonadism. In vivo studies performed in several species have confirmed the major role of kisspeptins in neuroendocrine regulation of the gonadotropic axis and therefore sexual maturation. The objective of this study was to specify the exact contribution of kisspeptins and GPR54 to the initiation of puberty in humans. Detailed neuroendocrine descriptions were performed in five patients with isolated hypogonadotropic hypogonadism bearing a new GPR54-inactivating mutation. A homozygous mutation (T305C) leading to a leucine substitution with proline (L102P) was found in the five affected patients. This substitution completely inhibited GPR54 signaling. Phenotypic analysis revealed variable expressivity in the same family, either partial or complete gonadotropic deficiency. LH pulsatility analysis showed peaks with normal frequency but low amplitude. Repeated GnRH tests performed between 12 and 21 yr of age in one affected male revealed progressive changes in pituitary response from an early pubertal to an almost full pubertal pattern. Double GnRH test stimulations performed at a 120-min interval showed reduced dynamic pituitary response in GPR54-mutated patients. GPR54 inactivation does not impede neuroendocrine onset of puberty; rather, it delays and slows down pubertal maturation of the gonadotropic axis. The L102P loss of function mutation in GPR54 results in a more quantitative than qualitative defect of gonadotropic axis activation.

  5. The effect of Aquablend Avian probiotic ® including Lactobacillus, Streptococcus and Bifidobacterium on systemic antibody response against Newcastle and Influenza disease vaccine in broiler chickens

    Directory of Open Access Journals (Sweden)

    Talazadeh

    2016-05-01

    Full Text Available Background Finding alternatives to antibiotics for poultry production is very important because there are increasing concerns about antibiotic resistance. So, researchers have been directed to the research back to natural antimicrobial products. Some researchers stated that probiotics can stimulate the immune system and play an important role in shaping the immune system. Objectives The aim of this study was to examine the effect of a commercial probiotic mixture (Aquablend Avian® supplementation to the drinking water of broiler chickens on the immune response against Newcastle and influenza diseases vaccines. Materials and Methods In this study, 180 one-day-old broiler chickens were purchased and divided randomly into 3 groups (n = 60 for each group. Chickens in groups A and B received 300 mg of the probiotic in drinking water for first 3 days and first 7 days, respectively. Chickens in group C were kept as a control group and did not receive probiotic. All groups were vaccinated with live Newcastle vaccine (B1 strain intraocularly on 8th day, and AI-ND killed vaccine (subtype H9N2 subcutaneously at the back of the neck on 8th day. Two mL of blood samples were collected before vaccination as well as on days 14, 28 and 35 postimmunization. Ten chickens of each group were bled randomly and an antibody titer against Newcastle disease vaccine and AI-ND killed vaccine (subtype H9N2 was determined by the hemagglutination-inhibition test. Results The results of the present study showed that oral administration of the probiotic for 7 days significantly increased the specific antibody response to Newcastle vaccine compared to the control group (0.75 - 1.6 log, based on log2, while the probiotic administration had no significant effect on antibody productions against avian influenza vaccine as compared to the control group. Conclusions Oral administration of Aquablend Avian® probiotic strains including Lactobacillus, Streptococcus and Bifidobacterium

  6. The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

    Science.gov (United States)

    Munier, C Mee Ling; van Bockel, David; Bailey, Michelle; Ip, Susanna; Xu, Yin; Alcantara, Sheilajen; Liu, Sue Min; Denyer, Gareth; Kaplan, Warren; Suzuki, Kazuo; Croft, Nathan; Purcell, Anthony; Tscharke, David; Cooper, David A; Kent, Stephen J; Zaunders, John J; Kelleher, Anthony D

    2016-10-17

    Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  7. Reclassification of neuroendocrine tumors improves the separation of carcinoids and the prediction of survival

    DEFF Research Database (Denmark)

    Skov, B.G.; Krasnik, M.; Lantuejoul, S.

    2008-01-01

    INTRODUCTION: The classification of neuroendocrine lung tumors has changed over the last decades. Reliable diagnoses are crucial for the quality of clinical databases. The purpose of this study is to determine to which extent the use of different diagnostic criteria of neuroendocrine lung tumors.......03). However, the number of removed lymph nodes were insufficient for definitive determination of the prognostic impact of node metastases. Regarding the revised diagnoses, a significant difference in survival between typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell...

  8. Update on neuroendocrine regulation and medical intervention of reproduction in birds.

    Science.gov (United States)

    Mans, Christoph; Taylor, W Michael

    2008-01-01

    In avian species, reproductive disorders and undesirable behaviors commonly reflect abnormalities in the neuroendocrine regulation of the reproductive system. Current treatment options are often disappointing, show no long-lasting effect, or have significant side effects. A possible reason for our lack of success is a dearth of knowledge of the underlying neuroendocrine, behavioral, and autonomous physiology of the reproductive processes. Tremendous progress has been made in the last few years in our understanding of the neuroendocrine control of reproduction in birds. Advantage should be taken of these experimentally derived data to develop appropriate and safe treatment protocols for avian patients suffering from reproductive disorders.

  9. An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3'-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients.

    Science.gov (United States)

    Swart, Marelize; Evans, Jonathan; Skelton, Michelle; Castel, Sandra; Wiesner, Lubbe; Smith, Peter J; Dandara, Collet

    2015-01-01

    Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy (HAART) in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in plasma concentrations has been reported. Poor treatment outcomes such as development of adverse drug reactions or treatment failure have been linked to EFV plasma concentrations outside the therapeutic range (1-4 μg/mL) in some studies. The drug metabolizing enzyme (DME), CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP1A2, CYP2A6, CYP3A4, CYP3A5, and UGT2B7. DME coding genes are also regulated by microRNAs through targeting the 3'-untranslated region. Expanded analysis of 30 single nucleotide polymorphisms (SNPs), including those in the 3'-UTR, was performed to identify pharmacogenetics determinants of EFV plasma concentrations in addition to CYP2B6 c.516G>T and c.983T>C SNPs. SNPs in CYP1A2, CYP2B6, UGT2B7, and NR1I2 (PXR) were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing the role of genetic variation in the 3'-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV. Despite evaluating thirty SNPs, CYP2B6 c.516G>T and c.983T>C SNPs remain the most prominent predictors of EFV plasma concentration. We have shown that CYP2B6 c.516G>T and c.983T>C SNPs are the most important predictors of EFV plasma concentration after taking into account all other SNPs, including genetic variation in the 3'-UTR, and variables affecting EFV metabolism.

  10. Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

    Science.gov (United States)

    Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

    2011-06-01

    Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

  11. Neuroendocrine Tumors of the Lung: Current Challenges and Advances in the Diagnosis and Management of Well-Differentiated Disease.

    Science.gov (United States)

    Hendifar, Andrew E; Marchevsky, Alberto M; Tuli, Richard

    2017-03-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, most commonly originating from the lungs and gastrointestinal tract. Lung NETs can be classified as well differentiated (low-grade typical carcinoids [TCs] and intermediate-grade atypical carcinoids [ACs]) and poorly differentiated (high-grade large cell neuroendocrine carcinoma or SCLC). The incidence of these tumors is increasing, but disease awareness remains low among thoracic specialists, who are often involved in the diagnosis and early treatment for these patients. An accurate and timely diagnosis can ensure the implementation of appropriate treatment and have a substantial impact on prognosis. However, lung NET classification and diagnosis, particularly for TCs/ACs, are complicated by several factors, including a variable natural history and nonspecific symptoms. Surgery remains the only curative option for TCs/ACs, but there is a lack of consensus between lung NET management guidelines regarding optimal treatment approaches in the unresectable/metastatic setting on account of the limited availability of high-level clinical evidence. As a result, a multidisciplinary approach to management of lung NETs is required to ensure a consistent and optimal level of care. RADIANT-4 is the first phase III trial involving a large subpopulation of patients with advanced well-differentiated lung NETs to report reductions in the risk for disease progression and death with everolimus over placebo. This led to the recent U.S. approval of everolimus-the first agent approved for advanced lung TCs/ACs. To further improve evidence-based care, additional randomized controlled trials in patients with lung carcinoids are needed. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  12. [Radioguided surgery in neuroendocrine tumors. A review of the literature].

    Science.gov (United States)

    García-Talavera, P; Ruano, R; Rioja, M E; Cordero, J M; Razola, P; Vidal-Sicart, S

    2014-01-01

    Radioguided surgery can be a useful technique in the localization of neuroendocrine tumors. It detects more and smaller lesions compared to pre-surgical imaging and intraoperative digital palpation by the surgeon. It detects residual lesions and also indicates the shortest access route to the lesion. Nevertheless, its use has not become widespread because of technical difficulties. There is a limited number of published series, a lack of standardized protocol because of the great variability regarding type of radiopharmaceutical, dose of radiotracer, timing between injection and surgery. In this paper, we review these issues, describing the experience of different authors in diverse tumors. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  13. Pulmonary neuroendocrine tumor in a female wolf (Canis lupus lupus).

    Science.gov (United States)

    Shiraki, Ayako; Yoshida, Toshinori; Kawashima, Masahi; Murayama, Hirotada; Nagahara, Rei; Ito, Nanao; Shibutani, Makoto

    2017-03-23

    A 17-year-old female wolf (Canis lupus lupus) had a right lung mass that was adhered to the thoracic cavity. Histopathological examination revealed that the mass consisted of sheets, cord or ribbon-like structures of monotonous, small, cuboidal cells with round, oval or short-spindle nuclei and scant clear cytoplasm, demarcated by a fine fibrovascular stroma. Focal necrosis, congestion and thrombi were observed. Immunohistochemically, the tumor cells diffusely expressed cytokeratin AE1/AE3, and some expressed chromogranin A, neural cell adhesion molecule (CD56) and thyroid transcription factor-1. The number of proliferating cell nuclear antigen-positive tumor cells was low. A diagnosis of pulmonary neuroendocrine tumor was based on the resemblance to carcinoids.

  14. Neuroendocrine Tumour of the Prostate: A Rare Variant

    Directory of Open Access Journals (Sweden)

    Ozer Ural Cakici

    2013-12-01

    Full Text Available About 95% of prostate cancers are adenocarcinomas. Neuroendocrine differentiation (NED is seen in virtually all cases of prostatic carcinoma, mostly in a focal pattern. Extensive NED is associated to aggressive disease with a poor prognosis and most cases are diagnosed in advanced stages.We present a 79-year- old male who was admitted to our department with severe lower urinary tract obstructive symptoms and weight loss. On digital rectal examination, the prostate was fixed to the rectum with irregular margins. Serum prostate-specific antigen (PSA level was 1.9 ng/ml.Transrectal ultrasound-guided prostate biopsies revealed small-cell carcinoma of the prostate. Multiple metastatic lesions in vertebral bones and iliac lymph nodes were detected by nuclear bone scan and abdominal computerised tomography CT. Thereafter, the patient was treated with cisplatin-based chemotherapy and palliative radiotherapy.

  15. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    Energy Technology Data Exchange (ETDEWEB)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J

    2003-07-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  16. Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

    Science.gov (United States)

    Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

    2014-02-01

    The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

  17. Immunohistochemical detection of dopamine D2 receptors in neuroendocrine tumours.

    Science.gov (United States)

    Pawlikowski, Marek; Pisarek, Hanna; Winczyk, Katarzyna

    2011-01-01

    Recently, dopamine D2 receptors (RD2) have been found to be expressed in neuroendocrine tumours (NET), the tumours which arise from the diffuse neuroendocrine cells. Moreover, successful trials of the treatment of NET with cabergoline - D2 agonist, have been reported. These findings increase the interest of investigating RD2 expression in NET. The expression of RD2 was investigated immunohistochemically using the antibody which recognises both short (S) and long (L) isoforms of the receptor in 17 NET samples taken from 15 patients. In 17 NET samples, a positive reaction with the anti-RD2 antibody occurred in 11 cases. In six cases, the localisation of the immunostaining was cytoplasmic and in nine cases it was nuclear. Only in one case was the receptor cell membrane-located, and in two cases the immunoreaction was also localised in the blood vessels walls. The relation between RD2 expression and the grade of malignancy examined by means of Ki-67 antigen expression needs further study. However, preliminary observations indicate that the nuclear localisation of RD2 is linked to higher tumour malignancy. The next investigated question was the co-expression of somatostatin and dopamine receptors. This question seems important because of the perspectives of somatostatin-dopamine chimeras application in NET treatment. In the samples examined by us, RD2 were co-expressed in 5/10 cases with sstr1, in 3/10 with sstr2A, in 2/9 with sstr2B, in 3/10 with sstr3, and in 5/10 with sstr5. Dopamine D2 receptors are revealed by means of immunohistochemistry in the majority of NET. They exhibit cytoplasmic and/or nuclear localisations, the latter being possibly linked to a higher grade of malignancy, and are often co-expressed with somatostatin receptors (mostly with subtypes1 and 5).

  18. Rb Loss is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Tan, Hsueh-Li; Sood, Akshay; Rahimi, Hameed A.; Wang, Wenle; Gupta, Nilesh; Hicks, Jessica; Mosier, Stacy; Gocke, Christopher D.; Epstein, Jonathan I.; Netto, George J.; Liu, Wennuan; Isaacs, William B.; De Marzo, Angelo M.; Lotan, Tamara L.

    2014-01-01

    Purpose Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide diagnosis and therapy of this aggressive tumor. Experimental Design We examined the status of RB1, TP53 and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy number alteration analysis and sequencing of formalin fixed paraffin-embedded specimens. Results We found Rb protein loss in 90% (26/29) of small cell carcinoma cases with RB1 allelic loss in 85% (11/13) of cases. Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3/7) showed Rb protein loss. In contrast, only 7% (10/150) of primary high grade acinar carcinomas, 11% (4/35) of primary acinar carcinomas with neuroendocrine differentiation, and 15% (2/13) of metastatic castrate resistant acinar carcinomas showed Rb protein loss. Loss of PTEN protein was seen in 63% (17/27) of small cell carcinomas, with 38% (5/13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% (14/25) of small cell carcinomas, with 60% (6/10) of cases showing TP53 mutation. Conclusions Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by validated IHC assay. As Rb protein loss rarely occurs in high grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target. PMID:24323898

  19. Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticals.

    Science.gov (United States)

    Bombardieri, E; Coliva, A; Maccauro, M; Seregni, E; Orunesu, E; Chiti, A; Lucignani, G

    2010-02-01

    Nuclear medicine can image some tumors by means of receptor specific radiopharmaceuticals, and offers the possibility to characterize cancer through the detection of its receptor expression. This is the case of neuroendocrine tumours (NETs), that are visualized by different radiolabelled somatostatin analogues that bind 5 distinct somatostatin receptor types (named sstr1-5) that show different tissue distribution. The subtypes sstr2 and sstr5 are the most commonly expressed in NETs. Until now the most widely used radiolabelled somatostatin analogue for planar and single photon emission computed tomography (SPECT) has been [(111)In]pentetreotide, because of its commercial availability. Other analogues labelled with gamma emitting radionuclides are [(99m)Tc]EDDA/HYNIC-TOC, [(99m)Tc]P829, [(111)In]DOTA-lanreotide, [(111)In]DOTA-NOC-ATE, [(111)In]DOTA-BOC-ATE. However, these compounds have not been successful for the routine use. Moreover, NETs express various receptors that can be depicted by different radiopharmaceuticals, such as [(123)I]VIP and [(111)In]GLP-1. Besides this, some precursors of the catecholamines metabolism, as meta-iodo-benzyl-guanidine (MIBG), labelled with (123)I or (131)I, accumulates in neuroendocrine tissues, in particular those of sympathoadrenal lineage. MIBG scintigraphy is currently indicated for neuroblastoma, paraganglioma and phaeocromocitoma. An impressive technological progress has been achieved recently with PET and, in particular, with the development of hybrid instrumentations (PET/CT) combining nuclear imaging with radiological imaging providing both functional and morphologic information. Among positron emitting tracers, the [(18)F]FDG is the most diffuse in oncology, but other more effective tracers are available for NETs, such as the analogues labelled with 68Ga. The diagnostic sensitivity and accuracy of these technology is superior to that of gamma emitting radiopharmaceuticals, but the fact that they are not still registered

  20. Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Simtniece, Zane; Vanags, Andrejs; Strumfa, Ilze; Sperga, Maris; Vasko, Ervins; Prieditis, Peteris; Trapencieris, Peteris; Gardovskis, Janis

    2015-06-01

    The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p<0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p=0.022), the World Health Organization 2004 and 2010 classification grades (p=0.021 and p=0.002), stage (p=0.028) and mitotic count (p=0.007) but among molecular markers--with CK19 (p=0.033) and vimentin (p=0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p=0.018), pR (p=0.025), vascular (p=0.020), perineural (p=0.026) and lymphatic invasion (p=0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.

  1. Clonality analysis of neuroendocrine cells in gastric adenocarcinoma

    Science.gov (United States)

    Wang, Ling-Ling; Yao, Gen-You; Zhao, Zhong-Sheng; Wei, Xiao-Li; Xu, Ru-Jun

    2013-01-01

    AIM: To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma. METHODS: In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study. Third, genome-wide microsatellite abnormalities [microsatellite instability (MSI), loss of heterozygosity (LOH)] and p53 mutation were detected by polymerase chain reaction (PCR)-single-strand conformation polymer- phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells. RESULTS: The total incidence rate of MSI was 27.4%, while LOH was 17.9%. Ten cases had a highest concordance for the two types of cells. The other samples had similar microsatellite changes, except for cases 7 and 10. Concordant p53 mutations exhibited in sample 4, 14, 21 and 27, and there were different mutations between two kinds of cells in case 7. In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis. In brief, NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30). In the other three cases, different MSI, LOH or p53 mutation occurred. CONCLUSION: NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation. PMID:23983439

  2. Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

    Directory of Open Access Journals (Sweden)

    Lyes eDerouiche

    2015-12-01

    Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

  3. Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors.

    Science.gov (United States)

    Walter, Robert Fred Henry; Vollbrecht, Claudia; Christoph, Daniel; Werner, Robert; Schmeller, Jan; Flom, Elena; Trakada, Georgia; Rapti, Aggeliki; Adamidis, Vasilis; Hohenforst-Schmidt, Wolfgang; Kollmeier, Jens; Mairinger, Thomas; Wohlschlaeger, Jeremias; Zarogoulidis, Paul; Porpodis, Konstantinos; Schmidt, Kurt Werner; Mairinger, Fabian Dominik

    2016-01-01

    Background : Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods : 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results : A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A , was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion : Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors.

  4. Age-Dependent Neuroendocrine Signaling from Sensory Neurons Modulates the Effect of Dietary Restriction on Longevity of Caenorhabditis elegans.

    Science.gov (United States)

    Fletcher, Marissa; Kim, Dennis H

    2017-01-01

    Dietary restriction extends lifespan in evolutionarily diverse animals. A role for the sensory nervous system in dietary restriction has been established in Drosophila and Caenorhabditis elegans, but little is known about how neuroendocrine signals influence the effects of dietary restriction on longevity. Here, we show that DAF-7/TGFβ, which is secreted from the C. elegans amphid, promotes lifespan extension in response to dietary restriction in C. elegans. DAF-7 produced by the ASI pair of sensory neurons acts on DAF-1/TGFβ receptors expressed on interneurons to inhibit the co-SMAD DAF-3. We find that increased activity of DAF-3 in the presence of diminished or deleted DAF-7 activity abrogates lifespan extension conferred by dietary restriction. We also observe that DAF-7 expression is dynamic during the lifespan of C. elegans, with a marked decrease in DAF-7 levels as animals age during adulthood. We show that this age-dependent diminished expression contributes to the reduced sensitivity of aging animals to the effects of dietary restriction. DAF-7 signaling is a pivotal regulator of metabolism and food-dependent behavior, and our studies establish a molecular link between the neuroendocrine physiology of C. elegans and the process by which dietary restriction can extend lifespan.

  5. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    Directory of Open Access Journals (Sweden)

    Severi S

    2017-01-01

    . Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided. Keywords: 90Y-Dotatoc, 177Lu-Dotatate, radiopharmaceutical, radiolabelled receptors, neuroendocrine malignancies, delivered activity

  6. Insulin/IGF-regulated size scaling of neuroendocrine cells expressing the bHLH transcription factor Dimmed in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jiangnan Luo

    Full Text Available Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS. By targeted genetic manipulations of insulin receptor (dInR expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM. Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B, whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin signaling components, such as Rheb (small GTPase, TOR and S6K (S6 kinase. After Dimm-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of Dimm. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.

  7. Pitfalls in the diagnosis of neuroendocrine tumors: atypical clinical and radiological findings as cause of medical mistakes.

    Science.gov (United States)

    Bajetta, Emilio; Catena, Laura; Ducceschi, Monika; Pusceddu, Sara; Milione, Massimo; Maccauro, Marco; Bajetta, Roberto; Procopio, Giuseppe; Buzzoni, Roberto; Formisano, Barbara; Di Guardo, Lorenza; Platania, Marco

    2009-01-01

    Carcinoids are infrequent neoplasms arising from neuroendocrine cells. Due to blurred symptoms and the presence of equivocal diagnostic findings, these tumors are sometimes misdiagnosed. Therefore, increased rates of false neuroendocrine tumors represent an emerging problem in clinical practice. Our aim is to alert clinicians on this matter by supplying them with useful warnings. In the specialized neuroendocrine tumor study Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a neuroendocrine tumor have been recognized as having false neuroendocrine tumors. The related clinical and instrumental findings leading to a previous wrong neuroendocrine tumor diagnosis are reported. From July 2006 to December 2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the remaining 80 cases a correct Net diagnosis was carried out. Watchful differential diagnoses and skill appraisal of laboratory investigations resulted in: chronic atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases), estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome (1), and sarcoidosis (1). Neuroendocrine tumors are still relatively known clinical entities. To discriminate false neuroendocrine tumors from neuroendocrine tumors requires a good expertise and a large daily practice with the disease. Good knowledge and skillfulness in identifying biochemical alterations and false radiological positive results could avoid both patient inconvenience and very expensive workup. The importance of a multidisciplinary approach in specialized centers is emphasized.

  8. A Delphic consensus assessment : imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

    NARCIS (Netherlands)

    Oberg, Kjell; Krenning, Eric; Sundin, Anders; Bodei, Lisa; Kidd, Mark; Tesselaar, Margot; Ambrosini, Valentina; Baum, Richard P.; Kulke, Matthew; Pavel, Marianne; Cwikla, Jaroslaw; Drozdov, Ignat; Falconi, Massimo; Fazio, Nicola; Frilling, Andrea; Jensen, Robert; Koopmans, Klaus; Korse, Tiny; Kwekkeboom, Dik; Maecke, Helmut; Paganelli, Giovanni; Salazar, Ramon; Severi, Stefano; Strosberg, Jonathan; Prasad, Vikas; Scarpa, Aldo; Grossman, Ashley; Walenkamp, Annemiek; Cives, Mauro; Virgolini, Irene; Kjaer, Andreas; Modlin, Irvin M.

    2016-01-01

    The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease,

  9. Middle ear adenoma with neuroendocrine differentiation: relate of two cases and literature review

    Directory of Open Access Journals (Sweden)

    Bittencourt, Aline Gomes

    2014-01-01

    Full Text Available Introduction: Adenomas with neuroendocrine differentiation are defined as neuroendocrine neoplasms, and they are rarely found in the head and neck. Objective: To describe two cases of a middle ear adenoma with neuroendocrine differentiation, with a literature review. Case Report: Patient 1 was a 41-year-old woman who presented with a 3-year history of left aural fullness associated with ipsilateral “hammer beating” tinnitus. Patient 2 was a 41-year-old male who presented with unilateral conductive hearing loss. Conclusion: Adenoma with neuroendocrine differentiation of the middle ear is a rare entity, but it should be considered in patients with tinnitus, aural fullness, and a retrotympanic mass and remembered as a diferential diagnosis of tympanic paraganglioma.

  10. Genetic and molecular coordinates of neuroendocrine lung tumors, with emphasis on small-cell lung carcinomas

    National Research Council Canada - National Science Library

    Koutsami, Marilena K; Doussis-Anagnostopoulou, Ipatia; Papavassiliou, Athanasios G; Gorgoulis, Vassilis G

    2002-01-01

    .... Current information on established and putative diagnostic and prognostic markers of neuroendocrine tumors are evaluated, with a special reference to small-cell lung carcinoma, due to its higher...

  11. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  12. Middle ear adenoma with neuroendocrine differentiation: relate of two cases and literature review

    Science.gov (United States)

    Bittencourt, Aline Gomes; Tsuji, Robinson Koji; Cabral, Francisco; Pereira, Larissa Vilela; Fonseca, Anna Carolina de Oliveira; Alves, Venâncio; Bento, Ricardo Ferreira

    2013-01-01

    Summary Introduction: Adenomas with neuroendocrine differentiation are defined as neuroendocrine neoplasms, and they are rarely found in the head and neck. Objective: To describe two cases of a middle ear adenoma with neuroendocrine differentiation, with a literature review. Case Report: Patient 1 was a 41-year-old woman who presented with a 3-year history of left aural fullness associated with ipsilateral “hammer beating” tinnitus. Patient 2 was a 41-year-old male who presented with unilateral conductive hearing loss. Conclusion: Adenoma with neuroendocrine differentiation of the middle ear is a rare entity, but it should be considered in patients with tinnitus, aural fullness, and a retrotympanic mass and remembered as a diferential diagnosis of tympanic paraganglioma. PMID:25992031

  13. Composite effects of group drumming music therapy on modulation of neuroendocrine-immune parameters in normal subjects.

    Science.gov (United States)

    Bittman, B B; Berk, L S; Felten, D L; Westengard, J; Simonton, O C; Pappas, J; Ninehouser, M

    2001-01-01

    Drum circles have been part of healing rituals in many cultures throughout the world since antiquity. Although drum circles are gaining increased interest as a complementary therapeutic strategy in the traditional medical arena, limited scientific data documenting biological benefits associated with percussion activities exist. To determine the role of group-drumming music therapy as a composite activity with potential for alteration of stress-related hormones and enhancement of specific immunologic measures associated with natural killer cell activity and cell-mediated immunity. A single trial experimental intervention with control groups. The Mind-Body Wellness Center, an outpatient medical facility in Meadville, Pa. A total of 111 age- and sex-matched volunteer subjects (55 men and 56 women, with a mean age of 30.4 years) were recruited. Six preliminary supervised groups were studied using various control and experimental paradigms designed to separate drumming components for the ultimate determination of a single experimental model, including 2 control groups (resting and listening) as well as 4 group-drumming experimental models (basic, impact, shamanic, and composite). The composite drumming group using a music therapy protocol was selected based on preliminary statistical analysis, which demonstrated immune modulation in a direction opposite to that expected with the classical stress response. The final experimental design included the original composite drumming group plus 50 additional age- and sex-matched volunteer subjects who were randomly assigned to participate in group drumming or control sessions. Pre- and postintervention measurements of plasma cortisol, plasma dehydroepiandrosterone, plasma dehydroepiandrosterone-to-cortisol ratio, natural killer cell activity, lymphokine-activated killer cell activity, plasma interleukin-2, plasma interferon-gamma, the Beck Anxiety Inventory, and the Beck Depression Inventory II. Group drumming resulted in

  14. From the brain-skin connection: the neuroendocrine-immune misalliance of stress and itch.

    Science.gov (United States)

    Arck, Petra; Paus, Ralf

    2006-01-01

    Perceived stress has long been allied with disturbances of the dynamic equilibrium established between the nervous, endocrine and immune systems, thus triggering or aggravating disease manifestation. Several common skin diseases are now acknowledged to be worsened by psychological stress, particularly immunodermatoses such as atopic dermatitis, psoriasis, seborrheic eczema, prurigo nodularis, lichen planus, chronic urticaria, alopecia areata and pruritus sine materia. Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus. A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold. In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune 'misalliance'. We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as 'central cellular switchboards of pruritogenic inflammation', need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases. Copyright (c) 2006 S. Karger AG, Basel.

  15. Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin

    OpenAIRE

    Grönberg, Malin

    2010-01-01

    The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs). In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghre...

  16. Carcinome neuroendocrine du sein: à propos d'un cas et revue de ...

    African Journals Online (AJOL)

    Le carcinome neuroendocrine primitif du sein est une tumeur rare qui a été reconnue par la dernière édition de la classification OMS du cancer du sein publiée en 2003. Le diagnostic est évoqué sur des critères morphologiques et confirmé par l'expression des marqueurs neuroendocrines (chromogranine et ...

  17. A path-following driver-vehicle model with neuromuscular dynamics, including measured and simulated responses to a step in steering angle overlay

    Science.gov (United States)

    Cole, David J.

    2012-04-01

    An existing driver-vehicle model with neuromuscular dynamics is improved in the areas of cognitive delay, intrinsic muscle dynamics and alpha-gamma co-activation. The model is used to investigate the influence of steering torque feedback and neuromuscular dynamics on the vehicle response to lateral force disturbances. When steering torque feedback is present, it is found that the longitudinal position of the lateral disturbance has a significant influence on whether the driver's reflex response reinforces or attenuates the effect of the disturbance. The response to angle and torque overlay inputs to the steering system is also investigated. The presence of the steering torque feedback reduced the disturbing effect of torque overlay and angle overlay inputs. Reflex action reduced the disturbing effect of a torque overlay input, but increased the disturbing effect of an angle overlay input. Experiments on a driving simulator showed that measured handwheel angle response to an angle overlay input was consistent with the response predicted by the model with reflex action. However, there was significant intra- and inter-subject variability. The results highlight the significance of a driver's neuromuscular dynamics in determining the vehicle response to disturbances.

  18. Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder.

    Science.gov (United States)

    de Koning, P P; Figee, M; Endert, E; van den Munckhof, P; Schuurman, P R; Storosum, J G; Denys, D; Fliers, E

    2016-01-26

    Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus-pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS.

  19. A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    M J Trott

    2016-05-01

    Full Text Available We present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs, although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking.

  20. UV-B-Responsive Association of the Arabidopsis bZIP Transcription Factor ELONGATED HYPOCOTYL5 with Target Genes, Including Its Own Promoter[W][OPEN

    Science.gov (United States)

    Binkert, Melanie; Kozma-Bognár, László; Terecskei, Kata; De Veylder, Lieven; Nagy, Ferenc; Ulm, Roman

    2014-01-01

    In plants subjected to UV-B radiation, responses are activated that minimize damage caused by UV-B. The bZIP transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) and promotes UV-B-induced photomorphogenesis and acclimation. Expression of HY5 is induced by UV-B; however, the transcription factor(s) that regulate HY5 transcription in response to UV-B and the impact of UV-B on the association of HY5 with its target promoters are currently unclear. Here, we show that HY5 binding to the promoters of UV-B-responsive genes is enhanced by UV-B in a UVR8-dependent manner in Arabidopsis thaliana. In agreement, overexpression of REPRESSOR OF UV-B PHOTOMORPHOGENESIS2, a negative regulator of UVR8 function, blocks UV-B-responsive HY5 enrichment at target promoters. Moreover, we have identified a T/G-box in the HY5 promoter that is required for its UV-B responsiveness. We show that HY5 and its homolog HYH bind to the T/GHY5-box cis-acting element and that they act redundantly in the induction of HY5 expression upon UV-B exposure. Therefore, HY5 is enriched at target promoters in response to UV-B in a UVR8 photoreceptor-dependent manner, and HY5 and HYH interact directly with a T/G-box cis-acting element of the HY5 promoter, mediating the transcriptional activation of HY5 in response to UV-B. PMID:25351492

  1. Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia.

    Directory of Open Access Journals (Sweden)

    Ignat Drozdov

    Full Text Available Small intestinal (SI neuroendocrine tumors (NET are increasing in incidence, however little is known about their biology. High throughput techniques such as inference of gene regulatory networks from microarray experiments can objectively define signaling machinery in this disease. Genome-wide co-expression analysis was used to infer gene relevance network in SI-NETs. The network was confirmed to be non-random, scale-free, and highly modular. Functional analysis of gene co-expression modules revealed processes including 'Nervous system development', 'Immune response', and 'Cell-cycle'. Importantly, gene network topology and differential expression analysis identified over-expression of the GPCR signaling regulators, the cAMP synthetase, ADCY2, and the protein kinase A, PRKAR1A. Seven CREB response element (CRE transcripts associated with proliferation and secretion: BEX1, BICD1, CHGB, CPE, GABRB3, SCG2 and SCG3 as well as ADCY2 and PRKAR1A were measured in an independent SI dataset (n = 10 NETs; n = 8 normal preparations. All were up-regulated (p<0.035 with the exception of SCG3 which was not differently expressed. Forskolin (a direct cAMP activator, 10(-5 M significantly stimulated transcription of pCREB and 3/7 CREB targets, isoproterenol (a selective ß-adrenergic receptor agonist and cAMP activator, 10(-5 M stimulated pCREB and 4/7 targets while BIM-53061 (a dopamine D(2 and Serotonin [5-HT(2] receptor agonist, 10(-6 M stimulated 100% of targets as well as pCREB; CRE transcription correlated with the levels of cAMP accumulation and PKA activity; BIM-53061 stimulated the highest levels of cAMP and PKA (2.8-fold and 2.5-fold vs. 1.8-2-fold for isoproterenol and forskolin. Gene network inference and graph topology analysis in SI NETs suggests that SI NETs express neural GPCRs that activate different CRE targets associated with proliferation and secretion. In vitro studies, in a model NET cell system, confirmed that transcriptional

  2. Collision of extensive exocrine and neuroendocrine neoplasms in multiple endocrine neoplasia type 1 revealed by cytogenetic analysis of loss of heterozygosity: a case report.

    Science.gov (United States)

    Moriyoshi, Koki; Minamiguchi, Sachiko; Miyagawa-Hayashino, Aya; Fujimoto, Masakazu; Kawaguchi, Michiya; Haga, Hironori

    2013-09-01

    The combination of exocrine and neuroendocrine neoplasms is rarely found in the pancreas. These combined lesions vary from a clonal tumor with mixed differentiation to the incidental co-existence of two or more independent tumors, but the differential diagnosis is sometimes difficult. Here we report a case of multiple endocrine neoplasia type 1 (MEN1) with extensive ductal and neuroendocrine neoplastic changes. These two types of tumors admixed markedly in some parts, which made it difficult to determine the pathological diagnosis based on histological findings. Cytogenetic analysis showed that loss of heterozygosity (LOH) of the MEN1 locus exists in neuroendocrine but not in exocrine neoplasms, indicating that independent mechanisms of tumorigenesis may occur in these two types of tumors. This case shows the usefulness of cytogenetic analysis for the diagnosis of combined tumors of the pancreas. Extensive exocrine neoplastic change, including pancreatic intraepithelial neoplasia (PanIN) in virtually all pancreatic ducts and a focus of intraductal papillary mucinous neoplasm (IPMN) with focal invasion, was a distinguishing feature of the present case. The possible association of ductal tumorigenesis and a MEN1 background is discussed. © 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  3. Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.

    Science.gov (United States)

    Cowell, Whitney J; Wright, Rosalind J

    2017-12-01

    Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos, and traffic-related air pollution). We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits, and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.

  4. Pulmonary neuroendocrine carcinoma mimicking neurocysticercosis: a case report.

    Science.gov (United States)

    Lam, John C; Robinson, Stephen R; Schell, Andrew; Vaughan, Stephen

    2016-06-02

    Neurocysticercosis occurs when the eggs of the pork tapeworm (Taenia solium) migrate and hatch into larvae within the central nervous system. Neurocysticercosis is the most common cause of seizures in the developing world and is characterized on brain imaging by cysts in different stages of evolution. In Canada, cases of neurocysticercosis are rare and most of these patients acquire the disease outside of Canada. We report the case of a patient with multiple intracranial lesions whose history and diagnostic imaging were consistent with neurocysticercosis. Pathological investigations ultimately demonstrated that her brain lesions were secondary to malignancy. Brain metastases are considered to be the most common cause of intracranial cystic lesions. We present the case of a 60-year-old Canadian-born Caucasian woman with a subacute history of ataxia, lower extremity hyper-reflexia, and otalgia who resided near a pig farm for most of her childhood. Computed tomography and magnetic resonance imaging showed that she had multiple heterogeneous intracranial cysts, suggestive of neurocysticercosis. Despite a heavy burden of disease, serological tests for cysticercosis were negative. This result and a lack of the central scolices on neuroimaging that are pathognomonic of neurocysticercosis prompted whole-body computed tomography imaging to identify another etiology. The whole-body computed tomography revealed right hilar lymphadenopathy associated with soft tissue nodules in her chest wall and abdomen. A biopsy of an anterior chest wall nodule demonstrated high-grade poorly differentiated carcinoma with necrosis, which stained strongly positive for thyroid transcription factor-1 and synaptophysin on immunohistochemistry. A diagnosis of stage 4 metastatic small cell neuroendocrine carcinoma was made and our patient was referred for oncological palliative treatment. This case illustrates the importance of the diagnostic approach to intracranial lesions. Our patient

  5. CLINICAL VALUE OF CHROMOGRANIN A IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

    Directory of Open Access Journals (Sweden)

    N. V. Lyubimova

    2015-01-01

    Full Text Available Background: Neuroendocrine tumors (NET is a heterogeneous group of neoplasms characterized by hypersecretion of biologically active sub- stances that manifests by specific syndromes and determines the clinical course of the disease. The most common NET types are those of gastrointestinal tract. The obligatory biochemical marker used in the examination of NET patients is chromogranin A (CgA.Aim: Evaluation of the CgA value for diagnostics and monitoring of gastrointestinal NETs.Materials and methods: A comparative study of plasma CgA levels was performed in 146 patients with gastroenteropancreatic neuroendocrine tu- mors and 66 healthy individuals using the enzyme immunoassay “Chromogranin A ELISA kit” (Dako A/S, Denmark.Results: CgA levels were significantly higher in patients with NETs of all localizations, such as pancreas, stomach, gut, small and large bowel, than in the healthy subjects (р < 0.000001. In NET patients, CgA secretion was highly variable, with the highest value in the group of patients with gastric NETs (102000 U/l. The highest CgA medians were detected in patients with small intestinal (183.9 U/l, colon (148.4 U/l and pancreatic (135.9 U/l NETs. There was an association between CgA secretion and extension or activity of NETs, with the highest median values in patients with hepatic metastases (395 U/l and those with carcinoid syndrome (352 U/l. The clinical significance of CgA as a NET marker was assessed using the cut-off value of 33 U/l, calculated according to the results in the control group. Overall diagnostic sensitivity of CgA in NET patients was high (85.8% with a specificity of 98.5%. Conclusion: The results obtained confirm a high sensitivity of CgA as a NET marker whose determination helps to improve accuracy of diagnostics and to assess NET prevalence.

  6. Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

    Science.gov (United States)

    Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

    2017-01-01

    Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

  7. Activation of human monocytes by live Borrelia burgdorferi generates TLR2-dependent and -independent responses which include induction of IFN-beta.

    Directory of Open Access Journals (Sweden)

    Juan C Salazar

    2009-05-01

    Full Text Available It is widely believed that innate immune responses to Borrelia burgdorferi (Bb are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-beta and a number of interferon-stimulated genes (ISGs, which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-alpha, IL-6, IL-10 and IL-1beta in monocytes than did lysates. Secreted IL-18, which, like IL-1beta, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-beta and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs.

  8. Interaction and developmental activation of two neuroendocrine systems that regulate light-mediated skin pigmentation.

    Science.gov (United States)

    Bertolesi, Gabriel E; Song, Yi N; Atkinson-Leadbeater, Karen; Yang, Jung-Lynn J; McFarlane, Sarah

    2017-07-01

    Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion. As embryogenesis proceeds, the pineal complex/melatonin circuit becomes the dominant regulator in the dark and induces lightening of the skin of larvae. The eye/α-MSH circuit continues to mediate darkening of embryos on a black background, but we propose the circuit is shut down in complete darkness in part by melatonin acting on receptors expressed by pituitary cells to inhibit the expression of pomc, the precursor of α-MSH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Neuroendocrine regulation of energy balance: Implications on the development and surgical treatment of obesity.

    Science.gov (United States)

    Farias, Gisele; Netto, Bárbara Dal Molin; Bettini, Solange Cravo; Dâmaso, Ana Raimunda; de Freitas, Alexandre Coutinho Teixeira

    2017-09-01

    Obesity, a serious public health problem, occurs mainly when food consumption exceeds energy expenditure. Therefore, energy balance depends on the regulation of the hunger-satiety mechanism, which involves interconnection of the central nervous system and peripheral signals from the adipose tissue, pancreas and gastrointestinal tract, generating responses in short-term food intake and long-term energy balance. Increased body fat alters the gut- and adipose-tissue-derived hormone signaling, which promotes modifications in appetite-regulating hormones, decreasing satiety and increasing hunger senses. With the failure of conventional weight loss interventions (dietary treatment, exercise, drugs and lifestyle modifications), bariatric surgeries are well-accepted tools for the treatment of severe obesity, with long-term and sustained weight loss. Bariatric surgeries may cause weight loss due to restriction/malabsorption of nutrients from the anatomical alteration of the gastrointestinal tract that decreases energy intake, but also by other physiological factors associated with better results of the surgical procedure. This review discusses the neuroendocrine regulation of energy balance, with description of the predominant hormones and peptides involved in the control of energy balance in obesity and all currently available bariatric surgeries. According to the findings of our review, bariatric surgeries promote effective and sustained weight loss not only by reducing calorie intake, but also by precipitating changes in appetite control, satiation and satiety, and physiological changes in gut-, neuro- and adipose-tissue-derived hormone signaling.

  10. Autonomic, behavioral and neuroendocrine correlates of paternal behavior in male prairie voles.

    Science.gov (United States)

    Kenkel, William M; Suboc, Gessa; Carter, C Sue

    2014-04-10

    Socially monogamous prairie voles (Microtus ochrogaster) are biparental and alloparental. In the present study, we compared behavioral, cardiovascular and neuroendocrine parameters in male prairie voles with experience caring for pups (Fathers), versus reproductively inexperienced Virgin males. Father and Virgins showed generally similar responses to unrelated pups. However, in the Fathers studied prior to and during pup exposure, heart rate was lower and respiratory sinus arrhythmia tended to be higher than that in Virgins. Fathers also displayed comparatively lower levels of anxiety-related behaviors in an open field test. In Fathers, compared to Virgin males, we also found higher levels of oxytocin-immunoreactivity in the paraventricular hypothalamus and two brainstem regions involved in the autonomic regulation of the heart--the nucleus ambiguus and nucleus tractus solitarius. However, Fathers had less oxytocin in the bed nucleus of the stria terminalis. Vasopressin did not differ significantly in these regions. Fathers also weighed less and had less subcutaneous fat and larger testes as a percentage of bodyweight. In conjunction with earlier findings in this species, the present study supports the hypothesis that oxytocin may be involved in the adaptation to fatherhood. These findings also support the hypothesis that males, with or without prior pup experience, may show simultaneous patterns of behavioral nurturance and autonomic states compatible with mobilization and vigilance. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Perfusion CT Changes in Liver Metastases from Pancreatic Neuroendocrine Tumors During Everolimus Treatment.

    Science.gov (United States)

    D'Onofrio, Mirko; Cingarlini, Sara; Ortolani, Silvia; Crosara, Stefano; DE Robertis, Riccardo; Vallerio, Paola; Grego, Elisabetta; Ciaravino, Valentina; Ruzzenente, Andrea; Landoni, Luca; Scarpa, Aldo; Bassi, Claudio; Tortora, Giampaolo

    2017-03-01

    To evaluate modifications of perfusional parameters assessed by perfusion computed tomography (P-CT) of liver metastases (LM) from pancreatic neuroendocrine tumors (PanNETs) during everolimus treatment. All patients with LMs from G1-2 PanNETs undergoing everolimus treatment between January 2013 and January 2015 were prospectively evaluated with P-CT at baseline, and after 2 and 4 months of therapy. Size, perfusion, blood volume (BV), peak enhancement intensity (PEI) and time to peak for each lesion were calculated. A total of 33 LMs in nine patients with G1-2 PanNETs were prospectively evaluated: 23/33 (69.7%) were responders, 10/33 (30.3%) were non-responders. Among perfusional parameters, only numerical peak enhancement intensity values significantly differed between the two groups at baseline (p=0.043). BV increase was the most significant perfusional modification identifying responding lesions, even at an early stage of treatment, with a high positive predictive value (89.47%). P-CT seems to be useful for prediction of response to everolimus of LMs from PanNETs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Kidd, Mark; Drozdov, Ignat; Lepensky, Christopher; Modlin, Irvin M. [Yale School of Medicine, Department of Surgery, New Haven, CT (United States); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Kwekkeboom, Dik J.; Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Baum, Richard P. [Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotheraphy and Molecular Imaging, Bad Berka (Germany)

    2015-01-15

    Peptide receptor radionuclide therapy (PRRT) with {sup 90}Y and {sup 177}Lu provides objective responses in neuroendocrine tumours, and is well tolerated with moderate toxicity. We aimed to identify clinical parameters predictive of long-term renal and haematological toxicity (myelodysplastic syndrome and acute leukaemia). Of 807 patients studied at IEO-Milan (1997-2013), 793 (98 %) received {sup 177}Lu (278, 34.4 %), {sup 90}Y (358, 44.4 %) or {sup 177}Lu and {sup 90}Y combined (157. 19.5 %), and 14 (2 %) received combinations of PRRT and other agents. Follow-up was 30 months (1-180 months). The parameters evaluated included renal risk factors, bone marrow toxicity and PRRT features. Data analysis included multiple regression, random forest feature selection, and recursive partitioning and regression trees. Treatment with {sup 90}Y and {sup 90}Y + {sup 177}Lu was more likely to result in nephrotoxicity than treatment with {sup 177}Lu alone (33.6 %, 25.5 % and 13.4 % of patients, respectively; p < 0.0001). Nephrotoxicity (any grade), transient and persistent, occurred in 279 patients (34.6 %) and was severe (grade 3 + 4) in 12 (1.5 %). In only 20-27 % of any nephrotoxicity was the disease modelled by risk factors and codependent associations (p < 0.0001). Hypertension and haemoglobin toxicity were the most relevant factors. Persistent toxicity occurred in 197 patients (24.3 %). In only 22-34 % of affected patients was the disease modelled by the clinical data (p < 0.0001). Hypertension (regression coefficient 0.14, p < 0.0001) and haemoglobin toxicity (regression coefficient 0.21, p < 0.0001) were pertinent factors. Persistent toxicity was associated with shorter PRRT duration from the first to the last cycle (mean 387 vs. 658 days, p < 0.004). Myelodysplastic syndrome occurred in 2.35 % of patients (modelled by the clinical data in 30 %, p < 0.0001). Platelet toxicity grade (2.05 ± 1.2 vs. 0.58 ± 0.8, p < 0.0001) and longer PRRT duration (22.6 ± 24 vs. 15.5

  13. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature.

    Science.gov (United States)

    Angarita, Fernando A; Rodríguez, Jorge L; Meek, Eugenio; Sánchez, Jesus O; Tawil, Mauricio; Torregrosa, Lilian

    2013-06-05

    Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor. We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neoadjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis. The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.

  15. NOTCH SIGNALLING MODULATES HYPOXIA-INDUCED NEUROENDOCRINE DIFFERENTIATION OF HUMAN PROSTATE CANCER CELLS

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    Danza, Giovanna; Di Serio, Claudia; Rosati, Fabiana; Lonetto, Giuseppe; Sturli, Niccolò; Kacer, Doreen; Pennella, Antonio; Ventimiglia, Giuseppina; Barucci, Riccardo; Piscazzi, Annamaria; Prudovsky, Igor; Landriscina, Matteo; Marchionni, Niccolò; Tarantini, Francesca

    2012-01-01

    Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation has been associated with tumor progression, poor prognosis and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavourable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells, in vitro. Results exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent down regulation of Notch-mediated signalling, as demonstrated by reduced levels of the Notch target genes, Hes1 and Hey1. Neuroendocrine differentiation was promoted by attenuation of Hes1 transcription, as cells expressing a dominant negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia down regulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen independent cell lines, PC3 and Du145, it did not change the extent of NE differentiation in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur. Conclusions hypoxia induces neuroendocrine differentiation of LNCaP cells in vitro, which appears to be driven by the inhibition of Notch signalling with subsequent down-regulation of Hes1 transcription. PMID:22172337

  16. Pancreatic neuroendocrine neoplasms: Correlation between MR features and pathological tumor grades.

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    Jin, Feng; Wang, Kai; Qin, Ting-Ting; Li, Xin; Guo, Feng; Ma, Gui-Na; Hu, Xue-Han; Han, Ping

    2017-08-01

    This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms (PNENs). A total of 31 PNENs patients were retrospectively evaluated, including 19 cases in grade 1, 5 in grade 2, and 7 in grade 3. Plain and contrastenhanced MRI was performed on all patients. MRI features including tumor size, margin, signal intensity, enhancement patterns, degenerative changes, duct dilatation and metastasis were analyzed. Chi square tests, Fisher's exact tests, one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades. It was found that patients with older age, tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs (all Pgrades (all Pgrade 3 from grade 1 and grade 2 tumors. Features of peripancreatic tissue or vascular invasion, and distant metastasis showed high specificity but relatively low sensitivity. In conclusion, larger size, poorlydefined margin, heterogeneous enhanced pattern during arterial phase, duct dilatation and the presence of metastases are common features of higher grade PNENs. Plain and contrast-enhanced MRI provides the ability to differentiate tumors with different pathological grades.

  17. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring

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    Clare M. Reynolds

    2017-09-01

    Full Text Available Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut–brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

  18. A unified multi-level model approach to assessing patient responsiveness including; return to normal, minimally important differences and minimal clinically important improvement for patient reported outcome measures.

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    Sayers, Adrian; Wylde, Vikki; Lenguerrand, Erik; Gooberman-Hill, Rachael; Dawson, Jill; Beard, David; Price, Andrew; Blom, Ashley W

    2017-07-21

    This article reviews and compares four commonly used approaches to assess patient responsiveness with a treatment or therapy (return to normal (RTN), minimal important difference (MID), minimal clinically important improvement (MCII), OMERACT-OARSI [Outcome Measures in Rheumatology-Osteoarthris Reseach Society International] (OO)) and demonstrates how each of the methods can be formulated in a multilevel modelling (MLM) framework. Cohort study. A cohort of patients undergoing total hip and knee replacement were recruited from a single UK National Health Service hospital. 400 patients from the Arthroplasty Pain Experience cohort study undergoing total hip (n=210) and knee (n=190) replacement who completed the Intermittent and Constant Osteoarthritis Pain questionnaire prior to surgery and then at 3, 6 and 12 months after surgery. The primary outcome was defined as a response to treatment following total hip or knee replacement. We compared baseline scores, change scores and proportion of individuals defined as 'responders' using traditional and MLM approaches with patient responsiveness. Using existing approaches, baseline and change scores are underestimated, and the variance of baseline and change scores overestimated in comparison with MLM approaches. MLM increases the proportion of individuals defined as responding in RTN, MID and OO criteria compared with existing approaches. Using MLM with the MCII criteria reduces the number of individuals identified as responders. MLM improves the estimation of the SD of baseline and change scores by explicitly incorporating measurement error into the model and avoiding regression to the mean when making individual predictions. Using refined definitions of responsiveness may lead to a reduction in misclassification when attempting to predict who does and does not respond to an intervention and clarifies the similarities between existing methods. © Article author(s) (or their employer(s) unless otherwise stated in the text

  19. Diverse responses to UV light exposure in Acinetobacter include the capacity for DNA damage-induced mutagenesis in the opportunistic pathogens Acinetobacter baumannii and Acinetobacter ursingii

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    Bradley, James A.; Lin, Ching-li; Elam, Tyler J.

    2012-01-01

    Error-prone and error-free DNA damage repair responses that are induced in most bacteria after exposure to various chemicals, antibiotics or radiation sources were surveyed across the genus Acinetobacter. The error-prone SOS mutagenesis response occurs when DNA damage induces a cell’s umuDC- or dinP-encoded error-prone polymerases. The model strain Acinetobacter baylyi ADP1 possesses an unusual, regulatory umuD allele (umuDAb) with an extended 5′ region and only incomplete fragments of umuC. Diverse Acinetobacter species were investigated for the presence of umuDC and their ability to conduct UV-induced mutagenesis. Unlike ADP1, most Acinetobacter strains possessed multiple umuDC loci containing either umuDAb or a umuD allele resembling that of Escherichia coli. The nearly omnipresent umuDAb allele was the ancestral umuD in Acinetobacter, with horizontal gene transfer accounting for over half of the umuDC operons. Despite multiple umuD(Ab)C operons in many strains, only three species conducted UV-induced mutagenesis: Acinetobacter baumannii, Acinetobacter ursingii and Acinetobacter beijerinckii. The type of umuDC locus or mutagenesis phenotype a strain possessed was not correlated with its error-free response of survival after UV exposure, but similar diversity was apparent. The survival of 30 Acinetobacter strains after UV treatment ranged over five orders of magnitude, with the Acinetobacter calcoaceticus–A. baumannii (Acb) complex and haemolytic strains having lower survival than non-Acb or non-haemolytic strains. These observations demonstrate that a genus can possess a range of DNA damage response mechanisms, and suggest that DNA damage-induced mutation could be an important part of the evolution of the emerging pathogens A. baumannii and A. ursingii. PMID:22117008

  20. Arabidopsis GROWTH-REGULATING FACTOR7 Functions as a Transcriptional Repressor of Abscisic Acid– and Osmotic Stress–Responsive Genes, Including DREB2A[W

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    Kim, June-Sik; Mizoi, Junya; Kidokoro, Satoshi; Maruyama, Kyonoshin; Nakajima, Jun; Nakashima, Kazuo; Mitsuda, Nobutaka; Takiguchi, Yuko; Ohme-Takagi, Masaru; Kondou, Youichi; Yoshizumi, Takeshi; Matsui, Minami; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2012-01-01

    Arabidopsis thaliana DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN2A (DREB2A) functions as a transcriptional activator that increases tolerance to osmotic and heat stresses; however, its expression also leads to growth retardation and reduced reproduction. To avoid these adverse effects, the expression of DREB2A is predicted to be tightly regulated. We identified a short promoter region of DREB2A that represses its expression under nonstress conditions. Yeast one-hybrid screening for interacting factors identified GROWTH-REGULATING FACTOR7 (GRF7). GRF7 bound to the DREB2A promoter and repressed its expression. In both artificial miRNA-silenced lines and a T-DNA insertion line of GRF7, DREB2A transcription was increased compared with the wild type under nonstress conditions. A previously undiscovered cis-element, GRF7-targeting cis-element (TGTCAGG), was identified as a target sequence of GRF7 in the short promoter region of DREB2A via electrophoretic mobility shift assays. Microarray analysis of GRF7 knockout plants showed that a large number of the upregulated genes in the mutant plants were also responsive to osmotic stress and/or abscisic acid. These results suggest that GRF7 functions as a repressor of a broad range of osmotic stress–responsive genes to prevent growth inhibition under normal conditions. PMID:22942381

  1. Arabidopsis growth-regulating factor7 functions as a transcriptional repressor of abscisic acid- and osmotic stress-responsive genes, including DREB2A.

    Science.gov (United States)

    Kim, June-Sik; Mizoi, Junya; Kidokoro, Satoshi; Maruyama, Kyonoshin; Nakajima, Jun; Nakashima, Kazuo; Mitsuda, Nobutaka; Takiguchi, Yuko; Ohme-Takagi, Masaru; Kondou, Youichi; Yoshizumi, Takeshi; Matsui, Minami; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2012-08-01

    Arabidopsis thaliana DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN2A (DREB2A) functions as a transcriptional activator that increases tolerance to osmotic and heat stresses; however, its expression also leads to growth retardation and reduced reproduction. To avoid these adverse effects, the expression of DREB2A is predicted to be tightly regulated. We identified a short promoter region of DREB2A that represses its expression under nonstress conditions. Yeast one-hybrid screening for interacting factors identified GROWTH-REGULATING FACTOR7 (GRF7). GRF7 bound to the DREB2A promoter and repressed its expression. In both artificial miRNA-silenced lines and a T-DNA insertion line of GRF7, DREB2A transcription was increased compared with the wild type under nonstress conditions. A previously undiscovered cis-element, GRF7-targeting cis-element (TGTCAGG), was identified as a target sequence of GRF7 in the short promoter region of DREB2A via electrophoretic mobility shift assays. Microarray analysis of GRF7 knockout plants showed that a large number of the upregulated genes in the mutant plants were also responsive to osmotic stress and/or abscisic acid. These results suggest that GRF7 functions as a repressor of a broad range of osmotic stress-responsive genes to prevent growth inhibition under normal conditions.

  2. An unusual association of neuroendocrine tumors in MEN 1A.

    Science.gov (United States)

    Varsavsky, Mariela; Reyes-García, Rebeca; Alonso García, Guillermo; Muñoz-Torres, Manuel

    2012-09-01

    Multiple Endocrine Neoplasia type 1 is an autonomic dominant disease with a high degree of penetrance. It is characterized by combinations of over 20 different endocrine and nonendocrine tumors. A 25-year-old woman was referred for 1 year-evolution amenorrhea and bilateral galactorrhea. She also had fasting hypoglycaemia and hypercalcemia, and she was diagnosed of Multiple Endocrine Neoplasia type 1A. Resection of three parathyroid glands was performed showing hyperplasia of principal cells. Post-parathyroidectomy serum levels of calcium and intact PTH were normal but 3 years later serum calcium levels rose again. A 99mTc-sestamibi scan showed increased uptake in the low right area compatible with adenoma. After biochemical test showing probable insulinoma, somatostatin receptor scintigraphy showed a focal captation in head and body of pancreas. MRI found two nodules in the same localization. An antral gastrectomy, total pancreatoduodenectomy, colecistectomy and truncal vagotomy was performed and histopathologic examination revealed a combination of neuroendocrine tumors: gastrinomas, somastotinomas, glucagonomas and insulinomas. After surgery she started with tingling in fingers, toes and lips, and calcium levels was 5.9 mg/dl and PTH intact 3 pg/ml. A new 99m Tc-sestamibi scan showed no captation and cervical ultrasonography was normal. Now, 2 years later, she continues with normal calcium and i-PTH levels. This report represents an unusual case of MEN 1A with association of insulinomas, gastrinomas glucagonomas and somatostatinomas in the same patient.

  3. [Genetic and neuroendocrine aspects in autism spectrum disorder].

    Science.gov (United States)

    Oviedo, Norma; Manuel-Apolinar, Leticia; de la Chesnaye, Elsa; Guerra-Araiza, Christian

    The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  4. Evaluation of neuroendocrine markers in renal cell carcinoma

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    Kauppila Saila

    2010-05-01

    Full Text Available Abstract Background The purpose of the study was to examine serotonin, CD56, neurone-specific enolase (NSE, chromogranin A and synaptophysin by immunohistochemistry in renal cell carcinomas (RCCs with special emphasis on patient outcome. Methods We studied 152 patients with primary RCCs who underwent surgery for the removal of kidney tumours between 1990 and 1999. The mean follow-up was 90 months. The expression of neuroendocrine (NE markers was determined by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, clinical stage, Fuhrman grade and patient outcome. Results Eight percent of tumours were positive for serotonin, 18% for CD56 and 48% for NSE. Chromogranin A immunostaining was negative and only 1% of the tumours were synaptophysin immunopositive. The NSE immunopositivity was more common in clear cell RCCs than in other subtypes (p = 0.01. The other NE markers did not show any association with the histological subtype. Tumours with an immunopositivity for serotonin had a longer RCC-specific survival and tumours with an immunopositivity for CD56 and NSE had a shorter RCC-specific survival but the difference was not significant. There was no relationship between stage or Fuhrman grade and immunoreactivity for serotonin, CD56 and NSE. Conclusions Serotonin, CD56 and NSE but not synaptophysin and chromogranin A are expressed in RCCs. However, the prognostic potential of these markers remains obscure.

  5. Ileal neuroendocrine tumors and heart: not only valvular consequences.

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    Calissendorff, Jan; Maret, Eva; Sundin, Anders; Falhammar, Henrik

    2015-04-01

    Ileal neuroendocrine tumors (NETs) often progress slowly, but because of their generally nonspecific symptoms, they have often metastasized to local lymph nodes and to the liver by the time the patient presents. Biochemically, most of these patients have increased levels of whole blood serotonin, urinary 5-hydroxyindoleacetic acid, and chromogranin A. Imaging work-up generally comprises computed tomography or magnetic resonance imaging and somatostatin receptor scintigraphy, or in recent years positron emission tomography with 68Ga-labeled somatostatin analogs, allowing for detection of even sub-cm lesions. Carcinoid heart disease with affected leaflets, mainly to the right side of the heart, is a well-known complication and patients routinely undergo echocardiography to diagnose and monitor this. Multitasking surgery is currently recognized as first-line treatment for ileal NETs with metastases and carcinoid heart disease. Open heart surgery and valve replacement are advocated in patients with valvular disease and progressive heart failure. When valvulopathy in the tricuspid valve results in right-sided heart failure, a sequential approach, performing valve replacement first before intra-abdominal tumor-reductive procedures are conducted, reduces the risk of bleeding. Metastases to the myocardium from ileal NETs are seen in heart metastases are detected, with the addition of diuretics and fluid restriction in cases of heart failure. Myocardial metastases are rarely treated by surgical resection.

  6. Outcome and CT differentiation of gallbladder neuroendocrine tumours from adenocarcinomas

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    Kim, Tae-Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital and Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lee, Kyoung Boon [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-02-15

    To retrospectively investigate clinical outcome and differential CT features of gallbladder (GB) neuroendocrine tumours (NETs) from adenocarcinomas (ADCs). Nineteen patients with poorly-differentiated (PD) NETs and 19 patients with PD ADCs were enrolled. Clinical outcome was compared by the Kaplan-Meier method. We assessed qualitative and quantitative CT features to identify significant differential CT features of PD NETs from ADCs using univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was used for quantitative CT features. PD NETs showed poorer prognosis with significantly shorter median survival days than ADCs (363 vs. 590 days, P = 0.03). On univariate analysis, NETs more frequently manifested as GB-replacing type and showed well-defined margins accompanied with intact overlying mucosa. On multivariate analysis, well-defined margin was the sole significant CT differentiator (odds ratio = 27.817, P = 0.045). Maximum size of hepatic and lymph node (LN) metastases was significantly larger in NETs (11.0 cm and 4.62 cm) than ADCs (2.40 cm and 2.41 cm). Areas under ROC curves for tumour-to-mucosa ratio, maximum size of hepatic and LN metastasis were 0.772, 0.932 and 0.919, respectively (P < 0.05). GB PD NETs show poorer prognosis than ADCs. Well-defined margin, larger hepatic and LN metastases are useful CT differentiators of GB NETs from ADCs. (orig.)

  7. The many faces of neuroendocrine differentiation in prostate cancer progression

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    Stephane eTerry

    2014-03-01

    Full Text Available In normal prostate, neuroendocrine (NE cells are rare and interspersed among the epithelium. These cells are believed to provide trophic signals to epithelial cell populations through the secretion of an abundance of neuropeptides that can diffuse to influence surrounding cells. In the setting of prostate cancer (PC, NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but in some cases adenocarcinoma cells themselves acquire NE characteristics. This epithelial plasticity is associated with decreased androgen receptor (AR signaling and the accumulation of neuronal and stem cell characteristics. Transformation to a NE phenotype is one proposed mechanism of resistance to contemporary AR targeted treatments, is associated with poor prognosis, and thought to represent up to 25% of lethal PCs. Importantly, the advent of high-throughput technologies has started to provide clues for understanding the complex molecular profiles of tumors exhibiting NE differentiation. Here, we discuss these recent advances, the multifaceted manner by which a NE-like state may arise during the different stages of disease progression, and the potential benefit of this knowledge for the management of patients with advanced PC

  8. Metabonomic profiling: a novel approach in neuroendocrine neoplasias.

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    Kinross, James M; Drymousis, Panagiotis; Jiménez, Beatriz; Frilling, Andrea

    2013-12-01

    A metabonomic phenotyping strategy was developed as part of a pilot study to define a diagnostic metabolic phenotype for neuroendocrine neoplasms (NEN). Twenty-eight patients with NEN were prospectively recruited: small bowel NEN, n = 8; pancreatic NEN, n = 10; and others, n = 10 (mean age 49.4 years [26–81] male/female ratio 17:11). There were 17 healthy control patients. Urine samples were subjected to 1H nuclear magnetic resonance spectroscopic profiling via the use of a Bruker Avance 600-MHz spectrometer (Bruker, Rheinstetten, Germany). Acquired spectral data were imported into SIMCA and MATLAB for supervised and unsupervised multivariate analysis. Partial least squares-discriminant analysis differentiated between NEN and healthy samples with accuracy (R(2)Y = 0.79, Q2Y = 0.53, area under the curve [AUC] 0.90). Orthogonal partial least squares-discriminant analysis was able to distinguish between small bowel NEN and pancreatic NEN (R2Y = 0.91, Q2Y = 0.35). Subclass analysis also demonstrated class separation between functional and nonfunctional NEN (R2Y = 0.98, Q2Y = 0.77, AUC 0.6) and those with metastases (R2Y = 0.72 , Q2 Y = 0.41, AUC 0.86) due to variations in hippurate metabolism (P < .0001). Metabonomic analysis suggests that subgroups of NEN may possess a stratified metabolic phenotype. Metabolic profiling could provide novel biomarkers for NEN.

  9. Post Hoc Analysis of the Phase II/III APRIL-SLE Study: Association Between Response to Atacicept and Serum Biomarkers Including BLyS and APRIL.

    Science.gov (United States)

    Gordon, Caroline; Wofsy, David; Wax, Stephen; Li, Yong; Pena Rossi, Claudia; Isenberg, David

    2017-01-01

    To assess the relationship between treatment response, baseline biomarker levels, and atacicept exposure in patients with systemic lupus erythematosus (SLE) in the phase II/III APRIL-SLE study. We performed a post hoc analysis of patients who received placebo, atacicept 75 mg, or atacicept 150 mg in a randomized, controlled, 52-week trial. Serum levels of BlyS and APRIL were measured at baseline, and serum levels of Ig and the numbers of naive B cells and plasma cells were measured at baseline and during treatment. Atacicept exposure was determined by assessment of the serum trough concentrations throughout the 52-week trial period. Associations between these parameters, treatment response (reduction in British Isles Lupus Assessment Group A or B flare), and infection rates were explored. Recurrent high baseline levels of both BLyS (≥1.6 ng/ml) and APRIL (≥2.2 ng/ml) correlated with a greater treatment response (flare rate 75.7% with placebo, and 50.0% and 32.0% with atacicept 75 mg and atacicept 150 mg, respectively) compared with lower baseline levels of both. Increased atacicept exposure correlated with reduced flare rates (60.5% with placebo; 63.4%, 61.0%, 48.8%, and 29.3% in the 4 quartiles, from lowest to highest atacicept exposure). Greater pharmacodynamic responses (reduced Ig levels and naive B cell and plasma cell numbers) were associated with greater reductions in the flare rate. Infection rates were similar regardless of biomarker levels at baseline or at the time of atacicept exposure. These post hoc analyses demonstrate a dose-response relationship between atacicept concentrations, reduced Ig levels, and reduced flare rates and suggest that baseline biomarkers such as elevated serum levels of BLyS and APRIL may help to identify the patients who are most likely to benefit from atacicept treatment. © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  10. Clinical analysis of 50 Eastern Asian patients with primary pulmonary large-cell neuroendocrine carcinoma

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    Zhang XK

    2015-05-01

    Full Text Available Xin-ke Zhang,1,* Tao Qin,1,* Yin-duo Zeng,1,2,* Yuan-yuan Zhao,1 Xue Hou,1 Wen-feng Fang,1 Shao-dong Hong,1 Ting Zhou,1 Zhi-huang Hu,1 Yun-peng Yang,1 Yu-xiang Ma,1 Cong Xue,1 Yan Huang,1 Hong-yun Zhao,1 Li Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: To understand the clinicopathological features of patients with primary pulmonary large-cell neuroendocrine carcinoma (LCNEC, including the frequency of epidermal growth factor receptor (EGFR mutation, and to explore prognostic factors.Methods: We investigated a cohort of 50 individuals from our center database who were diagnosed with operable pulmonary LCNEC and treated in Sun Yat-sen University Cancer Center. Serum albumin (ALB and neuron-specific enolase (NSE were also collected. Survival curves were obtained with the Kaplan–Meier method, and the differences between groups in survival were tested by the log-rank test.Results: The median age was 59 years (range, 40–80 years. Fourteen patients underwent mutational analysis of EGFR; of these, 12 had wild-type EGFR and the remaining two had EGFR mutations in exons. The median disease-free survival (DFS of pulmonary LCNEC was 49.3 months and that of overall survival (OS was not reached. DFS and OS were shorter for patients with decreased serum ALB than for patients with normal serum ALB (P=0.003 and P=0.004, respectively. Meanwhile, a high level of NSE was also significantly associated with short DFS and OS (P=0.005 and P=0.000, respectively. Multivariate analysis showed that decrease in serum ALB was an independent prognostic factor for OS (P=0.046.Conclusion: The frequency of EGFR mutation in LCNEC patients is low. Serum ALB and NSE levels are

  11. Neuroendocrine-Immune Support of Diuretic Effect of Balneotherapy on Truskavets Resort

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    Yu.S. Lukovych

    2015-04-01

    Full Text Available Objective: to identify concomitant changes in parameters of neuroendocrine-immune complex and colon microbiocenosis, which accompany diuretic effect of balneotherapy on Truskavets resort. Results. The study included 22 male patients with chronic pyelonephritis associated with cholecystitis, it is found that 10–12-day course of balneotherapy (drinking bioactive water Naftusia, ozokerit applications, mineral baths increases daily urine output by 28 % (p  0.05, in a greater degree due to increased PSD HF than LF. The basal level of plasma cortisol decreased by 20 % (p < 0.01, testosterone — by 15 % (p = 0.01, whereas levels of triiodothyronine increases by 4 % (p < 0.05 and especially calcitonin activity — by 92 % (p < 0.001, calculated by urinary excretion of phosphates and calcium. Leukocytic adaptation index of Popovich increases by 46 % (p < 0.02. As for the parameters of neutrophil phagocytic function, an increase of reduced killing index of Staphy­lococcus aureus by 19 % (p < 0.001 and Escherichia coli by 18 % (p < 0.01 was stated in the absence of changes in initially normal phagocytic index. Microbial count in relation to Staphylococcus aureus is normal, and intensity of phagocytosis of Escherichia coli, initially increased by 15 %, reduced by 8 % (p < 0.05. Regarding immunity parameters, it was revealed a significant increase in the blood of CD16+ lymphocytes only (+17 %, p < 0.01 in the absence of changes in levels of CD3+CD4+ and CD3+CD8+ T-lymphocytes and CD19+ B-lymphocytes. Neither serum Ig G, M, A or circulating immune complexes levels change significantly. Immunotropic effect is accompanied by a reduction of dysbiosis manifestations: Bifidumbacter content increases by 19 % (p < 0.02, Lactobacter — by 20 % (p < 0.05, and Escherichia coli — by 48 % (p < 0.01, while the part of strains with reduced enzymatic properties is decreased by 47 % (p < 0.001, with hemolytic properties — by 77 % (p < 0.01. Conclusion

  12. Small cell neuroendocrine carcinoma of tracheostomy site in a patient with a history of juvenile laryngeal papillomatosis.

    Science.gov (United States)

    Violet Wilmot, Victoria; Nixon, Iain James; Nixon, Ioanna Fragkandrea

    2016-08-09

    Juvenile laryngeal papillomatosis is the commonest cause of benign epithelial tumours of the larynx. Following diagnostic biopsy, surgical debulking is the mainstay of therapy. The condition is often recurrent with further papillomas forming after debridement, requiring serial procedures and occasionally demanding tracheostomy. Rarely, the disease can undergo malignant transformation; most commonly to squamous cell carcinoma. We describe the first reported case of small cell neuroendocrine carcinoma occurring in the previous tracheostomy site of a 29-year-old male with a history of juvenile laryngeal papillomatosis. The patient, with a background of multiple treatments for juvenile papillomas, presented with voice change, breathing difficultly and erythema at the site of previous tracheostomy. Induction chemotherapy followed by chemoradiation was used to treat the lesion with a good response to initial therapy. 2016 BMJ Publishing Group Ltd.

  13. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells

    Science.gov (United States)

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L.; Liao, Gongxian; Hoffman, Brad E.; Leong, Kam W.; Terhorst, Cox; Daniell, Henry

    2015-01-01

    Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody (“inhibitor”) formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)–dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80+ cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103+ and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4+ regulatory T cells (CD4+CD25−LAP+ cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4+CD25+ regulatory T cells systemically suppressed anti-FIX responses. PMID:25700434

  14. Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    2013-06-01

    Full Text Available We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

  15. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

    NARCIS (Netherlands)

    F.R.E. Nobels (Frank); D.J. Kwekkeboom (Dirk Jan); W. Coopmans; C.H.H. Schoenmakers (Christian); J. Lindemans (Jan); E.P. Krenning (Eric); R. Bouillon (Roger); S.W.J. Lamberts (Steven); W.W. de Herder (Wouter)

    1997-01-01

    textabstractChromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other

  16. Poorly-differentiated colorectal neuroendocrine tumour: CT differentiation from well-differentiated neuroendocrine tumour and poorly-differentiated adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ji Hee [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-09-15

    The differentiation of poorly-differentiated neuroendocrine tumours (PD-NETs), well-differentiated NETs (WD-NETs), and adenocarcinomas (ADCs) is important due to different management options and prognoses. This study is to find the differential CT features of colorectal PD-NETs from WD-NETs and ADCs. CT features of 25 colorectal WD-NETs, 36 PD-NETs, and 36 ADCs were retrospectively reviewed. Significant variables were assessed using univariate and multivariate analyses. Receiver operating characteristics analysis determined the optimal cut-off value of tumour and lymph node (LN) size. Large size, rectum location, ulceroinfiltrative morphology without intact overlying mucosa, heterogeneous attenuation with necrosis, presence of ≥3 enlarged LNs, and metastasis were significant variables to differentiate PD-NETs from WD-NETs (P < 0.05). High attenuation on arterial phase, persistently high enhancement pattern, presence of ≥6 enlarged LNs, large LN size, and wash-in/wash-out enhancement pattern of liver metastasis were significant variables to differentiate PD-NETs from ADCs (P < 0.05). Compared to WD-NETs, colorectal PD-NETs are usually large, heterogeneous, and ulceroinfiltrative mass without intact overlying mucosa involving enlarged LNs and metastasis. High attenuation on arterial phase, presence of enlarged LNs with larger size and greater number, and wash-in/wash-out enhancement pattern of liver metastasis can be useful CT discriminators of PD-NETs from ADCs. (orig.)

  17. An expanded analysis of pharmacogenetics determinants of efavirenz response that includes 3'-UTR single nucleotide polymorphisms among Black South African HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Marelize eSwart

    2016-01-01

    Full Text Available Introduction: Efavirenz (EFV is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in EFV plasma concentrations has been reported. Poor treatment outcomes such as the development of adverse drug reactions or treatment failure have been linked to EFV concentrations outside the therapeutic range (1 - 4 µg/mL. The drug metabolising enzyme (DME, CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP2A6, CYP3A4, CYP3A5, UGT2B7 and CYP1A2. Genes coding for DMEs have been shown to be regulated by microRNAs through targeting the 3'-untranslated region. Genetic variation in the 3'-UTR, in addition to genetic variation in the coding regions, could potentially be used to explain a larger proportion of the inter-individual variability observed in drug response. Methods: SNPs in CYP1A2, CYP2B6, UGT2B7 and NR1I2 (PXR were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing specifically the role of genetic variation in the 3'-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV.Results: In addition to CYP2B6 c.516G>T and c.983T>C SNPs, the CYP2B6 c.1355A>G SNP was identified as pharmacogenetics determinant of EFV concentration among CYP2B6 intermediate and extensive metabolisers (carriers of either c.516G/G+c.983T/T or c.516G/G+c.983T/C or c.516G/T+c.983T/T genotypes. NR1I2 c.522C>T and NR1I3 c.239-1089T>C SNPs were predictors of EFV concentration among CYP2B6 poor metabolisers (carriers of either c.516T/T or c.983C/C or both c.516G/T and c.983T/C genotypes.Conclusion: Genotyping results provide support for comprehensive studies of genetic variation in the 3'-UTR of genes coding for DMEs and their

  18. Pancreatic neuroendocrine tumour: Correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival.

    Science.gov (United States)

    Kim, Mimi; Kang, Tae Wook; Kim, Young Kon; Kim, Seong Hyun; Kwon, Wooil; Ha, Sang Yun; Ji, Sang A

    2016-03-01

    To evaluate the correlation between grade of pancreatic neuroendocrine tumours (pNETs) based on the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC), and to assess whether the ADC value and WHO classification can predict recurrence-free survival (RFS) after surgery for pNETs. This retrospective study was approved by the Institutional Review Board. The requirement for informed consent was waived. Between March 2009 and November 2014, forty-nine patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for single pNETs were included. Correlations among qualitative MR imaging findings, quantitative ADC values, and WHO classifications were assessed. An ordered logistic regression test was used to control for tumour size as a confounding factor. The association between ADC value (or WHO classification) and RFS was analysed. All tumors (n=49) were classified as low- (n=29, grade 1), intermediate- (n=17, grade 2), and high-grade (n=3, grade 3), respectively. The mean ADC of pNETs was moderately negatively correlated with WHO classification before and after adjustment for tumour size (ρ=-0.64, pcorrelated with WHO tumour grade, regardless of tumour size. However, the WHO tumour classification of pNET may be more suitable for predicting RFS than the ADC value. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Pancreatic splenosis mimicking neuroendocrine tumors: microhistological diagnosis by endoscopic ultrasound guided fine needle aspiration.

    Science.gov (United States)

    Ardengh, José Celso; Lopes, César Vivian; Kemp, Rafael; Lima-Filho, Eder Rios; Venco, Filadelfo; Santos, José Sebastião dos

    2013-01-01

    Pancreatic splenosis is a benign condition which can mimic a pancreatic neoplasm. To describe the role of the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic nodules suspicious for pancreatic splenosis. From 1997 to 2011, patients with pancreatic solid tumors suspicious for splenosis by computed tomography and/or magnetic resonance imaging were referred to EUS-FNA. Those cases with pancreatic splenosis confirmed by EUS-FNA or surgery were included. Endosonographic findings and clinicopathologic features were also analysed. A total of 2,060 patients with pancreatic solid tumors underwent EUS-FNA. Fourteen (0.6%) cases with pancreatic splenosis were found. After applying exclusion criteria, 11 patients were selected. Most patients were male (7), young (mean age: 42 years) and asymptomatic (8). Endoscopic ultrasound imaging alone suspected pancreatic splenosis in 6 cases, and neuroendocrine tumors in 5 cases. Pancreatic splenosis was found most commonly in the tail, was round, hypoechoic, with homogeneous pattern, regular borders, and with scintigraphy negative for somatostatin receptors. The average diameter of these nodules identified by endoscopic ultrasound was 2.15 cm. Microhistology obtained by EUS-FNA confirmed the diagnosis in 9/10 patients. Pancreatic splenosis can be diagnosed by EUS-FNA. Microhistology prevents unnecessary surgeries, and reassures asymptomatic patients with hypoechoic, homogeneous, and well circumscribed pancreatic nodules.

  20. PANCREATIC SPLENOSIS MIMICKING NEUROENDOCRINE TUMORS: microhistological diagnosis by endoscopic ultrasound guided fine needle aspiration

    Directory of Open Access Journals (Sweden)

    Jose Celso ARDENGH

    2013-03-01

    Full Text Available Context Pancreatic splenosis is a benign condition which can mimic a pancreatic neoplasm. Objective To describe the role of the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA of pancreatic nodules suspicious for pancreatic splenosis. Method From 1997 to 2011, patients with pancreatic solid tumors suspicious for splenosis by computed tomography and/or magnetic resonance imaging were referred to EUS-FNA. Those cases with pancreatic splenosis confirmed by EUS-FNA or surgery were included. Endosonographic findings and clinicopathologic features were also analysed. Results A total of 2,060 patients with pancreatic solid tumors underwent EUS-FNA. Fourteen (0.6% cases with pancreatic splenosis were found. After applying exclusion criteria, 11 patients were selected. Most patients were male (7, young (mean age: 42 years and asymptomatic (8. Endoscopic ultrasound imaging alone suspected pancreatic splenosis in 6 cases, and neuroendocrine tumors in 5 cases. Pancreatic splenosis was found most commonly in the tail, was round, hypoechoic, with homogeneous pattern, regular borders, and with scintigraphy negative for somatostatin receptors. The average diameter of these nodules identified by endoscopic ultrasound was 2.15 cm. Microhistology obtained by EUS-FNA confirmed the diagnosis in 9/10 patients. Conclusion Pancreatic splenosis can be diagnosed by EUS-FNA. Microhistology prevents unnecessary surgeries, and reassures asymptomatic patients with hypoechoic, homogeneous, and well circumscribed pancreatic nodules.

  1. MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations

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    Duan, Xiaohui; Zhang, Xiang; Hu, Huijun; Li, Guozhao; Wang, Dongye; Zhang, Fang; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou (China); Ban, Xiaohua [Sun Yat-Sen University, Medical Imaging and Minimally Invasive Interventional Center and State Key Laboratory of Oncology in Southern China, Cancer Center, Guangzhou, Guangdong (China); Wang, Charles Qian [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou (China); University of New South Wales, JMO, Westmead Hospital, Sydney (Australia)

    2016-12-15

    To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 x 10{sup -3} mm{sup 2}/s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. (orig.)

  2. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

    Directory of Open Access Journals (Sweden)

    Sangbin Park

    2011-08-01

    Full Text Available Drosophila neuroendocrine cells comprising the corpora cardiaca (CC are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

  3. Identification of candidate serum proteins for classifying well-differentiated small intestinal neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Spyros Darmanis

    Full Text Available BACKGROUND: Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NETs are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required. MATERIALS AND METHODS: Suspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases. RESULTS: A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification. CONCLUSIONS: We propose new potential protein biomarker candidates for classifying WD-SI-NETs at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NETs and their eventual use in diagnostics.

  4. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

    Science.gov (United States)

    Park, Sangbin; Bustamante, Erika L; Antonova, Julie; McLean, Graeme W; Kim, Seung K

    2011-08-01

    Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

  5. The Neuroendocrine System and Stress, Emotions, Thoughts and Feelings**

    Science.gov (United States)

    Vaillant, George E.

    2011-01-01

    The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions), and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. “left brain”) terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it “hears” are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, “Danger mines!!” However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of “love” being either Eros (raw, amoral instinct) or agape (noble, non-specific valuing of all other people) miss the motivational forest for the trees. Neither Eros (hypothalamic) nor agape (cortical) has a fraction of the power to relieve stress as attachment (limbic love), yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, “spiritual” positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points. PMID:21694965

  6. Maternal neuroendocrine serum levels in exclusively breastfeeding mothers.

    Science.gov (United States)

    Stuebe, Alison M; Meltzer-Brody, Samantha; Pearson, Brenda; Pedersen, Cort; Grewen, Karen

    2015-05-01

    Low milk supply is a common cause of early weaning, and supply issues are associated with dysregulation of thyroid function and prolactin. However, hormone levels compatible with successful breastfeeding are not well defined, limiting interpretation of clinical lab results. In this study we sought to quantify ranges for thyroid-stimulating hormone (TSH), free thyroxine (T4), total T4, and prolactin in a cohort of exclusively breastfeeding women. Women planning to breastfeed were recruited in the third trimester of pregnancy. Maternal endocrine function was assessed before and after a breastfeeding session at 2 and 8 weeks postpartum. We used paired t tests to determine whether values changed from the 2- to 8-week visit. Of 52 study participants, 28 were exclusively breastfeeding, defined as only breastmilk feeds in the prior 7 days, at both the 2- and 8-week study visits. Endocrine function changed with time since delivery: the TSH level was higher, whereas total T4, free T4, and prolactin levels were lower, at the 8-week visit than at the 2-week visit (by paired t test, p≤0.01). We found a wide range of prolactin values at the 8-week visit, with a 5th percentile value of 9 ng/dL before feeding and 74 ng/dL at 10 minutes after feeding. Neuroendocrine function changes during the first 8 weeks after birth, and a wide range of values is compatible with successful breastfeeding. Further studies are needed to define reference values in breastfeeding women.

  7. Lu-177 DOTATATE dosimetry for neuroendocrine tumor: single center experience

    Science.gov (United States)

    Said, MA; Masud, MA; Zaini, MZ; Salleh, RA; Lee, BN; Zainon, R.

    2017-05-01

    Lu-177 labelled with DOTATE is widely acceptable to treat Neuroendocrine Tumor (NET) disease and it better improvement of quality of patients’ life since few years ago. However, the radionuclide toxicity becomes the main limitation of the (NET) treatment. Therefore, we performed a pilot study aimed to estimate radiation absorbed doses to dose-limiting organs to develop a systemic therapy with Lu-177 in NET patients. In this study, five set of planar whole body images was acquired every 0.5 hour, 4 hours, 24 hours, 48 hours and 72 hours after Lu-177 administrations. The planar image acquisition was done using Philip Brightview X with Medium Energy General Purpose Collimator (MEGP) collimator. All patients’ images in Conjugate View (CV) format were transferred into PMOD 3.7 Software for Region of Interest (ROI) analysis. The ROI were drawn at selected organs such as kidneys, liver, spleen and bladder. This study found that the mean absorbed dose for kidneys 0.62 ± 0.26 Gy/GBq, liver 0.63 ± 0.28 Gy/GBq, spleen 0.83 ± 0.73 Gy/GBq and bladder 0.14 ± 0.07 Gy/GBq. The radionuclide kinetic for the whole body 99.7 ± 0.1 percent at 0.5 hours, 79.5 ± 10.7 percent at 4 hours, 56.6 ± 10.3 percent at 24 hours, 43.2 ± 7.9 percent at 48 hours and 37.1 ± 9.0 percent at 72 hours. This study verifies that this planar quantitative method able to determine organ at risk and the result line with other published data.

  8. The neuroendocrine system and stress, emotions, thoughts and feelings.

    Science.gov (United States)

    Vaillant, George E

    2011-01-01

    The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions), and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain") terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct) or agape (noble, non-specific valuing of all other people) miss the motivational forest for the trees. Neither Eros (hypothalamic) nor agape (cortical) has a fraction of the power to relieve stress as attachment (limbic love), yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.

  9. A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

    Directory of Open Access Journals (Sweden)

    Kjell Oberg

    2016-09-01

    Full Text Available The complexity of the clinical management of neuroendocrine neoplasia (NEN is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin; monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33 assessed current imaging strategies and biomarkers in NEN management. Consensus (>75% was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

  10. [Structural plasticity of the adult central nervous system: insights from the neuroendocrine hypothalamus].

    Science.gov (United States)

    Girardet, Clémence; Bosler, Olivier

    2011-01-01

    Accumulating evidence renders the dogma obsolete according to which the structural organization of the brain would remain essentially stable in adulthood, changing only in response to a need for compensatory processes during increasing age and degeneration. It has indeed become clear from investigations on various models that the adult nervous system can adapt to physiological demands by altering reversibly its synaptic circuits. This potential for structural and functional modifications results not only from the plastic properties of neurons but also from the inherent capacity of the glial cellular components to undergo remodeling as well. This is currently known for astrocytes, the major glial cells in brain which are well-recognized as dynamic partners in the mechanisms of synaptic transmission, and for the tanycytes and pituicytes which contribute to the regulation of neurosecretory processes in neurohemal regions of the hypothalamus. Studies on the neuroendocrine hypothalamus, whose role is central in homeostatic regulations, have gained good insights into the spectacular neuronal-glial rearrangements that may subserve functional plasticity in the adult brain. Following pioneering works on the morphological reorganizations taking place in the hypothalamo-neurohypophyseal system under certain physiological conditions such as dehydration and lactation, studies on the gonadotropic system that orchestrates reproductive functions have re-emphasized the dynamic interplay between neurons and glia in brain structural plasticity processes. This review summarizes the major contributions provided by these researches in the field and also addresses the question of the morphological rearrangements that occur on a 24-h basis in the central component of the circadian clock responsible for the temporal aspects of endocrine regulations. Taken together, the reviewed data highlight the close cooperation between neurons and glia in developing strategies for functional adaptation

  11. Failed Lactation and Perinatal Depression: Common Problems with Shared Neuroendocrine Mechanisms?

    Science.gov (United States)

    Grewen, Karen; Pedersen, Cort A.; Propper, Cathi; Meltzer-Brody, Samantha

    2012-01-01

    Abstract In the early postpartum period, mother and infant navigate a critical neuroendocrine transition from pregnancy to lactation. Two major clinical problems that occur during this transition are failed lactation and perinatal mood disorders. These disorders often overlap in clinical settings. Failed lactation is common. Although all major medical organizations recommend 6 months of exclusive breastfeeding, only 13% of women in the United States achieve this recommendation. Perinatal mood disorders affect 10% of mothers, with substantial morbidity for mother and child. We hypothesize that shared neuroendocrine mechanisms contribute to both failed lactation and perinatal mood disorders. In this hypothesis article, we discuss data from both animal models and clinical studies that suggest neuroendocrine mechanisms that may underlie these two disorders. Research to elucidate the role of these underlying mechanisms may identify treatment strategies both to relieve perinatal depression and to enable women to achieve their infant feeding goals. PMID:22204416

  12. [Aldehyde reductase activity and blood aldo-keto reductase spectrum in adolescents with neuroendocrine obesity].

    Science.gov (United States)

    Kuleshova, D K; Davydov, V V; Shvets, V N

    2012-01-01

    Investigation of aldehyde-reductase activity and blood aldo-keto reductase spectrum has been performed in 13-15 and 16-18-years old adolescents with obesity to clear up the mechanisms of neuroendocrine obesity at the age of puberty. It has been established that basal aldehyde reductase activity and blood aldo-keto reductase spectrum of healthy adolescents in early puberty do not differ from those of healthy adolescents in late puberty. A decreased aldehyde reductase activity and some alterations in blood aldo-keto reductase spectrum have been observed in late puberty in adolescents with neuroendocrine obesity. In adolescents with obesity there have been registered some changes in blood aldo-keto reductase spectrum which are not accompanied by any alterations in its aldehyde reductase activity. The results obtained suggest that certain prerequisites are formed in late puberty to complicate the course of neuroendocrine obesity.

  13. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    Science.gov (United States)

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-10-13

    Poorly-differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly-differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports and pathology slides were reviewed for demographics, clinical history and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1 and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61years old with 18 males and 19 females. The colorectum (n=20) was the most common primary site, other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%), and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly-differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017. Published by Elsevier Inc.

  14. Heterogeneity in Pseudomonas aeruginosa Biofilms Includes Expression of Ribosome Hibernation Factors in the Antibiotic-Tolerant Subpopulation and Hypoxia-Induced Stress Response in the Metabolically Active Population

    Science.gov (United States)

    Williamson, Kerry S.; Richards, Lee A.; Perez-Osorio, Ailyn C.; Pitts, Betsey; McInnerney, Kathleen; Stewart, Philip S.

    2012-01-01

    Bacteria growing in biofilms are physiologically heterogeneous, due in part to their adaptation to local environmental conditions. Here, we characterized the local transcriptome responses of Pseudomonas aeruginosa growing in biofilms by using a microarray analysis of isolated biofilm subpopulations. The results demonstrated that cells at the top of the biofilms had high mRNA abundances for genes involved in general metabolic functions, while mRNA levels for these housekeeping genes were low in cells at the bottom of the biofilms. Selective green fluorescent protein (GFP) labeling showed that cells at the top of the biofilm were actively dividing. However, the dividing cells had high mRNA levels for genes regulated by the hypoxia-induced regulator Anr. Slow-growing cells deep in the biofilms had little expression of Anr-regulated genes and may have experienced long-term anoxia. Transcripts for ribosomal proteins were associated primarily with the metabolically active cell fraction, while ribosomal RNAs were abundant throughout the biofilms, indicating that ribosomes are stably maintained even in slowly growing cells. Consistent with these results was the identification of mRNAs for ribosome hibernation factors (the rmf and PA4463 genes) at the bottom of the biofilms. The dormant biofilm cells of a P. aeruginosa Δrmf strain had decreased membrane integrity, as shown by propidium iodide staining. Using selective GFP labeling and cell sorting, we show that the dividing cells are more susceptible to killing by tobramycin and ciprofloxacin. The results demonstrate that in thick P. aeruginosa biofilms, cells are physiologically distinct spatially, with cells deep in the biofilm in a viable but antibiotic-tolerant slow-growth state. PMID:22343293

  15. Dehydration, with and without heat, in kangaroos from mesic and arid habitats: different thermal responses