Sample records for altering central vasopressin

  1. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

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    Coburn, C.G. [Environmental Toxicology, Univ. of California at Riverside, CA (United States); Gillard, E.; Curras-Collazo, M. [Cell Biology and Neuroscience, Univ. of California at Riverside, CA (United States)


    Despite the importance of systemic osmoregulation, the potential deleterious effects of persistent organochlorines, such as polychlorinated biphenyls (PCBs), on body fluid regulation has not been thoroughly investigated. In an effort to ameliorate this deficit, the current study explores the toxic effects of PCBs on osmoregulation, and in particular, on the activity of the magnocellular neuroendocrine cell (MNC) system of the hypothalamus. MNCs of the supraoptic nucleus (SON) release oxytocin (OXY) and vasopressin (VP) from terminals in the neurohypophysis in response to dehydration. The latter is released to effect water conservation in response to dehydration via its action upon the kidney and through extra-renal actions. MNCs also secrete VP from their cell bodies and dendrites locally i.e., into the extracellular space of the SON. Although it has been shown that both intranuclear and systemic release rise in response to dehydration the physiological significance of intranuclear release has not been fully elucidated. We chose to use voluntary ingestion as the route of PCB exposure since it is more reflective of natural exposure compared to ip injection. One unexpected observation that resulted from pilot studies using ip injection of PCBs was the deleterious effects of the vehicle (corn oil) resulting in pooling of lipid within the abdominal cavity, mottling of the liver, fatty liver and general discoloration of all abdominal viscera at time of sacrifice. Therefore, all work described in this series of experiments have employed voluntary ingestion of the toxin. Work described in this paper suggests that PCBs in concentrations reflecting realistic lifetime exposure levels may negatively impact homeostatic mechanisms responsible for body water balance by altering somatodendritic (intranuclear) VP secretion in response to dehydration in vivo. The downstream consequences of such influence is currently under investigation, and preliminary evidence suggests that the

  2. Central cholinergic control of vasopressin release in conscious rats

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    Iitake, K.; Share, L.; Ouchi, Y.; Crofton, J.T.; Brooks, D.P.


    Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 g icv), but not by the nicotinic blocker, hexamethonium (10 g icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and they very small elevation in the plasma vasopressin concentration induced by nicotine (10 g icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat.

  3. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

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    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl


    It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP...

  4. Endogenous vasopressin and the central control of heart rate during dynamic exercise

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    L.C. Michelini


    Full Text Available The present article contains a brief review on the role of vasopressinergic projections to the nucleus tractus solitarii in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise. The effects of vasopressin on exercise tachycardia are discussed on the basis of both the endogenous peptide content changes and the heart rate response changes observed during running in sedentary and trained rats. Dynamic exercise caused a specific vasopressin content increase in dorsal and ventral brainstem areas. In accordance, rats pretreated with the peptide or the V1 blocker into the nucleus tractus solitarii showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the pressure response to exercise. It is proposed that the long-descending vasopressinergic pathway to the nucleus tractus solitarii serves as one link between the two main neural controllers of circulation, i.e., the central command and feedback control mechanisms driven by the peripheral receptors. Therefore, vasopressinergic input could contribute to the adjustment of heart rate response (and cardiac output to the circulatory demand during exercise.

  5. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

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    Brust, P; Christensen, Thomas; Diemer, Nils Henrik


    The extracellular amino acid concentrations in the left and right dorsal hippocampus of male rats were studied before and during application of vasopressin into the right hippocampus. The method of intracerebral microdialysis was used for both arginine vasopressin administration and monitoring...... of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  6. Effects of Chronic Central Arginine Vasopressin (AVP on Maternal Behavior in Chronically Stressed Rat Dams

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    Benjamin C. Nephew


    Full Text Available Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3 and mid (day 10 lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing. AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress.

  7. The influence of vasopressin deficiency and acute desmopressin administration on melatonin secretion in patients with central diabetes insipidus. (United States)

    Catrina, S B; Rotarus, R; Wivall, I-L; Coculescu, M; Brismar, K


    Melatonin secretion is modulated by the light-dark schedule, mainly through a sympathetic input to the pineal gland. Besides this, arginine vasopressin (AVP) has been found in the pineal glands of several animal species and there is experimental evidence that AVP modulates melatonin secretion in animals. However, the interaction between vasopressin and melatonin secretion in humans has not been systematically investigated. We proposed to study the nocturnal melatonin pattern in patients with central diabetes insipidus (CDI) who lack endogenous secretion of AVP, and the effect on their melatonin secretion of the agonist for V2 type receptors: desmopressin (1-Desamino [8-D Arginine] vasopressin). Plasma melatonin levels were measured in 14 patients with CDI, every 2 h starting from 22:00 h until 06:00 h, following iv injection of saline (day 1) and 3 microg desmopressin (day 2) at 20:00 h. The lights were turned off at 22:30 h and the samples were taken in a dim light. The plasma melatonin secretion pattern was normal in patients with CDI. Desmopressin at a dose 3 times higher than the antidiuretic one did not modify the melatonin levels or the time of the peak secretion. In conclusion melatonin secretion is not modulated by AVP in humans.

  8. Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors. (United States)

    Grundwald, N J; Benítez, D P; Brunton, P J


    Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans.

  9. Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain. (United States)

    Bagdas, Deniz; Yucel-Ozboluk, Hasret; Orhan, Fulya; Kanat, Ozkan; Isbil-Buyukcoskun, Naciye; Gurun, Mine S


    Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

  10. Gene Regulation System of Vasopressin and Corticotoropin-Releasing Hormone

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    Masanori Yoshida


    Full Text Available The neurohypophyseal hormones, arginine vasopressin and corticotropin-releasing hormone (CRH, play a crucial role in the physiological and behavioral response to various kinds of stresses. Both neuropeptides activate the hypophysialpituitary-adrenal (HPA axis, which is a central mediator of the stress response in the body. Conversely, they receive the negative regulation by glucocorticoid, which is an end product of the HPA axis. Vasopressin and CRH are closely linked to immune response; they also interact with pro-inflammatory cytokines. Moreover, as for vasopressin, it has another important role, which is the regulation of water balance through its potent antidiuretic effect. Hence, it is conceivable that vasopressin and CRH mediate the homeostatic responses for survival and protect organisms from the external world. A tight and elaborate regulation system of the vasopressin and CRH gene is required for the rapid and flexible response to the alteration of the surrounding environments. Several important regulatory elements have been identified in the proximal promoter region in the vasopressin and CRH gene. Many transcription factors and intracellular signaling cascades are involved in the complicated gene regulation system. This review focuses on the current status of the basic research of vasopressin and CRH. In addition to the numerous known facts about their divergent physiological roles, the recent topics of promoter analyses will be discussed.

  11. Amygdala kindling elevates plasma vasopressin. (United States)

    Greenwood, R S; Meeker, R B; Hayward, J N


    Acute and chronic effects of epilepsy on endocrine function are known to occur in humans with partial seizures of limbic origin and in animals with limbic kindled seizures. The amygdala, a component of the limbic system, has dense hypothalamic connections and amygdala stimulation in monkeys and cats result in vasopressin release. In the present study we sought to determine if amygdala stimulation in the rats results in an immediate acute release of vasopressin and to determine if acute or chronic changes occur in vasopressin release in the fully kindled animal. Plasma vasopressin, osmolality and hematocrit were measured in blood samples drawn from rats with implanted venous catheters before and after stimulation and at different stages of kindling. Low-frequency (15 Hz) electrical stimulation of the amygdala was followed by an immediate, 3-fold increase in plasma vasopressin concentration. Moreover, although the 60 Hz kindling stimulus did not result in a significant immediate rise in plasma vasopressin prior to kindling, after kindling to stage 5 seizures the 60 Hz kindling stimulus resulted in seizures and a significant immediate rise in plasma vasopressin. In addition, we found that kindling was followed by a significant, though modest, rise in the resting plasma vasopressin without an accompanying change in osmolality or hematocrit. We conclude that kindling results in a persistent alteration in the vasopressinergic neuroendocrine system.

  12. Early rearing experience is related to altered aggression and vasopressin production following chronic social isolation in the prairie vole. (United States)

    Perkeybile, Allison M; Bales, Karen L


    Parent-offspring interactions early in life can permanently shape the developmental path of those offspring. Manipulation of maternal care has long been used to alter the early-life environment of infants and impacts their later social behavior, aggression, and physiology. More recently, naturally occurring variation in maternal licking and grooming behavior has been shown to result in differences in social behavior and stress physiology in adult offspring. We have developed a model of natural variation in biparental care in the prairie vole (Microtus ochrogaster) and have demonstrated an association between the amount of early care received and later social behavior. In this study, we investigate the relationship between early life care and later aggression and neuroendocrine responses following chronic social isolation. Male and female offspring were reared by their high-contact (HC) or low-contact (LC) parents, then housed for 4 weeks post-weaning in social isolation. After 4 weeks, half of these offspring underwent an intrasexual aggression test. Brains and plasma were collected to measure corticotropin-releasing hormone (CRH) and vasopressin (AVP) immunoreactivity and plasma corticosterone (CORT). Male offspring of LC parents engaged in more aggressive behavior in the intrasexual aggression test compared to HC males. Female offspring of HC parents had higher plasma CORT levels after chronic social isolation and increases in the number and density of AVP-immunopositive cells in the supraoptic nucleus following an intrasexual aggression test. These findings show that the impact of early life biparental care on behavior and HPA activity following a social stressor is both sex-dependent and early experience-specific.

  13. Experimental approaches for the study of oxytocin and vasopressin gene expression in the central nervous system (United States)

    Scordalakes, Elka M.; Yue, Chunmei; Gainer, Harold


    Intron-specific probes measure heteronuclear RNA (hnRNA) levels and thus approximate the transcription rates of genes, in part because of the rapid turnover of this intermediate form of RNA in the cell nucleus. Previously, we used oxytocin (Oxt)- and vasopressin (Avp)- intron-specific riboprobes to measure changes in Oxt and Avp hnRNA levels in the supraoptic nucleus (SON) by quantitative in situ hybridization (ISH) after various classical physiological perturbations, including acute and chronic salt loading, and lactation. In the present experiments, we used a novel experimental model to study the neurotransmitter regulation of Oxt and Avp gene expression in the rat SON in vivo. Bilateral cannulae connected via tubing to Alzet osmotic mini-pumps were positioned over the SON. In every experiment, one SON was infused with PBS and served as the control SON in each animal, and the contralateral SON received infusions of various neurotransmitter agonists and antagonists. Using this approach, we found that Avp but not Oxt gene expression increased after acute (2–5 h) combined excitatory amino acid agonist and GABA antagonist treatment, similar to what we found after an acute hyperosmotic stimulus. Since both OXT and AVP are known to be comparably and robustly secreted in response to acute osmotic stimuli in vivo and glutamate agonists in vitro, our results indicate a dissociation between OXT secretion and Oxt gene transcription in vivo. PMID:18655870

  14. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

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    Cam-Etoz, B.; Isbil-Buyukcoskun, N.; Ozluk, K. [Department of Physiology, Uludag University Medical Faculty, Gorukle/Bursa (Turkey)


    Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V{sub 1} receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (ΔMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP{sub 8-37}) and ADM receptor antagonist (ADM{sub 22-52}) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V{sub 1} receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl{sup 1}, O-me-Tyr{sup 2},Arg{sup 8}]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V{sub 1} receptors in the increasing effects of icv ADM on blood pressure and HR.

  15. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

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    B. Cam-Etoz


    Full Text Available Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g female rats (N = 7 in each group the effects of intracerebroventricularly (icv injected adrenomedullin (ADM on blood pressure and heart rate (HR, and to determine if ADM and calcitonin gene-related peptide (CGRP receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1 icv ADM (750 ng/10 µL caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm. 2 Pretreatment with a CGRP receptor antagonist (CGRP8-37 and ADM receptor antagonist (ADM22-52 blocked the effect of central ADM on blood pressure and HR. 3 The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv. 4 The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg, that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

  16. Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases. (United States)

    Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria


    Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

  17. Alteration of basaltic glasses from the Central Indian Ocean

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    Iyer, S.D.

    Textural, mineralogical and compositional characteristics of basaltic glasses from the Central Indian Ocean show them to be altered to varying extents through their interaction with the seawater, resulting in the formation of palagonite. The major...

  18. Arginine Vasopressin-Independent Mechanism of Impaired Water Excretion in a Patient with Sarcoidosis Complicated by Central Diabetes Insipidus and Glucocorticoid Deficiency

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    Katsunobu Yoshioka


    Full Text Available A 28-year-old man was admitted to our hospital because of reduced livido and increased fatigability. Four months before admission, he noticed polyuria, which was gradually relieved by admission. Magnetic resonance imaging revealed enhancing lesion centrally in the pituitary stalk. Biopsy from the skin revealed noncaseating granuloma composed of epithelioid cells, and a diagnosis of sarcoidosis was made. Although plasma arginine vasopressin (AVP was undetectable after administration of hypertonic saline, urinary output was within normal range (1.5 to 2.2 L/day. The urine osmolality became above plasma levels during the hypertonic saline test. Hormonal provocative tests revealed partial glucocorticoid deficiency. Soon after the glucocorticoid therapy was begun, moderate polyuria (from 3.5–4.0 liters daily occurred. At this time, plasma AVP was undetectable, and urine osmolality was consistently below plasma levels during the hypertonic saline test. In conclusion, we showed in human study that masked diabetes insipidus could be mediated by AVP-independent mechanisms.

  19. Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal collecting duct cells


    Bolger, Steven J.; Hurtado, Patricia A. Gonzales; Hoffert, Jason D.; Saeed, Fahad; Pisitkun, Trairak; Knepper, Mark A.


    Vasopressin regulates transport across the collecting duct epithelium in part via effects on gene transcription. Transcriptional regulation occurs partially via changes in phosphorylation of transcription factors, transcriptional coactivators, and protein kinases in the nucleus. To test whether vasopressin alters the nuclear phosphoproteome of vasopressin-sensitive cultured mouse mpkCCD cells, we used stable isotope labeling and mass spectrometry to quantify thousands of phosphorylation sites...

  20. Regulation of plasma osmolality: thirst and vasopressin. (United States)

    Toto, K H


    Sudden changes in plasma osmolality may have lethal consequences, because of abrupt changes in the volume of cells in the central nervous system. Acute osmotic disequilibrium can result in brain shrinkage or brain swelling. This article explores how the integrated responses of vasopressin and thirst maintain osmotic equilibrium through regulation of body water balance. These two mechanisms provide almost insurmountable barriers to excessive dilution or concentration of body fluids.

  1. Vasopressin and oxytocin in stress. (United States)

    Jezova, D; Skultetyova, I; Tokarev, D I; Bakos, P; Vigas, M


    Though oxytocin and vasopressin are similar in structure and are produced in the same brain regions, they show specific responses under stress conditions. In humans, increases in peripheral blood vasopressin appear to be a consistent finding during many acute stress situations, while in rats, vasopressin secretion is unresponsive to several stimuli known to induce ACTH and catecholamine release. Even decreases in vasopressin levels during stress were described. In accordance with others, we observed enhanced vasopressin release in response to stress stimuli with an osmotic component such as hypertonic saline injection but also during exposure of rats to a warm environment. Immobilization stress which fails to induce vasopressin release was reported to increase hypothalamic vasopressin mRNA and plasma vasopressin levels in chronically adreno-demedullated rats. Unlike vasopressin, oxytocin may be considered a typical stress hormone responding to osmotic as well as other stress stimuli. We found that acute exposure of rats to immobilization stress resulted in an increase in oxytocin mRNA level. In addition, we have shown that magnocellular neurons of the paraventricular nucleus, but not the supraoptic nucleus, are essential for oxytocin release during immobilization stress. The release of posterior pituitary hormones represents an important component of the stress response.

  2. Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats (United States)

    Golin, Raffaello M. A.; Gotoh, Eiji; Keil, Lanny C.; Shackelford, Roy L.; Ganong, William F.


    The congenital vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus is associated with elevated plasma renin activity at rest and supernormal responses to stimuli that increase renin secretion. The mechanism underlying this phenomenon was investigated by infusing homozygous and heterozygous Brattleboro rats with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. The resulting data indicate that increased renin secretion in homozygous rats results from increased sympathetic activity. Because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

  3. Consolidation of altered associability information by amygdala central nucleus. (United States)

    Schiffino, Felipe L; Holland, Peter C


    The surprising omission of a reinforcer can enhance the associability of the stimuli that were present when the reward prediction error was induced, so that they more readily enter into new associations in the future. Previous research from this laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event and to the subsequent expression of that altered associability in more rapid learning. These elements include the amygdala, the midbrain substantia nigra, the basal forebrain substantia innominata, the dorsolateral striatum, the secondary visual cortex, and the posterior parietal cortex. Here, we found that consolidation of a surprise-enhanced associability memory in a serial prediction task depends on processing in the amygdala central nucleus (CeA) after completion of sessions that included the surprising omission of an expected event. Post-surprise infusions of anisomycin, lidocaine, or muscimol prevented subsequent display of surprise-enhanced associability. Because previous studies indicated that CeA function is unnecessary for the expression of associability enhancements that were induced previously when CeA function was intact (Holland & Gallagher, 2006), we interpreted these results as indicating that post-surprise activity of CeA ("surprise replay") is necessary for the consolidation of altered associability memories elsewhere in the brain, such as the posterior parietal cortex (Schiffino et al., 2014a).

  4. Immersion diuresis without expected suppression of vasopressin (United States)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.


    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  5. Reduced cooperativeness and reward-dependence in depression with above-normal plasma vasopressin concentration

    NARCIS (Netherlands)

    Goekoop, J. G.; de Winter, R. F. P.; Wolterbeek, R.; Spinhoven, P.; Zitman, F. G.; Wiegant, V. M.


    The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of d

  6. Suprachiasmatic vasopressin and the circadian regulation of voluntary locomotor behavior. (United States)

    Cormier, Holly C; Della-Maggiore, Valeria; Karatsoreos, Ilia N; Koletar, Margaret M; Ralph, Martin R


    A role for arginine vasopressin in the circadian regulation of voluntary locomotor behavior (wheel running activity) was investigated in the golden hamster, Mesocricetus auratus. Spontaneous nocturnal running was suppressed in a dose-dependent manner by systemic injections of vasopressin, and also in a concentration-dependent manner by microinjections directly into the hypothalamic suprachiasmatic nucleus. Pre-injections of a vasopressin V1 receptor antagonist into the nucleus reduced the suppression of behavior by vasopressin. Ethogram analyses revealed that peripheral drug injections predominantly increased grooming, flank marking, and sleep-related behaviors. Central injections did not induce sleep, but increased grooming and periods of 'quiet vigilance' (awake but not moving). Nocturnal behavioral profiles following either peripheral or central injections were similar to those shown by untreated animals in the hour prior to the onset of nocturnal wheel running. Site control vasopressin injections into the medial preoptic area or periaqueductal gray increased flank marking and grooming, but had no significant effect on locomotion, suggesting behavioral specificity of a vasopressin target near the suprachiasmatic nucleus. Both peripheral and central administration increased FOS-like immunoreactivity in the retinorecipient core of the suprachiasmatic nucleus. The distribution of FOS-positive cells overlapped the calbindin subregion, but was more extensive, and most calbindin-positive cells did not co-express FOS. We propose a model of temporal behavioral regulation wherein voluntary behavior, such as nocturnal locomotor activity, is inhibited by the activity of neurons in the suprachiasmatic ventrolateral core that project to the posterior hypothalamus and are driven by rhythmic vasopressin input from the dorsomedial shell.

  7. Low HDL cholesterol, aggression and altered central serotonergic activity. (United States)

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P


    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  8. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats (United States)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.


    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  9. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion. (United States)

    Knigge, U; Kjaer, A; Kristoffersen, U; Madsen, K; Toftegaard, C; Jørgensen, H; Warberg, J


    Prostaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H1 or H2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose-dependently stimulated by intracerebroventricular infusion of 1 or 5 microg of PGE1, PGE2 or PGF2alpha, with PGE2 being the most potent of the compounds used. Prior central infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE1 but not by PGE2 or PGF2alpha. The stimulatory effect of PGE1 was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four- and two-fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose-dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE1, PGE2 or PGF2alpha interact in the regulation of oxytocin secretion, whereas histamine and only PGE1 interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.

  10. Diabetes insipidus: celebrating a century of vasopressin therapy. (United States)

    Qureshi, Sana; Galiveeti, Sneha; Bichet, Daniel G; Roth, Jesse


    Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

  11. The role of oxytocin and vasopressin in central nervous system activity and mental disorders [Rola oksytocyny i wazopresyny w czynności ośrodkowego układu nerwowego i w zaburzeniach psychicznych

    Directory of Open Access Journals (Sweden)

    Wójciak, Paweł


    Full Text Available Oxytocin and vasopressin, “peptides of love and fear”, except for their classic role in control of labor and breastfeeding and blood pressure regulation, are also implicated in various processes like sexual behaviours, social recognition and stress response. These hormones seems to be essential for appropriate and beneficial social interactions, play a very important role in maternal care and closeness, promote general trust and cooperation and prolong social memory. They also play a very important role in modulating fear and anxiety response, especially by regulating the hypothalamic-pituitary-adrenal axis and amygdala activity by its projections to the brain stem and hypothalamic structures. Both hormones, particularly oxytocin, appears to be activating sexual behaviour or is responsible for increased sexual arousal. Evidence from clinical trials suggests their potential role in pathogenesis of schizophrenia, depression, autism and addiction together with possible therapeutic use in the above conditions. In schizophrenia, patients with higher peripheral oxytocin levels showed less severe positive, general and social symptoms and better prosocial behaviours. Literature suggests that exogenous oxytocin may be effective as an adjunctive therapy for that illness. Some data suggest that naturally occurring autoantibodies reacting with oxytocin and vasopressin are involved in depression, eating disorders and conduct disorder genesis.

  12. San Antonio Vasopressin in Shock Symposium Report (United States)


    physiology and clinical strategies. Anesthesiology 2006;105:599–612, quiz 639–40. 7. Russell JA,Walley KR, Singer J, et al. Vasopressin versus...Medicine, Miami, FL, United States e University of British Columbia, Vancouver, BC, Canada f Department of Anesthesiology and Critical Care Medicine...after pulmonary contusion. J Trauma 2005;59:876–82, dis- cussion 882–3. 16. Voelckel WG, Raedler C, Wenzel V, et al. Arginine vasopressin, but not

  13. Vasopressin V1 receptors contribute to hemodynamic and sympathoinhibitory responses evoked by stimulation of adenosine A2a receptors in NTS. (United States)

    Scislo, Tadeusz J; O'Leary, Donal S


    Activation of adenosine A2a receptors in the nucleus of the solitary tract (NTS) decreases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas increases in preganglionic adrenal sympathetic nerve activity (pre-ASNA) occur, a pattern similar to that observed during hypotensive hemorrhage. Central vasopressin V1 receptors may contribute to posthemorrhagic hypotension and bradycardia. Both V1 and A2a receptors are densely expressed in the NTS, and both of these receptors are involved in cardiovascular control; thus they may interact. The responses elicited by NTS A2a receptors are mediated mostly via nonglutamatergic mechanisms, possibly via release of vasopressin. Therefore, we investigated whether blockade of NTS V1 receptors alters the autonomic response patterns evoked by stimulation of NTS A2a receptors (CGS-21680, 20 pmol/50 nl) in alpha-chloralose-urethane anesthetized male Sprague-Dawley rats. In addition, we compared the regional sympathetic responses to microinjections of vasopressin (0.1-100 ng/50 nl) into the NTS. Blockade of V1 receptors reversed the normal decreases in MAP into increases (-95.6 +/- 28.3 vs. 51.4 +/- 15.7 integralDelta%), virtually abolished the decreases in HR (-258.3 +/- 54.0 vs. 18.9 +/- 57.8 integralDeltabeats/min) and RSNA (-239.3 +/- 47.4 vs. 15.9 +/- 36.1 integralDelta%), and did not affect the increases in pre-ASNA (279.7 +/- 48.3 vs. 233.1 +/- 54.1 integralDelta%) evoked by A2a receptor stimulation. The responses partially returned toward normal values approximately 90 min after the blockade. Microinjections of vasopressin into the NTS evoked dose-dependent decreases in HR and RSNA and variable MAP and pre-ASNA responses with a tendency toward increases. We conclude that the decreases in MAP, HR, and RSNA in response to NTS A2a receptor stimulation may be mediated via release of vasopressin from neural terminals in the NTS. The differential effects of NTS V1 and A2a receptors on

  14. 中枢精氨酸加压素在大鼠促肾上腺皮质激素释放激素引起发热机制中的作用%The role of central arginine vasopressin in corticotropin releasing hormone-induced fever in rats

    Institute of Scientific and Technical Information of China (English)

    王华东; 王彦平; 胡巢凤; 戚仁斌; 严玉霞; 陆大祥; 李楚杰


    实验对大鼠进行第三脑室和脑腹中隔区插管, 用数字体温计测量大鼠的结肠温度, 用放射免疫分析法测定脑中隔区精氨酸加压素(arginine vasopressin, AVP)含量, 观察脑中隔区AVP在大鼠促肾上腺皮质激素释放激素(corticotrophin releasing hormone, CRH)性发热机制中的作用.结果发现: 脑室注射CRH (5.0 μg)引起大鼠结肠温度明显升高, 同时明显增高脑中隔区 AVP的含量.脑腹中隔区注射AVP V1受体拮抗剂本身并不导致大鼠结肠温度明显改变, 但能显著增强脑室注射CRH引起的发热反应.而且, 腹中隔区注射AVP显著抑制大鼠CRH性发热.结果提示: 发热时CRH是引起脑腹中隔区AVP释放的因素之一, 脑腹中隔区内源性AVP抑制中枢注射CRH引起的体温升高.%The purpose of the present study was to investigate the role of central arginine vasopressin (AVP) in corticotropin releasing hormone (CRH)-induced fever in the rat. Guide cannulae were inserted into the third ventricle and placed over the ventral septal area (VSA). The content of arginine vasopressin in the VSA of the brain was determined by radioimmunoassay. Colon temperature was monitored in lightly restrained rats by insertion of a catheter-mounted thermistor probe 5 cm in the rectum. The results demonstrated that intracerebroventricular (icv) injection of CRH increased AVP level in the VSA and the colonic temperature of the rats. Microinjection of AVP V1 antagonist into the VSA 10 min before CRH administration significantly enhanced CRH-induced febrile response, while AVP V1 antagonist itself did not have a significant effect on the colonic temperature. Furthermore, injection of AVP into the VSA 5 min before CRH administration (icv) suppressed the fever evoked by CRH. These findings suggest that CRH is an important factor that stimulates the release of AVP in the VSA during fever, and endogenous AVP in the VSA has an antipyretic action on the CRH-induced fever.

  15. Hydrothermal alteration studies of gabbros from Northern Central Indian Ridge and their geodynamic implications

    Indian Academy of Sciences (India)

    Dwijesh Ray; Catherine Mevel; Ranadip Banerjee


    Mylonitic gabbro and altered gabbro were recovered from off-axis high and corner high locations at ridge-transform intersection, adjacent to Vityaz transform fault of the slow spreading (32–35mm/yr, full spreading) Northern Central Indian Ridge. Both the varieties show signatures of extensive alteration caused due to interaction with sea water. Mylonitic gabbro represents high temperature metamorphism (∼700–800° C) and comprised of hornblende mineral which exhibits well defined foliation/gneissic appearance along with dynamically recrystallised plagioclase grains frequently intercalated with magnetite-ilmenite. Altered gabbro from corner high generally includes low temperature greenschist grade (∼300° C) mineralogical assemblages: chlorite, albite, quartz and locally magnesio hornblende. Crystal plastic deformation resulted in mylonite formation and often porphyroclasts of plagioclase and clinopyroxene grains, while altered gabbro locally exhibits cataclastic texture. Presence of Vityaz transform fault and adjacent megamullion at the weakly magmatic ridge-transform intersection and off-axis high locations prompted the present scenario very much conducive for hydrothermal circulation and further facilitate the exhumation of present suite of gabbro.

  16. Does Acupuncture Alter Pain-related Functional Connectivity of the Central Nervous System? A Systematic Review. (United States)

    Villarreal Santiago, María; Tumilty, Steve; Mącznik, Aleksandra; Mani, Ramakrishnan


    Acupuncture has been studied for several decades to establish evidence-based clinical practice. This systematic review aims to evaluate evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain. A systematic search of the literature was conducted to identify studies in which the central response of acupuncture in patients with musculoskeletal pain was evaluated by neuroimaging techniques. Databases searched were AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PEDro, Pubmed, SCOPUS, SPORTDiscuss, and Web of Science. Included studies were assessed by two independent reviewers for their methodological quality by using the Downs and Black questionnaire and for their levels of completeness and transparency in reporting acupuncture interventions by using Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. Seven studies met the inclusion criteria. Three studies were randomized controlled trials (RCTs) and four studies were nonrandomized controlled trials (NRCTs). The neuroimaging techniques used were functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Positive effects on the functional connectivity of the central nervous system more consistently occurred during long-term acupuncture treatment. The results were heterogeneous from a descriptive perspective; however, the key findings support acupuncture's ability to alter pain-related functional connectivity in the central nervous system in patients with musculoskeletal pain.

  17. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.


    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  18. Agroclimatic potential in central Siberia in an altered 21st century climate (United States)

    Soja, A.; Tchebakova, N.; Parfenova, E.; Lysanova, G.


    The largest temperature increases are currently found in Northern Hemishpere upper latitudes, and this is where temperature increases from climate change are predicted to be the greatest in the future. Alteration of boreal and Arctic landscapes is already apparent, particularly in Siberia. In this work, we will explore the current spatial and temporal patterns of agriculture potential in Siberia and then investigate potential future agriculture dynamics. Humans have traditionally cultivated steppe and forest-steppe on fertile soils for agriculture. It is predicted that forests will move northwards in a warmer climate and be replaced by forest-steppe and steppe ecosystems. Climate change impacts on agriculture in south-central Siberia are analyzed based on the hypothesis that agriculture in traditionally cold Siberia may benefit from warming. Simple models are used to determine crop range and regression models are constructed to determine crop yield, and these are applied to climate change scenarios for various time frames: pre-1960, 1960-1990, 1990-2010 using historic data and for 2020 and 2080 using HadCM3 B1 and A2 projections. From 50 to 85% of central Siberia is predicted to be climatically suitable for agriculture by the end of the century, and only soil potential would limit crop advance and expansion to the north. Crop production could increase twofold. Future climatic resources in Siberia would provide potential growth for a variety of crops that previously did not exist on these lands. Traditional Siberian crops could gradually shift as far as 500 km northwards (about 50-70 km per decade) within suitable soil conditions, and new crops, nonexistent today, may be introduced in the dry south that would necessitate irrigation. Agriculture in central Siberia would likely benefit from climate warming but would also result in different feedbacks to the atmosphere and climate systems, in terms of an altered landscape albedo, substantially modified hydrological

  19. Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain. (United States)

    Neziri, Alban Y; Bersinger, Nick A; Andersen, Ole K; Arendt-Nielsen, Lars; Mueller, Michael D; Curatolo, Michele


    Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

  20. Alterations of cortical excitability and central motor conduction time in Wilson's disease. (United States)

    Jhunjhunwala, Ketan; Prashanth, D K; Netravathi, M; Nagaraju, B C; Pal, Pramod Kr


    Wilson's disease (WD) leads to widespread structural alterations of central nervous system and our objectives were to determine the cortical excitability changes in WD by using transcranial magnetic stimulation (TMS). Thirteen patients with WD, diagnosed by the presence of Kayser-Fleischer ring and biochemical tests, were studied. TMS was performed using a figure-of-eight coil attached to Magstim 200 stimulator. Motor evoked potentials (MEP) were recorded from right first dorsal interosseous at rest. Resting motor threshold (RMT) was determined using standard techniques and central motor conduction time (CMCT) by 'F' wave method. Comparison was made with control data of our laboratory. Dysarthria was the presenting symptom in 5 patients (38.5%) and chorea, tremors, dystonia and abnormal gait in 2 patients each (15.4%). RMT was recordable in 10 patients and not recordable in 3. Compared to controls, patients in whom RMT was recordable, had significantly higher mean RMT (80.9 ± 14.8 vs. 41.1 ± 7, pRMT, MEP could be obtained with active contraction. CMCT in these 2 patients was also prolonged. Patients with WD have reduced cortical excitability and prolonged CMCT which may be due to the intracortical presynaptic motor dysfunction.

  1. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior. (United States)

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin


    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning.

  2. Central Thalamic Deep-Brain Stimulation Alters Striatal–Thalamic Connectivity in Cognitive Neural Behavior

    Directory of Open Access Journals (Sweden)

    Hui-Ching eLin


    Full Text Available Central thalamic deep brain stimulation (CT-DBS has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs induced by CT-DBS from the thalamic central lateral nuclei (CL and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr, and dorsal striatum (Dstr. LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2 and 4-nicotinic acetylcholine receptor (4-nAChR occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity’s ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning.

  3. Postnatal growth after intrauterine growth restriction alters central leptin signal and energy homeostasis.

    Directory of Open Access Journals (Sweden)

    Bérengère Coupé

    Full Text Available Intrauterine growth restriction (IUGR is closely linked with metabolic diseases, appetite disorders and obesity at adulthood. Leptin, a major adipokine secreted by adipose tissue, circulates in direct proportion to body fat stores, enters the brain and regulates food intake and energy expenditure. Deficient leptin neuronal signalling favours weight gain by affecting central homeostatic circuitry. The aim of this study was to determine if leptin resistance was programmed by perinatal nutritional environment and to decipher potential cellular mechanisms underneath.We clearly demonstrated that 5 months old IUGR rats develop a decrease of leptin sentivity, characterized by no significant reduction of food intake following an intraperitoneal injection of leptin. Apart from the resistance to leptin injection, results obtained from IUGR rats submitted to rapid catch-up growth differed from those of IUGR rats with no catch-up since we observed, for the first group only, fat accumulation, increased appetite for food rich in fat and increased leptin synthesis. Centrally, the leptin resistant state of both groups was associated with a complex and not always similar changes in leptin receptor signalling steps. Leptin resistance in IUGR rats submitted to rapid catch-up was associated with alteration in AKT and mTOR pathways. Alternatively, in IUGR rats with no catch-up, leptin resistance was associated with low hypothalamic expression of LepRa and LepRb. This study reveals leptin resistance as an early marker of metabolic disorders that appears before any evidence of body weight increase in IUGR rats but whose mechanisms could depend of nutritional environment of the perinatal period.

  4. Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Dorsa, D.M.; Brot, M.D.; Shewey, L.M.; Meyers, K.M.; Szot, P.; Miller, M.A.


    The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, /sup 3/H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. /sup 3/H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than /sup 3/H-AVP. The rank order of potency of various competitor peptides for /sup 3/H-AVP and /sup 3/H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. /sup 3/H-AVP and /sup 3/H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.

  5. Impaired behavioral sensitization to cocaine in vasopressin deficient rats. (United States)

    Post, R M; Contel, N R; Gold, P


    Behavioral sensitization to cocaine involves progressive and long-lasting increases in hyperactivity and stereotypy in response to the same daily dose. In order to test whether vasopressin, a neuro-hormone implicated in drug tolerance and in other models of learning and memory, affected behavioral sensitization, cocaine was administered daily to animals with hereditary absence of vasopressin. Brattleboro homozygotes which lack vasopressin show deficient onset and persistence of cocaine-induced behavioral sensitization compared to heterozygote, litter-mate controls. These data extend previous reports of vasopressin's role in memory and long-term coding of behavior to the model of pharmacologically-induced behavioral sensitization.

  6. Oxytocin and vasopressin: distinct receptors in myometrium

    Energy Technology Data Exchange (ETDEWEB)

    Guillon, G.; Balestre, M.N.; Roberts, J.M.; Bottari, S.P.


    The binding characteristics of (/sup 3/H)oxytocin (( /sup 3/H)OT) and (/sup 3/H)lysine vasopressin (( /sup 3/H)LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas (/sup 3/H)OT was found to bind to a single class of sites with high affinity (Kd, 1.5 +/- 0.4 (+/- SEM) nM) and low capacity (maximum binding (Bmax), 34 +/- 6 fmol/mg protein), (/sup 3/H)LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for (/sup 3/H)OT and (/sup 3/H)LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for (/sup 3/H)LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.

  7. Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Messenger Tara


    Full Text Available Abstract Background Alterations in arginine vasopressin regulation and secretion have been proposed as one possible biochemical abnormality in patients with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped scent marking behaviors. The intensity and repetition of the behaviors induced by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder in humans. The present experiments were carried out to test whether pharmacological agents used to alleviate obsessive compulsive disorder could inhibit arginine vasopressin-induced flank marking and grooming. Results Male golden hamsters were treated daily for two weeks with either vehicle, fluoxetine, clomipramine, or desipramine (an ineffective drug, before being tested for arginine vasopressin-induced flank marking and grooming. Flank marking was significantly inhibited in animals treated with fluoxetine or clomipramine but unaffected by treatment with desipramine. Grooming behavior was not affected by any treatment. Conclusion These data suggest that arginine vasopressin-induced flank marking may serve as an animal model for screening drugs used in the control of Obsessive Compulsive Disorder.

  8. Mapping of Gold Mineralization Alteration Zones in Central Eastern Desert Egypt using Spectral Angular Mapper and Aeromagnetic Data (United States)

    Hasan, E.; Fagin, T.; El Alfy, Z.


    Central Eastern Desert (CED), Egypt has long history of gold exploration and exploitation. In this study, we integrated Spectral Angular Mapper (SAM) technique and aeromagnetic data to map the gold mineralization associated within alteration zones in CED. The spectral reflectance curves of five main alteration minerals (Hematite, Illite, Kaolinite, Chlorite, and Quartz) were utilized as end members in the SAM supervised classification of ETM+ data. Each alteration mineral type was represented as a binary image that overlaid together to obtain single primary alteration map in CED. The possible pathways for the alteration migration was defined based on the subsurface and surface lineation features. For the subsurface lineation, Euler deconvolution filter was applied on the aeromagnetic data to locate the deep-seated faults. The surface lineation and shear zones were extracted from ETM+ data and used together with the subsurface lineation map to obtain a structural map. Layer intersection and fuzzy membership operation were applied for the entire datasets to identify the possible sites of alteration zones. Several GPS readings were taken from the field areas around the gold mine sites, and used as validation points for our primary results.

  9. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Caverson, M.M.; Ciriello, J.


    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  10. Effect of the selective vasopressin V2 receptor antagonists in hepatic cirrhosis patients with ascites: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG


    Full Text Available Objective To evaluate the efficacy and safety of selective vasopressin V2 receptor antagonists in the treatment of hepatic cirrhosis patients with ascites. Methods PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Database for Chinese Technical Periodical (VIP, Chinese Journal Full-Text Database (CNKI, and Wan Fang Digital Journal Full-text Database were retrieved to collect clinical randomized controlled trials of hepatic cirrhosis with ascites treated by selective vasopressin V2 receptor antagonists. Meta analysis was performed by using Review Manager 5.0. Results Nine randomized controlled trials including 1884 patients met the inclusion criteria. Meta-analysis showed that: 1 The selective vasopressin V2 receptor antagonists were associated with a significant reduction in body weight compared with placebo (WMD=–1.98kg, 95%CI:–3.24-–0.72kg, P=0.002. Treatment with selective vasopressin V2 receptor antagonists was associated with an improvement of low serum sodium concentration compared to placebo (WMD=3.74mmol/L, 95%CI: 0.91-6.58mmol/L, P=0.01. The percentage of patients with worsening ascites was higher in the group of patients treated with placebo (RR=0.51, 95%CI: 0.34-0.77, P=0.001. 2 The amplitude of increased urine volume was obviously higher in selective vasopressin V2 receptor antagonists group than in placebo group (WMD=1437.65ml, 95%CI: 649.01-2226.30ml, P=0.0004. The difference of serum creatinine in the selective vasopressin V2 receptor antagonists group was not statistically significant compared with the control group (WMD=–3.49μmol/L, 95%CI: –12.54¬5.56μmol/L, P=0.45. 3 There was no statistical significance between the two groups in the heart rate, systolic pressure, diastolic pressure and mortality (P>0.05. The rate of other adverse reactions was higher in the selective vasopressin V2 receptor antagonists group compared with that of placebo group (P=0.003. Conclusion

  11. Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats. (United States)

    Juif, Pierre-Eric; Poisbeau, Pierrick


    Oxytocin (OT) and arginine vasopressin (AVP) are 2 neuropeptides that display well-known effects on the reproductive system. Although still controversial, oxytocin and vasopressin were demonstrated to exert potent effects on the nociceptive system when administered directly in various central nervous structures. On the other hand, little is known about their peripheral (hormonal) actions on nociception and pain responses. The aim of the present work was to characterize the effects of physiological blood concentrations of OT and AVP on spinal nociception and on pain responses. To do so, growing doses of OT or AVP were administered intravenously and the nociceptive processing by spinal cord neurons was analyzed in anesthetized male rats in vivo. We observed that the action potentials mediated by C-type nociceptive fibers was strongly reduced (antinociception) after intravenous injections of low doses of OT (effects were fully abolished in the presence of the OT receptor antagonist and the AVP receptor antagonist type 1A (V1A), respectively. We confirmed this result with a behavioral model of forced swim stress-induced analgesia associated with plasmatic release of OT (and not vasopressin). Stress-induced analgesia was transiently lost after i.v. administration of OTR antagonist. Together, the present work provides straightforward evidence that blood levels of OT and AVP modulate nociception, windup plasticity and pain responses. The final target structures explaining these effects remains to be identified but are likely to be C-type nociceptors.

  12. Hyponatremia and brain injury: absence of alterations of serum brain natriuretic peptide and vasopressin Hiponatremia e traumatismo cranioencefálico: ausência de alteração sanguínea do peptídeo natriurético cerebral e hormônio antidiurético

    Directory of Open Access Journals (Sweden)

    Karina Nascimento Costa


    Full Text Available OBJECTIVE: To study any possible relation between hyponatremia following brain injury and the presence of cerebral salt-wasting syndrome (CSWS or the syndrome of inappropriate secretion of antidiuretic hormone (SIADH, and if vasopressin, brain natriuretic peptide (BNP and aldosterone have a role in its mechanism. METHOD: Patients with brain injury admitted to the intensive care unit were included and had their BNP, aldosterone and vasopressin levels dosed on day 7. RESULTS: Twenty six adult patients were included in the study. Nine (34.6% had hyponatremia and presented with a negative water balance and higher values of urinary sodium, serum potassium and diuresis than patients with normonatremia. The serum levels of BNP, aldosterone, and vasopressin were normal and no relation was observed between plasma sodium and BNP, aldosterone or vasopressin. CONCLUSION: The most likely cause of hyponatremia was CSWS and there was no correlation between BNP, aldosterone and vasopressin with serum sodium level.OBJETIVO: Estudar a possível relação entre a hiponatremia seguindo traumatismo cranioencefálico e a presença da síndrome cerebral perdedora de sal (SCPS ou a síndrome da secreção inapropriada do hormônio antidiurético (SSIHAD, e se a vasopressina, peptídeo natriurético cerebral (BNP e aldosterona têm um papel nesse mecanismo. MÉTODO: Foram incluídos pacientes com traumatismo cranioencefálico admitidos na unidade de terapia intensiva e foram dosados no sétimo dia seguindo o trauma, BNP, aldosterona e vasopressina. RESULTADOS: Vinte e seis pacientes foram incluídos no estudo. Nove (34,6% tiveram hiponatremia e apresentaram um balanço hídrico mais negativo e altos valores de sódio urinário, potássio sérico e diurese quando comparados com o grupo que apresentou normonatremia. Os níveis séricos de BNP, aldosterona e vasopressina foram normais e não foi observada relação entre o sódio sérico e BNP, aldosterona e vasopressina

  13. Remote sensing detection of gold related alteration zones in Um Rus area, Central Eastern Desert of Egypt (United States)

    Amer, Reda; Kusky, Timothy; El Mezayen, Ahmed


    Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Phased Array L-band Synthetic Aperture Radar (PALSAR) images covering the Um Rus area in the Central Eastern Desert of Egypt were evaluated for mapping geologic structure, lithology, and gold-related alteration zones. The study area is covered by Pan-African basement rocks including gabbro and granodiorite intruded into a variable mixture of metavolcanics and metasediments. The first three principal component analyses (PCA1, PCA2, PCA3) in a Red-Green-Blue (RGB) of the visible through shortwave-infrared (VNIR + SWIR) ASTER bands enabled the discrimination between lithological units. The results show that ASTER band ratios ((2 + 4)/3, (5 + 7)/6, (7 + 9)/8) in RGB identifies the lithological units and discriminates the granodiorite very well from the adjacent rock units.The granodiorites are dissected by gold-bearing quartz veins surrounded by alteration zones. The microscopic examination of samples collected from the alteration zones shows sericitic and argillic alteration zones. The Spectral Angle Mapper (SAM) and Spectral Information Divergence (SID) supervised classification methods were applied using the reference spectra of the USGS spectral library. The results show that these classification methods are capable of mapping the alteration zones as indicated by field verification work. The PALSAR image was enhanced for fracture mapping using the second moment co-occurrence filter. Overlying extracted faults and alteration zone classification images show that the N30E and N-S fractures represent potential zones for gold exploration. It is concluded that the proposed methods can be used as a powerful tool for ore deposit exploration.

  14. Identifying the Distribution of Alteration Zone Using Very Low Frequency Method in Candi Gedong Songo, Ungaran, Semarang, Central Java (United States)

    Alfianto, A. D.; Sari, D. P.; Almas, S. A.; Kurniawan, W. S.; Ambariani, S. G.; Suyanto, I.


    The alteration zone could be a key link and a proof to know where the paleo heat source was previously located. An electromagnetic survey to identify and to map the lateral and vertical distribution of alteration zone had been done at geothermal area Candi Gedong Songo, Ungaran, Central Java, from 9th - 19th of June 2014, using VLF method. The survey consisted of 6 profiles, with NW - SE direction, which were located nearby the fumaroles spots and then went down to the observed alteration zone. Each profile was 600 m long and the distance between each profile was 20 m. The space between each measurement point of a profile was 20 m. In this study, tilt and ellipticity data with frequency of 19.8 kHz (Japan) and 24 kHz (Panama) were used. First, the data was processed to get the cross features anomaly between tilt and ellipticity data on the chart. Then, the derivative fraser and the relative current density pseudosection were also made to support the cross features anomaly. The interpretation of this data was done qualitatively using fraser and relative current density pseudosection. The result shows that the alteration zone gives high response of conductivity compared to its surrounding area. This is supported by the anomaly cross features between tilt and ellipticity data on the chart, also by high value of fraser and relative current density. Thus, the alteration zone are located in meter 150 - 250 in V1 and V2 profiles, also in meter 180 - 250 in V5 and V6 profiles. This result indicates that the ancient heat source was previously located nearby the fumaroles area and it is physically shown by the presence of sulphuric clay mineral content at the alteration surface area.

  15. Mineral chemistry and alteration characteristics of spinel in serpentinised peridotites from the northern central Indian Ridge

    Digital Repository Service at National Institute of Oceanography (India)

    Banerjee, R.; Ray, Dwijesh; Ishii, T.

    S): implications for the evolution of MORB. Acta Geol. Sin. (English version), v. 81, v. 99-112. Ray, D., Banerjee, R., Iyer, S.D. and Mukhopadhyay, S. (2008). A new report of serpentinites from Northern Central Indian Ridge – an implication for hydrothermal... activity. Acta Geol. Sin. (English version), v. 82, v. 1213-1222. Ray, D., Misra. S., Banerjee, R. and Weis, D. (2011) Geochemical implications of gabbro from slow-spreading Northern Central Indian Ocean Ridge, Indian Ocean. Geol. Mag., v. 148(3), pp...

  16. Thyroid Hormone Receptor beta Mediates Acute Illness-Induced Alterations in Central Thyroid Hormone Metabolism

    NARCIS (Netherlands)

    A. Boelen; J. Kwakkel; O. Chassande; E. Fliers


    Acute illness in mice profoundly affects thyroid hormone metabolism in the hypothalamus and pituitary gland. It remains unknown whether the thyroid hormone receptor (TR)-beta is involved in these changes. In the present study, we investigated central thyroid hormone metabolism during lipopolysacchar

  17. Genomic effects of cold and isolation stress on magnocellular vasopressin mRNA-containing cells in the hypothalamus of the rat. (United States)

    Angulo, J A; Ledoux, M; McEwen, B S


    We assessed the effects of cold and isolation stress on arginine vasopressin (AVP) mRNA in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Vasopressin mRNA levels were determined by in situ hybridization histochemistry at the cellular level. In posterior magnocellular neurons of the PVN isolation stress for 7 or 14 days increased vasopressin mRNA levels 28 and 29%, respectively, compared to group-housed controls. No significant alterations in vasopressin gene expression were observed in the SON after 7 or 14 days of isolation stress. Scattered magnocellular AVP mRNA-expressing cells of the medial parvocellular PVN showed increases of 19 and 34% after 7 and 14 days of isolation, respectively. We also studied the effect of cold or combined cold and isolation stress on vasopressin gene expression in the PVN and SON. Cold stress for 3 h daily for 4 consecutive days increased AVP mRNA levels in the posterior magnocellular PVN by 15%. Cold-isolated animals showed an increase of 21%. No significant effect on AVP mRNA levels in the SON was observed. In contrast to the posterior magnocellular PVN, cold or cold-isolation stress increased AVP mRNA in magnocellular neurons of the medial parvocellular region of the PVN by 25 and 43%, respectively, relative to control rats. These results suggest that psychological and metabolic stress may be added to the list of stressors that activate the hypothalamo-neurohypophysial system.

  18. Biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin in Brattleboro rats

    Energy Technology Data Exchange (ETDEWEB)

    Janaky, T.; Laczi, F.; Laszlo, F.A.


    The biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin were determined in R-Amsterdam rats and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-lives of (/sup 3/H)LVP and (/sup 3/H)dDAVP in the Brattleboro rats did not differ significantly from that found in the control R-Amsterdam rats. The half-life of (/sup 3/H)dDAVP proved longer than that of (/sup 3/H)LVP in all three groups of animals. In the case of (/sup 3/H)LVP the highest radioactivities were observed in the neurohypophyses, adenohypophyses, and kidneys of both the R-Amsterdam and Brattleboro rats. The accumulation of tritiated material was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. In all three groups of rats, (/sup 3/H)dDAVP was accumulated to the greatest extent in the kidney and the small intestine. The kidney and small intestine contained less radioactivity in homozygous Brattleboro rats than in the controls. There was only a slight radioactivity accumulation in the adenohypophysis and neurohypophysis. From the results it was concluded that the decrease in the rate of enzymatic decomposition may play a role in the increased duration of antidiuretic action of dDAVP. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary diabetes insipidus.

  19. RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability.



    1 In a double-blind, placebo controlled study, the efficacy of Ro 15-1788, a new benzodiazepine antagonist, in blocking the cognitive, psychomotor and subjective effects of diazepam, was investigated in a group of six healthy male volunteers. 2 The central effects of orally administered diazepam (40 mg) were most pronounced 1 h after dosing and persisted for 9 h with decreasing severity. 3 Concurrent oral administration of Ro 15-1788 (200 mg) completely prevented the impairment in cognitive a...

  20. Agroclimatic potential across central Siberia in an altered twenty-first century (United States)

    Tchebakova, N. M.; Parfenova, E. I.; Lysanova, G. I.; Soja, A. J.


    Humans have traditionally cultivated steppe and forest-steppe on fertile soils for agriculture. Forests are predicted to shift northwards in a warmer climate and are likely to be replaced by forest-steppe and steppe ecosystems. We analyzed potential climate change impacts on agriculture in south-central Siberia believing that agriculture in traditionally cold Siberia may benefit from warming. Simple models determining crop range and regression models determining crop yields were constructed and applied to climate change scenarios for various time frames: pre-1960, 1960-90 and 1990-2010 using historic data and data taken from 2020 and 2080 HadCM3 B1 and A2 scenarios. From 50 to 85% of central Siberia is predicted to be climatically suitable for agriculture by the end of the century, and only soil potential would limit crop advance and expansion to the north. Crop production could increase twofold. Future Siberian climatic resources could provide the potential for a great variety of crops to grow that previously did not exist on these lands. Traditional Siberian crops could gradually shift as far as 500 km northwards (about 50-70 km/decade) within suitable soil conditions, and new crops nonexistent today may be introduced in the dry south that would necessitate irrigation. Agriculture in central Siberia would likely benefit from climate warming. Adaptation measures would sustain and promote food security in a warmer Siberia.

  1. The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

    Energy Technology Data Exchange (ETDEWEB)

    Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii


    It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe {sup i}n situ{sup .} The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs.

  2. Time course of central and peripheral alterations after isometric neuromuscular electrical stimulation-induced muscle damage.

    Directory of Open Access Journals (Sweden)

    Alexandre Fouré

    Full Text Available Isometric contractions induced by neuromuscular electrostimulation (NMES have been shown to result in a prolonged force decrease but the time course of the potential central and peripheral factors have never been investigated. This study examined the specific time course of central and peripheral factors after isometric NMES-induced muscle damage. Twenty-five young healthy men were subjected to an NMES exercise consisting of 40 contractions for both legs. Changes in maximal voluntary contraction force of the knee extensors (MVC, peak evoked force during double stimulations at 10 Hz (Db(10 and 100 Hz (Db(100, its ratio (10:100, voluntary activation, muscle soreness and plasma creatine kinase activity were assessed before, immediately after and throughout four days after NMES session. Changes in knee extensors volume and T2 relaxation time were also assessed at two (D2 and four (D4 days post-exercise. MVC decreased by 29% immediately after NMES session and was still 19% lower than the baseline value at D4. The decrease in Db(10 was higher than in Db(100 immediately and one day post-exercise resulting in a decrease (-12% in the 10:100 ratio. On the contrary, voluntary activation significantly decreased at D2 (-5% and was still depressed at D4 (-5%. Muscle soreness and plasma creatine kinase activity increased after NMES and peaked at D2 and D4, respectively. T2 was also increased at D2 (6% and D4 (9%. Additionally, changes in MVC and peripheral factors (e.g., Db(100 were correlated on the full recovery period, while a significant correlation was found between changes in MVC and VA only from D2 to D4. The decrease in MVC recorded immediately after the NMES session was mainly due to peripheral changes while both central and peripheral contributions were involved in the prolonged force reduction. Interestingly, the chronological events differ from what has been reported so far for voluntary exercise-induced muscle damage.

  3. Altered central sensitization and pain modulation in the CNS in chronic joint pain

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Skou, Søren Thorgaard; Nielsen, Thomas Arendt


    and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety......Musculoskeletal pain disorders are the second largest contributor to global disability underlining the significance of effective treatments. However, treating chronic musculoskeletal pain, and chronic joint pain (osteoarthritis (OA)) in particular, is challenging as the underlying peripheral...... of human quantitative pain assessment tools (quantitative sensory testing (QST)) have been developed providing new opportunities for profiling patients and reaching a greater understanding of the mechanisms involved in chronic joint pain. As joint pain is a complex interaction between many different pain...

  4. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik


    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  5. Contents of corticotropin-releasing hormone and arginine vasopressin immunoreativity in the spleen and thymus during a chronic inflammatory stress

    DEFF Research Database (Denmark)

    Chowdrey, H.S.; Lightman, S.L.; Harbuz, M.S.;


    Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin......Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin...

  6. Pyrethroids differentially alter voltage-gated sodium channels from the honeybee central olfactory neurons.

    Directory of Open Access Journals (Sweden)

    Aklesso Kadala

    Full Text Available The sensitivity of neurons from the honey bee olfactory system to pyrethroid insecticides was studied using the patch-clamp technique on central 'antennal lobe neurons' (ALNs in cell culture. In these neurons, the voltage-dependent sodium currents are characterized by negative potential for activation, fast kinetics of activation and inactivation, and the presence of cumulative inactivation during train of depolarizations. Perfusion of pyrethroids on these ALN neurons submitted to repetitive stimulations induced (1 an acceleration of cumulative inactivation, and (2 a marked slowing of the tail current recorded upon repolarization. Cypermethrin and permethrin accelerated cumulative inactivation of the sodium current peak in a similar manner and tetramethrin was even more effective. The slow-down of channel deactivation was markedly dependent on the type of pyrethroid. With cypermethrin, a progressive increase of the tail current amplitude along with successive stimulations reveals a traditionally described use-dependent recruitment of modified sodium channels. However, an unexpected decrease in this tail current was revealed with tetramethrin. If one considers the calculated percentage of modified channels as an index of pyrethroids effects, ALNs are significantly more susceptible to tetramethrin than to permethrin or cypermethrin for a single depolarization, but this difference attenuates with repetitive activity. Further comparison with peripheral neurons from antennae suggest that these modifications are neuron type specific. Modeling the sodium channel as a multi-state channel with fast and slow inactivation allows to underline the effects of pyrethroids on a set of rate constants connecting open and inactivated conformations, and give some insights to their specificity. Altogether, our results revealed a differential sensitivity of central olfactory neurons to pyrethroids that emphasize the ability for these compounds to impair detection and

  7. A novel polymorphism in the coding region of the vasopressin type 2 receptor gene

    Directory of Open Access Journals (Sweden)

    J.L. Rocha


    Full Text Available Nephrogenic diabetes insipidus (NDI is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R gene have also been reported. In the present study, we analyzed exon 3 of the V2(R gene in 20 unrelated individuals by direct sequencing. A C®T alteration in the third position of codon 331 (AGC®AGT, which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome

  8. Immunological alterations in patients with primary tumors in central nervous system

    Directory of Open Access Journals (Sweden)



    Full Text Available Natural killer (NK cells play an important role in immune surveillance against tumors. The present work aimed to study the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS. As controls 29 healthy subjects with the age range equivalent to the patients were studied. The methods employed were: a determination of cytotoxic activity of NK cells towards K562 target cells, evaluated by single cell-assay; b enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets defined by monoclonal antibodies; c the identification of tumors were done by histologic and immunochemistry studies. The results indicated that adults and children with tumor in CNS display reduced percentage of total T cells, helper/inducer subset and low helper/suppressor ratio. The cytotoxic activity of NK cells was decreased in patients with CNS tumors due mainly to a decrease in the proportion of target-binding lymphocytes. These results suggest that cytotoxic activity of NK cells may be affected by the immunoregulatory disturbances observed in patients with primary tumors in CNS.

  9. Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report

    NARCIS (Netherlands)

    G. Meynen; U.A. Unmehopa; J.J. van Heerikhuize; M.A. Hofman; D.F. Swaab; W.J.G. Hoogendijk


    Background: Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study

  10. Exploring the Altered Dynamics of Mammalian Central Carbon Metabolic Pathway in Cancer Cells: A Classical Control Theoretic Approach.

    Directory of Open Access Journals (Sweden)

    Debjyoti Paul

    Full Text Available In contrast with normal cells, most of the cancer cells depend on aerobic glycolysis for energy production in the form of adenosine triphosphate (ATP bypassing mitochondrial oxidative phosphorylation. Moreover, compared to normal cells, cancer cells exhibit higher consumption of glucose with higher production of lactate. Again, higher rate of glycolysis provides the necessary glycolytic intermediary precursors for DNA, protein and lipid synthesis to maintain high active proliferation of the tumor cells. In this scenario, classical control theory based approach may be useful to explore the altered dynamics of the cancer cells. Since the dynamics of the cancer cells is different from that of the normal cells, understanding their dynamics may lead to development of novel therapeutic strategies.We have developed a model based on the state space equations of classical control theory along with an order reduction technique to mimic the actual dynamic behavior of mammalian central carbon metabolic (CCM pathway in normal cells. Here, we have modified Michaelis Menten kinetic equation to incorporate feedback mechanism along with perturbations and cross talks associated with a metabolic pathway. Furthermore, we have perturbed the proposed model to reduce the mitochondrial oxidative phosphorylation. Thereafter, we have connected proportional-integral (PI controller(s with the model for tuning it to behave like the CCM pathway of a cancer cell. This methodology allows one to track the altered dynamics mediated by different enzymes.The proposed model successfully mimics all the probable dynamics of the CCM pathway in normal cells. Moreover, experimental results demonstrate that in cancer cells, a coordination among enzymes catalyzing pentose phosphate pathway and intermediate glycolytic enzymes along with switching of pyruvate kinase (M2 isoform plays an important role to maintain their altered dynamics.

  11. Arginine vasopressin and copeptin in perinatology

    Directory of Open Access Journals (Sweden)

    Katrina Suzanne Evers


    Full Text Available Arginine vasopressin (AVP plays a major role in the homeostasis of fluid balance, vascular tonus and the regulation of the endocrine stress response. The measurement of AVP levels is difficult due to its short half-life and laborious method of detection. Copeptin is a more stable peptide derived from the same precursor molecule, is released in an equimolar ratio to AVP and has a very similar response to osmotic, hemodynamic and stress-related stimuli. In fact, copeptin has been propagated as surrogate marker to indirectly determine circulating AVP concentrations in various conditions. Here, we present an overview of the current knowledge on AVP and copeptin in perinatology with a particular focus on the baby’s transition from placenta to lung breathing. We performed a systematic review of the literature on fetal stress hormone levels, including norepinephrine, cortisol, AVP and copeptin, in regard to birth stress. Finally, diagnostic and therapeutic options for copeptin measurement and AVP functions are discussed.

  12. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.


    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopre

  13. Radioprotection of the digestive tract by intravenous infusion of vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Juillard, G.J.F.; Peter, H.H.; Weisenburger, T.H.; Tesler, A.S.; Langdon, E.A.; Barenfus, M.; Lagasse, L.D.; Watring, W.E.; Smith, M.L.


    The effect of venous infusions of vasopressin during fractionated abdominal radiation exposures was evaluated in four pairs of dogs. In each pair, the control dog was given venous infusion of saline during irradiation. The results were analyzed from clinical observation, autopsy findings, and pathological examination. It appears that venous infusion of vasopressin has a definite and reproducible effect of radioprotection on the gastrointestinal tract, the dose modifying factor (DMF) being 1.5. Radiation therapy of the gynecologic malignancies would be one major application since the radiosensitivity of the intestinal tract is often a limiting factor in delivering high doses to the tumor, and further investigations are being done to study the effects of vasopressin on the radiosensitivity of malignant tumors.

  14. Angiotensin II, Vasopressin, and Collagen-IV Expression in the Subfornical Organ in a Case of Syndrome of Inappropriate ADH

    Directory of Open Access Journals (Sweden)

    Emilia M. Carmona-Calero


    Full Text Available The syndrome of inappropriate antidiuretic hormone (SIADH is a disease characterized by hyponatremia and hyperosmolarity of urine where vasopressin and angiotensin II are implicated in the alteration of salt water balance and cardiovascular and blood pressure regulation. The aim of this study is to analyse the expression of substances related with cardiovascular and salt water regulation in the subfornical organ in a case of SIADH. Two brains, one taken from a 66-year-old man with SIADH and the other from a 63-year-old man without SIADH, were used. Immunohistochemical study was performed using anti-angiotensin II, anti-vasopressin, and anti-collagen-VI as primary antibodies. Angiotensin and vasopressin immunoreaction were found in neurons, in perivascular spaces, and in the ependymal layer in the subfornical organ in both cases. However, in the SIADH case, the angiotensin II and collagen-IV expression in the SFO were different suggesting this organ’s possible participation in the physiopathology of SIADH.

  15. Effect of hydration on plasma vasopressin, renin, and aldosterone responses to head-up tilt (United States)

    Harrison, M. H.; Geelen, G.; Keil, L. C.; Wade, C. A.; Hill, L. C.


    If plasma vasopressin (PVP), plasma renin (PRA), and plasma aldosterone (PA) responses to change in posture are mediated only by alterations in intrathoracic baroreceptor activity hydration status should have minimal influence on these responses. To test this hypothesis, six male subjects underwent 45 min of 70 deg head-up tilt (HUT) following 26 h dehydration, and again, 105 min later, following rehydration. Compared with preceding supine hydrated control values, PVP, PRA, and PA increased (p less than 0.001) during dehydrated HUT, but only PVP and PRA increased during rehydrated HUT (p less than 0.001). The dissociation during rehydrated HUT of PRA and PA may have been related more to the reduction (p less than 0.001) in plasma potassium concentration than to the accompanying decrease (p less than 0.001) in plasma osmolality and sodium concentration. Although increases in PVP and PRA during HUT were attenuated (p less than 0.01) following rehydration, this attenuation was associated with the absence of symptoms of overt hypotension following rehydration. However, since rehydration did not abolish the increases in PVP and PRA induced by HUT, it is concluded that the present observations support the concept of intrathoracic baroreceptor involvement in the regulation of vasopressin secretion and renin release.

  16. Localized Climate and Surface Energy Flux Alterations across an Urban Gradient in the Central U.S.

    Directory of Open Access Journals (Sweden)

    Jason A. Hubbart


    Full Text Available Long-term urban and rural climate data spanning January 1995 through October 2013 were analyzed to investigate the Urban Heat Island (UHI effect in a representative mid-sized city of the central US. Locally distributed climate data were also collected at nested low density urban, recently developed, and high density urban monitoring sites from June through September 2013 to improve mechanistic understanding of spatial variability of the UHI effect based upon urban land use intensity. Long-term analyses (1995–2013 indicate significant differences (p < 0.001 between average air temperature (13.47 and 12.89 °C, at the urban and rural site respectively, relative humidity (69.11% and 72.51%, urban and rural respectively, and average wind speed (2.05 and 3.15 m/s urban and rural respectively. Significant differences (p < 0.001 between urban monitoring sites indicate an urban microclimate gradient for all climate variables except precipitation. Results of analysis of net radiation and soil heat flux data suggest distinct localized alterations in urban energy budgets due to land use intensity. Study results hold important implications for urban planners and land managers seeking to improve and implement better urban management practices. Results also reinforce the need for distributed urban energy balance investigations.

  17. Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

    Directory of Open Access Journals (Sweden)

    Gonzalez Ana M


    Full Text Available Abstract Background Adult rat hypothalamo-pituitary axis and choroid plexus are rich in basic fibroblast growth factor (FGF2 which likely has a role in fluid homeostasis. Towards this end, we characterized the distribution and modulation of FGF2 in the human and rat central nervous system. To ascertain a functional link between arginine vasopressin (AVP and FGF2, a rat model of chronic dehydration was used to test the hypothesis that FGF2 expression, like that of AVP, is altered by perturbed fluid balance. Methods Immunohistochemistry and confocal microscopy were used to examine the distribution of FGF2 and AVP neuropeptides in the normal human brain. In order to assess effects of chronic dehydration, Sprague-Dawley rats were water deprived for 3 days. AVP neuropeptide expression and changes in FGF2 distribution in the brain, neural lobe of the pituitary and kidney were assessed by immunohistochemistry, and western blotting (FGF2 isoforms. Results In human hypothalamus, FGF2 and AVP were co-localized in the cytoplasm of supraoptic and paraventricular magnocellular neurons and axonal processes. Immunoreactive FGF2 was associated with small granular structures distributed throughout neuronal cytoplasm. Neurohypophysial FGF2 immunostaining was found in axonal processes, pituicytes and Herring bodies. Following chronic dehydration in rats, there was substantially-enhanced FGF2 staining in basement membranes underlying blood vessels, pituicytes and other glia. This accompanied remodeling of extracellular matrix. Western blot data revealed that dehydration increased expression of the hypothalamic FGF2 isoforms of ca. 18, 23 and 24 kDa. In lateral ventricle choroid plexus of dehydrated rats, FGF2 expression was augmented in the epithelium (Ab773 as immunomarker but reduced interstitially (Ab106 immunostaining. Conclusions Dehydration altered FGF2 expression patterns in AVP-containing magnocellular neurons and neurohypophysis, as well as in choroid

  18. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas;


    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...

  19. Effects of vasopressin on active and passive avoidance behavior

    NARCIS (Netherlands)

    Bohus, B.; Ader, R.; Wied, D. de


    Male rats were trained in an active avoidance and/or a “step-through” type of passive avoidance situation. Lysine vasopressin administration resulted in resistance to extinction of active avoidance behavior if it was injected 1 hr prior to the third and final acquisition session; peptide treatment 6

  20. Arginine vasopressin and oxytocin modulate human social behavior. (United States)

    Ebstein, Richard P; Israel, Salomon; Lerer, Elad; Uzefovsky, Florina; Shalev, Idan; Gritsenko, Inga; Riebold, Mathias; Salomon, Shahaf; Yirmiya, Nurit


    Increasing evidence suggests that two nonapeptides, arginine vasopressin and oxytocin, shape human social behavior in both nonclinical and clinical subjects. Evidence is discussed that in autism spectrum disorders genetic polymorphisms in the vasopressin-oxytocin pathway, notably the arginine vasopressin receptor 1a (AVPR1a), the oxytocin receptor (OXTR), neurophysin I and II, and CD38 (recently shown to be critical for social behavior by mediating oxytocin secretion) contribute to deficits in socialization skills in this group of patients. We also present first evidence that CD38 expression in lymphoblastoid cells derived from subjects diagnosed with autism is correlated with social skill phenotype inventoried by the Vineland Adaptive Behavioral Scales. Additionally, we discuss molecular genetic evidence that in nonclinical subjects both AVPR1a and OXTR genes contribute to prosocial or altruistic behavior inventoried by two experimental paradigms, the dictator game and social values orientation. The role of the AVPR1a is also analyzed in prepulse inhibition. Prepulse inhibition of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. First results are presented showing that intranasal administration of arginine vasopressin increases salivary cortisol levels in the Trier Social Stress test. To summarize, accumulating studies employing a broad array of cutting-edge tools in psychology, neuroeconomics, molecular genetics, pharmacology, electrophysiology, and brain imaging are beginning to elaborate the intriguing role of oxytocin and arginine vasopressin in human social behavior. We expect that future studies will continue this advance and deepen our understanding of these complex events.

  1. Changes in vasopressin-converting aminopeptidase activity in the rat pineal gland during summer : Relationship to vasopressin contents

    NARCIS (Netherlands)

    Liu, B.; Burbach, J.P.H.


    Vasopressin (VP)-converting aminopeptidase (VP-AP) activity and VP contents were measured in single rat pineal glands during the summer of two successive years. The peptidase activity decreased significantly in August. The lowest activity (±SEM) of 0.18±0.02 pmol·hour−1 was recorded on August 14, co

  2. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

    NARCIS (Netherlands)

    Gispen, W.H.; Chepkova, A.N.; French, P.; Wied, D. de; Ontskul, A.H.; Ramakers, G.M.J.; Skrebitski, V.G.; Urban, I.J.A.


    Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into

  3. Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Moeller, H B; Fenton, R A; Zeuthen, T;


    following pathologies such as brain injuries, brain tumours, and cerebral ischemia. As vasopressin and its G-protein-coupled receptor (V1(a)R) have been shown to affect the outcome of brain edema, we have investigated the regulatory interaction between AQP4 and V1(a)R by heterologous expression in Xenopus......Aquaporin 4 (AQP4) is abundantly expressed in the perivascular glial endfeet in the central nervous system (CNS), where it is involved in the exchange of fluids between blood and brain. At this location, AQP4 contributes to the formation and/or the absorption of the brain edema that may arise......)R may prove to be a potential therapeutic target in the prevention and treatment of brain edema....

  4. Vasopressin Proves Es-sense-tial: Vasopressin and the Modulation of Sensory Processing in Mammals

    Directory of Open Access Journals (Sweden)

    Janet Kay Bester-Meredith


    Full Text Available As mammals develop, they encounter increasing social complexity in the surrounding world. In order to survive, mammals must show appropriate behaviors toward their mates, offspring, and same-sex conspecifics. Although the behavioral effects of the neuropeptide arginine vasopressin (AVP have been studied in a variety of social contexts, the effects of this neuropeptide on multimodal sensory processing has received less attention. AVP is widely distributed through sensory regions of the brain and has been demonstrated to modulate olfactory, auditory, gustatory, and visual processing. Here we review the evidence linking AVP to the processing of social stimuli in sensory regions of the brain and explore how sensory processing can shape behavioral responses to these stimuli. In addition, we address the interplay between hormonal and neural AVP in regulating sensory processing of social cues. Because AVP pathways show plasticity during development, early life experiences may shape life-long processing of sensory information. Furthermore, disorders of social behavior such as autism and schizophrenia that have been linked with AVP also have been linked with dysfunctions in sensory processing. Together, these studies suggest that AVP’s diversity of effects on social behavior across a variety of mammalian species may result from the effects of this neuropeptide on sensory processing.

  5. Circadian variation of plasma arginine vasopressin concentration, or arginine vasopressin in enuresis. (United States)

    Aikawa, T; Kasahara, T; Uchiyama, M


    The objective of these studies was to determine a relationship between primary nocturnal enuresis and arginine vasopressin (AVP) secretion. The first study compared 24-h AVP secretion profiles of enuretic (n = 9) and non-enuretic children (n = 8). Blood samples were collected at 1-h intervals for 24 h. In the second study, nocturnal AVP secretion in group A (n = 40)--with low urinary osmotic pressure (UOP) and large nocturnal urine output (NUO)--was compared with that in group D (n = 11) with normal UOP and small NUO. Plasma AVP levels were measured at 30-min intervals, immediately after falling asleep until 06.00 the following morning. The results of the first study showed that the plasma AVP level was significantly lower (p < 0.05-0.001) in the enuretic group between 23.00 and 04.00. The second study showed that group A had significantly lower AVP levels (p < 0.05-0.001) than group D throughout the night. The mean AVP level during night sleep was 0.64 +/- 0.23 pg/ml in group A and 1.43 +/- 0.66 pg/ml in group D. The results of the first study suggest that decreased nocturnal AVP secretion is a cause of bedwetting. However, the results of the second study suggest that nocturnal enuresis cannot be explained by a decrease in nocturnal AVP secretion alone.

  6. Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

    DEFF Research Database (Denmark)

    Miani, Alessandro


    Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based...... on the fact that the sexually dimorphic neuropeptide vasopressin has its receptors in the part of the brain involved in music and dance performance (the basal ganglia), and its concentrations rise during sexual arousal in men. In addition, music, dance, and courtship phenotypes seem to be in part regulated...... by vasopressin and its genes. Hence, to test this hypothesis, a rhythmic synchronization task was employed here on one male subject during sexual arousal. Results revealed a significant effect of sexual arousal on rhythm synchronization. This is the first report that empirically supports the hypothesis...

  7. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels;


    of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe......In order to elucidate the molecular basis and the clinical characteristics of X-linked recessive nephrogenic diabetes insipidus (CNDI) in a kindred of Danish descent, we performed direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene in five members of the family, as well...... as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron...

  8. Hemodilution, vasopressin suppression, and diuresis during water immersion in man (United States)

    Greenleaf, J. E.; Keil, L. C.; Shvartz, E.


    The possible role of hemodilution in the early stages of water immersion in the suppression of antidiuretic hormone (vasopressin) and subsequent diuresis in man is investigated. Parameters characterizing hemodilution as well as water balance and intercompartmental fluid levels were measured before, during and after the immersion of ten subjects in a semireclining position in tap water up to their necks at 34.6 C for 8 hr. Results indicate that hemodilution and the suppression of vasopressin and plasma renin activity were present by the second hour of immersion, with the early hemodilution due to a slight increase in plasma volume with no change in plasma sodium or osmotic contents, even though urine volume and osmotic excretion rates increased significantly. Hyponatremia, hyposmotemia and plasma renin activity suppression are observed to continue to the end of immersion, resulting in final decreases of 15.6% in plasma volume, 18.8% in extracellular volume, 19.6% in interstitial volume and 10.7% in red cell volume. Findings suggest the transfer of hypotonic fluid into the vascular system, which contributes to vasopressin suppression observed during immersion.

  9. Syndromes related to sodium and arginine vasopressin alterations in post-operative neurosurgery Síndromes relacionadas com alterações de sódio e arginina-vasopressina no pós-operatório de neurocirurgia

    Directory of Open Access Journals (Sweden)

    Ana P.D. Cardoso


    Full Text Available BACKGROUND: Cerebral salt wasting syndrome (CSWS, syndrome of inappropriate antidiuretic hormone secretion (SIADH and diabetes insipidus (DI are frequently found in postoperative neurosurgery. PURPOSE: To identify these syndromes following neurosurgery. METHOD: The study included 30 patients who had been submitted to tumor resection and cerebral aneurysm clipping. Sodium levels in serum and urine and urine volume were measured daily up to the 5th day following surgery. Plasma arginine vasopressin (AVP was measured on the first, third and fifth days post-surgery. RESULTS: CSWS was found in 27/30 patients (90%, in 14 (46.7% of whom it was associated with a reduction in the levels of plasma AVP (mix syndrome. SIADH was found in 3/30 patients (10%. There was no difference between the two groups of patients. CONCLUSION: CSWS was the most common syndrome found, and in half the cases it was associated with DI. SIADH was the least frequent syndrome found.INTRODUÇÃO: A síndrome perdedora de sal (SPS, síndrome da secreção inapropriada do hormônio antidiurético (SIADH e diabetes insipidus (DI são freqüentemente encontradas no pós-operatório de neurocirurgia. OBJETIVO: Identificar essas síndromes relacionadas à neurocirurgia. MÉTODO: Foram estudados 30 pacientes submetidos à ressecção de tumor (n=19 e clipagem de aneurisma (n=11 cerebral durante os primeiros cinco dias do pós-operatório. Os pacientes foram submetidos a dosagens diárias de sódio sérico e urinário até o 5º dia pós-operatório, com controle de volume urinário neste período e dosagem de arginina-vasopressina (AVP plasmática no 1º, 3º e 5º dias pós-operatórios. RESULTADOS: A SPS foi encontrada em 27/30 pacientes (90%, em 14/27 (46,7% associada à diminuição dos níveis de AVP plasmática (síndrome mista. A SIADH foi encontrada em 3/30 pacientes (10%. Não houve diferença entre os dois grupos de pacientes. CONCLUSÃO: A SPS foi a síndrome mais freq

  10. Altered pain perception in children with chronic tension-type headache: Is this a sign of central sensitisation?

    DEFF Research Database (Denmark)

    Soee, AL; Thomsen, LL; Kreiner, S


    The aim of this article is to investigate if children (7-17 years) with frequent episodic tension-type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls.......The aim of this article is to investigate if children (7-17 years) with frequent episodic tension-type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls....

  11. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: Study in vasopressin-deficient Brattleboro rats


    Bardoux, Pascale; Martin, Hélène; Ahloulay, Mina; Schmitt, François; Bouby, Nadine; Trinh-Trang-Tan, Marie-Marcelle; Bankir, Lise


    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattlebor...

  12. Modified forms of vasopressin and oxytocin in a bovine pineal preparation

    NARCIS (Netherlands)

    Noteborn, H.P.J.M.; Burbach, J.P.H.; Ebels, I.


    A bovine pineal acid extract displays a vasotocin-like bioactivity in several bioassays, and is recognized by antibodies against the Pro-Arg-Gly-amide ending common to vasopressin and vasotocin. By using molecular sieve filtration and reversed-phase HPLC, a vasopressin- and oxytocin-like peptide was

  13. Radioimmunoassay measurement of plasma oxytocin and vasopressin in cows during machine milking

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R.; Wehowsky, G.; Schulz, J.; Schulze, H.; Bothur, D. (Forschungsinstitut fuer Koerperkultur und Sport, Leipzig (German Democratic Republic); Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin)


    The response of plasma oxytocin and vasopressin to machine milking in cows was studied by radioimmunoassay. Depending on the method of machine milking used, plasma oxytocin increased to a greater or lesser degree after teat cup application. Plasma vasopressin was not affected by the milking procedures.

  14. The effects of vasopressin deficiency on aggression and impulsiveness in male and female rats. (United States)

    Fodor, Anna; Barsvari, Beata; Aliczki, Mano; Balogh, Zoltan; Zelena, Dora; Goldberg, Steven R; Haller, Jozsef


    The role of vasopressin in aggression received much attention in recent years. However, vasopressin has complex roles on social behavior, which are affected by social experience, motivation and hormonal background, suggesting that its effects depend on the condition of subjects. This hypothesis was tested here by studying the impact of vasopressin deficiency on aggressiveness in reproductively naive and reproductively experienced males, as well as in lactating females, with special reference to the patterns and contexts of attack behavior. We also studied effects on impulsiveness, a behavioral feature strongly related to aggression. Vasopressin deficiency did not affect aggressiveness in reproductively experienced males, decreased the share of violent attacks in reproductively inexperienced males without affecting total attack counts, and suppressed maternal aggression in both early and late phases of lactation; violent forms of attack were decreased in the latter but not the former phase. Changes in aggression appeared unrelated to general changes in maternal behaviors. Impulsivity in the delay discounting task was markedly decreased by vasopressin deficiency in lactating females but not males. Taken together, our findings confirm that vasopressin has an impact on aggressiveness, but show that this impact depends on the condition of subjects, and suggest that the effects of vasopressin on maternal aggression develop in conjunction with impulsivity. Interestingly, overall effects on aggression and specific effects on violent attacks dissociated in both males and females, which hints to the possibility that vasopressin has distinct roles in the development of escalated forms of aggression.

  15. Fate of copper complexes in hydrothermally altered deep-sea sediments from the Central Indian Ocean Basin.

    Digital Repository Service at National Institute of Oceanography (India)

    Chakraborty, P.; Sander, S.G.; Jayachandran, S.; Nath, B.N.; Nagaraju, G.; Chennuri, K.; Vudamala, K.; Lathika, N.; Mascarenhas-Pereira, M.B.L.

    flux from this sediment to the water column in this area. This study suggests that most of the Cu was strongly associated with different binding sites in Fe-oxide phases of the hydrothermally altered sediments with stabilities higher than that of Cu...

  16. [Agonist of V2 vasopressin receptor reduces depressive disorders in post-stroke patients]. (United States)

    Belokoskova, S G; Stepanov, I I; Tsikunov, S G


    Poststroke depression is one of the common psychiatric complications after stroke. Thus, the research of new ways for treatment depressed mood after stroke is actual. The previous researches revealed vasopressin to be effective in patients with memory, speech and motor function disorders after stroke. The purpose of the study was to investigate influence of vasopressin on depression after stroke. Fourteen patients with affective disorders have been treated with subendocrine doses of 1-desamino-8-D-arginin-vasopressin (DDAVP) daily by intranasal application during 1,5-2 months. Vasopressin was effective in correcting both apatoadinamic and anxious depression. Treatment effect was durable, lasts for 0,5-1 year after the first course of therapy. The results of this pilot study demonstrate perspective of using selective agonist of vasopressin V2 receptors, DDAVP, in therapy of post-stroke depression.

  17. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation (United States)

    Brooks, V. L.; Keil, L. C.


    Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

  18. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity (United States)

    Central carbon metabolism (CCM) is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species and thus have not been obvious targets as candidates for crop improvement. We test this functional conservatio...

  19. Long-term effects of early adolescent methamphetamine exposure on depression-like behavior and the hypothalamic vasopressin system in mice. (United States)

    Joca, Lauren; Zuloaga, Damian G; Raber, Jacob; Siegel, Jessica A


    Methamphetamine (MA) has neurotoxic effects on the adult human brain that can lead to deficits in behavior and cognition. However, relatively little research has examined the behavioral or neurotoxic effects of MA in adolescents. The rising rates of adolescent MA use make it imperative that we understand the long-term effects of MA exposure on the adolescent brain and how these effects may differ from those seen in adults. In this study, the long-term effects of MA exposure during early adolescence on behavior and the vasopressin system in the paraventricular nucleus of the hypothalamus in late adolescent and adult male and female C57BL/6J mice were examined. MA exposure increased depression-like behavior in the Porsolt forced swim test in both late adolescent and adult male and female mice. Late adolescent male mice exposed to MA also showed a decrease in the number of vasopressin-immunoreactive neurons in the paraventricular nucleus compared to sex-matched saline-treated controls. Thus, similar to humans exposed to MA during adolescence, mice exposed to MA during adolescence show increased depression-like behavior later in life. These changes in behavior may be related to MA-induced alterations in vasopressin and the hypothalamic-pituitary-adrenal axis, especially in males.

  20. Vasopressin content in the cerebrospinal fluid and fluid perfusing cerebral ventricles in rats after the afferent vagus nerve fibres stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii


    Experiments were carried out on male rats in urethane anaesthesia. Cerebroventricular system was perfused with McIlwain-Rodniht`s solution from lateral ventricles to cerebellomedullary cistern. Both vagus nerves were cut and the central ends of the nerves were electrically stimulated during the collection of the third 30-min portion of perfusing fluid. Vasopressin (AVP) was determined by radioimmunoassay in samples of the cerebrospinal fluid (CSF) (the first portion) and in five successive samples of the perfusing fluid. AVP concentration in the CSF was several times greater than in the fluid perfusing cerebral ventricles. Alternate electrical stimulation of both vagus nerves did not change considerably the release of AVP into the fluid perfusing the cerebral ventricles in rat, although a certain upward tendency could be observed. It seems that only AVP raised in circulating blood and not in CSF, after vagus nerves stimulation may act on the central nervous structures. (author). 37 refs, 3 figs, 1 tab.

  1. Binding of oxytocin and 8-arginine-vasopressin to neurophysin studied by /sup 15/N NMR using magnetization transfer and indirect detection via protons

    Energy Technology Data Exchange (ETDEWEB)

    Live, D.H.; Cowburn, D.


    NMR was used to monitor the binding to neurophysin of oxytocin and 8-arginine-vasopressin, /sup 15/N labeling being used to identify specific backbone /sup 15/N and /sup 1/H signals. The most significant effects of binding were large downfield shifts in the amino nitrogen resonance of Phe-3 of vasopressin and in its associated proton, providing evidence that the peptide bond between residues 2 and 3 of the hormones is hydrogen-bonded to the protein within hormone-neurophysin complexes. Suggestive evidence for hydrogen bonding of the amino nitrogen of Tyr-2 was also obtained in the form of decreased proton exchange rates on binding; however, the chemical shift changes of this nitrogen and its associated proton indicated that such hydrogen bonding, if present, is probably weak. Shifts in the amino nitrogen of Asn-5 and in the -NH protons of both Asn-5 and Cys-6 demonstrated that these residues are significantly perturbed by binding, suggesting conformational changes of the ring on binding and/or the presence of binding sites on the hormone outside the 1-3 region. No support was obtained for the thesis that there is a significant second binding site for vasopressin on each neutrophysin chain. The behavior of both oxytocin and vasopressin on binding was consistent with formation of 1:1 complexes in slow exchange with the free state under most pH conditions. At low pH there was evidence of an increased exchange rate. Additionally, broadening of /sup 15/N resonances in the bound state at low pH occurred without a corresponding change in the resonances of equilibrating free hormone. The results suggest significant conformational alteration in neurophysin-hormone complexes at low pH possibly associated with protonation of the carboxyl group of the hormone-protein salt bridge.

  2. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus. (United States)

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E; Carlson, Noel G; Baqi, Younis; Strasburg, David L; Heiney, Kristina M; Villanueva, Karie; Kohan, Donald E; Kishore, Bellamkonda K


    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.

  3. Phosphorylation of UT-A1 urea transporter at serines 486 and 499 is important for vasopressin-regulated activity and membrane accumulation. (United States)

    Blount, Mitsi A; Mistry, Abinash C; Fröhlich, Otto; Price, S Russ; Chen, Guangping; Sands, Jeff M; Klein, Janet D


    The UT-A1 urea transporter plays an important role in the urine concentrating mechanism. Vasopressin (or cAMP) increases urea permeability in perfused terminal inner medullary collecting ducts and increases the abundance of phosphorylated UT-A1, suggesting regulation by phosphorylation. We performed a phosphopeptide analysis that strongly suggested that a PKA consensus site(s) in the central loop region of UT-A1 was/were phosphorylated. Serine 486 was most strongly identified, with other potential sites at serine 499 and threonine 524. Phosphomutation constructs of each residue were made and transiently transfected into LLC-PK1 cells to assay for UT-A1 phosphorylation. The basal level of UT-A1 phosphorylation was unaltered by mutation of these sites. We injected oocytes, assayed [14C]urea flux, and determined that mutation of these sites did not alter basal urea transport activity. Next, we tested the effect of stimulating cAMP production with forskolin. Forskolin increased wild-type UT-A1 and T524A phosphorylation in LLC-PK1 cells and increased urea flux in oocytes. In contrast, the S486A and S499A mutants demonstrated loss of forskolin-stimulated UT-A1 phosphorylation and reduced urea flux. In LLC-PK1 cells, we assessed biotinylated UT-A1. Wild-type UT-A1, S486A, and S499A accumulated in the membrane in response to forskolin. However, in the S486A/S499A double mutant, forskolin-stimulated UT-A1 membrane accumulation and urea flux were totally blocked. We conclude that the phosphorylation of UT-A1 on both serines 486 and 499 is important for activity and that this phosphorylation may be involved in UT-A1 membrane accumulation.

  4. Apoptosis of supraoptic AVP neurons is involved in the development of central diabetes insipidus after hypophysectomy in rats

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    Huang Lijin


    Full Text Available Abstract Background It has been reported that various types of axonal injury of hypothalamo-neurohypophyseal tract can result in degeneration of the magnocellular neurons (MCNs in hypothalamus and development of central diabetes insipidus (CDI. However, the mechanism of the degeneration and death of MCNs after hypophysectomy in vivo is still unclear. This present study was aimed to disclose it and to figure out the dynamic change of central diabetes insipidus after hypophysectomy. Results The analysis on the dynamic change of daily water consumption (DWC, daily urine volume(DUV, specific gravity of urine(USG and plasma vasopressin concentration showed that the change pattern of them was triphasic and neuron counting showed that the degeneration of vasopressin neurons began at 10 d, aggravated at 20 d and then stabilized at 30 d after hypophysectomy. There was marked upregulation of cleaved Caspase-3 expression of vasopressin neurons in hypophysectomy rats. A "ladder" pattern of migration of DNA internucleosomal fragments was detected and apoptotic ultrastructure was found in these neurons. There was time correlation among the occurrence of diabetes insipidus, the changes of plasma vasopressin concentration and the degeneration of vasopressin neurons after hypophysectomy. Conclusion This study firstly demonstrated that apoptosis was involved in degeneration of supraoptic vasopressin neurons after hypophysectomy in vivo and development of CDI. Our study on time course and correlations among water metabolism, degeneration and apoptosis of vasopressin neurons suggested that there should be an efficient therapeutic window in which irreversible CDI might be prevented by anti-apoptosis.

  5. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

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    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P. (Univ. of Pittsburgh School of Medicine, PA (USA))


    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of (35S)cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of (35S)cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, (35S)cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes.

  6. Altered activity in the central medial thalamus precedes changes in the neocortex during transitions into both sleep and propofol anesthesia. (United States)

    Baker, Rowan; Gent, Thomas C; Yang, Qianzi; Parker, Susan; Vyssotski, Alexei L; Wisden, William; Brickley, Stephen G; Franks, Nicholas P


    How general anesthetics cause loss of consciousness is unknown. Some evidence points toward effects on the neocortex causing "top-down" inhibition, whereas other findings suggest that these drugs act via subcortical mechanisms, possibly selectively stimulating networks promoting natural sleep. To determine whether some neuronal circuits are affected before others, we used Morlet wavelet analysis to obtain high temporal resolution in the time-varying power spectra of local field potentials recorded simultaneously in discrete brain regions at natural sleep onset and during anesthetic-induced loss of righting reflex in rats. Although we observed changes in the local field potentials that were anesthetic-specific, there were some common changes in high-frequency (20-40 Hz) oscillations (reductions in frequency and increases in power) that could be detected at, or before, sleep onset and anesthetic-induced loss of righting reflex. For propofol and natural sleep, these changes occur first in the thalamus before changes could be detected in the neocortex. With dexmedetomidine, the changes occurred simultaneously in the thalamus and neocortex. In addition, the phase relationships between the low-frequency (1-4 Hz) oscillations in thalamic nuclei and neocortical areas are essentially the same for natural sleep and following dexmedetomidine administration, but a sudden change in phase, attributable to an effect in the central medial thalamus, occurs at the point of dexmedetomidine loss of righting reflex. Our data are consistent with the central medial thalamus acting as a key hub through which general anesthesia and natural sleep are initiated.

  7. The effects of lactation on impulsive behavior in vasopressin-deficient Brattleboro rats. (United States)

    Aliczki, Mano; Fodor, Anna; Balogh, Zoltan; Haller, Jozsef; Zelena, Dora


    Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral profile, which-among other things-include altered cognitive performance. This profile is markedly affected by alterations in neuroendocrine state of the animal such as during lactation. Given the links between AVP and cognition we hypothesized that AVP deficiency may lead to changes in impulsivity that is under cognitive control and the changes might be altered by lactation. Comparing virgin and lactating AVP-deficient female Brattleboro rats to their respective controls, we assessed the putative lactation-dependent effects of AVP deficiency on impulsivity in the delay discounting paradigm. Furthermore, to investigate the basis of such effects, we assessed possible interactions of AVP deficiency with GABAergic and serotonergic signaling and stress axis activity, systems playing important roles in impulse control. Our results showed that impulsivity was unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced increase in impulsivity was abolished by AVP deficiency in lactating females. We also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine-induced enhancement of serotonergic activity in virgins led to increased and decreased impulsivity, respectively. In contrast, during lactation these effects were visible only in AVP-deficient rats. These rats also exhibited increased stress axis activity compared to virgin animals, an effect that was abolished by AVP deficiency. Taken together, AVP appears to play a role in the regulation of impulsivity exclusively during lactation: it has an impulsivity increasing effect which is potentially mediated via stress axis-dependent mechanisms and fine-tuning of GABAergic and serotonergic function.

  8. Vasopressin V1a and V1b receptors: from molecules to physiological systems. (United States)

    Koshimizu, Taka-aki; Nakamura, Kazuaki; Egashira, Nobuaki; Hiroyama, Masami; Nonoguchi, Hiroshi; Tanoue, Akito


    The neurohypophysial hormone arginine vasopressin (AVP) is essential for a wide range of physiological functions, including water reabsorption, cardiovascular homeostasis, hormone secretion, and social behavior. These and other actions of AVP are mediated by at least three distinct receptor subtypes: V1a, V1b, and V2. Although the antidiuretic action of AVP and V2 receptor in renal distal tubules and collecting ducts is relatively well understood, recent years have seen an increasing understanding of the physiological roles of V1a and V1b receptors. The V1a receptor is originally found in the vascular smooth muscle and the V1b receptor in the anterior pituitary. Deletion of V1a or V1b receptor genes in mice revealed that the contributions of these receptors extend far beyond cardiovascular or hormone-secreting functions. Together with extensively developed pharmacological tools, genetically altered rodent models have advanced the understanding of a variety of AVP systems. Our report reviews the findings in this important field by covering a wide range of research, from the molecular physiology of V1a and V1b receptors to studies on whole animals, including gene knockout/knockdown studies.

  9. Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice. (United States)

    Ruan, Chao; Zhang, Zhibin


    The process of domestication is recognized to exert significant effects on the social behaviors of various animal species, including defensive and cognitive behaviors that are closely linked to the expression of oxytocin (OT) and vasopressin (AVP) in selected areas of the brain. However, it is still unclear whether the behavioral changes observed under domestication have resulted in differences in the neurochemical systems that regulate them. In this study, we compared the differences in distribution patterns and regional quantities of OT and/or AVP staining in the forebrains of wild and laboratory strains of rats and mice. Our results indicated that, in the anterior hypothalamus (AH), laboratory strains showed significantly higher densities of OT-ir (immunoreactive) and AVP-ir cells than wild strains, while no significant difference in the densities of those cells in the lateral hypothalamus (LH) was detected between wild and laboratory strains. Laboratory strains showed higher densities of OT-ir and AVP-ir cells than wild strains in the medial preoptic area (MPOA), and differed in almost every MPOA subnucleus. Our results suggest that domestication significantly alters the expression of OT and AVP in related brain areas of laboratory rats and mice, an observation that could explain the identified changes in behavioral patterns.

  10. Primary central nervous system degeneration in elderly patients. Characteristic imaging features; Primaere Degeneration des ZNS im Alter. Bildgebung charakteristischer Atrophiemuster

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    Weidauer, S.; Lanfermann, H. [Klinikum der Johann-Wolfgang-Goethe-Universitaet, Institut fuer Neuroradiologie, Frankfurt (Germany); Nichtweiss, M. [HANSE-Klinikum Wismar GmbH, Neurologische Klinik, Wismar (Germany)


    Despite further development of new magnetic resonance imaging techniques, e.g., diffusion tensor imaging and 1H magnetic resonance spectroscopy, structural imaging will continue to play a major role in the diagnosis of primary central nervous system degeneration in ageing. Characteristic imaging patterns of multisystem atrophies and primary dementias as well as differential diagnostic features are demonstrated. While such features may have high specificity, their sensitivity is low especially in cross-sectional studies. Longitudinal studies are the optimal method to characterize the dynamic neuroanatomical correlates of the disease. However, according to disease duration and progression, neuroimaging will show increased overlapping and convergence of pathological changes in multisystem atrophy as well as in dementia. (orig.) [German] Trotz der Weiterentwicklung innovativer magnetresonanztomographischer Methoden wie der Diffusionstensormessung und der 1H-Magnetresonanzspektroskopie hat die strukturelle Bildgebung nach wie vor einen zentralen Stellenwert in der Diagnostik altersassoziierter pathologischer Degenerationen des Zentralnervensystems. Es werden typische bildmorphologische Muster bei Multisystematrophien und primaer demenziellen Erkrankungen aufgezeigt und differenzialdiagnostische Merkmale dargestellt. Diese haben insbesondere bei Querschnittuntersuchungen eine hohe Spezifitaet, jedoch geringe Sensitivitaet. Verlaufs- oder Laengsschnittuntersuchungen koennen zwar einerseits die Dynamik und mitunter charakteristische Befunde besser darstellen, andererseits zeigt sich sowohl bei den Multisystematrophien mit initial betont motorischer Symptomatik als auch bei Demenzen mit zunehmender Krankheitsdauer eine Konvergenz und Ueberlappung der Atrophiemuster. (orig.)

  11. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

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    Nengyi Zhang

    Full Text Available BACKGROUND: Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system. METHODOLOGY/PRINCIPAL FINDINGS: We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C., in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  12. Effects of vasopressin administration on diuresis of water immersion in normal humans (United States)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.


    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  13. Hypervolemia and plasma vasopressin response during water immersion in men (United States)

    Greenleaf, J. E.; Morse, J. T.; Barnes, P. R.; Silver, J.; Keil, L. C.


    Immersion studies were performed on seven mildly dehydrated male subjects to examine the effect of suppression of plasma vasopressin (PVP) on diuresis in water immersion. The water was kept at close to 34.5 C and the subjects remained in the water for 4 hr after sitting for 2 hr. Na and K levels in the serum and urine were analyzed, as were osmolality, red blood cell count, renin activity, total protein, albumin amounts, hematocrit, and hemoglobin. Plasma volume was monitored from samples drawn at specified intervals during immersion. The plasma volume increased significantly 30 min after immersion, but no PVP was observed. The dehydration induced elevated serum osmotic concentrations. It is concluded that the hydration condition before immersion and the volume of fluid intake during immersion affects the hemodilution during immersion.

  14. [Radioimmunoassay for human plasma 8-arginine-vasopressin (author's transl)]. (United States)

    Conte-Devolx, B; Rougon-Rapuzzi, G; Millet, Y


    The authors have developed a radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormon (ADH) levels as low as 0,8 pg/ml. The average plasma level of AVP after overnight water restriction was found to be 14,3 pg/ml (sd = 4,4 pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2 mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion; in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated.

  15. HIV-1 alters neural and glial progenitor cell dynamics in the central nervous system: coordinated response to opiates during maturation. (United States)

    Hahn, Yun Kyung; Podhaizer, Elizabeth M; Hauser, Kurt F; Knapp, Pamela E


    HIV-associated neurocognitive disorders (HANDs) are common sequelae of human immunodeficiency virus (HIV) infection, even when viral titers are well controlled by antiretroviral therapy. Evidence in patients and animal models suggests that neurologic deficits are increased during chronic opiate exposure. We have hypothesized that central nervous system (CNS) progenitor cells in both adult and developing CNS are affected by HIV infection and that opiates exacerbate these effects. To examine this question, neural progenitors were exposed to HIV-1 Tat(1-86) in the developing brain of inducible transgenic mice and in vitro. We examined whether Tat affected the proliferation or balance of progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was further tested by exposing human-derived progenitors to supernatant from HIV-1 infected monocytes. Studies concentrated on striatum, a region preferentially targeted by HIV and opiates. Results were similar among experimental paradigms. Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2(+)) progenitors and oligodendroglial (Olig2(+)) progenitors. Coexposure to morphine exacerbated the effects of Tat or HIV-1(SF162) supernatant, but partially reversed HIV-1(IIIB) supernatant effects. Populations of Sox2(+) and Olig2(+) cells were also reduced by Tat exposure, although progenitor survival was unaffected. In rare instances, p24 immunolabeling was detected in viable human progenitors by confocal imaging. The vulnerability of progenitors is likely to distort the dynamic balance among neuron/glial populations as the brain matures, perhaps contributing to reports that neurologic disease is especially prevalent in pediatric HIV patients. Pediatric disease is atypical in developed regions but remains a serious concern in resource-limited areas where infection occurs commonly at birth and through breast feeding.

  16. [A sensitive and specific radioimmunoassay for arginine vasopressin and its validation]. (United States)

    Oki, Y; Ohgo, S; Yoshimi, T


    A sensitive and specific radioimmunoassay (RIA) for arginine vasopressin (AVP) has been developed and validated. Synthetic AVP was coupled to bovine serum albumin (BSA) with glutaraldehyde. Antisera against AVP were raised in three rabbits immunized with AVP-BSA complex. After 6 months, at the 16th injection, one of the antisera had a titer high enough to be utilizable for RIA at a final dilution of 1:400,000. The labeling of AVP with 125I Na was performed with the modified chloramine T method, and the purification of iodinated AVP was done with gel filtration chromatography on a Sephadex G-25 fine column (1 X 20 cm) with an elution buffer of 0.01 M acetic acid containing 0.1% BSA. Radioactivities from the Sephadex G-25 were eluted in three peaks. 125I-AVP, which was reactive to the antiserum, was contained in the third peak, and 125I-AVP in the fractions on the down slope of the peak was used for the radioligand in the amount of 1000 cpm. The specific activity of purified 125I-AVP was about 400 muCi/microgram. Diluted antiserum and samples, unlabeled AVP or related peptides were preincubated at 4 degrees C for 24 hr, and then 125I-AVP was added to the mixture and incubated for a further 72 hr. Separation of B and F was done with polyethyleneglycol. The minimal detection limit of AVP, which was 95% of the confidence limit of the mean value of B0, was 0.4 pg/tube. The cross-reactivities with lysine vasopressin, arginine vasotocin, DDAVP and oxytocin were 0.1%, 30%, 1% and 0%, respectively. AVP in plasma was extracted with cold acetone and petroleum ether. The recoveries of synthetic AVP from plasma which was added (2-16 pg) were more than 94%. The intra and inter-assay coefficients of variation determined by plasma of AVP concentration of about 4.8 pg/ml were 8.7% and 11.3%, respectively. The RIA detected AVP of concentration as low as 1 pg/ml following the extraction procedure. AVP immunoreactivity was detected without extraction in urine, and the lyophilized

  17. Extra-neurohypophyseal axonal projections from individual vasopressin-containing magnocellular neurons in rat hypothalamus

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    Vito Salvador Hernandez


    Full Text Available Conventional neuroanatomical, immunohistochemical techniques and electrophysiological recording, as well as in vitro labeling methods may fail to detect long range extra-neurohypophyseal-projecting axons from vasopressin (AVP-containing magnocellular neurons (magnocells in the hypothalamic paraventricular nucleus (PVN. Here, we used in vivo extracellular recording, juxtacellular labeling, post hoc anatomo-immunohistochemical analysis and camera lucida reconstruction to address this question. We demonstrate that all well-labeled AVP immunopositive neurons inside the PVN possess main axons joining the tract of Greving and multi-axon-like processes, as well as axonal collaterals branching very near to the somata, which project to extra-neurohypophyseal regions. The detected regions in this study include the medial and lateral preoptical area, suprachiasmatic nucleus, lateral habenula, medial and central amygdala and the conducting systems, such as stria medullaris, the fornix and the internal capsule. Expression of vesicular glutamate transporter 2 was observed in axon-collaterals. These results, in congruency with several previous reports in the literature, provided unequivocal evidence that AVP magnocells have an uncommon feature of possessing multiple axon-like processes emanating from somata or proximal dendrites. Furthermore, the long-range non-neurohypophyseal projections are more common than an occasional phenomenon as previously thought.

  18. Examining the role of vasopressin in the modulation of parental and sexual behaviors

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    Josi Maria eZimmermann-Peruzatto


    Full Text Available Vasopressin (VP and VP-like neuropeptides are evolutionarily stable peptides found in all vertebrate species. In non-mammalian vertebrates, vasotocin (VT plays a role similar to mammalian VP, whereas mesotocin and isotocin are functionally similar to mammalian oxytocin (OT. Here, we review the involvement of VP in brain circuits, synaptic plasticity, evolution, and function, highlighting the role of VP in social behavior. In all studied species, VP is encoded on chromosome 20p13, and in mammals, VP is produced in specific hypothalamic nuclei and released by the posterior pituitary. The role of VP is mediated by the stimulation of the V1a, V2, and V1b receptors, as well as the oxytocinergic and purinergic receptors. VT and VP functions are usually related to osmotic and cardiovascular homeostasis when acting peripherally. However, these neuropeptides are also critically involved in the central modulation of social behavior displays, such as pairing recognition, pair-bonding, social memory, sexual behavior, parental care, maternal and aggressive behavior. Evidence suggests that these effects are primarily mediated by V1a receptor in specific brain circuits that provide important information for the onset and control of social behaviors in normal and pathological conditions.

  19. Androgen manipulation and vasopressin binding in the rat brain and peripheral organs

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    Gao, Xin; Phillips, P.; Oldfield, B.; Trinder, D.; Risvanis, J.; Stephenson, J.; Johnston, C. (Univ. of Melbourne, Parkville, Victoria (Australia))


    It is now widely recognized that there is a sexual dimorphism in the development of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and that changes in brain AVP immunoreactivity change with manipulation of androgen status. The aim of the present experiment was to determine specifically any AVP receptor changes in response to manipulation of androgen levels using a selective V[sub 1] antagonist radioligand. Following castration, plasma testosterone levels fell and AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the stria terminalis. With testosterone supplementation in castrated animals, the immunoreactivity in these regions was restored to a higher degree than in sham-operated animals. Central and peripheral V[sub 1] AVP receptor binding (as determined using the selective AVP V)[sub 1] antagonist radioligand [[sup 125]I](d(CH[sub 2])[sub 5],sarcosine[sup 7]) AVP was not changed in any of the brain regions studied or in liver or kidney membranes from the three groups. The study demonstrates that there is no change in brain AVP receptor binding despite changes in regional AVP immunoreactivity in the brain, and excludes any confounding interaction with changes in oxytocin receptors. 23 refs., 1 fig., 2 tabs.

  20. Quantitative Proteomics Identifies Vasopressin-Responsive Nuclear Proteins in Collecting Duct Cells


    Schenk, Laura K.; Bolger, Steven J.; Luginbuhl, Kelli; Gonzales, Patricia A.; Rinschen, Markus M.; Yu, Ming-Jiun; Hoffert, Jason D.; Pisitkun, Trairak; Knepper, Mark A.


    Vasopressin controls transport in the renal collecting duct, in part, by regulating transcription. This complex process, which can involve translocation and/or modification of transcriptional regulators, is not completely understood. Here, we applied a method for large-scale profiling of nuclear proteins to quantify vasopressin-induced changes in the nuclear proteome of cortical collecting duct (mpkCCD) cells. Using stable isotope labeling and tandem mass spectrometry, we quantified 3987 nucl...

  1. Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia. (United States)

    Rofe, A M; Williamson, D H


    The effects of vasopressin on the metabolism of starved rats were investigated by using a constant-infusion regimen (50 pmol/kg body wt. per min, after an initial loading dose of 150 pmol/kg body wt.). 2. Blood ketone bodies decreased by 50% in 10 min, and this was accompanied by a 60% decrease in the plasma non-esterified fatty acids. 3. Blood glucose increased by 0.9 mM within 5 min and decreased to control values over the 40 min infusion. Small increases in lactate and pyruvate also occurred. 4. Plasma insulin was not increased by vasopressin infusion. 5. The net decrease in blood ketone bodies caused by vasopressin was similar when somatostatin was infused simultaneously (1 nmol/kg body wt. per min). 6. Hepatic ketone bodies were significantly decreased by vasopressin, as was the 3-hydroxybutyrate/acetoacetate ratio. A small increase in the hepatic concentration of several glycolytic intermediates also occurred. 7. Vasopressin did not decrease the ketonaemia produced by infusions of octanoate or long-chain triacylglycerol in rats that had been pre-treated with the anti-lipolytic agent 3,5-dimethylpyrazole. 8. In comparison with vasopressin, the infusion of adrenaline or glucose had much smaller effects in decreasing the ketonaemia of starvation, despite the 4-fold increase in plasma insulin, at 10 min, with the glucose infusion. 9. The primary metabolic effect of vasopressin in the starved rat appears to be that of decreased supply of non-esterified fatty acid to the liver. It is suggested that vasopressin has a direct anti-lipolytic effect in adipose tissue. PMID:6135420

  2. {sup 222}Rn and CO{sub 2} soil-gas geochemical characterization of thermally altered clays at Orciatico (Tuscany, Central Italy)

    Energy Technology Data Exchange (ETDEWEB)

    Voltattorni, N., E-mail: [Istituto Nazionale di Geofisica e Vulcanologia, Via di Vigna Murata 605, 00143 Rome (Italy); Lombardi, S. [Earth Science Department, University ' La Sapienza' , Piazzale A. Moro 5, 00185 Rome (Italy); Rizzo, S. [Via Tito, 1/A, 00061 Anguillara Sabazia, Rome (Italy)


    Research highlights: {yields} Soil-gas technique is applied to study gas permeability of Orciatico clay units. {yields} Clay permeability depends on thermal and mechanical alteration degree. {yields} Soil-gas distributions are due to shallow fracturing of clays. {yields} Rn and CO{sub 2} soil-gas anomalies highlight secondary permeability in clay sequence. {yields} Soil-gas results are supported by detailed geoelectrical surveys. - Abstract: The physical properties of clay allow argillaceous formations to be considered geological barriers to radionuclide migration in high-level radioactive-waste isolation systems. As laboratory simulations are short term and numerical models always involve assumptions and simplifications of the natural system, natural analogues are extremely attractive surrogates for the study of long-term isolation. The clays of the Orciatico area (Tuscany, Central Italy), which were thermally altered via the intrusion of an alkali-trachyte laccolith, represent an interesting natural model of a heat source which acted on argillaceous materials. The study of this natural analogue was performed through detailed geoelectrical and soil-gas surveys to define both the geometry of the intrusive body and the gas permeability of a clay unit characterized by different degrees of thermal alteration. The results of this study show that gas permeability is increased in the clay sequences subjected to greater heat input from the emplacement of the Orciatico intrusion, despite the lack of apparent mineral and geotechnical variations. These results, which take into consideration long time periods in a natural, large-scale geological system, may have important implications for the long-term safety of underground storage of nuclear waste in clay formations.

  3. Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: Alcohol and CRF effects. (United States)

    Herman, Melissa A; Varodayan, Florence P; Oleata, Christopher S; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa


    The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes.

  4. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man (United States)

    Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.


    The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

  5. Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system. (United States)

    Kjaer, A; Knigge, U; Jørgensen, H; Warberg, J


    In rats, the hypothalamic neurotransmitter histamine participates in regulation of vasopressin secretion and seems to be of physiological importance, because blockade of the histaminergic system reduces dehydration-induced vasopressin secretion. We investigated whether histamine is also involved in regulation of vasopressin secretion during dehydration in humans. We found that 40 h of dehydration gradually increased plasma osmolality by 10 mosmol/kg and induced a fourfold increase in vasopressin levels. Pretreatment with the H(2)-receptor antagonists cimetidine or ranitidine significantly reduced the dehydration-induced increase in vasopressin levels approximately 40% after 34 and 37 h of dehydration, whereas this was not the case with the H(1)-receptor antagonist mepyramine. Dehydration reduced aldosterone secretion by approximately 50%. This effect of dehydration was reduced by both H(1)- and H(2)-receptor blockade after 16 and/or 34 h of dehydration. We conclude that vasopressin secretion in response to dehydration in humans is under the regulatory influence of histamine and that the effect seems to be mediated via H(2)-receptors. In addition, the regulation of aldosterone secretion during dehydration also seems to involve the histaminergic system via H(1) and H(2) receptors.

  6. Vasopressin regulation of the renal UT-A3 urea transporter. (United States)

    Stewart, G S; Thistlethwaite, A; Lees, H; Cooper, G J; Smith, Craig


    Facilitative urea transporters in the mammalian kidney play a vital role in the urinary concentrating mechanism. The urea transporters located in the renal inner medullary collecting duct, namely UT-A1 and UT-A3, are acutely regulated by the antidiuretic hormone vasopressin. In this study, we investigated the vasopressin regulation of the basolateral urea transporter UT-A3 using an MDCK-mUT-A3 cell line. Within 10 min, vasopressin stimulates urea flux through UT-A3 transporters already present at the plasma membrane, via a PKA-dependent process. Within 1 h, vasopressin significantly increases UT-A3 localization at the basolateral membrane, causing a further increase in urea transport. While the basic trafficking of UT-A3 to basolateral membranes involves both protein kinase C and calmodulin, its regulation by vasopressin specifically occurs through a casein kinase II-dependent pathway. In conclusion, this study details the effects of vasopressin on UT-A3 urea transporter function and hence its role in regulating urea permeability within the renal inner medullary collecting duct.

  7. Vasopressin regulation of multisite phosphorylation of UT-A1 in the inner medullary collecting duct. (United States)

    Hoban, Carol A; Black, Lauren N; Ordas, Ronald J; Gumina, Diane L; Pulous, Fadi E; Sim, Jae H; Sands, Jeff M; Blount, Mitsi A


    Vasopressin signaling is critical for the regulation of urea transport in the inner medullary collecting duct (IMCD). Increased urea permeability is driven by a vasopressin-mediated elevation of cAMP that results in the direct phosphorylation of urea transporter (UT)-A1. The identification of cAMP-sensitive phosphorylation sites, Ser(486) and Ser(499), in the rat UT-A1 sequence was the first step in understanding the mechanism of vasopressin action on the phosphorylation-dependent modulation of urea transport. To investigate the significance of multisite phosphorylation of UT-A1 in response to elevated cAMP, we used highly specific and sensitive phosphosite antibodies to Ser(486) and Ser(499) to determine cAMP action at each phosphorylation site. We found that phosphorylation at both sites was rapid and sustained. Furthermore, the rate of phosphorylation of the two sites was similar in both mIMCD3 cells and rat inner medullary tissue. UT-A1 localized to the apical membrane in response to vasopressin was phosphorylated at Ser(486) and Ser(499). We confirmed that elevated cAMP resulted in increased phosphorylation of both sites by PKA but not through the vasopressin-sensitive exchange protein activated by cAMP pathway. These results elucidate the multisite phosphorylation of UT-A1 in response to cAMP, thus providing the beginning of understanding the intracellular factors underlying vasopressin stimulation of urea transport in the IMCD.

  8. Characterization of a FGF19 variant with altered receptor specificity revealed a central role for FGFR1c in the regulation of glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Hongfei Ge

    Full Text Available Diabetes and associated metabolic conditions have reached pandemic proportions worldwide, and there is a clear unmet medical need for new therapies that are both effective and safe. FGF19 and FGF21 are distinctive members of the FGF family that function as endocrine hormones. Both have potent effects on normalizing glucose, lipid, and energy homeostasis, and therefore, represent attractive potential next generation therapies for combating the growing epidemics of type 2 diabetes and obesity. The mechanism responsible for these impressive metabolic effects remains unknown. While both FGF19 and FGF21 can activate FGFRs 1c, 2c, and 3c in the presence of co-receptor βKlotho in vitro, which receptor is responsible for the metabolic activities observed in vivo remains unknown. Here we have generated a variant of FGF19, FGF19-7, that has altered receptor specificity with a strong bias toward FGFR1c. We show that FGF19-7 is equally efficacious as wild type FGF19 in regulating glucose, lipid, and energy metabolism in both diet-induced obesity and leptin-deficient mouse models. These results are the first direct demonstration of the central role of the βKlotho/FGFR1c receptor complex in glucose and lipid regulation, and also strongly suggest that activation of this receptor complex alone might be sufficient to achieve all the metabolic functions of endocrine FGF molecules.

  9. Characterization of a FGF19 variant with altered receptor specificity revealed a central role for FGFR1c in the regulation of glucose metabolism. (United States)

    Ge, Hongfei; Baribault, Helene; Vonderfecht, Steven; Lemon, Bryan; Weiszmann, Jennifer; Gardner, Jonitha; Lee, Ki Jeong; Gupte, Jamila; Mookherjee, Paramita; Wang, Minghan; Sheng, Jackie; Wu, Xinle; Li, Yang


    Diabetes and associated metabolic conditions have reached pandemic proportions worldwide, and there is a clear unmet medical need for new therapies that are both effective and safe. FGF19 and FGF21 are distinctive members of the FGF family that function as endocrine hormones. Both have potent effects on normalizing glucose, lipid, and energy homeostasis, and therefore, represent attractive potential next generation therapies for combating the growing epidemics of type 2 diabetes and obesity. The mechanism responsible for these impressive metabolic effects remains unknown. While both FGF19 and FGF21 can activate FGFRs 1c, 2c, and 3c in the presence of co-receptor βKlotho in vitro, which receptor is responsible for the metabolic activities observed in vivo remains unknown. Here we have generated a variant of FGF19, FGF19-7, that has altered receptor specificity with a strong bias toward FGFR1c. We show that FGF19-7 is equally efficacious as wild type FGF19 in regulating glucose, lipid, and energy metabolism in both diet-induced obesity and leptin-deficient mouse models. These results are the first direct demonstration of the central role of the βKlotho/FGFR1c receptor complex in glucose and lipid regulation, and also strongly suggest that activation of this receptor complex alone might be sufficient to achieve all the metabolic functions of endocrine FGF molecules.

  10. Flow cytometry of cerebrospinal fluid (CSF) lymphocytes: alterations of blood/CSF ratios of lymphocyte subsets in inflammation disorders of human central nervous system (CNS). (United States)

    Kleine, T O; Albrecht, J; Zöfel, P


    Flow cytometry was adapted to measure lymphocytes in human cerebrospinal fluid (CSF). The method was sufficiently precise, reproducible and accurate despite low cell counts. In lumbar CSF of controls with 500 to 3500 (10(3)/l) leukocytes, lymphocyte counts correlated with those in corresponding venous blood: blood/CSF ratios of approximately 2000 : 1 were found for total T cells (CD3+) and CD3+ HLA-DR-, CD3+4+, CD3+8+ subsets, ratios were increased for the lymphocyte subsets CD3+ HLA-DR+ blood-brain and blood-CSF barriers) to blood lymphocyte subsets which favor the transfer of T subsets. Correlation of the subset ratios to the CD3+ ratio indicates distinct barrier properties which changed differently with acute and subacute inflammations and neuroimmunological diseases of central nervous system (CNS) in lumbar or ventricular CSF, but not with simple protein barrier disturbance. HLA DR+ T ratios were higher than HLA DR- T ratios only with controls and some neuroimmunological diseases. Lymphocyte barrier characteristics were related to protein leakage situated at the same barriers, indicating for the lymphocyte subsets selective transfer routes in control subjects and non-selective routes in patients with CNS inflammation where altered ratios revealed a mixture of both routes.

  11. Plasma arginine vasopressin response to water load during labour

    Energy Technology Data Exchange (ETDEWEB)

    Singhi, S. (West Indies Univ., Mona (Jamaica). Dept. of Child Health); Parshad, O. (West Indies Univ., Mona (Jamaica). Dept. of Physiology)


    To find out whether plasma vasopressin (Psub(AVP)) response to a water load during pregnancy is inappropriately high, as had been speculated, we measured Psub(AVP)by radioimmunoassay in 30 women at the time of delivery. Ten women had received infusion of aqueous glucose solution during labour for hydration (GW group); another ten received infusion of glucose solution as a vehicle for oxytocin (IOT group), and ten women did not receive any intrapartum intravenous fluid therapy (controls). Serum sodium and osmolality were also determined in all the subjects. Psub(AVP) levels were significantly lower in GW (0.70 +- 0.4 pg/ml) and OT groups (0.7 +- 0.6 pg/ml) (P < 0.05). Significant negative correlation was seen between the amount of glucose solution infused and levels of Psub(AVP) (r = -0.66; P < 0.01), while a significant positive correlation was seen between Psub(AVP) and serum sodium (r = 0.61; P < 0.01). These findings suggest that during labour, the physiological relationship between serum osmolality and Psub(AVP) in intact, and the infusion of a water load in the form of aqueous glucose solution is attended by an expected lowering of Psub(AVP). We infer that inappropriate ADH response is not the cause of water retention and hyponatremia often seen in women receiving aqueous glucose solution during labor.

  12. Oral hypertonic saline causes transient fall of vasopressin in humans

    Energy Technology Data Exchange (ETDEWEB)

    Seckl, J.R.; Williams, D.M.; Lightman, S.L.


    After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration. AVP was measured by radioimmunoassay.

  13. Functions of vasopressin and oxytocin in bone mass regulation (United States)

    Sun, Li; Tamma, Roberto; Yuen, Tony; Colaianni, Graziana; Ji, Yaoting; Cuscito, Concetta; Bailey, Jack; Dhawan, Samarth; Lu, Ping; Calvano, Cosima D.; Zhu, Ling-Ling; Zambonin, Carlo G.; Di Benedetto, Adriana; Stachnik, Agnes; Liu, Peng; Grano, Maria; Colucci, Silvia; Davies, Terry F.; New, Maria I.; Zallone, Alberta; Zaidi, Mone


    Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr−/− mice have osteopenia, and Avpr1α−/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr−/−:Avpr1α−/− double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α−/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling. PMID:26699482

  14. Oxytocin, Vasopressin and Williams syndrome: Epigenetic effects on Abnormal Social Behavior

    Directory of Open Access Journals (Sweden)

    Brian W. Haas


    Full Text Available Williams syndrome is a condition caused by a deletion of ~26-28 genes on chromosome 7q11.23 often characterized by abnormal social behavior and disrupted oxytocin and vasopressin functioning. The observation that individuals with Williams syndrome exhibit oxytocin and vasopressin dysregulation is compelling. There is currently a lack of evidence that any of the genes typically deleted in Williams syndrome have any direct effect on either oxytocin or vasopressin. In this perspective article, we present a novel epigenetic model describing how DNA methylation may impact the expression of key genes within the oxytocin and vasopressin systems, which may ultimately influence the social behavior observed in Williams syndrome. We draw support from data pooled from a prior empirical research study (Henrichsen, et al., 2011, demonstrating that OXTR is overexpressed in Williams syndrome. These preliminary findings may create new opportunities to target the oxytocin and vasopressin systems with the specific goal of improving outcomes in Williams syndrome and other psychiatric conditions.

  15. Intergenerational transmission of alloparental behavior and oxytocin and vasopressin receptor distribution in the prairie vole

    Directory of Open Access Journals (Sweden)

    Allison M Perkeybile


    Full Text Available Variation in the early environment has the potential to permanently alter offspring behavior and development. We have previously shown that naturally occurring variation in biparental care of offspring in the prairie vole is related to differences in social behavior of the offspring. It was not, however, clear whether the behavioral differences seen between offspring receiving high compared to low amounts of parental care were the result of different care experiences or were due to shared genetics with their high-contact or low-contact parents. Here we use cross-fostering methods to determine the mode of transmission of alloparental behavior and oxytocin receptor (OTR and vasopressin V1a receptor (V1aR binding from parent to offspring. Offspring were cross-fostered or in-fostered on postnatal day 1 and parental care received was quantified in the first week postpartum. At weaning, offspring underwent an alloparental care test and brains were then collected from all parents and offspring to examine OTR and V1aR binding. Results indicate that alloparental behavior of offspring was predicted by the parental behavior of their rearing parents. Receptor binding for both OTR and V1aR tended to be predicted by the genetic mothers for female offspring and by the genetic fathers for male offspring. These findings suggest a different role of early experience and genetics in shaping behavior compared to receptor distribution and support the notion of sex-dependent outcomes, particularly in the transmission of receptor binding patterns.

  16. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T;


    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  17. The Vasopressin 1b Receptor Antagonist A-988315 Blocks Stress Effects on the Retrieval of Object-Recognition Memory

    NARCIS (Netherlands)

    Barsegyan, A.; Atsak, P.; Hornberger, W.B.; Jacobson, P.B.; Gaalen, M.M. van; Roozendaal, B.


    Stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and high circulating glucocorticoid levels are well known to impair the retrieval of memory. Vasopressin can activate the HPA axis by stimulating vasopressin 1b (V1b) receptors located on the pituitary. In the present s

  18. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats. (United States)

    Bardoux, P; Martin, H; Ahloulay, M; Schmitt, F; Bouby, N; Trinh-Trang-Tan, M M; Bankir, L


    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

  19. Effect of a multistage ultraendurance triathlon on aldosterone, vasopressin, extracellular water and urine electrolytes. (United States)

    Knechtle, B; Morales, N P Hernández; González, E Ruvalcaba; Gutierrez, A A Aguirre; Sevilla, J Noriega; Gómez, R Amézquita; Robledo, A R Estrada; Rodríguez, A L Marroquín; Fraire, O Salas; Andonie, J L; Lopez, L C; Kohler, G; Rosemann, T


    Prolonged endurance exercise over several days induces increase in extracellular water (ECW). We aimed to investigate an association between the increase in ECW and the change in aldosterone and vasopressin in a multistage ultraendurance triathlon, the 'World Challenge Deca Iron Triathlon' with 10 Ironman triathlons within 10 days. Before and after each Ironman, body mass, ECW, urinary [Na(+)], urinary [K(+)], urinary specific gravity, urinary osmolality and aldosterone and vasopressin in plasma were measured. The 11 finishers completed the total distance of 38 km swimming, 1800 km cycling and 422 km running within 145.5 (18.8) hours and 25 (22) minutes. ECW increased by 0.9 (1.1) L from 14.6 (1.5) L prerace to 15.5 (1.9) L postrace (P triathlon, but vasopressin did not. The increase in ECW and the increase in aldosterone were not associated.

  20. Expression of hippocampal corticosteroid receptors, as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus, in fornix transected rats

    Institute of Scientific and Technical Information of China (English)

    Fang Han; Hong Liu; Yanhui Zhang; Yuxiu Shi


    BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventdcular nucleus receives neuronal input from the hippocampus via the fornix.OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fomix.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008.MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster.METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n=45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection.MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection.RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventricular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopressin expression in the paraventricular nucleus were observed (P < 0.05-0.01).CONCLUSION: Negative feedback from the

  1. Quantitative proteomics identifies vasopressin-responsive nuclear proteins in collecting duct cells. (United States)

    Schenk, Laura K; Bolger, Steven J; Luginbuhl, Kelli; Gonzales, Patricia A; Rinschen, Markus M; Yu, Ming-Jiun; Hoffert, Jason D; Pisitkun, Trairak; Knepper, Mark A


    Vasopressin controls transport in the renal collecting duct, in part, by regulating transcription. This complex process, which can involve translocation and/or modification of transcriptional regulators, is not completely understood. Here, we applied a method for large-scale profiling of nuclear proteins to quantify vasopressin-induced changes in the nuclear proteome of cortical collecting duct (mpkCCD) cells. Using stable isotope labeling and tandem mass spectrometry, we quantified 3987 nuclear proteins and identified significant changes in the abundance of 65, including previously established targets of vasopressin signaling in the collecting duct. Vasopressin-induced changes in the abundance of the transcription factors JunB, Elf3, Gatad2b, and Hmbox1; transcriptional co-regulators Ctnnb1 (β-catenin) and Crebbp; subunits of the Mediator complex; E3 ubiquitin ligase Nedd4; nuclear transport regulator RanGap1; and several proteins associated with tight junctions and adherens junctions. Bioinformatic analysis showed that many of the quantified transcription factors have putative binding sites in the 5'-flanking regions of genes coding for the channel proteins Aqp2, Aqp3, Scnn1b (ENaCβ), and Scnn1g (ENaCγ), which are known targets of vasopressin. Immunoblotting demonstrated that the increase in β-catenin in nuclear fractions was accompanied by an even larger increase in its phosphorylated form (pSer552). The findings provide a new online database resource for nuclear proteomics ( and generate new hypotheses regarding vasopressin-mediated transcriptional regulation in the collecting duct.

  2. Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

    Directory of Open Access Journals (Sweden)

    Andreas Ebneter

    Full Text Available Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001 compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001. Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

  3. Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients. (United States)

    Thibonnier, M; Kilani, A; Rahman, M; DiBlasi, T P; Warner, K; Smith, M C; Leenhardt, A F; Brouard, R


    We assessed the clinical and pharmacological profile of the orally active V(1) vascular vasopressin (AVP) receptor nonpeptide antagonist SR49059 (SR) during the osmotic stimulation of AVP release in hypertensive patients. In a double-blind crossover-versus-placebo study, 24 untreated stage I or II essential hypertensive patients (12 whites and 12 blacks) received a single 300 mg oral dose of SR 2 hours before the stimulation of AVP secretion with a 5% hypertonic saline infusion. Hemodynamic, humoral, and hormonal parameters were monitored for up to 28 hours after drug administration. SR did not alter blood pressure or heart rate before the saline infusion and did not reduce the blood pressure increment induced by the hypertonic saline infusion. However, the blood pressure peak at the end of the hypertonic saline infusion was slightly lower in the presence of SR (P=0.04). Heart rate was significantly faster between 4 and 6 hours after SR administration (P=0.02). The rise in plasma sodium and osmolality triggered by the saline infusion was not modified by SR, but AVP release was slightly greater in the presence of SR (P<0.0003). AVP-induced aggregation of blood platelets in vitro was significantly reduced by SR, with a peak effect 2 hours after drug administration that coincided with the SR peak plasma concentration. Plasma renin activity and aldosterone before and after the saline infusion were not modified by SR. Urine volume and osmolality were not altered by SR administration. SR effects were similar in the 2 ethnic groups as well as in salt-sensitive versus salt-resistant patients. In a situation of AVP osmotic release and volume expansion in hypertensive patients, a single oral dose of the V(1) vascular AVP receptor nonpeptide antagonist SR49059, which is able to block AVP-induced platelet aggregation, exerts a transient vasodilation effect that is not associated with a sustained blood pressure reduction. SR49059 is a pure V(1) vascular receptor antagonist that

  4. Microinjection of glycine into the hypothalamic paraventricular nucleus produces diuresis, natriuresis, and inhibition of central sympathetic outflow. (United States)

    Krowicki, Zbigniew K; Kapusta, Daniel R


    Strychnine-sensitive glycine receptors and glycine-immunoreactive fibers are expressed in the hypothalamic paraventricular nucleus (PVN), yet the functional significance of this innervation is unclear. Therefore, these studies examined the changes in cardiovascular and renal function and renal sympathetic nerve activity (RSNA) produced by the microinjection of glycine (5 and 50 nmol) into the PVN of conscious Sprague-Dawley rats. Microinjection of glycine into, but not outside of, the PVN dose-dependently increased urine flow rate and urinary sodium excretion and decreased RSNA. At the higher dose, PVN glycine also decreased heart rate; neither 5 nor 50 nmol PVN glycine altered mean arterial pressure. The glycine (50 nmol)-evoked diuresis and natriuresis were abolished in rats continuously infused intravenously with [Arg(8)]-vasopressin. Furthermore, chronic bilateral renal denervation prevented the bradycardia and diuresis to PVN glycine and blunted the natriuresis. In other studies, unilateral PVN pretreatment with the glycine receptor antagonist strychnine (1.6 nmol) prevented the effects of PVN glycine (50 nmol) on heart rate, RSNA, and renal excretory function. When microinjected bilaterally, PVN strychnine (1.6 nmol per site) evoked a significant increase in heart rate and RSNA without altering renal excretory function. These findings demonstrate that in conscious rats glycine acts in the PVN to enhance the renal excretion of water and sodium and decrease central sympathetic outflow to the heart and kidneys. Although endogenous PVN glycine inputs elicit a tonic control of heart rate and RSNA, the renal excretory responses to PVN glycine seem to be caused primarily by the inhibition of arginine vasopressin secretion.

  5. The contributions of oxytocin and vasopressin pathway genes to human behavior. (United States)

    Ebstein, Richard P; Knafo, Ariel; Mankuta, David; Chew, Soo Hong; Lai, Poh San


    Arginine vasopressin (AVP) and oxytocin (OXT) are social hormones and mediate affiliative behaviors in mammals and as recently demonstrated, also in humans. There is intense interest in how these simple nonapeptides mediate normal and abnormal behavior, especially regarding disorders of the social brain such as autism that are characterized by deficits in social communication and social skills. The current review examines in detail the behavioral genetics of the first level of human AVP-OXT pathway genes including arginine vasopressin 1a receptor (AVPR1a), oxytocin receptor (OXTR), AVP (AVP-neurophysin II [NPII]) and OXT (OXT neurophysin I [NPI]), oxytocinase/vasopressinase (LNPEP), ADP-ribosyl cyclase (CD38) and arginine vasopressin 1b receptor (AVPR1b). Wherever possible we discuss evidence from a variety of research tracks including molecular genetics, imaging genomics, pharmacology and endocrinology that support the conclusions drawn from association studies of social phenotypes and detail how common polymorphisms in AVP-OXT pathway genes contribute to the behavioral hard wiring that enables individual Homo sapiens to interact successfully with conspecifics. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  6. Effect of methadone on plasma arginine vasopressin level and urine production in conscious dogs

    NARCIS (Netherlands)

    Hellebrekers, L.J.; Mol, J.A.; Brom, W.E. van den; Wimersma Greidanus, T.B. van


    The aim of this study was to examine the effect of i.v. methadone on the plasma arginine-vasopressin (AVP) levels and urine production in 9 conscious dogs. A highly significant increase from the baseline plasma AVP values of below 3 pg/ml occurred within 5 min following methadone administration. Max

  7. Vasopressin receptors V1a and V2 are not osmosensors

    DEFF Research Database (Denmark)

    Pedersen, Kasper Lykke; Assentoft, Mette; Fenton, Robert A;


    Herein, we investigated whether G protein-coupled signaling via the vasopressin receptors of the V1a and V2 subtypes (V1aR and V2R) could be obtained as a direct response to hyperosmolar challenges and/or whether hyperosmolar challenges could augment classical vasopressin-dependent V1aR signaling....... The V1aR-dependent response was monitored indirectly via its effects on aquaporin 4 (AQP4) when heterologously expressed in Xenopus oocytes and V1aR and V2R function was directly monitored following heterologous expression in COS-7 cells. A tendency toward an osmotically induced, V1aR-mediated reduction...... in AQP4-dependent water permeability was observed, although osmotic challenges failed to mimic vasopressin-dependent V1aR-mediated internalization of AQP4. Direct monitoring of inositol phosphate (IP) production of V1aR-expressing COS-7 cells demonstrated an efficient vasopressin-dependent response...

  8. Lateral septal vasopressin in rats : Role in social and object recognition?

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM


    The capacity of male rats to remember familiar conspecifics is called social recognition. It is a form of short-term memory modulated by lateral septal (LS) vasopressin (VP). The specificity of this phenomenon was studied by examining whether recognition of previously investigated objects is also un

  9. Reduced preabsorptive insulin response in aged rats : differential effects of amphetamine and arginine-vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Strubbe, J.H.; Bohus, B.


    The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studie

  10. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates. (United States)

    Minakata, Hiroyuki


    Recent advances in peptide search methods have revealed two peptide systems that have been conserved through metazoan evolution. Members of the oxytocin/vasopressin-superfamily have been identified from protostomian and deuterostomian animals, indicating that the oxytocin/vasopressin hormonal system represents one of the most ancient systems. In most protostomian animals, a single member of the superfamily shares oxytocin-like and vasopressin-like actions. Co-occurrence of two members has been discovered in modern cephalopods, octopus, and cuttlefish. We propose that cephalopods have developed two peptides in the molluscan evolutionary lineage like vertebrates have established two lineages in the oxytocin/vasopressin superfamily. The existence of gonadotropin-releasing hormone (GnRH) in protostomian animals was initially suggested by immunohistochemical analysis using chordate GnRH antibodies. A peptide with structural features similar to those of chordate GnRHs was originally isolated from octopus, and an identical peptide has been characterized from squid and cuttlefish. Novel forms of GnRH-like molecules from other molluscs, an annelid, arthropods, and nematodes demonstrate somewhat conserved structures at the N-terminal regions; but structures of the C-terminal regions critical to gonadotropin-releasing activity are diverse. These findings may be important for the study of the molecular evolution of GnRH in protostomian animals.

  11. Neuroendocrine adaptation to stress in pigs, CRH and vasopressin in the paraventricular nucleus

    NARCIS (Netherlands)

    Karman, A.G.


    Differences in coping strategy present at birth as well as housing conditions may influence autonomic and endocrine stress responses.In rodents,corticotropin-releasing hormone (CRH) and vasopressin (VP) signaling in the

  12. Urinary concentration does not exclusively rely on plasma vasopressin. A study between genders

    DEFF Research Database (Denmark)

    Graugaard-Jensen, Charlotte; Hvistendahl, Gitte M; Frøkiaer, Jørgen


    AimWe investigated the influence of gender on the diurnal regulation of urine production with special focus on vasopressin, oxytocin and prostaglandin E2. MethodsFifteen young women in mid-follicular phase and 22 young men (20-33years) were included. All participants underwent a 24-h circadian in...

  13. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.


    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  14. Oxytocin/vasopressin-like immunoreactivity is present in the nervous system of hydra

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Dierickx, K; Boer, G J


    Nerve cells have been found in hydra, which react with antisera to oxytocin, vasopressin and mesotocin. These nerve cells have a high density in the ectoderm of basal disk and tentacles and lower density in the ectoderm of peduncle, gastric region and hypostome. A very small number of nerve cells...

  15. Sevoflurane-induced down-regulation of hippocampal oxytocin and arginine vasopressin impairs juvenile social behavioral abilities. (United States)

    Zhou, Zhi-Bin; Yang, Xiao-Yu; Yuan, Bao-Long; Niu, Li-Jun; Zhou, Xue; Huang, Wen-Qi; Feng, Xia; Zhou, Li-Hua


    Cumulative evidence indicates that early childhood anesthesia can alter a child's future behavioral performance. Animal researchers have found that sevoflurane, the most commonly used anesthetic for children, can produce damage in the neonatal brains of rodents. To further investigate this phenomenon, we focused on the influence of sevoflurane anesthesia on the development of juvenile social behavioral abilities and the pro-social proteins oxytocin (OT) and arginine vasopressin (AVP) in the neonatal hippocampus. A single 6-h sevoflurane exposure for postnatal day 5 mice resulted in decreased OT and AVP messenger RNA (mRNA) and protein levels in the hippocampus. OT and AVP proteins became sparsely distributed in the dorsal hippocampus after the exposure to sevoflurane. Compared with the air-treated group, mice in the sevoflurane-treated group showed signs of impairment in social recognition memory formation and social discrimination ability. Sevoflurane anesthesia reduces OT and AVP activities in the neonatal hippocampus and impairs social recognition memory formation and social discrimination ability in juvenile mice.

  16. Effects of neural androgen receptor disruption on aggressive behavior, arginine vasopressin and galanin systems in the bed nucleus of stria terminalis and lateral septum. (United States)

    Marie-Luce, Clarisse; Raskin, Kalina; Bolborea, Matei; Monin, Marion; Picot, Marie; Mhaouty-Kodja, Sakina


    In the present study, we investigated the role of the androgen receptor (AR) in the nervous system in the regulation of aggressive behavior and arginine vasopressin and galanin systems by testosterone. For this purpose, we used a conditional mouse line selectively lacking AR gene in the nervous system, backcrossed onto the C57BL/6J strain. Adult males were gonadectomized and supplemented with similar amounts of testosterone. When tested on two consecutive days in the resident intruder paradigm, fewer males of the mutant group exhibited aggressive behavior compared to their control littermates. In addition, a high latency to the first offensive attack was observed for the few animals that exhibited fighting behavior. This alteration was associated with a normal anogenital chemoinvestigation of intruder males. In olfactory discrimination tasks, sexual experience enhanced preference towards female-soiled bedding rather than male-soiled bedding and estrus females rather than intact males, regardless of genotype. This indicated that the behavioral alteration induced by neural AR mutation occurs in brain areas located downstream from the olfactory bulb. Quantification of the sexually dimorphic cell populations expressing preprovasopressin and galanin mRNAs in the bed nucleus of stria terminalis (BNST) and vasopressin-neurophysin 2 and galanin immunoreactivity in the lateral septum showed no significant differences between the two genotypes. The present findings indicate that the neural AR is required in the expression of aggressive behavior but not in the sexual differentiation of AVP and galanin cell number in the BNST and fiber immunoreactivity in the lateral septum. They also suggest that AR in the nervous system could mediate activational effects of testosterone in the regulation of aggressive behavior during adulthood.


    Institute of Scientific and Technical Information of China (English)


    Background. Our previous studies indicated that the increased arginine vasopressin(AVP) in ischemic brain regions of gerbils could exacerbate the ischemic brain edema. This experiments is further clarify the relation between AVP and cerebral ischemia at the molecular level. Methods. The contents of AVP, AVP mRNA, AVP immunoreactive(ir) neurons in supraoptic nucleus(SON)and paraventricular nucleus(PVN) after cerebral ischemia and reperfusion were respectively determined by radioim-munoassay(RIA), immunocytochemistry( Ⅱ C), situ hybridization and computed image pattem analysis. Results. The contents of AVP in SON, PVN were increased, and the AVP ir positive neurons in SON and PVN were also significantly increased as compared with the controls after ischemia and reperfusion. And there were very light staining of AVP ir positive neurons in the other brain areas such as suprachiasmatic nucleus (SC) and periven-tricular hypothalamic nucleus (PE), but these have no significant changes as compared with the controls. During dif-ferent periods of cerebral ischemia (30~ 120 min) and reperfusion (30 min), AVP mRNA expression in SON and PVN were more markedly increased than the controls. Condusions. The transcription of AVP gene elevated, then promoting synthesis and release of AVP in SON,PVN. Under the specific condition of cerebral ischemia and repeffusion, the activity and contents of central AVP in-creased abnormally is one of the important factors which causes ischemia brain damage.

  18. Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raggenbass, M.; Tribollet, E.; Dreifuss, J.J.


    Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist (2-phenylalanine,8-ornithine)vasotocin but not by the selective antidiuretic agonist 1-deamino(8-D-arginine)vasopressin. In a parallel study, sites that bind (/sup 3/H)AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM (/sup 3/H)AVP and, in addition, with 100 nM (2-phenylalanine,8-ornithine)vasotocin or 1-deamino(8-D-arginine)vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced (/sup 3/H)AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons.

  19. Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study

    Directory of Open Access Journals (Sweden)

    Baikoussis Nikolaos G


    Full Text Available Abstract Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP, central venous pressure (CVP, systemic vascular resistance (SVR, ejection fracture (EF, heart rate (HR, mean pulmonary artery pressure (MPAP, cardiac index (CI and pulmonary vascular resistance (PVR were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20% in group A and B respectively (p = 0,042. Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF

  20. Central neuropeptide Y receptors are involved in 3rd ventricular ghrelin induced alteration of colonic transit time in conscious fed rats

    Directory of Open Access Journals (Sweden)

    Ritter Michael


    Full Text Available Abstract Background Feeding related peptides have been shown to be additionally involved in the central autonomic control of gastrointestinal functions. Recent studies have shown that ghrelin, a stomach-derived orexigenic peptide, is involved in the autonomic regulation of GI function besides feeding behavior. Pharmacological evidence indicates that ghrelin effects on food intake are mediated by neuropeptide Y in the central nervous system. Methods In the present study we examine the role of ghrelin in the central autonomic control of GI motility using intracerobroventricular and IP microinjections in a freely moving conscious rat model. Further the hypothesis that a functional relationship between NPY and ghrelin within the CNS exists was addressed. Results ICV injections of ghrelin (0.03 nmol, 0.3 nmol and 3.0 nmol/5 μl and saline controls decreased the colonic transit time up to 43%. IP injections of ghrelin (0.3 nmol – 3.0 nmol kg-1 BW and saline controls decreased colonic transit time dose related. Central administration of the NPY1 receptor antagonist, BIBP-3226, prior to centrally or peripherally administration of ghrelin antagonized the ghrelin induced stimulation of colonic transit. On the contrary ICV-pretreatment with the NPY2 receptor antagonist, BIIE-0246, failed to modulate the ghrelin induced stimulation of colonic motility. Conclusion The results suggest that ghrelin acts in the central nervous system to modulate gastrointestinal motor function utilizing NPY1 receptor dependent mechanisms.

  1. Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats. (United States)

    Demeter, Kornél; Török, Bibiána; Fodor, Anna; Varga, János; Ferenczi, Szilamér; Kovács, Krisztina J; Eszik, Ildikó; Szegedi, Viktor; Zelena, Dóra


    Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases.

  2. Effect of exercise on plasma concentrations of arginine vasopressin, angiotensin II and aldosterone in hypertensive and normotensive renal transplant recipients. (United States)

    Pedersen, E B; Danielsen, H; Nielsen, A H; Knudsen, F; Jensen, T; Kornerup, H J; Madsen, M


    Plasma concentrations of angiotensin II (A II), aldosterone (Aldo) and arginine vasopressin (AVP), and serum osmolality (Sosm) were determined before and after gradually increasing exercise loads on a bicycle ergometer in 10 hypertensive (group I) and 10 normotensive renal transplant recipients (group II), and in 15 healthy control subjects (group III). Working capacity was reduced in groups I and II. The A II, Aldo, AVP, Sosm increased in all groups after exercise. The A II was higher in group I than II and the percentage changes were significantly lower in groups I and II than in group III. There were no significant differences in Aldo between the groups either before or after exercise. The AVP was the same in groups I and II, and AVP in these groups was higher than in group III. The Sosm and AVP were significantly correlated in all groups. Neither A II, Aldo nor AVP were significantly correlated to systolic blood pressure (BP). Alterations in AVP, but not in A II or Aldo, were correlated to the degree of exercise load. It can be concluded that the renin-angiotensin-aldosterone system and the osmoregulatory system are stimulated during exercise in renal transplant recipients. The A II is elevated in post-renal transplant hypertension, but the responsiveness is reduced in both hypertensive and normotensive recipients. The alterations in AVP are probably secondary to changes in Sosm, and the higher AVP levels in recipients could be due to a decreased responsiveness of the renal tubules to AVP. Our findings are in good agreement with the hypothesis that hypertension after renal transplantation is angiotensin II-dependent.

  3. Comparison of stress-induced and LPS-induced depressive-like behaviors and the alterations of central proinflammatory cytokines mRNA in rats. (United States)

    Guan, Xi-Ting; Lin, Wen-Juan; Tang, Ming-Ming


    Although proinflammatory cytokine changes in depression have been studied widely, few investigations have searched for specific and common changes in cytokines. In the present study, two animal models of depression were compared: a chronic stress model using forced swim stress and an immune activation model using repeated central lipopolysaccharide (LPS) infusion. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 mRNA were examined in the brain regions of the prefrontal cortex, amygdala, and hippocampus using real-time polymerase chain reaction (RT-PCR). It was found that both chronic swim stress and repeated central LPS infusion induced depressive-like behaviors, including decreased body weight, reduced saccharin preference, and increased immobility time or shortened latency of immobility in the tail suspension test. Central TNF-α mRNA expression was elevated in both models and central IL-6 mRNA expression was unchanged in both models. Central IL-1β mRNA expression was increased only in the chronic immune activation model. The findings from this study suggest that TNF-α may be a common risk factor for inflammation in depressive disorders.

  4. Diagenetic and post-diagenetic alteration (thermicity, oxidation) of carboniferous coals from the French Massif Central (Saint-Etienne, Graissessac and other areas); Alteration diagenetique et post-diagenetique (thermicite, oxydation) des charbons carboniferes du Massif Central francais (Saint-Etienne, Graissessac et autres lieux)

    Energy Technology Data Exchange (ETDEWEB)

    Copard, Y.


    This work deals with some prominent properties of the organic matter (OM), such as its to record the thermal history of basins, (hydro)thermal events of more limited influence or oxidising processes. Two of these topics have been developed in the frame of the study of Carboniferous coals sampled in several basins in the Massif Central. As a consequence of the tectonic regime that prevailed at the end of Hercynian orogenesis, thermal domes and even faults acting as conduits for hydrothermal fluids, have generated a heterogeneous hyper-thermicity in the studied basins. Local coalification conditions such as Maximum Paleo-temperatures of Burial (MP TB), paleo-burial depths, durations of maturation, have been estimated. A compilation of OM characteristic parameters suggests that some mature coals have been affected by a restricted hyperthermal activity, while others lave solely recorded a simple oxidation. Astonishingly, this latter process that occurred at low temperature, is characterised by an increase in. Tmax (and a decrease in Hydrogen Index), which mimics a classical thermal degradation. This peculiar behaviour is reinforced both by the study of profiles of weathered mature coals and by oxidation experiments. The considered oxidation process consists in two successive reaction stages. The first is defined by a notable loss in hydrogen and a weak gain in oxygen, while the second, is characterised by a weak loss in hydrogen and a gain in oxygen. The increase in Tmax occurs at the beginning of the second stage, this later one being reached all the more -faster than the raw coal is poor in hydrogen (i.e. has reached a high level of maturity). This alteration process preferentially affects the periphery of the carbon skeleton (Base Structural Units) by provoking the degradation of 'thermo-labile / oxi-labile' functional groups. -fence, these features Justify and explain the strong similarity evidenced between the effects of thermal and oxidising processes

  5. Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Vitting, K.E.; Gardenswartz, M.H.; Zabetakis, P.M.; Tapper, M.L.; Gleim, G.W.; Agrawal, M.; Michelis, M.F. (Lenox Hill Hospital, New York, NY (USA))


    The frequency and pathophysiology of hyponatremia were studied in the acquired immunodeficiency syndrome. Of 71 hospitalized patients surveyed retrospectively, hyponatremia was observed in 37 (52%). Of 48 patients studied prospectively, 27 (56%) were hyponatremic. In 16 hyponatremic patients, volume status; serum and urine osmolalities; renal, adrenal, and thyroid function; and plasma vasopressin levels were assessed. Urine osmolalities were inappropriately elevated relative to serum osmolalities. Four patients had moderate renal insufficiency. Plasma vasopressin levels, measured by radioimmunoassay, were elevated in 15 patients, with the highest levels seen in patients who died. Hyponatremia of multiple etiologies occurred in a majority of inpatients with the acquired immunodeficiency syndrome, often following the administration of hypotonic fluids, and was associated with a 30% (8/27) short-term mortality.

  6. Specificity of a cytochemical bioassay for arginine-vasopressin and its validation for plasma measurement. (United States)

    Smith, A; McIntosh, N


    The total Na+/K+ ATP-ase activity of the thick ascending limb of the loop of Henle may be stimulated by arginine-vasopressin (AVP). Lysine-vasopressin (LVP), oxytocin (OT), and arginine-vasotocin (AVT) produce less than 5% of the enzyme activity induced by the same concentration of AVP. Physiological concentrations of a mixture of other hormones with known activity on the kidney (T3, T4, aldosterone, angiotensin II, and OT) did not significantly increase total Na+/K+ ATP-ase activity. Specific AVP antiserum consistently removed greater than 90% of the stimulatory effect of plasma. The concentration of AVP in plasmas from dehydrated subjects was greater than 10 times that of the same subjects hydrated. Intra-assay coefficient of variation was 35% and 52% from 200 microliters and 20 microliters of plasma respectively. The interassay coefficient of variation was 53% and 55% from plasma pools with high and low AVP content.

  7. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G


    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  8. Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

    Energy Technology Data Exchange (ETDEWEB)

    Kruisbrink, J.; Boer, G.J.


    Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero.


    Directory of Open Access Journals (Sweden)

    Manoj G Tyagi


    Full Text Available Vasopressin, a posterior pituitary hormone is responsible for water reabsorption by the kidneys and maintenance of cardio-vascular homeostasis. Vasopressin receptors are characterized as VR 1 (V1a, VR2 (V2, and VR3 (V1b. VR1, which is abundant in vascular smooth muscles, causes vasoconstriction by increasing intracellular calcium via the phosphatidylinositol bisphosphonate pathway and a positive inotropic effect in cardiac muscle. VR2 has also been shown to be expressed in the heart. There is emerging role for vasopressin receptors in health and disease. This study describes the application of Western blotting to elucidate the importance of vasopressin receptors in the heart cells.

  10. Study of V2 vasopressin receptor hormone binding site using in silico methods. (United States)

    Sebti, Yeganeh; Sardari, Soroush; Sadeghi, Hamid Mir Mohammad; Ghahremani, Mohammad Hossein; Innamorati, Giulio


    The antidiuretic effect of arginine vasopressin (AVP) is mediated by the vasopressin V2 receptor. The docking study of AVP as a ligand to V2 receptor helps in identifying important amino acid residues that might be involved in AVP binding for predicting the lowest free energy state of the protein complex. Whereas previous researchers were not able to detect the exact site of the ligand-receptor binding, we designed the current study to identify the vasopressin V2 receptor hormone binding site using bioinformatic methods. The 3D structure of nonapeptide hormone vasopressin was extracted from Protein Data Bank. Since no suitable template resembling V2 receptor was found, an ab initio approach was chosen to model the protein receptor. Using protein docking methods such as Hex protein-protein docking, the model of V2 receptor was docked to the peptide ligand AVP to identify possible binding sites. The residues that involved in binding site are W293, W296, D297, A300, and P301. The lowest free energy state of the protein complex was predicted after mutation in the above residues. The amount of gained energies permits us to compare the mutant forms with native forms and help to asses critical changes such as positive and negative mutations followed by ranking the best mutations. Based on the mutation/docking predictions, we found some mutants such as W293D and A300E possess positively inducing effect in ligand binding and some of them such as A300R present negatively inducing effect in ligand binding.

  11. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups. (United States)

    Kim, P A; Voskresenskaya, O G; Kamensky, A A


    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  12. The Effect of Drinking on Plasma Vasopressin and Renin in Dehydrated Human Subjects (United States)

    Geelen, G.; Keil, L. C.; Kravik, S. E.; Wade, C. E.; Thrasher, T. N.; Barnes, P. R.; Pyka, G.; Nesvig, C.; Greenleaf, J. E.


    Oropharyngeal mechanisms activated by drinking have been shown to induce a rapid decline in plasma vasopressin which preceeds postabsorptive changes in plasma composition in the dehydrated dog. The present study was undertaken to determine what factor(s) inhibit(s) vasopressin secretion after rehydration in water deprived human subjects. Hematocrit (Hct) and hemoglobin (Hb) were determined on the day of the experiment, together with electrolytes and osmolalities which were measured on freshly separated serum. Plasma was immediately frozen and further analyzed by radioimmunoassay for renin activity (PRA), vasopressin (AVP), and aldosterone. The data were analyzed using an analysis of variance for repeated measurements and significant differences between the dehydrated control period and various time points after the start of rehydration were determined using a multiple-range test. began and reached water replete levels 15 minutes after drinking in the absence of any detectable decline in serum sodium or osmolality, we conclude that 427 oropharyngeal factors, alone or combined with gastric distension account for the extremely rapid inhibition of AVP secretion after drinking in the water-deprived human, as has been shown to be the case in dogs. Our findings are also in agreement wiht the recent demonstration that at the onset of drinking in the dehydrated monkey, there is an abrupt fall in plasma AVP concentration associated with a considerable decrease in the firing rate of the supraoptic neurosecretory neurons.

  13. A perifusion method for examining arginine vasopressin (AVP release from hypothalamo-neurohypophyseal system.

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    Full Text Available A perifusion method has been developed using rat hypothalamo-neurohypophyseal system (HNS or neural lobe to investigate the control mechanism of arginine vasopressin (AVP release. A specific radioimmunoassay (RIA for AVP was developed to measure AVP in perifusion medium employing anti-AVP serum which was obtained by immunizing rabbits. At a final dilution of 1/12,000, the antiserum showed less than 0.66 and 0.01% cross reactivity with lysine-vasopressin and oxytocin, respectively. But it did not cross reacted with other peptide hormones. The lowest detectable level of vasopressin was 0.5 pg/tube. The intra-assay coefficient of variation averaged 10.4%. The dilution curve of perifused medium was well paralled to the standard curve of AVP assay. AVP release from HNS or neural lobe gradually declined to the stable level in 90-120 min after the initiation of perifusion. Good repeatability of the AVP release from neural lobe was recognized by repeated stimulation with 10 min perifusion of 60 mM KCl at every 60 min. HNS released AVP in dose related manner to the osmotic challenge of sodium or glucose, and AVP release was stimulated from HNS by prostaglandin E2, but not by dopamine. These results show that the perifusion methods using AVP-RIA is a useful method to examine the AVP release from HNS or neural lobe.

  14. An overview of SSR149415, a selective nonpeptide vasopressin V(1b) receptor antagonist for the treatment of stress-related disorders. (United States)

    Serradeil-Le Gal, Claudine; Wagnon, Jean; Tonnerre, Bernard; Roux, Richard; Garcia, Georges; Griebel, Guy; Aulombard, Alain


    Vasopressin (AVP) and corticotropin-releasing factor (CRF) are key mediators in the organism's neuro-adaptive response to stress. Through pituitary and central vasopressin V(1b) receptors, AVP participates in the control of the hypothalamic-pituitary-adrenal axis (HPA) and is involved in various emotional processes. SSR149415 is the first selective, orally active vasopressin V(1b) receptor antagonist yet described. It is a competitive antagonist with nanomolar affinity for animal and human V(1b) receptors and displays a highly selective profile with regard to a large number of receptors or enzymes. In vitro, SSR149415 potently antagonizes functional cellular events associated with V(1b) receptor activation by AVP, such as intracellular Ca(2+) increase or proliferation in various cell systems. Pharmacological studies, performed by measuring ACTH secretion induced by various stimulants such as hormones (AVP or AVP + CRF) or physical stress (restraint or forced swimming stress and dehydration) in conscious rats or mice, confirm the antagonist profile of SSR149415 and its efficacy in normalizing ACTH secretion in vivo. SSR149415 is active by the oral route, at doses from 3 mg/kg, it potentiates CRF effect and displays a long-lasting oral effect in the different models. At 10 mg/kg p.o. its duration of action is longer than 4 h. This molecule also decreases anxiety and exerts marked antidepressant-like activity in several predictive animal models. The anxiolytic effects of SSR149415 have been demonstrated in various Generalized Anxiety Disorders (GAD) models (four-plate, punished drinking, elevated plus-maze, light dark, mouse defense test battery, fear-potentiated startle and social interaction tests). It is as effective as the benzodiazepine diazepam in the acute stress exposure test. SSR149415 has similar efficacy to the reference antidepressant drug, fluoxetine, in acute (forced-swimming) and chronic (chronic mild stress and subordination stress) situations in

  15. Preventive effect of CuCl₂ on behavioral alterations and mercury accumulation in central nervous system induced by HgCl2 in newborn rats. (United States)

    Moraes-Silva, L; Siqueira, L F; Oliveira, V A; Oliveira, C S; Ineu, R P; Pedroso, T F; Fonseca, M M; Pereira, M E


    This study investigated the benefits of Cu preexposition on Hg effects on behavioral tests, acetylcholinesterase (AChE) activity and Hg, and essential metal contents in the cerebrum and cerebellum of neonate rats. Wistar rats received (subcutaneous) saline or CuCl2 ·2H2O (6.9 mg/kg/day) when they were 3 to 7 days old and saline or HgCl2 (5.0 mg/kg/day) when they were 8 to 12 days old. Mercury exposure reduced the performance of rats in the negative geotaxis (3-13 days) and beaker test (17-20 days), inhibited cerebellum AChE activity (13 days), increased cerebrum and cerebellum Hg (13 days), cerebrum Cu (13 days), and cerebrum and cerebellum Zn levels (33 days). The performance of rats in the tail immersion and rotarod tests as well as Fe and Mg levels were not altered by treatments. Copper prevented all alterations induced by mercury. These results are important to open a new perspective of prevention and/or therapy for mercury exposure.

  16. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring. (United States)

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P


    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure.

  17. Acutely elevated vasopressin increases circulating concentrations of cortisol and aldosterone in fasting northern elephant seal (Mirounga angustirostris) pups (United States)

    Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo; Talamantes, Frank


    The physiological actions of vasopressin (VP) in marine mammals are not well defined. To help elucidate its hormonal and renal effects in this group of mammals, northern elephant seal (Mirounga angustirostris) pups (N=7; 99+/-4 kg) were first infused with 0.9% saline (control; 220 ml), followed 24 h later with VP (as a 20 ng kg(-1) bolus, then 2 ng kg(-1) min(-1) for approximately 35 min in 225+/-16 ml saline). During both control and VP periods, blood samples were collected prior to infusion, and 15, 30, 60, 120 min and 24 h after infusion to examine the hormonal responses of the pups to VP. Renal responses were quantified from 24 h urine samples obtained prior to infusion (control) and 24 h post-infusion. Compared to the control period, infusion of VP increased plasma concentrations of cortisol over a 120 min period and aldosterone over 30 min, while plasma renin activity (PRA) was decreased for a 120 min period. The plasma urea:creatinine ratio was elevated following infusion of VP. Urine output and osmotic clearance were increased by 69+/-18% (mean +/- S.E.M.) and 36+/-10%, respectively, but free water clearance and glomerular filtration rate were not significantly altered 24 h post-infusion of VP. Solute (osmolality, Na(+), K(+) and Cl(-)) excretion and fractional excretion of electrolytes were also increased when compared to control values. The increase in cortisol concentration suggests that VP may possess corticotropin releasing hormone-like activity in elephant seals. If osmotic diuresis and natriuresis are typical consequences of elevated [VP] in fasting pups, then not increasing VP normally during the fast may serve as a protective mechanism to avoid the potential loss of Na(+) induced by elevated [VP]. Therefore, under natural fasting conditions, pups may be highly sensitive to small changes in [VP], resulting in the maintenance of water and electrolyte balance.

  18. Alteration in the etiology of penile fracture in the Middle East and Central Asia regions in the last decade; a literature review

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    Ahmad A Majzoub


    Full Text Available Penile fracture is a well-recognized, relatively uncommon medical condition and its etiology differs according to geographic area. In this review article, we evaluated literature reported in the past decade, aiming to verify whether there has been any change in the etiology of this condition. A literature review was done for studies published in the past 10 years and focusing on the etiology of penile fracture. Inclusion criteria comprised articles in English language, of sample size more than 10 patients and originating from the Middle East and Central Asia. Data relating to the studied population, etiology of penile fracture, clinical presentation, investigations, management, and outcome was analyzed. One thousand six hundred and twenty-nine patients from 21 original articles were included in the study. The mean age ΁ standard deviation of the patients was 33.3 ΁ 3.23 years. Etiologies of penile fracture were vigorous sexual intercourse, manual bending of erect penis, vigorous masturbation, rolling over in bed and blunt trauma in 41%, 29%, 10%, 14% and 6% patients, respectively. Treatment choices were surgery and conservative, in 1580 (95%, 83 (5% patients, respectively. A higher incidence of complications was found in conservatively treated patients. As a conclusion, in the last 10 years, vigorous sexual intercourse was the commonest etiology of penile fracture in the Middle East and Central Asia regions. Surgery remains the preferred treatment option for patients diagnosed with penile fracture.

  19. Early, but not late therapy with a vasopressin V-1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A. K. M.; Tahara, Atsua; Kluppel, Alex C. A.; de Zeeuw, Dick; Henning, Robert H.; van Dokkum, Richard P. E.


    Introduction. Vasopressin, mainly through the VIA-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V-1a-receptor-selective antagonist,

  20. Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A K M; Tahara, Atsua; Kluppel, Alex C A; de Zeeuw, Dick; Henning, Robert H; van Dokkum, Richard P E


    INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist,

  1. The Level of Vasopressin is not solely resulted from the Concentration of Endotoxin but Proportional to Creatinine in Dogs with Pyometra

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    W. Y. Shia1, K. C. Tung1, 2, S. C. Chang1, 2, C. H. Yang1, 2, C. H. Lee2, C. C. Chou1 and W. M. Lee1, 2*


    Full Text Available Pyometra is one of the most common reproductive disorder characterized as fluid accumulation mainly pus and Gram-negative bacteria isolated from uterus in bitches. Impaired function of vasopressin is found in the disease. The impact of the circulating endotoxin concentration on vasopressin involved water regulation is still unclear. To document the effect of endotoxin on vasopressin-involved water regulation in dogs with pyometra, blood samples were collected for examination of circulating endotoxin concentration, osmolarity values, vasopressin concentrations, blood urea nitrogen (BUN, and creatinine. The results indicated that the concentration change of endotoxin was contrary to BUN and creatinine in dogs with pyometra. The trends of concentrations change of BUN and creatinine were similar with osmolarity and vasopressin. Pyometric dogs with high level of circulating endotoxin had significantly lower (P 20 mg/dL and creatinine (> 1.5 mg/dL also had plasma vasopressin significantly higher (P<0.05 than those with low levels of BUN and creatinine and control dogs. The overall results suggested that elevated vasopressin was not mainly associated with the circulating endotoxin concentration and some other factors may collaborate with endotoxin causing impaired function of vasopressin.

  2. The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats. (United States)

    Kis, Gyöngyi K; Molnár, Andor H; Daruka, Leila; Gardi, János; Rákosi, Kinga; László, Ferenc; László, Ferenc A; Varga, Csaba


    The effects of the centrally administered neuropeptides orexin-A on water intake and vasopressin (VP) secretion were studied in male Wistar rats (180-250 g). Different doses (10, 30, and 90 μg/10 μl) of the orexins and the specific orexin receptor-1 (OX(1)) antagonist SB 408124 (30 μg/10 μl) were administered intracerebroventricularly (i.c.v.) under anaesthesia, and the water consumption was measured during 6 h. A plasma VP level elevation was induced by histamine (10 mg/kg) or 2.5% NaCl (10 ml/kg) administered intraperitoneally (i.p.). The plasma VP levels were measured by radioimmunoassay. Increased water consumption was observed after the administration of 30 μg/10 μl orexin-A. There were no changes in basal VP secretion after the administration of different doses of the orexins. A significant increase in plasma VP concentration was detected following histamine administration. After 2.5% NaCl administration, there was a moderate VP level enhancement. Intracerebroventricularly administered orexin-A (30 μg/10 μl) blocked the VP level increase induced by either histamine or 2.5% NaCl administration. The inhibitory effects were prevented by the specific OX(1) receptor antagonist. In conclusion, the orexins increased water consumption. After 30 μg/10 μl orexin-A administration, the polydipsia was more pronounced. The OX(1) receptor antagonist significantly decreased the polydipsia. Histamine or hyperosmotic VP release enhancement was blocked by previously administered orexin. This inhibition was not observed following OX(1) receptor antagonist administration. Our results suggest that the effects of the orexins on water consumption or blockade of the histamine and osmosis-induced VP level increase are mediated by the OX(1) receptor.

  3. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

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    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  4. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats. (United States)

    Febo, Marcelo; Ferris, Craig F


    Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav.


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    Full Text Available ObjectiveNocturnal enuresis is a common childhood problem and has various  treatments.This study was carried out to compare oral and nasal vasopressin in the treatment of nocturnal enuresis in 5- to 12-year-old children who were referred to the Shahid Beheshti Clinic in 2008.Materials & MethodsThis study included 100 children (62 males and 38 females with nocturnal enuresis. One group (50 patients received 20 mcg nasal vasopressin which increased up to 40 mcg, depending on the patients' response. The other group (50 patients received 0.2 mg oral vasopressin which increased up to 0.4 mg.The patients were followed up for one month after response to the last dose of drug. Data were recorded in prepared forms and analyzed using Chi-Square and Fisher Test.ResultsThe success rate with oral and nasal method was 80% and 92%, respectively (P=0.08. Only 2% of the children had complications during the treatment; one child treated orally developed gastroenteritis and another child treated with the nasal method developed convulsions (P=1. Sixteen percent of the children treated with the oral method and 28% of the children treated with the nasal method had recurrence (P=0.148.ConclusionOral and nasal forms of vasopressin have equal therapeutic effects. However, oral form of the treatment has fewer serious side effects and is easier to use. Therefore, the use of oral medicine is recommended.Keywords:Nasal vasopressin, Nocturnal enuresis, Oral vasopressin

  6. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide (United States)

    di Giglio, Maria Giulia; Muttenthaler, Markus; Harpsøe, Kasper; Liutkeviciute, Zita; Keov, Peter; Eder, Thomas; Rattei, Thomas; Arrowsmith, Sarah; Wray, Susan; Marek, Ales; Elbert, Tomas; Alewood, Paul F.; Gloriam, David E.; Gruber, Christian W.


    Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.

  7. Effect of vasopressin on Na(+)-K(+)-2Cl(-) cotransporter (NKCC) and the signaling mechanisms on the murine late distal colon. (United States)

    Xue, Hong; Tang, Xudong


    It has been demonstrated that the antidiuretic hormone vasopressin is able to regulate the expression of Na-K-Cl cotransporters (NKCC1 and NKCC2) in the kidney. The present study investigated the effects of long- and short-term administration of vasopressin on NKCC and the possible signaling mechanism of vasopressin in the mouse distal colon using the siRNA, real-time PCR, western blotting and Ussing chambers method. The results showed the presence of NKCC2 expression in the colon, which was verified with a siRNA technique. The mRNA and protein expression level of NKCC2 significantly increased by about 40% and 90% respectively in response to restricting water intake to 1ml/day/20g for 7 days. In contrast, the NKCC1 expression level was unchanged in the colon. To determine the short-term activation of NKCC2 by vasopressin in vitro, we found that the administration of vasopressin caused a 3-fold increase in mouse colon NKCC2 phosphorylation, which was detected with phosphospecific antibody R5. In addition, the Ussing chamber results showed that NKCC2, cAMP and Ca(2+) signaling pathway may be involved in the vasopressin-induced response. Further, adenylate cyclase inhibitor MDL-12330A and PKA inhibitor H89 and Ca(2+) chelator BAPTA-AM reversed the vasopressin induced NKCC2 phosphorylation level increase by about 35%, 28% and 42% respectively suggesting vasopressin stimulate NKCC2 phosphorylation increase mediated by cAMP-PKA and Ca(2+) signaling in the colon. Collectively, these data suggest that the expression and phosphorylation of NKCC2 are increased in the colon by vasopressin stimulation, in association with enhanced activity of the vasopressin/cAMP and Ca(2+) pathways.

  8. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

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    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  9. Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans

    DEFF Research Database (Denmark)

    Pump, B; Damgaard, M; Gabrielsen, A;


    During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing...... in eight healthy males, we tested the hypothesis that with similar increases in LA diameter, suppression of AVP release is dependent on the degree of increase in PP. LA diameter increased similarly during the posture change and negative pressure breathing (-9 to -24 mmHg) from between 30 and 31 +/- 1 to 34...... +/- 1 mm (P breathing from 36 +/- 3 to 42 +/- 3 mmHg (P

  10. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers. (United States)

    Adderley, Shaquria P; Lawrence, Curtis; Madonia, Eyong; Olubadewo, Joseph O; Breslin, Jerome W


    The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity.

  11. Fluids preserved in variably altered graphitic pelitic schists in the Dufferin Lake Zone, south-central Athabasca Basin, Canada: implications for graphite loss and uranium deposition (United States)

    Pascal, Marjolaine; Boiron, Marie-Christine; Ansdell, Kevin; Annesley, Irvine R.; Kotzer, Tom; Jiricka, Dan; Cuney, Michel


    The Athabasca Basin (Canada) contains the highest grade unconformity-type uranium deposits in the world. Underlying the Athabasca Group sedimentary rocks of the Dufferin Lake Zone are variably graphitic, pelitic schists (VGPS), altered to chlorite and hematite (Red/Green Zone: RGZ). They were locally bleached near the unconformity during paleoweathering and/or later fluid interaction. Overall, graphite was lost from the RGZ and the bleached zone relative to the original VGPS. Fluid inclusions were examined in different generations of quartz veins, using microthermometry and Raman spectroscopy, to characterize and compare the different fluids that interacted with the RGZ and the VGPS. In the VGPS, CH4-, and N2-rich fluid inclusions, which homogenize into the vapor phase between -100 and -74 °C, and -152 and -125 °C, respectively, and CO2-rich fluid inclusions, homogenizing either into vapor or liquid between 20 and 28 °C, are present. Carbonic fluids could be the result of the breakdown of graphite to CH4 + CO2, whereas N2-rich fluid is interpreted to be the result of breakdown of feldspars/micas to NH4 ++N2. In the RGZ, the presence of fluid inclusions with low ice melting temperature (-38 to -16 °C) reflect the presence of CaCl2, and fluid inclusions with halite daughter minerals that dissolve between 190 and 240 °C indicate the presence of highly saline fluids. These fluids are interpreted to be derived from the Athabasca Basin. The circulation of carbonic fluids and brines occurred during two different events related to different P-T conditions of trapping. The carbonic fluids interacted with basement rocks during retrograde metamorphism of the basement rocks before deposition of the Athabasca Basin, whereas the brines circulated after the deposition of the Athabasca Basin. These latter fluids are similar to brines related to uranium mineralization at McArthur River and thus, in addition to possibly being related to graphite depletion in the RGZ, they could

  12. Examination of chloritization of biotite as a tool for reconstructing the physicochemical parameters of mineralization and associated alteration in the Zafarghand porphyry copper system, Ardestan, Central Iran: mineral-chemistry and stable isotope analyses (United States)

    Aminroayaei Yamini, Maryam; Tutti, Faramarz; Aminoroayaei Yamini, Mohammad Reza; Ahmadian, Jamshid; Wan, Bo


    The chloritization of biotite and stable isotopes of silicate have been studied for the Zafarghand porphyry copper deposit, Ardestan, Iran. The studied area, in the central part of the Urumieh-Dokhtar magmatic belt, contains porphyry-style Cu mineralization and associated hydrothermal alteration within the Miocene (19-26 Ma, Zircon U-Pb age) granodioritc stock and adjacent andesitic to rhyodacitic volcanic rocks (ca. 56 Ma, zircon U-Pb age). The primary and secondary biotite that formed during potassic alteration in this porphyry and these volcanic host rocks are variably chloritized. Chloritization of biotite pseudomorphically is characterized by an increase in MgO, FeOt, and MnO, with decreasing in SiO2, K2O, and TiO2. Based on the Ti-in-biotite geothermometer of Henry et al. (Am Mineral 90:316-328, 2005) and Al-in-chlorite geothermometer of Cathelineau (Clay Miner 23:417-485, 1988), crystallization temperatures of primary biotite representative of magmatic conditions and later chloritization temperature range from 617° to 675 °C ± 24 °C and 177° to 346 °C, respectively. Calculated isotopic compositions of fluids that chloritized primary and secondary biotite display isotopic compositions of 1.1 to 1.7 per mil for δ18O and -19.9 to -20.5 per mil for δD consistent with meteoric water. Sericite, barren, and A-type-quartz veins from phyllic alteration were produced by mixed magmatic and meteoric water with δ18O values from -2.8 to 2.5 and δD values of ˜ -23 per mil; the narrow range of δD values of the propylitic epidote may be due to a meteoric water with δ18O values from 0.8 to 1.6 and δD values from -14.6 to -16.9 per mil.

  13. Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female rats. (United States)

    McNamara, Robert K; Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W


    FLX treatment on central 5-HT turnover or behavior in the FST in female rats.

  14. Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus. (United States)

    Tian, Dan; Cen, Jing; Nie, Min; Gu, Feng


    Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

  15. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin. (United States)

    Bisagno, Verónica; Cadet, Jean Lud


    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

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

    LENUS (Irish Health Repository)

    Dinan, T G


    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.

  17. Arginine vasopressin as a target in the treatment of acute heart failure

    Institute of Scientific and Technical Information of China (English)

    Nisha; A; Gilotra; Stuart; D; Russell


    Congestive heart failure(CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1 a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis(free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.

  18. Personality is Tightly Coupled to Vasopressin-Oxytocin Neuron Activity in a Gregarious Finch

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    Aubrey M Kelly


    Full Text Available Nonapeptides of the vasopressin-oxytocin family modulate social processes differentially in relation to sex, species, behavioral phenotype, and human personality. However, the mechanistic bases for these differences are not well understood, in part because multidimensional personality structures remain to be described for common laboratory animals. Based upon principal components (PC analysis of extensive behavioral measures in social and nonsocial contexts, we now describe three complex dimensions of phenotype (personality for the zebra finch, a species that exhibits a human-like social organization that is based upon biparental nuclear families embedded within larger social groups. These dimensions can be characterized as Social competence/dominance, Gregariousness, and Anxiety. We further demonstrate that the phasic Fos response of nonapeptide neurons in the paraventricular nucleus of the hypothalamus and medial bed nucleus of the stria terminalis are significantly predicted by personality, sex, social context, and their interactions. Furthermore the behavioral PCs are each associated with a distinct suite of neural PCs that incorporate both peptide cell numbers and their phasic Fos responses, indicating that personality is reflected in complex patterns of neuromodulation arising from multiple peptide cell groups. These findings provide novel insights into the mechanisms underlying sex- and phenotype-specific modulation of behavior, and should be broadly relevant, given that vasopressin-oxytocin systems are strongly conserved across vertebrates.

  19. Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes (United States)

    Asai, Kai; Ivandini, Tribidasari A.; Einaga, Yasuaki


    The electrochemical detection of oxytocin using boron-doped diamond (BDD) electrodes was studied. Cyclic voltammetry of oxytocin in a phosphate buffer solution exhibits an oxidation peak at +0.7 V (vs. Ag/AgCl), which is attributable to oxidation of the phenolic group in the tyrosyl moiety. Furthermore, the linearity of the current peaks obtained in flow injection analysis (FIA) using BDD microelectrodes over the oxytocin concentration range from 0.1 to 10.0 μM with a detection limit of 50 nM (S/N = 3) was high (R2 = 0.995). Although the voltammograms of oxytocin and vasopressin observed with an as-deposited BDD electrode, as well as with a cathodically-reduced BDD electrode, were similar, a clear distinction was observed with anodically-oxidized BDD electrodes due to the attractive interaction between vasopressin and the oxidized BDD surface. By means of this distinction, selective measurements using chronoamperometry combined with flow injection analysis at an optimized potential were demonstrated, indicating the possibility of making selective in situ or in vivo measurements of oxytocin.

  20. Vasopressin contributes to maintenance of arterial blood pressure in dehydrated baboons. (United States)

    Ryan, K L; Thornton, R M; Proppe, D W


    This study primarily sought to determine whether the role of vasopressin (VP) in maintenance of arterial blood pressure is enhanced in awake, chronically instrumented baboons after 68-72 h of dehydration. This question was approached by pharmacologically blocking vasopressin V1-receptors in euhydrated and dehydrated baboons with or without a normally functioning renin-angiotensin system (RAS). VP blockade during dehydration produced a rapidly occurring (within 5 min), statistically significant (P less than 0.05) decrease in mean arterial pressure (MAP) of 5 +/- 1 mmHg in the RAS-intact condition and an identical decline in MAP (5 +/- 1 mmHg) during blockade of the RAS by captopril, an angiotensin I-converting enzyme inhibitor. At 15 min after induction of VP blockade, heart rate was elevated by 9 +/- 2 beats/min in the RAS-intact condition and by 20 +/- 5 beats/min in the RAS-blocked condition. In addition, VP blockade in the dehydrated state produced small and equal increases in hindlimb vascular conductance in RAS-intact and RAS-blocked conditions. None of these cardiovascular changes were produced by VP blockade in the euhydrated state. RAS blockade produced modest declines in MAP in both hydration states, but the fall was larger by 7 +/- 4 mmHg in the dehydrated state. Thus both VP and the RAS contribute to the maintenance of arterial blood pressure during dehydration in the conscious baboon.

  1. The Modulatory Effect of Ischemia and Reperfusion on Arginine Vasopressin-Induced Arterial Reactions. (United States)

    Szadujkis-Szadurska, Katarzyna; Malinowski, Bartosz; Piotrowska, Małgorzata; Grześk, Grzegorz; Wiciński, Michał; Gajdus, Marta


    Aim of the Study. The purpose of this study was to investigate the impact of ischemia and reperfusion on the resistance of arteries to AVP (arginine vasopressin), with a particular emphasis on the role of smooth muscle cells in the action of vasopressin receptors and the role of the cGMP-associated signalling pathway. Materials and Methods. Experiment was performed on the perfunded tail arteries from male Wistar rats. The constriction triggered by AVP after 30 minutes of ischemia and 30 and 90 minutes of reperfusion was analysed. Analogous experiments were also carried out in the presence of 8Br-cGMP. Results. Ischemia reduces and reperfusion increases in a time-dependent manner the arterial reaction to AVP. The presence of 8Br-cGMP causes a significant decrease of arterial reactivity under study conditions. Conclusions. Ischemia and reperfusion modulate arterial contraction triggered by AVP. The effect of 8Br-cGMP on reactions, induced by AVP after ischemia and reperfusion, indicates that signalling pathway associated with nitric oxide (NO) and cGMP regulates the tension of the vascular smooth muscle cells.

  2. The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network. (United States)

    Albers, H Elliott


    Neuropeptides in the arginine vasotocin/arginine vasopressin (AVT/AVP) family play a major role in the regulation of social behavior by their actions in the brain. In mammals, AVP is found within a circuit of recriprocally connected limbic structures that form the social behavior neural network. This review examines the role played by AVP within this network in controlling social processes that are critical for the formation and maintenance of social relationships: social recognition, social communication and aggression. Studies in a number of mammalian species indicate that AVP and AVP V1a receptors are ideally suited to regulate the expression of social processes because of their plasticity in response to factors that influence social behavior. The pattern of AVP innervation and V1a receptors across the social behavior neural network may determine the potential range and intensity of social responses that individuals display in different social situations. Although fundamental information on how social behavior is wired in the brain is still lacking, it is clear that different social behaviors can be influenced by the actions of AVP in the same region of the network and that AVP can act within multiple regions of this network to regulate the expression of individual social behaviors. The existing data suggest that AVP can influence social behavior by modulating the interpretation of sensory information, by influencing decision making and by triggering complex motor outputs. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  3. Stimulation tests of human growth hormone secretion by insulin, lysine vasopressin, pyrogen and glucagon

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    Full Text Available Firstly, comparisons have been made of the secretion of human growth hormone (HGH that was induced by insulin, lysine vasopressin and pyrogen injections in order to study whether these substances can be utilized as a rapid test of HGH secretion. In insulin test, a fall of the fasting blood glucose level by 28.6% or more seemed to be sufficient to provoke adequate HGH elevation, and 9.4 ng/ml or higher HGH increment was recognized as being normal, because lysine vasopressin and pyrogen produce varying degrees of side-effects and are less specific and unpredictable in the release of HGH. Secondly, the pharmacologic effects and mechanism of action of exogenous glucagon upon the HGH secretion were studied. In normal subjects after one mg sc glucagon, there was a mean peak blood glucose level of 142. 4±3.l mg/lOO ml at 30 min, HGH levels reached a mean peak level of 22. 6±4. 8 ng/ml at 150 min, and no false negative response was noted. In patients with hypopituitarism, there was no positive response in plasma HGH levels after the sc glucagon. The present study revealed that the rise and subsequent fall of blood glucose are not the sole mechanism responsible for the effct of glucagon on HGH secretion, and that the HGH secretion in response to the sc glucagon was not triggered by cathecholamine via the stimulation of the adrenal medulla.

  4. Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy. (United States)

    Uzefovsky, F; Shalev, I; Israel, S; Edelman, S; Raz, Y; Mankuta, D; Knafo-Noam, A; Ebstein, R P


    Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.

  5. Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Tahri-Joutei, A.; Pointis, G.


    Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. (/sup 3/H)-AVP was found to bind to a single class of sites with high affinity and low capacity. Binding displacements with specific selection analogs of AVP indicated the presence of V/sub 1/ subtype receptors on Leydig cells. The ability of AVP to displace (/sup 3/H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace (/sup 3/H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells. This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation. AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation. This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels.

  6. Oxytocin and Vasopressin: Linking Pituitary Neuropeptides and their Receptors to Social Neurocircuits

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    Danielle Andrea Baribeau


    Full Text Available Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.

  7. The Effect of Maternal Stress Activation on the Offspring during Lactation in Light of Vasopressin

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    Anna Fodor


    Full Text Available Although it is obvious that preconceptional effects as well as stressors during pregnancy profoundly influence the progeny, the lactation period seems to be at least as important. Here we summarize how maternal stressors during the lactation period affect the offspring. As vasopressin is one of the crucial components both for stress adaptation and social behavior, special emphasis was given to this neuropeptide. We can conclude that stressing the mother does not have the same acute effect on the hypothalamo-pituitary-adrenocortical axis (as the main target of stress adaptation of the pups as stressing the pups, but later endocrine and behavioral consequences can be similar. Vasopressin plays a role in acute and later consequences of perinatal stressor applied either to the mother or to the offspring, thereby contributing to transmitting the mothers’ stress to the progeny. This mother-infant interaction does not necessarily mean a direct transmission of molecules, but rather is the result of programming the brain development through changes in maternal behavior. Thus, there is a time lag between maternal stress and stress-related changes in the offspring. The interactions are bidirectional as not only stress in the dam but also stress in the progeny has an effect on nursing.

  8. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. (United States)

    Wolff, Kim; Tsapakis, E M; Winstock, A R; Hartley, D; Holt, D; Forsling, M L; Aitchison, Katherine J


    Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p ecstasy-using "clubbers", which has important clinical implications.

  9. Vasopressin in Hemorrhagic Shock: A Systematic Review and Meta-Analysis of Randomized Animal Trials

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    Andrea Pasquale Cossu


    Full Text Available Objective. The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP, or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock. Design. A meta-analysis of randomized controlled animal trials. Participants. A total of 433 animals from 15 studies were included. Interventions. The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine, or placebo was investigated. Measurements and Main Results. Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15% in the AVP group versus 164/259 (63% in the control arms; OR=0.09; 95% CI 0.05 to 0.15; P for effect < 0.001; P for heterogeneity = 0.30; I2=14%. Conclusions. Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials.

  10. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice. (United States)

    Cox, Kimberly H; Quinnies, Kayla M; Eschendroeder, Alex; Didrick, Paula M; Eugster, Erica A; Rissman, Emilie F


    Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders.


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    Full Text Available ObjectiveNocturnal enuresis is a common childhood problem and has various treatments.This study was carried out to compare oral and nasal vasopressin in the treatment of nocturnal enuresis in 5- to 12-year-old children who were referred to the Shahid Beheshti Clinic in 2008.Materials & MethodsThis study included 100 children (62 males and 38 females with nocturnal enuresis. One group (50 patients received 20 mcg nasal vasopressin which increased up to 40 mcg, depending on the patients' response. The other group (50 patients received 0.2 mg oral vasopressin which increased up to 0.4 mg.The patients were followed up for one month after response to the last dose of drug. Data were recorded in prepared forms and analyzed using Chi-Square and Fisher Test.ResultsThe success rate with oral and nasal method was 80% and 92%, respectively (P=0.08. Only 2% of the children had complications during the treatment; one child treated orally developed gastroenteritis and another child treated with the nasal method developed convulsions (P=1. Sixteen percent of the children treated with the oral method and 28% of the children treated with the nasal method had recurrence (P=0.148.ConclusionOral and nasal forms of vasopressin have equal therapeutic effects. However, oral form of the treatment has fewer serious side effects and is easier to use. Therefore, the use of oral medicine is recommended.

  12. Changes in cerebrospinal fluid levels of vasopressin and oxytocin of the rat during various light-dark regimes

    NARCIS (Netherlands)

    Mens, W.B.J.; Andringa-Bakker, E.A.D.; Wimersma Greidanus, T.B. van


    Levels of arginine-vasopressin (AVP) and oxytocin (OXT) in cerebrospinal fluid (CSF) of rats were determined at various times of the day and the night under normal and changed light-dark conditions. During a regular daily 14 h and 10 h dark cycle (lights on 06.00 h, off 20.00 h), AVP in CSF reached

  13. Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition, and anxiety-related behaviors in rats

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM


    The role of lateral septal vasopressin (VP) in the modulation of spatial memory, social memory, and anxiety-related behavior was studied in adult, male Wistar rats. Animals were equipped with osmotic minipumps delivering the VP-antagonist d(CH2)5-D-Tyr(Et)VAVP (1 ng/0.5 mu l per h) bilaterally into

  14. Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild-type and tau mutant Syrian hamsters

    NARCIS (Netherlands)

    Van der Zee, EA; Oklejewicz, M; Jansen, K; Daan, S; Gerkema, MP


    Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in studies of circadian rhythms, there are no data available on the temporal dynamics of the neuropeptide vasopressin (AVP), a major output system of the suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in vi

  15. Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

    Directory of Open Access Journals (Sweden)

    Justin Fulkerson, MSN


    Full Text Available Introduction: This study compared the effects of vasopressin via tibial intraosseous (IO and intravenous (IV routes on maximum plasma concentration (Cmax, the time to maximum concentration (Tmax, return of spontaneous circulation (ROSC, and time to ROSC in a hypovolemic cardiac arrest model. Methods: This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7, IO tibia (n=7, cardiopulmonary resuscitation (CPR + defibrillation (n=7, and a control group that received just CPR (n=7. Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using highperformance liquid chromatography. Results: There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0 but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031 and IV compared to the CPR-only group (p=0.001. There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031 and IO compared to the CPR-only group (p=0.001. There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127. There was no significant difference in Cmax between the IO and IV groups (p=0.079. The mean ± standard deviation of Cmax of the IO group was 58,709±25,463pg/mL compared to the IV group, which was 106,198±62,135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084. There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion: Prompt access to the vascular system using the IO route can circumvent

  16. Copeptin as a marker for arginine-vasopressin/antidiuretic hormone secretion in the diagnosis of paraneoplastic syndrome of inappropriate ADH secretion. (United States)

    Wuttke, A; Dixit, K C; Szinnai, G; Werth, S C; Haagen, U; Christ-Crain, M; Morgenthaler, N; Brabant, G


    Direct measurement of arginine-vasopressin/antidiuretic hormone (AVP/ADH) concentrations is not included in the standard diagnostic procedures for paraneoplastic syndrome of inappropriate ADH secretion (SIADH). Here, we evaluate the potential of copeptin measurement as a surrogate marker of AVP/ADH secretion for the direct diagnosis of suspected SIADH in cancer patients. Forty-six unselected cancer patients with serum sodium concentrations permanently below 135 mmol/L were included in this study. We compared standard diagnostic criteria for SIADH to the measurement of plasma copeptin in relation to osmolality. Normative data for comparison were constructed from 24 healthy controls studied under basal conditions, experimental dehydration, and hypotonic hypervolemia as well as from 222 hospital patients with no suspicion of an altered ADH regulation. Log transformation of copeptin revealed a linear relationship to plasma osmolality in the controls (R = 0.495, p < 0.001). Compared to these normative data, copeptin levels in most cancer patients were inappropriately high for plasma osmolality and were not significantly correlated. These results, suggestive for paraneoplastic SIADH, could be confirmed by conventional diagnostic procedures for SIADH. Current strategies to diagnose SIADH are difficult to perform under outpatients conditions. Our approach allows screening from a single plasma sample for true paraneoplastic ADH oversecretion and thus rapid selection for a specific therapy with an AVP receptor antagonist.

  17. Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin. (United States)

    Geddes, B J; Harding, T C; Lightman, S L; Uney, J B


    The ability of adenovirus (Ad) to transfect most cell types efficiently has already resulted in human gene therapy trials involving the systemic administration of adenoviral constructs. However, because of the complexity of brain function and the difficulty in noninvasively monitoring alterations in neuronal gene expression, the potential of Ad gene therapy strategies for treating disorders of the CNS has been difficult to assess. In the present study, we have used an Ad encoding the arginine vasopressin cDNA (AdAVP) in an AVP-deficient animal model of diabetes insipidus (the Brattleboro rat), which allowed us to monitor chronically the success of the gene therapy treatment by noninvasive assays. Injection of AdAVP into the supraoptic nuclei (SON) of the hypothalamus resulted in expression of AVP in magnocellular neurons. This was accompanied by reduced daily water intake and urine volume, as well as increased urine osmolality lasting 4 months. These data show that a single gene defect leading to a neurological disorder can be corrected with an adenovirus-based strategy. This study highlights the potential of using Ad gene therapy for the long-term treatment of disorders of the CNS.

  18. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin. (United States)

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B


    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  19. Effect of Hyperosmotic Stimulation and Adrenalectomy on Vasopressin mRNA Levels in the Paraventricular and Supraoptic Nuclei of the Hypothalamus:

    Directory of Open Access Journals (Sweden)



    Full Text Available The effects of salt loading and adrenalectomy on arginine vasopressin (AVP mRNA levels in the paraventricular nucleus (PVN and the supraoptic nucleus (SON of the hypothalamus were studied by semiquantitative in situ hybridization histochemistry, using a synthetic oligonucleotide probe and a computer-assisted image analysis system. Salt loading (2% NaCl for 7 days produced marked increases in AVP mRNA levels in the magnocellular neurons of the PVN, SON, and accessory nuclei. Adrenalectomy caused an increase in AVP mRNA expression in the magnocellular part of the PVN and the expansion of hybridization signals into its medial parvocellular region, where the cell bodies of corticotropin-releasing hormone (CRH neurons are located. No apparent alteration of AVP mRNA levels was observed in the SON following adrenalectomy. These results indicate that hyperosmotic stimulation and the loss of circulating glucocorticoids had differential effects on AVP gene expression in the PVN and SON, and that the magnocellular PVN and SON neurons responded in different manners to the loss of feedback signals.

  20. Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Shuai Mu


    Full Text Available Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by 1H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate.

  1. Enkephalin inhibition of angiotensin-stimulated release of oxytocin and vasopressin (United States)

    Keil, L. C.; Chee, O.; Rosella-Dampman, L. M.; Emmert, S.; Summy-Long, J. Y.


    The effect of intracerebroventricular (ICV) pretreatment with 100 ng/5 microliter leucine(5)-enkephalin (LE) on the increase in plasma oxytocin (OT) and vasopressin (VP) caused by ICV injection of 10, 50, or 100 ng/5 microliter of angiotensin II (AII) is investigated experimentally in conscious adult male Sprague-Dawley rats; the effects of water-deprivation dehydration and lactation/suckling (in female rats) are also studied. An OT radioimmunoassay (RIA) with a sensitivity of 800 fg/ml (described in detail) and the VP RIA technique of Keil and Severs (1977) are employed. Administration of AII or dehydration for 48 or 72 h cause a significant increase in OT and VP without affecting the ratio, while lactation and suckling increase OT only. LE pretreatment inhibits significantly but does not suppress the AII-stimulated OT-VP response.

  2. Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat. (United States)

    Yang, Jun; Chen, Jian-Min; Liu, Wen-Yan; Song, Cao-You; Wang, Cheng-Hai; Lin, Bao-Cheng


    Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

  3. Vasopressin elevation of Na+/H+ exchange is inhibited by genistein in human blood platelets. (United States)

    Aharonovits, O; Zik, M; Livne, A A; Granot, Y


    The regulation of intracellular Na+ and pHi in human blood platelets is known to be controlled by the function of the Na+/H+ exchanger. The phosphorylation state of the Na+/H+ exchanger which determines the exchanger activity in human blood platelets is regulated by the activities of protein kinases and protein phosphatases. Observations in this study indicate that arginine vasopressin (AVP) that interacts with a V1 receptor, activates the Na+/H+ exchange in human blood platelets through a genistein-inhibited mechanism. The AVP-activated Na+/H+ exchange is probably not regulated by protein kinase C (PKC), since this activation is not inhibited by staurosporine. The multiple ways in which platelet Na+/H+ exchange can be modulated may indicate the critical role played by this exchanger in the homeostasis control of pHi in human blood platelets.

  4. Increased concentration of vasopressin in plasma of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; Warberg, J.


    The effect of essential fatty acid deficiency (EFA-D) on the plasma concentration of arginine-vasopressin (AVP) and the urinary AVP excretion was investigated. Weanling rats were fed a fat-free diet (FF-rats). Control rats received the same diet in which 6% by wt. of sucrose was replaced by arachis...... oil. After 4-6 weeks of feeding, urine and plasma were analysed for AVP, osmolality, sodium and potassium. When compared to control rats FF-rats had decreased urine volume (6.0 ± 1.6 ml/24 hr versus 11.7 ± 3.2 ml/24 hr), increased urine osmolality (2409 ± 691 mOsm/kg versus 1260 ± 434 m...

  5. Sheehan's syndrome with central diabetes insipidus. (United States)

    Laway, Bashir Ahmad; Mir, Shahnaz Ahmad; Dar, Mohd Iqbal; Zargar, Abdul Hamid


    Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

  6. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

    LENUS (Irish Health Repository)

    Tansey, Katherine E


    Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  7. Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking. (United States)

    Tiulpakov, Anatoly; White, Carl W; Abhayawardana, Rekhati S; See, Heng B; Chan, Audrey S; Seeber, Ruth M; Heng, Julian I; Dedov, Ivan; Pavlos, Nathan J; Pfleger, Kevin D G


    Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5.8 years. We show that, compared with wild-type V2R, the L312S mutation results in the constitutive production of cAMP, indicative of the gain-of-function NSIAD profile. Interestingly, like the previously described F229V and I130N NSIAD-causing mutants, this appears to both occur in the absence of notable constitutive β-arrestin2 recruitment and can be reduced by the inverse agonist Tolvaptan. In addition, to understand the effect of various V2R substitutions on the full receptor "life-cycle," we have used and further developed a bioluminescence resonance energy transfer intracellular localization assay using multiple localization markers validated with confocal microscopy. This allowed us to characterize differences in the constitutive and ligand-induced localization and trafficking profiles of the novel L312S mutation as well as for previously described V2R gain-of-function mutants (NSIAD; R137C and R137L), loss-of-function mutants (nephrogenic diabetes insipidus; R137H, R181C, and M311V), and a putative silent V266A V2R polymorphism. In doing so, we describe differences in trafficking between unique V2R substitutions, even at the same amino acid position, therefore highlighting the value of full and thorough characterization of receptor function beyond simple signaling pathway analysis.

  8. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A: implications for autism

    Directory of Open Access Journals (Sweden)

    Tansey Katherine E


    Full Text Available Abstract Background Arginine vasopressin (AVP has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs (rs3803107, rs1042615, rs3741865, rs11174815 and three microsatellites (RS3, RS1 and AVR at the AVPR1A gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively. Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  9. Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors. (United States)

    Kjaer, A; Larsen, P J; Knigge, U; Jørgensen, H; Warberg, J


    Centrally administered histamine (HA) stimulates the secretion of the pro-opiomelanocortin-derived peptides ACTH and beta-endorphin as well as prolactin. The effect of HA on secretion of these adenohypophysial hormones is indirect and may involve activation of hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) or oxytocin (OT). We studied the effect of activating central HA receptors by central infusion of HA, HA agonists or antagonists on expression of CRH, AVP and OT mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intracerebroventricular infusion of HA (270 nmol), the H1-receptor agonist 2-thiazolylethylamine or the H2-receptor agonist 4-methylhistamine increased the level of CRH mRNA in the PVN, and OT mRNA in the SON. In contrast, none of these compounds had any effect on expression of AVP mRNA in the PVN or SON. Administration of the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine had no effect on basal expression of CRH, AVP or OT mRNA in the PVN and/or SON except for a slight inhibitory effect of cimetidine on CRH mRNA expression in the PVN. Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-induced increase in OT mRNA levels but had no effect on the HA-induced increase in CRH mRNA levels in the PVN. We conclude that HA stimulates hypothalamic CRH and OT neurons by increasing mRNA levels, and this effect seems to be mediated via activation of both HA H1 and H2 receptors.

  10. Prior Exercise Alters Responses to Hemorrhage (United States)


    similarly in both groups. Posthemorrhage lactate and glucose concentrations were lower in exercise. The increase in plasma epinephrine was reduced in...exercise, with significantly lower levels in epinephrine and norepinephrine noted posthemorrhage. Vasopressin levels and plasma renin activity were...of a patient with hemorrhage caused by traumatic injuries. KEYWORDS—Cardiac output, blood pressure, vasopressin, catecholamines, plasma renin activity

  11. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis]. (United States)

    Morin, Denis


    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

  12. Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau-Merck, M.F.; Derre, J.; Berger, R. [INSERM, Paris (France)] [and others


    Vasopressin exerts its physiological effects on liver metabolism, fluid osmolarity, and corticotrophic response to stress through a set of at least three receptors, V1a, V2, and V3 (also called V1b), respectively. These receptors constitute a distinct group of the superfamily of G-protein-coupled cell surface receptors. When bound to vasopressin, they couple to G proteins activating phospholipase C for the V1a and V3 types and adenylate cyclase for the V2. The vasopressin receptor subfamily also includes the receptor for oxytocin, a structurally related hormone that signals through the activation of phospholipase C. The chromosomal position of the V2 receptor gene has been assigned to Xq28-qter by PCR-based screening of somatic cell hybrids, whereas the oxytocin receptor gene has been mapped to chromosome 3q26.2 by fluorescence in situ hybridization (FISH). The chromosomal location of the V1a gene is currently unknown. We recently cloned the cDNA and the gene coding for the human pituitary-specific V3 receptor (HGMW-approved symbol AVPR3). We report here the chromosomal localization of this gene by two distinct in situ hybridization techniques using radioactive and fluorescent probes. 11 refs., 1 fig.

  13. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant). (United States)

    Bichet, Daniel G; Bockenhauer, Detlef


    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.

  14. Central administration of neuromedin U suppresses food intake in chicks. (United States)

    Kamisoyama, Hiroshi; Honda, Kazuhisa; Saneyasu, Takaoki; Sugahara, Kunio; Hasegawa, Shin


    The appetite-suppressive action of brain-gut peptides is similar in both chickens and mammals. In mammals, the brain-gut peptide neuromedin U (NMU) suppresses food intake via hypothalamic neuropeptides, corticotropin-releasing factor (CRF), oxytocin, and arginine-vasopressin. In chickens, central administration of CRF, oxytocin, or arginine-vasotocin (AVT, a nonmammalian equivalent of arginine-vasopressin) suppresses food intake. However, the anorexigenic action of NMU in chickens has not yet been identified. In the present study, we analyzed the effects of the central administration of NMU on food intake and hypothalamic mRNA levels of CRF, AVT and mesotocin (a nonmammalian equivalent of oxytocin) in chicks. Intracerebroventricular administration of NMU in chicks significantly suppressed food intake and induced wing-flapping behavior. NMU also significantly upregulated mRNA expression of CRF and AVT, but did not influence mRNA expression of mesotocin in the hypothalamus. These results suggest that NMU functions as an appetite-suppressive peptide via CRF and AVT in the central nervous system in chicks.

  15. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    Directory of Open Access Journals (Sweden)

    Ostergaard L


    Full Text Available Louise Ostergaard,1,2,* Alain Rudiger,3,* Sven Wellmann,2,4,5 Elena Gammella,6 Beatrice Beck-Schimmer,2,3 Joachim Struck,7 Marco Maggiorini,2,8 Max Gassmann,1,2,9 1Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, 2Zürich Center for Integrative Human Physiology, 3Institute of Anesthesiology, 4Division of Neonatology, University Hospital Zürich, Zürich, 5Department of Neonatology, University Children's Hospital Basel, Basel, Switzerland; 6Department of Human Morphology and Biomedical Science, University of Milan, Milan, Italy; 7Research Department, B•R•A•H•M•S Biomarkers, Thermo Fisher Scientific, Hennigsdorf, Germany; 8Medical Intensive Care Unit, University Hospital Zürich, Zürich, Switzerland; 9Universidad Peruana Cayetano Heredia, Lima, Peru *These authors contributed equally to this work and share first authorship Background: A reduced oxygen supply puts patients at risk of tissue hypoxia, organ damage, and even death. In response, several changes are activated that allow for at least partial adaptation, thereby increasing the chances of survival. We aimed to investigate whether the arginine vasopressin marker, copeptin, can be used as a marker of the degree of acclimatization/adaptation in rats exposed to hypoxia. Methods: Sprague-Dawley rats were exposed to 10% oxygen for up to 48 hours. Arterial and right ventricular pressures were measured, and blood gas analysis was performed at set time points. Pulmonary changes were investigated by bronchoalveolar lavage, wet and dry weight measurements, and lung histology. Using a newly developed specific rat copeptin luminescence immunoassay, the regulation of vasopressin in response to hypoxia was studied, as was atrial natriuretic peptide (ANP by detecting mid-regional proANP. Results: With a decreasing oxygen supply, the rats rapidly became cyanotic and inactive. Despite continued exposure to 10% oxygen, all animals recuperated within 16 hours and

  16. Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men (United States)

    Greenleaf, J. E.; Simanonok, K.; Bernauer, E. M.; Wade, C. E.; Keil, L. C.


    The purpose of this research was to test the hypotesis that a reduction in blood volume would attenuate or eliminate immersion-induced increases in cardiac output (Q(sub co)) and urine excretion, and to investigate accompanying vasoactive and fluid-electrolyte hormonal responses. Eight men (19-23 yr) were supine during a 2-hr control period in air, and then sat for 5-hr test periods in air at 20 C (dry control, DC); water at 34.5 C (wet control, WC); and water (34.5 C) after hemorrhage (WH) of 14.8 plus or minus 0.3 percent of their blood volume. Blood volume was -11.6 plus or minus 0.6 percent at immersion (time 0). Mean (bar-X hrs 1-5) Q(sub co) was unchanged in WC (5.3 plus or minus 0.01 l/min) and in WH (4.5 plus or minus 0.1 l/min), but decreased (P less than 0.05) in DC to 3.6 plus or minus 0.1 l/min. Mean urine excretion rates were 1.0 plus or minus 0.2 ml/min for DC and 1.1 plus or minus 0.2 ml/min for WH; both were lower (P less than 0.05) than that for WC of 2.0 plus or minus 0.4 ml/min. Plasma (Na+) and (Osm) were unchanged in all experiments. Mean plasma vasopressin (PVP) (bar-X hrs 1-5) was 1.1 plus or minus 0.1 pg/ml in WC, and higher (P less than 0.05) in DC (2.1 plus or minus 0.2 pg/ml)and WH (2.1 plus or minus 0.1 pg/ml); it was unchanged during air and water test periods. Thus, hemorrhage attenuated the immersion-induced increase in Q(sub co), eliminated the WC diuresis, maintained plasma renin activity and PVP at DC levels and did not change immersion-induced aldosterone suppression; the osmotic diuresis during control immersion is apparently not due to either aldosterone suppression or vasopressin suppression.

  17. The renin-angiotensin system and the central nervous system. (United States)

    Ganong, W F


    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  18. Guipi decoction effects on arginine vasopressin protein and gene expression in the hippocampus, ventromedial hypothalamic nucleus, and prefrontal lobe in rats with spleen deficiency

    Institute of Scientific and Technical Information of China (English)

    Huinan Qian; Xueqin Hu; Libo Shen


    BACKGROUND: Arginine vasopressin has been shown to enhance learning in experimental animal models.OBJECTIVE: To determine whether Guipi decoction enhances memory and learning by increasing arginine vasopressin levels, and to verify the influence of Guipi decoction on arginine vasopressin protein and gene expression in the hippocampal CAI region, prefrontal lobe cortex, and ventral nucleus of hypothalamus in rats with spleen deficiency.DESIGN, TIME AND SETTING: The randomized, neuropharmacological, control study was performed in the College of Basic Medical Sciences, Beijing University of Chinese Medicine between March 2002 and March 2005.MATERIALS: Sixty, healthy, male, Wistar rats were used to establish spleen deficiency models according to the traditional Chinese medicine principle of bitter drugs for purgation, improper diet, and overstrain. Arginine vasopressin-I polyclonal anti-rabbit antibody immunohistocbemistry kit and arginine vasopressin in situ hybridization kit were provided by Department of Neuroanatomy in Shanghai Second Military Medical University of Chinese PLA.METHODS: Sixty rats were divided into five groups at random: normal control (n = 11), model (n = 13), Guipi decoction (n = 12), recipe control A (n = 12), and recipe control B groups (n = 12). Rats in the latter four groups received 7.5 g/kg of the drugs by intragastric administration each morning, which comprised Dahuang, Houpu, and Zhishi, prepared at a ratio of 2:1 : 1. The rats were lasted every other day, but were allowed free access to water at all times. The rats were forced to swim in 25℃ water until fatigued. Rats in the Guipi decoction and two recipe control groups were intragastrically administered 7.5 g/kg Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellets, respectively, each afternoon. Rats in the normal group were intragastrically administered the same amount of normal saline. All rats were treated for 6 weeks.MAIN OUTCOME MEASURES: At 6 weeks after drug

  19. Computer-Aided Mapping of Vasopressin Neurons in the Hypothalamus of the Male Golden Hamster: Evidence of Magnocellular Neurons that do not Project to the Neurohypophysis. (United States)

    Mahoney, P D; Koh, E T; Irvin, R W; Ferris, C F


    Abstract Vasopressin-sensitive neurons in the region of the anterior hypothalamus are necessary for the mediation of flank marking behavior in the Golden hamster. The precise nature of the vasopressinergic innervation to the anterior hypothalamus is unknown. In this study we seek to examine the potential sources of this innervation by mapping and counting the vasopressin-immunoreactive neurons that contribute to the hypothalamo-neurohypophysial system, and those that do not. Vasopressin-immunoreactive neurons in the hypothalamus were visualized by immunocytochemistry. Sections were mapped with a computer-aided microscope system, and labeled neurons counted. Two-dimensional maps were stacked into a three-dimensional wireframe model which could be manipulated for further examination. The average number of vasopressin neurons was 3,135, with over 60% of all perikarya localized to the lateral supraoptic nucleus. In a double-labeling study, neurons contributing to the hypothalamo-neurohypophysial system were retrogradely labeled by the injection of horseradish peroxidase into the neurohypophysis. The enzyme reaction product was visualized by treatment with tetramethylbenzidine followed by nickel-conjugated diaminobenzidine. Sections were subsequently stained for vasopressin by immunocytochemistry. Single- and double-stained neurons from serial sections were mapped and counted. Wireframe and contoured three-dimensional representations were generated. The average number of neurons projecting to the neurohypophysis was 5,619. However, an average of 981 neurons was immunoreactive to vasopressin but devoid of horseradish peroxidase. The greatest number of these non-projecting perikarya were found in and around the anterior hypothalamus, localized primarily in the lateral and medial aspect of the supraoptic nuclei, the ventral area of the paraventricular nucleus, and the nucleus circularis. By comparing the number of non-projecting neurons found by double-staining to the

  20. Oroxylin A, but Not Vasopressin, Ameliorates Cardiac Dysfunction of Endotoxemic Rats

    Directory of Open Access Journals (Sweden)

    Chin-Hung Liu


    Full Text Available The mortality in septic patients with myocardial dysfunction is higher than those without it. Beneficial effects of flavonoid oroxylin A (Oro-A on endotoxemic hearts were evaluated and compared with that of arginine vasopressin (AVP which is used to reverse hypotension in septic patients. Endotoxemia in rats was induced by one-injection of lipopolysaccharides (LPS, 10 mg/kg, i.p., and hearts were isolated 5-hrs or 16-hrs later. Isolated hearts with constant-pressure or constant-flow mode were examined by Langendorff technique. Rate and force of contractions of isolated atrial and ventricular strips were examined by tissue myography. Isolated endotoxemic hearts were characterized by decreased or increased coronary flow (CF in LPS-treated-for-5hr and LPS-treated-for-16-hr groups, respectively, with decreased inotropy in both groups. Oro-A-perfusion ameliorated while AVP-perfusion worsened the decreased CF and inotropy in both preparations. Oro-A and AVP, however, did not affect diminished force or rate of contraction of atrial and ventricular strips of endotoxemic hearts. Oro-A-induced CF increase was not affected following coronary endothelium-denudation with saponin. These results suggest that Oro-A ameliorates LPS-depressed cardiac functions by increasing CF, leading to positive inotropy. In contrast, AVP aggravates cardiac dysfunction by decreasing CF. Oro-A is a potentially useful candidate for treating endotoxemia complicated with myocardial dysfunction.

  1. Oxytocin and arginine vasopressin receptor evolution: implications for adaptive novelties in placental mammals (United States)

    Paré, Pamela; Paixão-Côrtes, Vanessa R.; Tovo-Rodrigues, Luciana; Vargas-Pinilla, Pedro; Viscardi, Lucas Henriques; Salzano, Francisco Mauro; Henkes, Luiz E.; Bortolini, Maria Catira


    Abstract Oxytocin receptor (OXTR) and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2) are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs. OXTR seems to be under evolutionary constraint in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher evolutionary rates, suggesting that they have been under relaxed or experienced positive selection. In addition, we describe here, for the first time, that the OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder content, while this condition varies among the paralogues. Finally, our results reveal the presence of short linear interaction motifs, indicating possible functional adaptations related to physiological and/or behavioral taxa-specific traits. PMID:27505307

  2. Chimpanzee sociability is associated with vasopressin (Avpr1a) but not oxytocin receptor gene (OXTR) variation. (United States)

    Staes, Nicky; Koski, Sonja E; Helsen, Philippe; Fransen, Erik; Eens, Marcel; Stevens, Jeroen M G


    The importance of genes in regulating phenotypic variation of personality traits in humans and animals is becoming increasingly apparent in recent studies. Here we focus on variation in the vasopressin receptor gene 1a (Avpr1a) and oxytocin receptor gene (OXTR) and their effects on social personality traits in chimpanzees. We combine newly available genetic data on Avpr1a and OXTR allelic variation of 62 captive chimpanzees with individual variation in personality, based on behavioral assessments. Our study provides support for the positive association of the Avpr1a promoter region, in particular the presence of DupB, and sociability in chimpanzees. This complements findings of previous studies on adolescent chimpanzees and studies that assessed personality using questionnaire data. In contrast, no significant associations were found for the single nucleotide polymorphism (SNP) ss1388116472 of the OXTR and any of the personality components. Most importantly, our study provides additional evidence for the regulatory function of the 5' promoter region of Avpr1a on social behavior and its evolutionary stable effect across species, including rodents, chimpanzees and humans. Although it is generally accepted that complex social behavior is regulated by a combination of genes, the environment and their interaction, our findings highlight the importance of candidate genes with large effects on behavioral variation.

  3. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats. (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S


    The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.

  4. Renal function, aldosterone, and vasopressin excretion following repeated long-distance running. (United States)

    Wade, C E; Dressendorfer, R H; O'Brien, J C; Claybaugh, J R


    Renal and endocrine responses were studied in 10 male runners during a 20-day 500-km race. Overnight urine and prerun blood samples were taken prior to running on days 1, 2, 5, 8, 14, 17, and 20. Day 13 followed 70 h of rest. Urine flow rate, osmotic clearance, tubular free water reabsorption, urinary vasopressin excretion rate, and body weight were not significantly changed. Creatinine clearance was constant except for an elevation on day 5. Plasma osmolality was elevated on days 2, 14, and 17. Plasma sodium was increased (P less than 0.05) on days 2 and 13 but reduced on day 20. The percentage of filtered sodium excreted was significantly reduced on all nights following running and elevated on recovery day 13. Urinary aldosterone excretion rate was significantly elevated 162, 117, and 97% on days 5, 8, and 20 and returned to control levels on day 13 after 70 h of rest. These data suggest that in response to repeated long-distance running normal fluid balance is regained within 12 h. However, it is necessary to conserve sodium for at least 24 h after exercise as evidenced by the decrease in the percent filtered sodium excreted and continued elevation of aldosterone excretion.

  5. A review of the nonpressor and nonantidiuretic actions of the hormone vasopressin

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    Gaurang P Mavani


    Full Text Available The pressor and antidiuretic actions of arginine vasopressin (AVP have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior and cognitive function. Important cellular responses including cell proliferation, inflammation and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic-pituitary-adrenal access are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance.

  6. A Review of the Nonpressor and Nonantidiuretic Actions of the Hormone Vasopressin (United States)

    Mavani, Gaurang P.; DeVita, Maria V.; Michelis, Michael F.


    The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior, and cognitive function. Important cellular responses including cell proliferation, inflammation, and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic–pituitary–adrenal axis are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance. PMID:25853137

  7. Vasopressin as a target for antidepressant development: an assessment of the available evidence.

    LENUS (Irish Health Repository)

    Scott, Lucinda V


    Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.


    Institute of Scientific and Technical Information of China (English)

    刘新峰; 金泳清; 陈光辉


    Mongolian gerbils were used as delayed neuronal damage (DND) animal models.At the end of 15 minute cerebral ischermia and at various reperfusion time ranging from 1 to 96 hours,the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassy.Furthermore,we also examined the effect of intracerebroventricular (ICV) injection of AVP,AVP antiserum on calcium,Na+,K+-ATP ase activity in the CA1 sector after ischemia and 96 hour reperfusion.The results showed that AVP Contents of CA1 sector of hippocampus during 6 to 96 hour recirculation,and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased.After ICV injection of AVP,the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased,and the Na+,K+-AT-tion of AVP antiserum,the water contenr and calcium in CA1 sector were significantly decreased as compared with that of control.These suggested that AVP was involved in the pathopysiologic process of DND in hippocampus following cerbral ischemia and reprfusion.Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca inos over-load of neuron and inhibit the Na+,K+-ATPase activity,thereby to exacerbate the DND in hippocampus.

  9. Conformational preferences of proline derivatives incorporated into vasopressin analogues: NMR and molecular modelling studies. (United States)

    Sikorska, Emilia; Sobolewski, Dariusz; Kwiatkowska, Anna


    In this study, arginine vasopressin analogues modified with proline derivatives - indoline-2-carboxylic acid (Ica), (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid (Nmp), (2S,4S)-4-aminopyroglutamic acid (APy) and (2R,4S)-4-aminopyroglutamic acid, (Apy) - were examined using NMR spectroscopy and molecular modelling methods. The results have shown that Ica is involved in the formation of the cis peptide bond. Moreover, it reduces to a great extent the conformational flexibility of the peptide. In turn, incorporation of (2S,4R)-Nmp stabilizes the backbone conformation, which is heavily influenced by the pyrrolidine ring. However, the aromatic part of the Nmp side chain exhibits a high degree of conformational freedom. With analogues IV and V, introduction of the 4-aminopyroglumatic acid reduces locally conformational space of the peptides, but it also results in weaker interactions with the dodecylphosphocholine/sodium dodecyl sulphate micelle. Admittedly, both analogues are adsorbed on the micelle's surface but they do not penetrate into its core. With analogue V, the interactions between the peptide and the micelle seem to be so weak that conformational equilibrium is established between different bound states.

  10. Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment. (United States)

    Bukovetzky, Elena; Fares, Fuad; Schwimmer, Hagit; Haim, Abraham


    Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

  11. Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia

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    Malardo Thiago


    Full Text Available Abstract Background Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert as therapeutic agent requires further investigation. Results Here, we showed that plasmid DNA (pcDNA3 at low doses inhibits the production of IL-6 and TNF-α by lipopolysaccharide (LPS-stimulated macrophage cell line J774. These findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5 mg/kg of LPS and 10 or 20 μg of plasmid DNA had a remarkable attenuation of mean arterial blood pressure (MAP drop at 2 hours after treatment when compared with rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was associated with decreased expression of IL-6 in liver and increased concentration of plasma vasopressin (AVP, a known vasoconstrictor that has been investigated in hemorrhagic shock management. No difference was observed in relation to nitric oxide (NO production. Conclusion Our results demonstrate for the first time that plasmid DNA vector at low doses presents anti-inflammatory property and constitutes a novel approach with therapeutic potential in inflammatory diseases.

  12. The Effects of Acute Arginine Vasopressin Administration on Social Cognition in Healthy Males

    Directory of Open Access Journals (Sweden)

    Amanda R. Kenyon


    Full Text Available The structurally similar neuropeptides and hormones oxytocin (OT and arginine vasopressin (AVP play significant and complex roles in modulating a range of social behaviours, including social recognition and bond formation. Although OT has well-known roles in facilitating prosocial behaviors and enhancing emotion recognition, AVP has received increasing interest for diverging effects on social cognition behaviour most notably in males. The current study aimed to determine whether AVP also modulates the ability to understand emotion. Using a randomised double blind procedure, 45 healthy young males received either an AVP or placebo nasal spray and completed the Reading the Mind in the Eyes Test (RMET. In contrast to previous findings, there were no significant differences observed in performance on the RMET between AVP and placebo groups, even after examining items separated by task difficulty, emotional valence, and gender. This study provides diverging evidence from previous findings and adds to the growing body of research exploring the influence of neuropeptide hormones in social behaviour. It demonstrates that in this sample of participants, AVP does not enhance the ability to understand higher order emotion from others. Implications and suggestions for future AVP administration studies are discussed.

  13. Experiment K-7-20: Pituitary Oxytocin and Vasopressin Content of Rats Flown on Cosmos 2044 (United States)

    Keil, L.; Evans, J.; Grindeland, R. (Editor); Krasnov, I.


    Pituitary levels of oxytocin (OT) and vasopressin (VP) were measured in rats exposed to 14 days of spaceflight (FLT) as well as in ground-based controls; one group synchronously maintained in flight-type cages with similar feeding schedules (SYN), one group in vivarium cages (VIV), and a group of tail suspended (SUS) animals. Flight rats had significantly less (p less than 0.05) pituitary OT and VP (4.48 +/- 0.31 and 7.48 +/- 0.53 mg hormone / mg protein, n = 5) than either the SYN (6.66 +/- 0..59 and 10.98 + 1.00, n = 5), VIV (6.14 +/- 0.40 and 10.98 +/- 0..81, n = 5) or SUS (5.73 +/- 0.24, n = 4) control groups, respectively. The reduced levels of pituitary OT and VP are similar to measurements made on rats from the previous 12.5 day Cosmos 1887 mission and appear to be a direct result of exposure to spaceflight.

  14. Pituitary oxytocin and vasopressin content of rats flown on Cosmos 2044 (United States)

    Keil, L.; Evans, J.; Grindeland, R.; Krasnov, I.


    Preliminary studies in rats (COSMOS 1887) suggested that levels of posterior pituitary hormones were reduced by exposure to spaceflight. To confirm these preliminary findings, pituitary tissue from rats flown for 14 days on Cosmos 2044 is obtained. Posterior pituitary content of oxytocin (OT) and vasopressin (VP) were measured in these tissues as well as those from ground-based controls. The synchronous control group had feeding and lighting schedules synchronized to those in the spacecraft and were maintained in flight-type cages. Another group was housed in vivarium cages; a third group was tail suspended (T), a method used to simulate microgravity. Flight rats showed an average reduction of 27 in pituitary OT and VP compared with the three control groups. When hormone content was expressed in terms of pituitary protein (microg hormone/mg protein), the average decrease in OT and VP for the flight animals ranged from 20 to 33 percent compared with the various control groups. Reduced levels of pituitary OT and VP were similar to preliminary measurements from the Cosmos 1887 mission and appear to result from exposure to spaceflight. These data suggest that changes in the rate of hormone secretion or synthesis may have occurred during exposure to microgravity.

  15. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy. (United States)

    Wu, Nan; Shang, Siyuan; Su, Yanjie


    The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non-clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality.

  16. Oxytocin and arginine vasopressin receptor evolution: implications for adaptive novelties in placental mammals

    Directory of Open Access Journals (Sweden)

    Pamela Paré

    Full Text Available Abstract Oxytocin receptor (OXTR and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2 are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs. OXTR seems to be under evolutionary constraint in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher evolutionary rates, suggesting that they have been under relaxed or experienced positive selection. In addition, we describe here, for the first time, that the OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder content, while this condition varies among the paralogues. Finally, our results reveal the presence of short linear interaction motifs, indicating possible functional adaptations related to physiological and/or behavioral taxa-specific traits.

  17. Simultaneous measurement of arginine vasopressin and oxytocin in plasma and neurohypophysis by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R. (Deutsche Hochschule fuer Koerperkultur, Leipzig (German Democratic Republic). Forschungsinstitut Koerperkultur und Sport)


    Arginine vasopressin (AVP) and oxytocin (OXT) were measured simultaneously in the same sample by specific and sensitive radioimmunoassays (RIAs). The antibodies used did not cross-react to a variety of analogs and related peptides. The extraction procedure using Vycor glass powder resulted in mean recoveries of 84.4% (AVP) and 64.6% (OXT). In both assays, the sensitivity was 1 to 2 pg/ml plasma. A preincubation procedure that depresses plasma levels of both AVP and OXT selectively, provided specific blank values for a given plasma sample. To confirm the validity of the RIAs, dehydration experiments were performed. In rats, the basal levels of plasma AVP and OXT (means: 2,63 pg/ml and 6.80 pg/ml, respectively) are increased significantly after 24 h, 48 h and 72 h of water deprivation. Relationships are presented between both neurohormones in the plasma and neurohypophyses of control and dehydrated animals. As shown in cows, a significant correlation exists between plasma AVP and plasma osmolality but not between plasma OXT and osmolality or plasma AVP and OXT. Basal levels as well as physiological changes in plasma and neurohypophyseal AVP and OXT can be measured by the RIAs described.

  18. Radioimmunoassay of arginine vasopressin in Rhesus Monkey plasma. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Hayward, J.N.; Pavasuthipaisit, K.; Perez-Lopez, F.R.; Sofroniew, M.V.


    Using a new antiserum and an enzymatic radioiodination of arginine vasopressin (AVP), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +- 0.6 (SD) and 298 +- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +- 0.2 and 282 +- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.

  19. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors. (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi


    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

  20. Vasopressin needs an audience: neuropeptide elicited stress responses are contingent upon perceived social evaluative threats. (United States)

    Shalev, Idan; Israel, Salomon; Uzefovsky, Florina; Gritsenko, Inga; Kaitz, Marsha; Ebstein, Richard P


    The nonapeptide arginine vasopressin (AVP) plays an important role in hypothalamus-pituitary-adrenal axis regulation and also functions as a social hormone in a wide variety of species, from voles to humans. In the current report we use a variety of stress inducing tasks, including the Trier Social Stress Test (TSST) and intranasal administration of AVP to show that intranasal administration of this neuropeptide leads to a significant increase in salivary cortisol and pulse rate, specifically in conditions where subjects perform tasks in the presence of a social evaluative threat (task performance could be negatively judged by others). In contrast, in conditions without a social evaluative threat (no task condition, modified TSST without audience and bike ergometry), subjects receiving AVP did not differ from subjects receiving placebo. Thus exogenous AVP's influence is contingent upon a circumscribed set of initial conditions that constitute a direct threat to the maintenance of our social selves. Stress evoked by social threat is an integral part of social life and is related to self-esteem and in extreme forms, to poor mental health (e.g., social phobia). Our findings suggest that AVP is a key component in the circuit that interlaces stress and social threat and findings offer inroads to our understanding of individual differences in sociability and in stress response elicited in threatening social situations.

  1. Sexually dimorphic role for vasopressin in the development of social play

    Directory of Open Access Journals (Sweden)

    Matthew J. Paul


    Full Text Available Despite the well-established role of vasopressin (AVP in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of play. Unexpectedly, play emerged more rapidly in weanling-aged females than in males, resulting in a sex difference opposite of that typically reported for older, juvenile rats. AVP mRNA and play were correlated in males only, with a negative correlation in the bed nucleus of the stria terminalis and a positive correlation in the paraventricular nucleus of the hypothalamus. These findings support the hypothesis that AVP acts differentially on multiple systems in a sex-specific manner to regulate social play and suggest a role for PVN and BNST AVP systems in the development of play. Differential neuropeptide regulation of male and female social development may underlie well-documented sex differences in incidence, progression, and symptom severity of behavioral disorders during development.

  2. Pituitary oxytocin and vasopressin content of rats flown on COSMOS 2044. (United States)

    Keil, L; Evans, J; Grindeland, R; Krasnov, I


    Preliminary studies in rats (COSMOS 1887) suggested that levels of posterior pituitary hormones were reduced by exposure to spaceflight. To confirm these preliminary findings, we obtained pituitary tissue from rats flown for 14 days on COSMOS 2044. Posterior pituitary content of oxytocin (OT) and vasopressin (VP) were measured in these tissues as well as those from ground-based controls. The synchronous control group had feeding and lighting schedules synchronized to those in the spacecraft and were maintained in flight-type cages. Another group was housed in vivarium cages; a third group was tail suspended (T), a method used to stimulate microgravity. Flight rats showed an average reduction of 27% (P less than 0.05) in pituitary OT and VP compared with the three control groups. When hormone content was expressed in terms of pituitary protein (micrograms hormone/mg protein), the average decrease in OT and VP for the flight animals ranged from 20 to 33% (P less than 0.05) compared with the various control groups. Reduced levels of pituitary OT and VP were similar to preliminary measurements from the COSMOS 1887 mission and appear to result from exposure to spaceflight. These data suggest that changes in the rate of hormone secretion or synthesis may have occurred during exposure to microgravity.

  3. Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

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    Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)


    Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

  4. Regulation of corticosterone production by vasopressin during water restriction and after drinking in rats. (United States)

    Wotus, Cheryl; Osborn, John W; Nieto, Pilar Ariza; Engeland, William C


    Plasma vasopressin (VP) and corticosterone have each been shown to be rapidly suppressed after drinking in different models of osmotic stimulation in rats; however, no causal relationship between these responses has been investigated. Studies were performed to determine if plasma VP and corticosterone are reduced in parallel after drinking and if manipulation of plasma VP affects plasma, ACTH corticotropins and corticosterone in a model of water restriction. A strong correlation between changes in plasma VP and corticosterone, but not between plasma ACTH and corticosterone, was observed after drinking induced by 6 days of water restriction. Similarly, ingestion of isotonic saline resulted in a biphasic VP response that was paralleled by adrenal and plasma corticosterone, but not by plasma ACTH. Administration of an immunoneutralizing antibody directed against VP resulted in a rapid decrease in plasma corticosterone, but not ACTH, in water-restricted rats, but not in rats receiving water ad libitum. These data suggest that during dehydration, elevated plasma VP can stimulate the production of corticosterone by the adrenal, independently of ACTH. Moreover, they support the hypothesis that the decline in corticosterone after restriction-induced drinking is due, in part, to a decline in plasma VP.

  5. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats. (United States)

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki


    A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.

  6. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat. (United States)

    Nasimi, Ali; Kafami, Marzieh


    The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release.

  7. Effects of a histamine H2-receptor antagonist, ranitidine on the vasopressin and oxytocin responses to novelty stress in the rat. (United States)

    Yagi, K


    Effects of an intraperitoneally (i.p.) administered histamine H2-receptor antagonist, ranitidine, on plasma levels of vasopressin and oxytocin were studied in male rats under unstressed or stressed conditions. In the rats injected i.p. with the vehicle (saline) solution, plasma vasopressin level was significantly lower and plasma oxytocin level was significantly higher after weak electric foot shocks (10 ms pulses of 0.8 mA, 50 Hz and 1 s duration, repeated at 30 s intervals for a period of 5 min) than those levels in the unshocked control rats. Ranitidine injected i.p. at a dose of 100 mg per kg body weight blocked the suppressive vasopressin but not the facilitatory oxytocin response to the shocks. Novel environmental stimuli were applied to rats in such a way that the animals were transferred to an experimental room, placed in a white-painted plastic pail and administered an intermittent 2 kHz and 70 dB pure tone of 2 s duration that was repeated at 10 s intervals for 2 min. In the rats injected i.p. with the vehicle solution, plasma vasopressin level was lower and oxytocin level was higher after the novel stimuli than in the unstimulated control rats. Ranitidine injected i.p. at a dose of 100 mg per kg body weight blocked the suppressive vasopressin but not the facilitatory oxytocin response to the novel stimuli. Ranitidine administered i.p. at doses of 10, 20, 50 and 100 mg per kg body weight was tested for the suppressive vasopressin response to the novel stimuli given for periods of 2 or 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effect of Rehydration Fluid Osmolality on Plasma Volume and Vasopressin in Resting Dehydrated Men (United States)

    Geelen, Ghislaine; Greenleaf, J. E.; Keil, L. C.; Wade, Charles E. (Technical Monitor)


    Elevated plasma vasopressin concentration [PVP], which may act as a dipsogen, decreases promptly following the ingestion of fluids in many mammals including humans. The purpose for this study was to determine whether fluids of varied electrolyte and carbohydrate composition and osmolality (Osm] would modify post-drinking decreases in [PVP] which could be attributed to interaction with plasma volume (PV)- or fluid-electrolyte interactive hormones. Five men (23-41 yr, 78.0 +/- SD 8.2 kg), water deprived for 24 h, drank six fluids (12 ml/kg, at 16.5C in 4.0-6.2 min): water (30 m0sm/kg), NaCl (70 mOsm/kg), NaCl + NaCitrate (270 mOsm/kg), NaCl + 9.7% glucose (650 mOsm/kg), and two commercial drinks containing various ionic and carbohydrate contents (380 and 390 mOsm/kg). Blood (20 ml/sample) was drawn at -5 min before and at +3, +9, +15, +30, and +70 min after drinking. Heart rate, blood pressures, and plasma renin activity, {Na+], [K+], [Osm], aldosterone, atrial natriuretic peptide, and epinephrine concentrations were unchanged after drinking. Post-drinking [PVP] decreased from 1.7 - 3.7 pg/ml within 3 min with all fluids independently of their composition, [Osm], or delta PV; with maximal depression to 0.1-0.7 pg/ml (pplasma (Osm] but 1.8-7.6% increases (pplasma norepinephrine concentrations [PNE] at 15 min correlated -0.70 (P<0.10) suggesting that about half the variability in [PVP I I depression was associated with [PNE]. Thus, part of the mechanism for post-drinking [PVP] depression may involve a drinking stimulated norepinephrine (neural) factor.

  9. Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity. (United States)

    Rubin, Leah H; Yao, Li; Keedy, Sarah K; Reilly, James L; Bishop, Jeffrey R; Carter, C Sue; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Clementz, Brett A; Hill, Scot K; Liao, Wei; Ji, Gong-Jun; Lui, Su; Sweeney, John A


    Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic influences on cognition and emotion. How these hormones regulate relevant functional brain systems is not well understood. OT and AVP serum concentrations were assayed in 60 healthy individuals (36 women). Brain functional networks assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were constructed with graph theory-based approaches that characterize brain networks as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed higher nodal degree (connectedness) and efficiency (information propagation capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed higher nodal betweenness (being part of paths between nodes) in right putamen and left inferior parietal gyrus (IPG). Higher hormone levels were associated with less intrinsic connectivity. In men, higher AVP was associated with lower nodal degree and efficiency in left IFG (pars orbitalis) and left STG and less efficiency in left IFG (pars triangularis). In women, higher AVP was associated with lower betweenness in left IPG, and higher OT was associated with lower nodal degree in left IFG (pars orbitalis). Hormones differentially correlate with brain networks that are important for emotion processing and cognition in men and women. AVP in men and OT in women may regulate orbital frontal cortex connectivity, which is important in emotion processing. Hormone associations with STG and pars triangularis in men and parietal cortex in women may account for well-established sex differences in verbal and visuospatial abilities, respectively. © 2016 Wiley Periodicals, Inc.

  10. Vasopressin use in critically ill cirrhosis patients with catecholamine-resistant septic shock: The CVICU cohort (United States)

    Myc, Lukasz A; Stine, Jonathan G; Chakrapani, Rinita; Kadl, Alexandra; Argo, Curtis K


    AIM To examine patient-centered outcomes with vasopressin (AVP) use in patients with cirrhosis with catecholamine-refractory septic shock. METHODS We conducted a single center, retrospective cohort study enrolling adult patients with cirrhosis treated for catecholamine-resistant septic shock in the intensive care unit (ICU) from March 2011 through December 2013. Other etiologies of shock were excluded. Multivariable regression models were constructed for seven and 28-d mortality comparing AVP as a second-line therapy to a group of all other vasoactive agents. RESULTS Forty-five consecutive patients with cirrhosis were treated for catecholamine-resistant septic shock; 21 received AVP while the remaining 24 received another agent [phenylephrine (10), dopamine (6), norepinephrine (4), dobutamine (2), milrinone (2)]. In general, no significant differences in baseline demographics, etiology of cirrhosis, laboratory values, vital signs or ICU mortality/severity of illness scores were observed with the exception of higher MELD scores in the AVP group (32.4, 95%CI: 28.6-36.2 vs 27.1, 95%CI: 23.6-30.6, P = 0.041). No statistically significant difference was observed in unadjusted 7-d (52.4% AVP vs 58.3% and P = 0.408) or 28-d mortality (81.0% AVP vs 87.5% non-AVP, P = 0.371). Corticosteroid administration was associated with lower 28-d mortality (HR = 0.37, 95%CI: 0.16-0.86, P = 0.021) independent of AVP use. CONCLUSION AVP is similar in terms of patient centered outcomes of seven and 28-d mortality, in comparison to all other vasopressors when used as a second line vasoactive agent in catecholamine resistant septic shock. Large-scale prospective study would help to refine current consensus standards and provide further support to our findings. PMID:28144392

  11. Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1. (United States)

    Kajdácsi, Erika; Jani, Péter K; Csuka, Dorottya; Varga, Lilian; Prohászka, Zoltán; Farkas, Henriette; Cervenak, László


    The elevation of bradykinin (BK) level during attacks of hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) is well known. We previously demonstrated that endothelin-1 (ET-1) level also increases during C1-INH-HAE attacks. Although BK and ET-1 are both potent vasoactive peptides, the vasoregulatory aspect of the pathomechanism of C1-INH-HAE has not yet been investigated. Hence we studied the levels of vasoactive peptides in controls and in C1-INH-HAE patients, as well as evaluated their changes during C1-INH-HAE attacks. The levels of arginine vasopressin (AVP), adrenomedullin (ADM) and ET-1 were measured in the plasma of 100 C1-INH-HAE patients in inter-attack periods and of 111 control subjects, using BRAHMS Kryptor technologies. In 18 of the 100 C1-INH-HAE patients, the levels of vasoactive peptides were compared in blood samples obtained during attacks, or in inter-attack periods. AVP, ADM and ET-1 levels were similar in inter-attack samples from C1-INH-HAE patients and in the samples of controls, although cardiovascular risk has an effect on the levels of vasoactive peptides in both groups. The levels of all three vasoactive peptides increased during C1-INH-HAE attacks. Moreover, the levels of ET-1 and ADM as well as their changes during attacks were significantly correlated. This study demonstrated that vascular regulation by vasoactive peptides is affected during C1-INH-HAE attacks. Our results suggest that the cooperation of several vasoactive peptides may be necessary to counterbalance the actions of excess BK, and to terminate the attacks. This may reveal a novel pathophysiological aspect of C1-INH-HAE.

  12. Oxytocin and vasopressin are dysregulated in Williams Syndrome, a genetic disorder affecting social behavior.

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    Li Dai

    Full Text Available The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS, a condition caused by deletion of ~28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT and arginine vasopressin (AVP regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music, and a negative physical stressor (cold. We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behavior.

  13. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits (United States)

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John


    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID:26858594

  14. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model. (United States)

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L


    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

  15. Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli pedigree. (United States)

    Teltsh, Omri; Kanyas-Sarner, Kyra; Rigbi, Amihai; Greenbaum, Lior; Lerer, Bernard; Kohn, Yoav


    We have previously studied the genetics of schizophrenia in a large inbred Arab-Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus harbours four strong candidate genes for schizophrenia: atractin (ATRN), pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this study we further explored the association of these genes with schizophrenia in the pedigree and searched for the disease-causing variants. A mutation screening of affected individuals from the pedigree was performed by using intensive sequencing in these four genes of interest. Then, we studied the prevalence of the identified variants in all family members (n=56) as well as in Arab-Israeli nuclear families (n=276) and a Jewish case-control sample (n=545). We also studied the possible functional role of these variants by examining their association with gene expression in the brain (n=104). We identified seven genetic variants in the OXT-AVP cluster in affected individuals from the pedigree. Three of these variants were significantly associated with schizophrenia in this pedigree. A 7-SNP haplotype was also significantly associated with disease. We found significant association of some of these variants in the two samples from the general population. Expression data analysis showed a possible functional role of two of these variants in regulation of gene expression. Involvement of OXT and AVP in the aetiology of schizophrenia has been suggested in the past. This study demonstrates, for the first time, a significant genetic association of these neuropeptides with schizophrenia and strongly supports this hypothesis.

  16. Vasopressin-stimulated Ca2+ spiking in vascular smooth muscle cells involves phospholipase D. (United States)

    Li, Y; Shiels, A J; Maszak, G; Byron, K L


    Physiological concentrations of [Arg(8)]vasopressin (AVP; 10-500 pM) stimulate oscillations of cytosolic free Ca2+ concentration (Ca2+ spikes) in A7r5 vascular smooth muscle cells. We previously reported that this effect of AVP was blocked by a putative phospholipase A2 (PLA2) inhibitor, ONO-RS-082 (5 microM). In the present study, the products of PLA2, arachidonic acid (AA), and lysophospholipids were found to be ineffective in stimulating Ca2+ spiking, and inhibitors of AA metabolism did not prevent AVP-stimulated Ca2+ spiking. Thin layer chromatography was used to monitor the release of AA and phosphatidic acid (PA), which are the products of PLA2 and phospholipase D (PLD), respectively. AVP (100 pM) stimulated both AA and PA formation, but only PA formation was inhibited by ONO-RS-082 (5 microM). Exogenous PLD (type VII; 2.5 U/ml) stimulated Ca2+ spiking equivalent to the effect of 100 pM AVP. AVP stimulated transphosphatidylation of 1-butanol (a PLD-catalyzed reaction) but not 2-butanol, and 1-butanol (but not 2-butanol) completely prevented AVP-stimulated Ca2+ spiking. Protein kinase C (PKC) inhibition, which completely prevents AVP-stimulated Ca2+ spiking, did not inhibit AVP-stimulated phosphatidylbutanol formation. These results suggest that AVP-stimulated Ca2+ spiking depends on activation of PLD rather than PLA2 and that PKC activation may be downstream of PLD in the signaling cascade.

  17. Radioimmunoassay of (8-arginine)-vasopressin. II. Application to determination of antidiuretic hormone in urine. (United States)

    Merkelbach, U; Czernichow, P; Gaillard, R C; Vallotton, M B


    A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72%. The blank value measured in extracted samples of urine was 0.29 pg/ml +/- 0.21 (SEM) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13% and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.

  18. Relationship between urinary concentrating ability, arginine vasopressin in plasma and blood pressure after renal transplantation. (United States)

    Pedersen, E B; Danielsen, H; Nielsen, A H; Knudsen, F; Jensen, T; Kornerup, H J; Madsen, M


    Arginine vasopressin (AVP) and serum osmolality (Sosm) were determined in plasma before and after a 24-h period of water deprivation in 19 patients with post-renal-transplant hypertension (group I), 14 patients with normal blood pressure after renal transplantation (group II), and 16 healthy control subjects (group III). Urine was collected in four periods of 6 h each for measurement of urine volume (V), urine osmolality (Uosm) and tubular capacity for reabsorption of water (Tc water). AVP and Sosm increased significantly in all groups. The AVP levels were the same in groups I and II, but higher in group I than III both before and after water deprivation. In group II, AVP was higher than in group III only after water deprivation; V was significantly reduced in all groups. In groups I and II, V, Tc water and Uosm were the same. In group III, V was significantly lower than in groups I and II in the last three 6-h periods, and in group III, Tc water was higher in the first 6-h period than in groups I and II. There was a significant positive correlation between AVP and Sosm in all groups. In conclusion, renal water excretion cannot be reduced as rapidly and to the same degree in renal transplant recipients as in control subjects because of a decreased renal capacity for reabsorption of water. The higher AVP level in the transplant recipients may be a compensatory phenomenon for the decreased responsiveness of the renal collecting ducts in the transplanted kidneys. The sensitivity of the osmoreceptors to changes in osmotic stimuli was normal.

  19. Rural Electric Network Alteration Spurs Cable Production

    Institute of Scientific and Technical Information of China (English)


    <正>Most aluminum cable enterprises in Yunnan and Zhejiang focus their production capacity on overhead cables needed in rural electric network alteration. During the 12th Five-Year Plan period, China launched the rural electric network alteration & upgrade project. As of the middle of 2011, the budget of the central government for the rural electric network alteration & upgrade project planned by the National Development and Reform Commission has reached up to RMB 64.96 billion.

  20. A differential response in the reproductive system and energy balance of spiny mice Acomys populations to vasopressin treatment. (United States)

    Wube, Tilaye; Fares, Fuad; Haim, Abraham


    Increased dietary salinity suppressed reproduction of the xeric adapted golden spiny mouse, Acomys russatus. Testicular and uterine mass were reduced, suppressed spermatogenesis and vaginal closure were observed. The anti-diuretic hormone, vasopressin (VP), was suggested to mediate such effects. However, increased dietary salinity did not affect reproductive status of a mesic adapted population of the common spiny mouse, A. cahirinus. In the present study, the effect of exogenous VP on the reproductive status and energy balance of both males and females of A. russatus and of a mesic population of A. cahirinus was tested. Vasopressin (Sigma, 50 microg/kg) was injected intraperitoneally in three-day intervals for four weeks. In VP-treated A. russatus, spermatogenesis was significantly suppressed while the change in testis mass did not show significant difference. Both control and VP-treated females lost body mass (W(b)) significantly and the latter also exhibited a higher energy expenditure compared to their male counterparts. VP did not affect reproductive status in both sexes of A. cahirinus. Also it did not have a significant effect on W(b), energy intake, and energy expenditure in this species. Our results support the idea that VP mediates the effects of increased diet salinity on reproduction in A. russatus. The results also reinforce previous knowledge that different physiological systems could be integrated by a single biochemical signal.

  1. Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Leemin (National Yang-Ming Medical College, Taipei (Taiwan)); Pan, Jenntser (Michigan State Univ., East Lansing (USA))


    The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 {mu}g/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 {mu}g/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 {mu}g/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective.

  2. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion. (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan


    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

  3. Conformational studies of vasopressin and mesotocin using NMR spectroscopy and molecular modelling methods. Part I: Studies in water. (United States)

    Sikorska, Emilia; Rodziewicz-Motowidło, Sylwia


    Arginine vasopressin (AVP) and mesotocin (MT) belong to the neurohypophyseal hormone family. The former plays a very important role in the control of urine concentration and the blood pressure in mammals, whereas the latter stimulates uterine concentration and initiates birth in amphibians, marsupials, wallabies, birds, and fishes. Analysis of their 3D structure could be helpful for understanding the evolutionary relationship between all vasopressin- and oxytocin-like hormones. In addition, it allows design of new analogs with appropriate biological activity for humans and animals. In this paper, we present the conformational studies of AVP and MT, under the aqueous conditions. In our investigations, we used 2D NMR spectroscopy and time-averaged molecular dynamics calculations in explicit water. Our studies have shown that both peptides, despite displaying a high sequence homology, differ from each other with regard to the three-dimensional structure. They are in conformational equilibrium as a result of the cis/trans isomerization across the Cys(6)-Pro(7) peptide bond. Both peptides form beta-turns in their cyclic part, wherein the C-terminal fragment of MT is bent, whereas that of AVP is extended.

  4. The bed nucleus of the stria terminalis in the Syrian hamster (Mesocricetus auratus): absence of vasopressin expression in standard and wild-derived hamsters and galanin regulation by seasonal changes in circulating sex steroids. (United States)

    Bolborea, M; Ansel, L; Weinert, D; Steinlechner, S; Pévet, P; Klosen, P


    The bed nucleus of the stria terminalis (BNST) is a nucleus of the forebrain highly sensitive to sex steroids and containing vasopressin neurons implicated in several social- and reproduction-related behaviours such as scent-marking, aggression, pair bonding and parental behaviour. Sexually dimorphic vasopressin expression in BNST neurons has been reported in almost all rodents, with the notable exception of the Syrian hamster. In this species, vasopressin expression is completely absent in the BNST. Because almost all Syrian hamsters used in research are derived from a very small breeding stock captured in 1930, we compared commercially available Syrian hamsters with a recently captured, wild-derived breeding stock. We checked for vasopressin expression using in situ hybridization and immunohistochemistry. Vasopressin expression in BNST neurons was completely absent in both breeding stocks, confirming the absence of BNST vasopressin expression in Mesocricetus auratus and ruling out a breeding artefact. Because vasopressin expression in BNST neurons appears to be strictly dependent on circulating sex steroids, the absence of vasopressin expression in Syrian hamster BNST neurons might be due to an insensitivity of these neurons to sex steroids. BNST vasopressin neurons also express galanin. Although galanin expression in the BNST is not sexually dimorphic in the Syrian hamster, it appears to be regulated by sex steroids. In the Djungarian hamster, photoperiodically driven seasonal variations of circulating sex steroids result in a seasonal rhythm of galanin expression in BNST neurons. We analysed the sex steroid dependence of galanin expression in the Syrian hamster. Castration and short photoperiod-induced sexual quiescence both resulted in downregulation of galanin mRNA in cell bodies (BNST) and immunoreactivity in the fibres (lateral septum). Testosterone supplementation of short photoperiod-adapted animals was able to restore galanin expression. Thus Syrian

  5. Transcutaneous Electrical Acupoint Stimulation in Children with Autism and Its Impact on Plasma Levels of Arginine-Vasopressin and Oxytocin: A Prospective Single-Blinded Controlled Study (United States)

    Zhang, Rong; Jia, Mei-Xiang; Zhang, Ji-Sui; Xu, Xin-Jie; Shou, Xiao-Jing; Zhang, Xiu-Ting; Li, Li; Li, Ning; Han, Song-Ping; Han, Ji-Sheng


    Acupuncture increases brain levels of arginine-vasopressin (AVP) and oxytocin (OXT), which are known to be involved in the modulation of mammalian social behavior. Transcutaneous electrical acupoint stimulation (TEAS) is often used clinically to produce a similar stimulation to that of acupuncture on the acupoints. In the present study, TEAS was…

  6. Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin-neurophysin II gene. (United States)

    Luo, Yongfeng; Wang, Binbin; Qiu, Yu; Zhang, Chuan; Jin, Chengluo; Zhao, Yakun; Zhu, Qingguo; Ma, Xu


    The objective of this study is to identify the genetic defects in a Chinese family with autosomal dominant familial neurohypophyseal diabetes insipidus. Complete physical examination, fluid deprivation, and DDAVP tests were performed in three affected and three healthy members of the family. Genomic DNA was extracted from leukocytes of venous blood of these individuals for polymerase chain reaction amplification and direct sequencing of all three coding exons of arginine vasopressin-neurophysin II (AVP-NPII) gene. Seven members of this family were suspected to have symptomatic vasopressin-deficient diabetes insipidus. The water deprivation test in all the patients confirmed the diagnosis of vasopressin-deficient diabetes insipidus, with the pedigree demonstrating an autosomal dominant inheritance. Direct sequence analysis revealed a novel mutation (c.193T>A) and a synonymous mutation (c.192C>A) in the AVP-NPII gene. The missense mutation resulted in the substitution of cysteine by serine at a highly conserved codon 65 of exon 2 of the AVP-NPII gene in all affected individuals, but not in unaffected members. We concluded that a novel missense mutation in the AVP-NPII gene caused neurohypophyseal diabetes insipidus in this family, due to impaired neurophysin function as a carrier protein for AVP. The Cys65 is essential for NPII in the formation of a salt bridge with AVP. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the normal expression of vasopressin.

  7. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette;


    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

  8. Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation

    DEFF Research Database (Denmark)

    Siggaard, C; Rittig, S; Corydon, T J


    The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations ...

  9. ASD and genetic associations with receptors for oxytocin and vasopressin – AVPR1A, AVPR1B, and OXTR

    Directory of Open Access Journals (Sweden)

    Sunday M Francis


    Full Text Available Background: There are limited treatments available for autism spectrum disorder (ASD. Studies have reported significant associations between the receptor genes of oxytocin (OT and vasopressin (AVP and ASD diagnosis, as well as, ASD-related phenotypes. Researchers have also found the manipulation of these systems affect social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B, oxytocin (OXTR and ASD diagnosis along with related subphenotypes.Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e. rs53576-rs2254298-rs2268493 were also analyzed due to previously published associations.Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p=0.005, rs35369693, p=0.025 and diagnosis. As in other studies, OXTR rs2268493 (p=0.050 was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p=0.013 and insistence on sameness (p=0.039. Further analyses demonstrated that the haplotype, rs2254298-rs2268493 was found to be significantly associated with diagnosis (A-T; p=0.026. FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3. Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction

  10. Deployable centralizers

    Energy Technology Data Exchange (ETDEWEB)

    Grubelich, Mark C.; Su, Jiann-Cherng; Knudsen, Steven D.


    A centralizer assembly is disclosed that allows for the assembly to be deployed in-situ. The centralizer assembly includes flexible members that can be extended into the well bore in situ by the initiation of a gas generating device. The centralizer assembly can support a large load carrying capability compared to a traditional bow spring with little or no installation drag. Additionally, larger displacements can be produced to centralize an extremely deviated casing.

  11. Transient Intraoperative Central Diabetes Insipidus in Moyamoya Patients Undergoing Revascularization Surgery: A Mere Coincidence? (United States)

    Hong, Joe C; Ramos, Emilio; Copeland, Curtis C; Ziv, Keren


    We present 2 patients with Moyamoya disease undergoing revascularization surgery who developed transient intraoperative central diabetes insipidus with spontaneous resolution in the immediate postoperative period. We speculate that patients with Moyamoya disease may be predisposed to a transient acute-on-chronic insult to the arginine vasopressin-producing portion of their hypothalamus mediated by anesthetic agents. We describe our management, discuss pertinent literature, and offer possible mechanisms of this transient insult. We hope to improve patient safety by raising awareness of this potentially catastrophic complication.

  12. Early changes of endothelin, nitric oxide and arginine-vasopressin in patients with acute cerebral injury

    Institute of Scientific and Technical Information of China (English)

    杨云梅; 黄卫东; 吕雪英


    Objective: To investigate the early changes and clinical significance of plasma endothelin (ET), nitric oxide (NO) and arginine-vasopressin (AVP) in patients with acute moderate or severe cerebral injury. Methods: The early (at 24 hours after injury) plasma concentrations of ET, NO and AVP were measured with radioimmunoassay and Green technique in 48 cases of acute moderate (GCS≤8 in 27cases ) or severe (GCS>8 in 21 cases) cerebral injury (Group A), in 42 cases of non-cerebral injury (Group B) and in 38 normal individuals (Group C), respectively. Results: The early plasma concentrations of ET (109.73 ng/L±12.61 ng/L), NO (92.82 μmol/L±18.21 μmol/L) and AVP (49.78 ng/L±14.29 ng/L) in Group A were higher than those in Group B (67.90 ng/L±11.33 ng/L, 52.66 μmol/L±12.82 μmol/L and 29.93 ng/L±12.11 ng/L, respectively, P<0.01) and Group C (50.65 ng/L±17.12 ng/L, 36.12 μmol/L±12.16 μmol/L and 5.18 ng/L±4.18 ng/L, respectively, P<0.001). The amounts of ET, NO and AVP in patients with severe cerebral injury were 116.18 ng/L±18.12 ng/L, 108.19 μmol/L±13.28 μmol/L and 58.13 ng/L±16.78 ng/L, respectively, which were significantly higher than that of the patients with moderate cerebral injury (92.33 ng/L±16.32 ng/L, 76.38 μmol/L±12.71 μmol/L and 36.18 ng/L±12.13 ng/L respectively, P<0.01). The early levels of ET, NO and AVP in Group A were negatively related to the GCS scales. The amounts of ET, NO and AVP were 126.23 ng/L±15.23 ng/L, 118.18 μmol/L±10.12 μmol/L and 63.49 ng/L±14.36 ng/L respectively in patients with subdural hematoma, which were significantly higher than those in patients with epidural hematoma (81.13 ng/L±12.37 ng/L, 68.02 μmol/L±13.18 μmol/L and 45.63 ng/L±12.41 ng/L respectively, P<0.01). The plasma concentrations of ET, NO and AVP in stable duration (at 336 hours after injury) in Group A and Group B were similar to those in Group C.Conclusions: ET, NO and AVP were related to the pathophysiological process that occurs in

  13. Serum specific vasopressin-degrading activity is related to blood total cholesterol levels in men but not in women. (United States)

    Ramírez-Expósito, María Jesús; Arrazola, Marcelina; Carrera-González, María Pilar; Arias de Saavedra, José Manuel; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, José Manuel


    The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated with hypertension, although the underlying mechanism is not known. Here we analyze the relationship between blood total cholesterol levels and serum vasopressin- degrading cystyl-aminopeptidase activity (AVP-DA) in healthy humans, and the differences between men and women. Linear correlation coefficients were calculated to test relationships between AVP-DA and blood total cholesterol levels. Sex differences were observed for AVP-DA, being this activity higher in men than in women. According to the linear model of the regression analysis, AVP-DA showed a significant negative correlation with blood total cholesterol levels in men, whereas no correlation was observed in women. Several studies in humans demonstrate the existence of greater plasma AVP concentrations in normal men compared to normal women, which could explain the gender-differences observed in the present work in relation with AVP-DA. However, AVP-DA is related to blood cholesterol levels only in men, although in our hands, women showed higher blood cholesterol levels than men. This could indicate that the risk of high cholesterol-related hypertension is more probable in men than in women. Although AVP-DA misregulation could be involved in the pathogenesis of hypertension, its relation with cholesterol levels appears only in men, but not in women.

  14. /sup 125/I)-(d(CH2)5, Sar7)AVP: a selective radioligand for V1 vasopressin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, J.M.; Abrahams, J.M.; Phillips, P.A.; Mendelsohn, F.A.; Grzonka, Z.; Johnston, C.I.


    Arginine8-vasopressin (AVP) acts on vascular and hepatic V1 receptors to influence blood pressure and glycogenolysis respectively. We have radioiodinated the AVP V1 receptor antagonist, (1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic-acid), 7-sarcosine, 8-arginine) vasopressin ((d(CH2)5, Sar7)AVP) and determined its receptor-binding properties in rat liver and kidney plasma membranes. The binding was of high affinity to single classes of receptors (liver: Kd = 3.0 nM and Bmax = 530 +/- 10 fmol/mg protein, kidney: Kd = 0.5 +/- 0.9 nM and Bmax = 11 +/- 8 fmol/mg protein). Competition of (125I)-(d(CH2)5, Sar7)AVP binding by unlabelled AVP analogues gave the following order of potency in both tissues, consistent with that expected for binding to a V1 receptor: (d(CH2)5, Tyr(Me)2)AVP greater than AVP greater than (d(CH2)5, D-Ile2, Ile4) AVP greater than DDAVP. No degradation of (125I)-(d(CH2)5, Sar7)AVP during incubation or storage was detected by HPLC analysis. We have used (125I)-(d(CH2)5, Sar7)AVP and in vitro autoradiography to demonstrate its use in localizing brain AVP receptors. These studies suggest that (125I)-(d(CH2)5, Sar7)AVP is a suitable selective radioligand for labelling V1 receptors and will provide a valuable tool for the study of the localization and regulation of AVP V1 receptors in tissues and in receptor isolation.

  15. Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei. (United States)

    Zhang, L; Hernández, V S


    The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. Immuno-positive fibres were present in all areas (CA1-3, dentate gyrus) of the whole septo-temporal extent of the hippocampus; they had the highest density in the CA2 region, strongly increasing in density towards the ventral hippocampus. Two types of fibres were identified, both establishing synaptic junctions. Type A had large varicosities packed with immuno-positive large-granulated peptidergic vesicles and few small clear vesicles forming type I synaptic junctions with pyramidal neuron dendrites, dendritic spines and with axonal spines. Type B had smaller varicosities containing mostly small clear vesicles and only a few large-granulated vesicles and established type II synaptic junctions mainly with interneuron dendrites. The AVP-positive axons in stratum oriens appeared to follow and contact metabotropic glutamate receptor 1α (mGluR1α)-immuno-positive interneuron dendrites. Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.

  16. Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach. (United States)

    Mutig, Kerim; Borowski, Tordis; Boldt, Christin; Borschewski, Aljona; Paliege, Alexander; Popova, Elena; Bader, Michael; Bachmann, Sebastian


    The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na(+)-K(+)-2Cl(-)-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear. We hypothesized that V2R-mediated effects in TAL essentially determine its reabsorptive function. To test this, we reevaluated V2R expression. Basolateral membranes of medullary and cortical TAL were clearly stained, whereas cells of the macula densa were unreactive. A dominant-negative, NDI-causing truncated V2R mutant (Ni3-Glu242stop) was then introduced into the rat genome under control of the Tamm-Horsfall protein promoter to cause a tissue-specific AVP-signaling defect exclusively in TAL. Resulting Ni3-V2R transgenic rats revealed decreased basolateral but increased intracellular V2R signal in TAL epithelia, suggesting impaired trafficking of the receptor. Rats displayed significant baseline polyuria, failure to concentrate the urine in response to water deprivation, and hypercalciuria. NKCC2 abundance, phosphorylation, and surface expression were markedly decreased. In summary, these data indicate that suppression of AVP-V2R signaling in TAL causes major impairment in renal fluid and electrolyte handling. Our results may have clinical implications.

  17. Hormonal status modifies renin-angiotensin system-regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal axis of female mice. (United States)

    García, María Jesús; Martínez-Martos, José Manuel; Mayas, María Dolores; Carrera, María Pilar; De la Chica, Susana; Cortés, Pedro; Ramírez-Expósito, María Jesús


    The hypothalamus-pituitary-adrenal axis (HPA) participates in the maintenance of cardiovascular functions and in the control of blood pressure. By other hand, it is known that blood pressure regulation and HPA activity are affected by sex hormones. The aim of the present work is to analyze the influence of estradiol and progesterone on renin-angiotensin system (RAS)-regulating aminopeptidase A, aminopeptidase B and aminopeptidase N activities and vasopressin-degrading activity in the HPA axis of ovariectomized mice and ovariectomized mice treated subscutaneously with different doses of estradiol and progesterone. Our data suggest that in female mice, estradiol and progesterone influence RAS-regulating and vasopressin-degrading activities at different levels of the HPA axis.

  18. The pituitary hormones arginine vasopressin-neurophysin II and oxytocin-neurophysin I show close linkage with interleukin-1 on mouse chromosome 2

    Energy Technology Data Exchange (ETDEWEB)

    Marini, J.C.; Nelson, K.K.; Siracusa, L.D. (Jefferson Cancer Institute, Philadelphia, PA (United States)); Battey, J. (National Institutes of Health/National Cancer Institute, Bethesda, MD (United States))


    Arginine vasopressin (AVP) and oxytocin (OXT) are posterior pituitary hormones. AVP is involved in fluid homeostasis, while OXT is involved in lactation and parturition. AVP is derived from a larger precursor, prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NP II; AVP), and is physically linked to prepro-oxytocin-neurophysin I (prepro-OXT-NPI1; OXT). The genes for AVP and OXT are separated by only 12 kb of DNA in humans, whereas in the mouse 3.5 kb of intergenic sequence lies between Avp and Oxt. Interspecific backcross analysis has now been used to map the Avp/Oxt complex to chromosome 2 in the mouse. This map position confirms and extends the known region of linkage conservation between mouse chromosome 2 and human chromosome 20. 16 refs., 2 figs., 1 tab.

  19. Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine. (United States)

    Aydin, Leyla; Mogulkoc, R; Baltaci, A K


    This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P PTU group and the highest in the L-thyroxine treated group (P PTU group (P PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.

  20. Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.


    Williams, B.; Tsai, P.; Schrier, R W


    Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface recepto...

  1. Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention

    DEFF Research Database (Denmark)

    Krag, Aleksander; Pedersen, Erling B; Møller, Søren;


    Terlipressin is a vasopressin analogue used for its potent V1a effects in cirrhotic patients. Recent data suggest that terlipressin has affinity to renal V2 receptors and modulates Aquaporin 2 (AQP2) expression and free water clearance. Stimulation of renal V2 receptors may also affect sodium tra...... transport via the Epithelial Sodium Channel (ENaC). Furthermore, endothelial V2 receptors may indirectly affect proximal sodium handling by increasing plasma cAMP....

  2. Hydrothermal alteration and melting of the crust during the Columbia River Basalt-Snake River Plain transition and the origin of low-δ18O rhyolites of the central Snake River Plain (United States)

    Colón, Dylan P.; Bindeman, Ilya N.; Ellis, Ben S.; Schmitt, Axel K.; Fisher, Christopher M.


    We present compelling isotopic evidence from ~15 Ma rhyolites that erupted coeval with the Columbia River Basalts in southwest Idaho's J-P Desert and the Jarbidge Mountains of northern Nevada at that suggests that the Yellowstone mantle plume caused hydrothermal alteration and remelting of diverse compositions of shallow crust in the area where they erupted. These rhyolites also constitute the earliest known Miocene volcanism in the vicinity of the Bruneau-Jarbidge and Twin Falls (BJTF) volcanic complexes, a major center of voluminous (103-104 km3) low-δ18O rhyolitic volcanism that was previously defined as being active from 13 to 6 Ma. The Jarbidge Rhyolite has above-mantle δ18O (δ18O of +7.9‰ SMOW) and extremely unradiogenic εHf (- 34.7) and εNd (- 24.0). By contrast, the J-P Desert units are lower in δ18O (+4.5 to 5.8‰), and have more moderately unradiogenic whole-rock εHf (- 20.3 to - 8.9) and εNd (- 13.4 to - 7.7). The J-P Desert rhyolites are geochemically and petrologically similar to the younger rhyolites of the BJTF center (the one exception being their high δ18O values), suggesting a common origin for J-P Desert and BJTF rhyolites. The presence of low-δ18O values and unradiogenic Nd and Hf isotopic compositions, both of which differ greatly from the composition of a mantle differentiate, indicate that some of these melts may be 50% or more melted crust by volume. Individual J-P Desert units have isotopically diverse zircons, with one lava containing zircons ranging from - 0.6‰ to + 6.5‰ in δ18O and from - 29.5 to - 2.8 in εHf. Despite this diversity, zircons all have Miocene U/Pb ages. The range of zircon compositions fingerprints the diversity of their source melts, which in turn allow us to determine the compositions of two crustal end-members which melted to form these rhyolites. These end-members are: 1) Archean basement with normal to high-δ18O and unradiogenic εHf and 2) hydrothermally altered, shallow, young crust with low

  3. Synchrony and Specificity in the Maternal and the Paternal Brain: Relations to Oxytocin and Vasopressin (United States)

    Atzil, Shir; Hendler, Talma; Zagoory-Sharon, Orna; Winetraub, Yonatan; Feldman, Ruth


    Objective: Research on the neurobiology of parenting has defined "biobehavioral synchrony," the coordination of biological and behavioral responses between parent and child, as a central process underpinning mammalian bond formation. Bi-parental rearing, typically observed in monogamous species, is similarly thought to draw on mechanisms of…

  4. Central hypersensitivity in chronic musculoskeletal pain. (United States)

    Curatolo, Michele; Arendt-Nielsen, Lars


    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity.

  5. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars


    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold...... standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...... level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity....

  6. [Altered states of consciousness]. (United States)

    Gora, E P


    The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over. It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed.

  7. Interactions of galanin with endomorphin-2, vasopressin and oxytocin in nociceptive modulation of the trigemino-hypoglossal reflex in rats. (United States)

    Zubrzycka, M; Janecka, A


    Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and micro-selective beta-funaltrexamine (beta-FNA). In contrast, a delta-opioid receptor antagonist, naltrindole (NTI) or the kappa-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL.

  8. Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4. (United States)

    Wang, Fei; Lu, Xiaohan; Peng, Kexin; Fang, Hui; Zhou, Li; Su, Jiahui; Nau, Adam; Yang, Kevin T; Ichihara, Atsuhiro; Lu, Aihua; Zhou, Shu-Feng; Yang, Tianxin


    Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4 Notably, EP4 also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4 and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4 antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4 receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.

  9. Diet salinity and vasopressin as reproduction modulators in the desert-dwelling golden spiny mouse (Acomys russatus). (United States)

    Shanas, Uri; Haim, Abraham


    The time for reproduction in mammals largely depends on the availability of water and food in their habitat. Therefore, in regions where rains are limited to definite seasons of the year, mammals presumably will restrict their breeding correspondingly. But while mammals living in predictable ecosystems would benefit by timing their season to an ultimate predictable cue, such as photoperiod, in unpredictable ecosystems (e.g., deserts) they will need to use a more proximate signal. We suggest a mechanism by which water shortage (low water content in plants) could act as a proximate cue for ending the reproductive season. The golden spiny mouse (Acomys russatus), a diurnal rodent living in extreme deserts, may face an increased dietary salt content as the summer progresses and the vegetation becomes dry. Under laboratory conditions, increased diet salinity lead to reproductive hiatus in females, notable in imperforated vagina, and a significant decrease in the ovaries, uteri, and body masses. In females treated with vasopressin (VP), a hormone expressed during water stress, the uteri and body masses have decreased significantly, and the ovaries exhibited an increased number of atretic follicles. VP has also led to a significant decrease in relative medullary thickness (RMT) of the kidney. It is thus suggested that VP could act as a modulator linking the reproductive system with water economy in desert rodents, possibly through its act on the energetic pathways.

  10. Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

    Directory of Open Access Journals (Sweden)

    Renato De Vecchis


    Full Text Available In the congestive heart failure (CHF setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.

  11. Oxytocin, but not vasopressin, impairs social cognitive ability among individuals with higher levels of social anxiety: a randomized controlled trial. (United States)

    Tabak, Benjamin A; Meyer, Meghan L; Dutcher, Janine M; Castle, Elizabeth; Irwin, Michael R; Lieberman, Matthew D; Eisenberger, Naomi I


    Individuals with social anxiety are characterized by a high degree of social sensitivity, which can coincide with impairments in social cognitive functioning (e.g. theory of mind). Oxytocin (OT) and vasopressin (AVP) have been shown to improve social cognition, and OT has been theorized as a potential therapeutic agent for individuals with social anxiety disorder. However, no study has investigated whether these neuropeptides improve social cognitive ability among socially anxious individuals. In a randomized, double-blind, placebo controlled, between-subjects design we investigated whether social anxiety moderated the effects of OT or AVP (vs placebo) on social working memory (i.e. working memory that involves manipulating social information) and non-social working memory. OT vs placebo impaired social working memory accuracy in participants with higher levels of social anxiety. No differences were found for non-social working memory or for AVP vs placebo. Results suggest that OT administration in individuals with higher levels of social anxiety may impair social cognitive functioning. Randomized-controlled trial registration: NCT01680718.

  12. Nutritional state-dependent ghrelin activation of vasopressin neurons via retrograde trans-neuronal-glial stimulation of excitatory GABA circuits. (United States)

    Haam, Juhee; Halmos, Katalin C; Di, Shi; Tasker, Jeffrey G


    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal-glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal-glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal-glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis.

  13. Distribution of vasopressin, oxytocin and vasoactive intestinal polypeptide in the hypothalamus and extrahypothalamic regions of tree shrews. (United States)

    Ni, R-J; Shu, Y-M; Wang, J; Yin, J-C; Xu, L; Zhou, J-N


    Vasopressin (VP), oxytocin (OXT) and vasoactive intestinal polypeptide (VIP) in the brain modulate physiological and behavioral processes in many vertebrates. Day-active tree shrews, the closest relatives of primates, live singly or in pairs in territories that they defend vigorously against intruding conspecifics. However, anatomy concerning peptidergic neuron distribution in the tree shrew brain is less clear. Here, we examined the distribution of VP, OXT and VIP immunoreactivity in the hypothalamus and extrahypothalamic regions of tree shrews (Tupaia belangeri chinensis) using the immunohistochemical techniques. Most of VP and OXT immunoreactive (-ir) neurons were found in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. In addition, VP-ir or OXT-ir neurons were scattered in the preoptic area, anterior hypothalamic areas, dorsomedial hypothalamic nucleus, stria terminalis, bed nucleus of the stria terminalis and medial amygdala. Interestingly, a high density of VP-ir fibers within the ventral lateral septum was observed in males but not in females. Both VP-ir and VIP-ir neurons were found in different subdivisions of the suprachiasmatic nucleus (SCN) with partial overlap. VIP-ir cells and fibers were also scattered in the cerebral cortex, anterior olfactory nucleus, amygdala and dentate gyrus of the hippocampus. These findings provide a comprehensive description of VIP and a detailed mapping of VP and OXT in the hypothalamus and extrahypothalamic regions of tree shrews, which is an anatomical basis for the participation of these neuropeptides in the regulation of circadian behavior and social behavior.

  14. Small doses of arginine vasopressin in combination with norepinephrine "buy" time for definitive treatment for uncontrolled hemorrhagic shock in rats. (United States)

    Liu, Liangming; Tian, Kunlun; Xue, Mingying; Zhu, Yu; Lan, Dan; Peng, Xiaoyong; Wu, Yue; Li, Tao


    Implementation of fluid resuscitation and blood transfusion are greatly limited in prehospital or evacuation settings after severe trauma or war wounds. With uncontrolled hemorrhagic shock rats, we investigated if arginine vasopressin (AVP) in combination with norepinephrine (NE) is independent (or slightly dependent) of fluid resuscitation and can "buy" time for the subsequently definitive treatment of traumatic hemorrhagic shock in the present study. The results showed that AVP (0.4 U/kg) alone or with NE (3 μg/kg) with one-eighth and one-fourth volumes of total blood volume of lactated Ringer's infusion significantly increased and maintained the mean arterial pressure. Among all groups, 0.4 U/kg of AVP + NE (3 μg/kg) with one-eighth volume of lactated Ringer's infusion had the best effect: it significantly increased and maintained hemodynamics and prolonged the survival time. This early treatment strategy significantly improved the effects of subsequently definitive treatments (after bleeding controlled): it increased the subsequent survival, improved the hemodynamic parameters, improved the cardiac function, and increased the tissue blood flow and oxygen delivery. These results suggested that early application of small doses of AVP (0.4 U/kg) + NE before bleeding control can "buy" time for the definitive treatment of uncontrolled hemorrhagic shock, which may be an effective measure for the early treatment of traumatic hemorrhagic shock.

  15. Metastatic Prostate Adenocarcinoma Presenting Central Diabetes Insipidus

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    Hakkı Yılmaz


    Full Text Available The pituitary gland and infundibulum can be involved in a variety of medical conditions, including infiltrative diseases, fungal infections, tuberculosis, and primary and metastatic tumors. Metastases to the pituitary gland are absolutely rare, and they are generally secondary to pulmonary carcinoma in men and breast carcinoma in women. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The posterior lobe involvement may explain why patients with pituitary metastases frequently present with diabetes insipidus. We are presenting a case report of a 78-year-old male patient who had metastatic prostate with sudden onset of polyuria and persistent thirst. He had no electrolyte imbalance except mild hypernatremia. The MRI scan of the brain yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI of pituitary. Water deprivation test was compatible with DI. A clinical response to nasal vasopressin was achieved and laboratory results revealed central diabetes insipidus. As a result, the intrasellar and suprasellar masses decreased in size, and urinary output accordingly decreased.

  16. Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients. (United States)

    Pedersen, E B; Danielsen, H; Knudsen, F; Nielsen, A H; Jensen, T; Kornerup, H J; Madsen, M


    Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

  17. Central line infections - hospitals (United States)

    ... infection; Central venous catheter - infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired ...

  18. The role of the histaminergic system in the central cardiovascular regulation in haemorrhagic hypotension. (United States)

    Jochem, Jerzy; Kasperska-Zajac, Alicja


    The histaminergic system consists of neurons located in tuberomammillary nucleus of the posterior hypothalamus. It affects many functions of the central nervous system, including regulation of the brainstem cardiovascular center. In this paper, we present current review of the literature concerning the role of the histaminergic system in the cardiovascular regulation in haemorrhagic hypotension. Experimental studies demonstrate that in both, normotension and critical hemorrhagic hypotension, histamine, acting as a central neurotransmitter, evokes the pressor effect. Interestingly, increases in mean arterial pressure are significantly higher in hypovolaemic than in normovolaemic animals. Many lines of evidence support the hypothesis that in haemorrhagic shock, the histaminergic system is able to activate neural and humoral compensatory mechanisms involving the sympathetic nervous and renin-angiotensin systems, arginine vasopressin and proopiomelanocortin-derived peptides. We suggest that the histaminergic system could be a new target for treatment of hemorrhagic hypotension.

  19. Vasopressin V1A receptor mediates cell proliferation through GRK2-EGFR-ERK1/2 pathway in A7r5 cells. (United States)

    Zhang, Lingling; Wang, Xiaojun; Cao, Hong; Chen, Yunxuan; Chen, Xianfan; Zhao, Xi; Xu, Feifei; Wang, Yifan; Woo, Anthony Yiu-Ho; Zhu, Weizhong


    Abnormal proliferation and hypertrophy of vascular smooth muscle (VSMC), as the main structural component of the vasculature, is an important pathological mechanism of hypertension. Recently, increased levels of arginine vasopressin (AVP) and copeptin, the C-terminal fragment of provasopressin, have been shown to correlate with the development of preeclampsia. AVP targets on the Gq-coupled vasopressin V1A receptor and the Gs-coupled V2 receptor in VSMC and the kidneys to regulate vascular tone and water homeostasis. However, the role of the vasopressin receptor on VSM cell proliferation during vascular remodeling is unclear. Here, we studied the effects of AVP on the proliferation of the rat VSMC-derived A7r5 cells. AVP, in a time- and concentration-dependent manner, promoted A7r5 cell proliferation as indicated by the induction of proliferating cell nuclear antigen expression, methylthiazolyldiphenyl-tetrazolium reduction and incorporation of 5'-bromodeoxyuridine into cellular DNA. These effects, coupled with the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), were blocked by a V1A receptor antagonist SR45059 but not by a V2 receptor antagonist lixivaptan. Although acute activation of V1A receptor induced ERK1/2 phosphorylation via a protein kinase C-dependent pathway, this effect was not involved in cell proliferation. Cell proliferation and ERK1/2 phosphorylation in response to prolonged stimulation with AVP were abolished by inhibition of G protein-coupled receptor kinase 2 (GRK2) and epidermal growth factor receptor (EGFR) using specific inhibitors or small hairpin RNA knock-down. These results suggest that activation of V1A, but not V2 receptor, produces a cell proliferative signal in A7r5 cells via a GRK2/EGFR/ERK1/2-dependent mechanism.

  20. Relationship between urinary prostaglandin E2 and F2 alpha excretion and plasma arginine vasopressin during renal concentrating and diluting tests in renal transplant recipients. (United States)

    Pedersen, E B; Christensen, P; Danielsen, H; Eiskjaer, H; Jespersen, B; Knudsen, F; Kornerup, H J; Leyssac, P P; Nielsen, A H; Sørensen, S S


    Urinary excretion of prostaglandin E2 (PGE2 and F2 alpha (PGF2 alpha) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2 alpha remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2 alpha were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2 alpha increased in both groups but, contrary to PGF2 alpha, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2 alpha and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.

  1. Vasopressin increases expression of UT-A1, UT-A3, and ER chaperone GRP78 in the renal medulla of mice with a urinary concentrating defect. (United States)

    Cai, Qi; Nelson, Sarah K; McReynolds, Matthew R; Diamond-Stanic, Maggie Keck; Elliott, David; Brooks, Heddwen L


    Activation of V2 receptors (V2R) during antidiuresis increases the permeability of the inner medullary collecting duct to urea and water. Extracellular osmolality is elevated as the concentrating capacity of the kidney increases. Osmolality is known to contribute to the regulation of collecting duct water (aquaporin-2; AQP2) and urea transporter (UT-A1, UT-A3) regulation. AQP1KO mice are a concentrating mechanism knockout, a defect attributed to the loss of high interstitial osmolality. A V2R-specific agonist, deamino-8-D-arginine vasopressin (dDAVP), was infused into wild-type and AQP1KO mice for 7 days. UT-A1 mRNA and protein abundance were significantly increased in the medullas of wild-type and AQP1KO mice following dDAVP infusion. The mRNA and protein abundance of UT-A3, the basolateral urea transporter, was significantly increased by dDAVP in both wild-type and AQP1KO mice. Semiquantitative immunoblots revealed that dDAVP infusion induced a significant increase in the medullary expression of the endoplasmic reticulum (ER) chaperone GRP78. Immunofluorescence studies demonstrated that GRP78 expression colocalized with AQP2 in principal cells of the papillary tip of the renal medulla. Using immunohistochemistry and immunogold electron microscopy, we demonstrate that vasopressin induced a marked apical targeting of GRP78 in medullary principal cells. Urea-sensitive genes, GADD153 and ATF4 (components of the ER stress pathway), were significantly increased in AQP1KO mice by dDAVP infusion. These findings strongly support an important role of vasopressin in the activation of an ER stress response in renal collecting duct cells, in addition to its role in activating an increase in UT-A1 and UT-A3 abundance.

  2. N-benzoyl-1,5-benzothiazepine and its S-oxide as vasopressin receptor ligands: insight into the active stereochemistry around the seven-membered ring. (United States)

    Yoneda, Tetsuya; Tabata, Hidetsugu; Tasaka, Tomohiko; Oshitari, Tetsuta; Takahashi, Hideyo; Natsugari, Hideaki


    The stereochemistry of N-benzoyl-1,5-benzothiazepine and its S-oxide derivatives as vasopressin receptor ligands was examined in detail by freezing the conformation with a methyl group at the C6 or C9 of 1,5-benzothiazepine. It was revealed that the active forms recognized by the receptors are (cis,aS) for 1,5-benzothiazepine (5-7)-II and (cis,1S,aS) (syn) for its S-oxide (8-10)-II. The C9-methyl derivative of 1,5-benzothiazepine S-oxide (10-II) was designed and synthesized, achieving the putative active syn-isomer.

  3. The brain vasopressin system mediates maternal behaviour in lactating rats - impact of V1b receptors in hypothalamic and limbic brain regions


    Bayerl, Doris


    Adequate maternal behaviour offers the best chance for the offspring to survive to maturity. This pro-social behaviour is known to be regulated by the nonapeptide arginine-vasopressin (AVP) amongst other peptidergic and non-peptidergic systems in rodents as well as in humans. Most research regarding the AVP system in maternal behaviour has focussed on the peptide itself and its V1a receptor (V1aR), and revealed a pivotal involvement in the regulation of different aspects of maternal behaviour...

  4. Serotonin and arginine-vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain. (United States)

    Terranova, Joseph I; Song, Zhimin; Larkin, Tony E; Hardcastle, Nathan; Norvelle, Alisa; Riaz, Ansa; Albers, H Elliott


    There are profound sex differences in the incidence of many psychiatric disorders. Although these disorders are frequently linked to social stress and to deficits in social engagement, little is known about sex differences in the neural mechanisms that underlie these phenomena. Phenotypes characterized by dominance, competitive aggression, and active coping strategies appear to be more resilient to psychiatric disorders such as posttraumatic stress disorder (PTSD) compared with those characterized by subordinate status and the lack of aggressiveness. Here, we report that serotonin (5-HT) and arginine-vasopressin (AVP) act in opposite ways in the hypothalamus to regulate dominance and aggression in females and males. Hypothalamic injection of a 5-HT1a agonist stimulated aggression in female hamsters and inhibited aggression in males, whereas injection of AVP inhibited aggression in females and stimulated aggression in males. Striking sex differences were also identified in the neural mechanisms regulating dominance. Acquisition of dominance was associated with activation of 5-HT neurons within the dorsal raphe in females and activation of hypothalamic AVP neurons in males. These data strongly indicate that there are fundamental sex differences in the neural regulation of dominance and aggression. Further, because systemically administered fluoxetine increased aggression in females and substantially reduced aggression in males, there may be substantial gender differences in the clinical efficacy of commonly prescribed 5-HT-active drugs such as selective 5-HT reuptake inhibitors. These data suggest that the treatment of psychiatric disorders such as PTSD may be more effective with the use of 5-HT-targeted drugs in females and AVP-targeted drugs in males.

  5. Oxytocin and vasopressin receptor gene variation as a proximate base for inter- and intraspecific behavioral differences in bonobos and chimpanzees.

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    Nicky Staes

    Full Text Available Recent literature has revealed the importance of variation in neuropeptide receptor gene sequences in the regulation of behavioral phenotypic variation. Here we focus on polymorphisms in the oxytocin receptor gene (OXTR and vasopressin receptor gene 1a (Avpr1a in chimpanzees and bonobos. In humans, a single nucleotide polymorphism (SNP in the third intron of OXTR (rs53576 SNP (A/G is linked with social behavior, with the risk allele (A carriers showing reduced levels of empathy and prosociality. Bonobos and chimpanzees differ in these same traits, therefore we hypothesized that these differences might be reflected in variation at the rs53576 position. We sequenced a 320 bp region surrounding rs53576 but found no indications of this SNP in the genus Pan. However, we identified previously unreported SNP variation in the chimpanzee OXTR sequence that differs from both humans and bonobos. Humans and bonobos have previously been shown to have a more similar 5' promoter region of Avpr1a when compared to chimpanzees, who are polymorphic for the deletion of ∼ 360 bp in this region (+/- DupB which includes a microsatellite (RS3. RS3 has been linked with variation in levels of social bonding, potentially explaining part of the interspecies behavioral differences found in bonobos, chimpanzees and humans. To date, results for bonobos have been based on small sample sizes. Our results confirmed that there is no DupB deletion in bonobos with a sample size comprising approximately 90% of the captive founder population, whereas in chimpanzees the deletion of DupB had the highest frequency. Because of the higher frequency of DupB alleles in our bonobo population, we suggest that the presence of this microsatellite may partly reflect documented differences in levels of sociability found in bonobos and chimpanzees.

  6. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice.

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    Emil Zeynalov

    Full Text Available Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB disruption, and is often accompanied by increased release of arginine-vasopressin (AVP. AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2 and tolvaptan (V2 are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke.Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan or orally (tolvaptan for 48 hours. Physiological variables, neurological deficit scores (NDS, plasma and urine sodium and osmolality were recorded. Brain water content (BWC and Evans Blue (EB extravasation index were evaluated at the end point.Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle. Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05.Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke.

  7. Arginine vasopressin, via activation of post-junctional V1 receptors, induces contractile effects in mouse distal colon. (United States)

    Mastropaolo, Mariangela; Zizzo, Maria Grazia; Auteri, Michelangelo; Mulè, Flavia; Serio, Rosa


    The aim of this study was to analyze whether arginine vasopressin (AVP) may be considered a modulator of intestinal motility. In this view, we evaluated, in vitro, the effects induced by exogenous administration of AVP on the contractility of mouse distal colon, the subtype(s) of receptor(s) activated and the action mechanism. Isometric recordings were performed on longitudinal and circular muscle strips of mouse distal colon. AVP (0.001 nM-100 nM) caused concentration-dependent contractile effects only on the longitudinal muscle, antagonized by the V1 receptor antagonist, V-1880. AVP-induced effect was not modified by tetrodotoxin, atropine and indomethacin. Contractile response to AVP was reduced in Ca(2+)-free solution or in the presence of nifedipine, and it was abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-free medium with addition of cyclopiazonic acid. U-73122, an inhibitor of the phospholipase C, effectively antagonized AVP effects, whilst it was not affected by an adenylyl cyclase inhibitor. Oxytocin induced an excitatory effect in the longitudinal muscle of distal colon at very high concentrations, effect antagonized by V-1880. The results of this study shown that AVP, via activation of V1 receptors, is able to modulate positively contractile activity of longitudinal muscle of mouse distal colon, independently by enteric nerve activation and prostaglandin synthesis. Contractile response is achieved by increase in cytoplasmatic Ca(2+) concentration via extracellular Ca(2+) influx from L-type Ca(2+) channels and via Ca(2+) release from intracellular stores through phospholipase C pathway. No modulation has been observed on the contractility of the circular muscle.

  8. Are plasma oxytocin and vasopressin levels reflective of amygdala activation during the processing of negative emotions? A preliminary study

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    Kosuke eMotoki


    Full Text Available Plasma oxytocin (OT and arginine vasopressin (AVP are associated with individual differences in emotional responses and behaviors. The amygdala is considered to be an important brain region for regulating emotion-based behavior, with OT and AVP modulating activity in the amygdala during the processing of negative emotions. In particular, increased OT levels may diminish amygdala activation (anxiolytic effects and enhanced AVP levels may augment amygdala activation (anxiogenic effects when negative emotions are processed. A growing body of research has shown that the effects of OT and AVP are modulated by sex: the aforementioned anxiolytic effects of OT and the anxiogenic effects of AVP occur in men, but not in women. However, we have little knowledge regarding the biological mechanisms underlying OT and AVP plasma levels or their respective anxiogenic and anxiolytic effects; similarly, little is known about the causes and nature of sex differences related to these neuropeptides and their effects on emotional processing. In the current study, we focused on the neural functions associated with the biological mechanisms underlying such effects. We hypothesized that amygdala activation would correlate with plasma OT (anxiolytic effects and AVP (anxiogenic effects levels because the amygdala is thought to affect the coordinated release of these neuropeptides following affective experiences. We further hypothesized that the effects would be modulated by sex. We assessed 51 participants (male and female using a paradigm involving negative emotion in conjunction with functional magnetic resonance imaging and measurements of plasma OT and AVP levels. We determined that increased plasma AVP levels were positively associated with amygdala activation (anxiogenic effects in men, but not in women. These findings highlight the potential underlying neural mechanisms of plasma AVP levels in men.

  9. Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells

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    Carolina Monteiro de Lemos Barbosa


    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the development of multiple, progressive, fluid-filled renal cysts that distort the renal parenchyma, leading to end-stage renal failure, mainly after the fifth decade of life. ADPKD is caused by a mutation in the PKD1 or PKD2 genes that encode polycystin-1 (PC-1 and polycystin-2 (PC-2, respectively. PC-1 is an important regulator of several signaling pathways and PC-2 is a nonselective calcium channel. The CFTR chloride channel is responsible for driving net fluid secretion into the cysts, promoting cyst growth. Arginine vasopressin hormone (AVP, in turn, is capable of increasing cystic intracellular cAMP, contributing to cell proliferation, transepithelial fluid secretion, and therefore to disease progression. The aim of this study was to assess if AVP can modulate CFTR and whether PC-1 plays a role in this potential modulation. Methods: M1 cells, derived from mouse cortical collecting duct, were used in the current work. The cells were treated with 10-7 M AVP hormone and divided into two main groups: transfected cells superexpressing PC-1 (Transf and cells not transfected (Ctrl. CFTR expression was assessed by immunodetection, CFTR mRNA levels were quantified by quantitative reverse transcription-polymerase chain reaction, and CFTR net ion transport was measured using the Ussing chamber technique. Results: AVP treatment increased the levels of CFTR protein and mRNA. CFTR short-circuit currents were also increased. However, when PC-1 was overexpressed in M1 cells, no increase in any of these parameters was detected. Conclusions: CFTR chloride channel expression is increased by AVP in M1 cells and PC-1 is capable of regulating this modulation.

  10. Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions. (United States)

    Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K


    Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

  11. Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia. (United States)

    Kubo, Asako; Shinoda, Masamichi; Katagiri, Ayano; Takeda, Mamoru; Suzuki, Tatsuro; Asaka, Junichi; Yeomans, David C; Iwata, Koichi


    Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor-immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

  12. Structure, sequence, expression, and chromosomal localization of the human V{sub 1a} vasopressin receptor gene

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    Thibonnier, M.; Graves, M.K.; Wagner, M.S. [Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States)] [and others


    We recently reported the structure and functional expression of a human V{sub 1a} vasopressin receptor (V{sub 1a}R) cDNA isolated from human liver cDNA libraries. To understand further the expression and regulation of the V{sub 1a}R, we now describe the genomic characteristics, tissue expression, chromosomal localization, and regional mapping of the human V{sub 1a}R gene, AVPR1A. Tissue distribution of the human V{sub 1a}R mRNA explored by Northern blot analysis of various human tissues or organs revealed the presence of a 5.5-kb mRNA transcript expressed in the liver and to a lesser degree in the heart, the kidney, and skeletal muscle. Screening of human genomic libraries revealed that the human AVPR1A gene is included entirely within a 6.4-kb rated by a 2.2-kb intron located before the corresponding seventh transmembrane domain of the receptor sequence. The first exon also contains 2 kb of 5{prime}-untranslated region, and the second exon includes 1 kb of 3{prime}-untranslated region. 5{prime}-RACE analysis of human liver mRNA by PCR localized the V{sub 1a}R mRNA transcription start site 1973 bp upstream of the translation the intron sequence were used as primers in polymerase chain reaction (PCR) analysis of human/rodent somatic cell hybrids. AVPR1A was localized by PCR analysis of a somatic cell hybrid panel to chromosome 12. Fluorescence in situ hybridization using a yeast artificial chromosome physically mapped AVPR1A to region 12q14-q15. 34 refs., 4 figs.

  13. Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus. (United States)

    Hiroi, Maiko; Morishita, Yoshiaki; Hayashi, Masayuki; Ozaki, Nobuaki; Sugimura, Yoshihisa; Nagasaki, Hiroshi; Shiota, Akira; Oiso, Yutaka; Arima, Hiroshi


    Familial neurohypophysial diabetes insipidus (FNDI) is a rare disease that is inherited in an autosomal dominant manner. In a previous study, we made a mouse model for FNDI, which showed progressive polyuria accompanied by inclusion bodies in the arginine vasopressin (AVP) neurons formed by aggregates in the endoplasmic reticulum. The present study was conducted to determine whether the activities of AVP neurons are related to the phenotype progression in the FNDI model. In the first experiment, female heterozygous mice were administered either desmopressin (dDAVP) or a vehicle (control) subcutaneously with osmotic minipumps for 30 days. The dDAVP treatment significantly decreased the urine volume, AVP mRNA expression, and inclusion bodies in the AVP neurons. Urine volume in the dDAVP group remained significantly less than the control for 14 days even after the minipumps were removed. In the second experiment, the males were fed either a 0.2% Na or 2.0% Na diet for 6 mo. Urine AVP excretion was significantly increased in the 2.0% Na group compared with the 0.2% Na group for the first 2 mo but gradually decreased thereafter. Throughout the experiments, urine volume increased progressively in the 2.0% Na group but not in the 0.2% Na group. Immunohistochemical analyses revealed that inclusion bodies in the AVP cells had significantly increased in the 2.0% Na compared with the 0.2% Na group. These data demonstrated that activation of AVP neurons could accelerate the aggregate formation as well as the progression of the polyuria in the FNDI model mice.

  14. Roles of forebrain GABA receptors in controlling vasopressin secretion and related phenomena under basal and hyperosmotic circumstances in conscious rats. (United States)

    Yamaguchi, Ken'ichi; Yamada, Takaho


    Although the anteroventral third ventricular region (AV3V), a forebrain area essential for homeostatic responses, includes receptors for gamma-aminobutyric acid (GABA), the roles of these receptors in controlling vasopressin (AVP) secretion and related phenomena have not been clarified as yet. This study aimed to pursue this problem in conscious rats implanted with indwelling catheters. Cerebral injection sites were determined histologically. Applications of bicuculline, a GABA(A) receptor antagonist, to the AV3V induced prompt and marked augmentations in plasma AVP, osmolality, glucose, arterial pressure and heart rate, without affecting plasma electrolytes. Such phenomena did not occur when phaclofen, a GABA(B) receptor antagonist, was applied to the AV3V. All of the effects of AV3V-administered bicuculline were abolished by preadministration of the GABA(A) receptor agonist muscimol. Preadministration of either MK-801 or NBQX, ionotropic glutamatergic receptor antagonists, was also potent to abolish the AVP response to AV3V bicuculline. When hypertonic saline was infused intravenously, plasma AVP increased progressively, in parallel with rises in plasma osmolality, sodium and arterial pressure. AV3V application of muscimol or baclofen, a GABA(B) receptor agonist, was found to abolish the response of plasma AVP, without inhibiting that of the osmolality or sodium. The response of arterial pressure was also blocked by muscimol treatment, but not by baclofen treatment. Based on these results, we concluded that, under basal conditions, GABA receptors in the AV3V or vicinity may tonically operate to attenuate AVP secretion and cardiovascular functions through mechanisms associated with glutamatergic activity, and that plasma hyperosmolality may cause facilitation of AVP release by decreasing forebrain GABAergic activity.

  15. Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta

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    Tamara Aliza Rachel Weinstein


    Full Text Available The neuropeptides oxytocin (OT and vasopressin (AVP are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques’ (Macaca mulatta friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center. Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay. Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject, multiplex friendships (friendships displayed in more than one behavioral domain, and total number of friendships. Females’ number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males’ plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual’s psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in

  16. P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine-vasopressin secretion. (United States)

    Cuadra, Adolfo E; Custer, Edward E; Bosworth, Elizabeth L; Lemos, José R


    Arginine-vasopressin (AVP) plays a major role in maintaining cardiovascular function and related pathologies. The mechanism involved in its release into the circulation is complex and highly regulated. Recent work has implicated the purinergic receptor, P2X7R, in a role for catecholamine-enhanced AVP release in the rat hypothalamic-neurohypophysial (NH) system. However, the site of P2X7R action in this endocrine system, and whether or not it directly mediates release in secretory neurons have not been determined. We hypothesized that the P2X7R is expressed and mediates AVP release in NH terminals. P2X7R function was first examined by patch-clamp recordings in isolated NH terminals. Results revealed that subpopulations of isolated terminals displayed either high ATP-sensitivity or low ATP-sensitivity, the latter of which was characteristic of the rat P2X7R. Additional recordings showed that terminals showing sensitivity to the P2X7R-selective agonist, BzATP, were further inhibited by P2X7R selective antagonists, AZ10606120 and brilliant blue-G. In confocal micrographs from tissue sections and isolated terminals of the NH P2X7R-immunoreactivity was found to be localized in plasma membranes. Lastly, the role of P2X7R on AVP release was tested. Our results showed that BzATP evoked sustained AVP release in NH terminals, which was inhibited by AZ10606120. Taken together, our data lead us to conclude that the P2X7R is expressed in NH terminals and corroborates its role in AVP secretion.

  17. Dehydration-induced drinking decreases Fos expression in hypothalamic paraventricular neurons expressing vasopressin but not corticotropin-releasing hormone. (United States)

    Wotus, Cheryl; Arnhold, Michelle M; Engeland, William C


    Water-restricted (WR) rats exhibit a rapid suppression of plasma corticosterone following drinking. The present study monitored Fos-like immunoreactivity (Fos) to assess the effect of WR-induced drinking on the activity of vasopressin (VP)-positive magnocellular and parvocellular neurons and corticotropin-releasing hormone (CRH)-positive parvocellular neurons in the paraventricular nucleus of the hypothalamus. Adult male rats received water for 30 min (WR) in the post meridiem (PM) each day for 6 days and were killed without receiving water or at 1 h after receiving water for 15 min. In WR rats, Fos increased in VP magnocellular and parvocellular neurons but not CRH neurons. After drinking, Fos was reduced in VP magnocellular and parvocellular neurons but did not change in CRH neurons. To assess the severity of osmotic stress, rats were sampled throughout the final day of WR. Plasma osmolality, hematocrit and plasma VP were increased throughout the day before PM rehydration, and plasma ACTH and corticosterone were elevated at 1230 and 1430, respectively, showing that WR activates hypothalamic-pituitary-adrenal activity during the early PM before the time of rehydration. To determine the effects of WR-induced drinking on CRH neurons activated by acute stress, WR rats underwent restraint. Restraint increased plasma ACTH and corticosterone and Fos in CRH neurons; although rehydration reduced plasma ACTH and Fos expression in VP neurons, Fos in CRH neurons was not affected. These results suggest that inhibition of VP magnocellular and parvocellular neurons, but not CRH parvocellular neurons, contributes to the suppression of corticosterone after WR-induced drinking.

  18. Central Solenoid

    CERN Multimedia


    The Central Solenoid (CS) is a single layer coil wound internally in a supporting cylinder housed in the cryostat of the Liquid Argon Calorimeter. It was successfully tested at Toshiba in December 2000 and was delivered to CERN in September 2001 ready for integration in the LAr Calorimeter in 2003. An intermediate test of the chimney and proximity cryogenics was successfully performed in June 2002.

  19. Europa central

    Directory of Open Access Journals (Sweden)

    Karel BARTOSEK


    Full Text Available La investigación francesa continúa interesándose por Europa Central. Desde luego, hay límites a este interés en el ambiente general de mi nueva patria: en la ignorancia, producto del largo desinterés de Francia por este espacio después de la Segunda Guerra Mundial, y en el comportamiento y la reflexión de la clase política y de los medios de comunicación (una anécdota para ilustrar este ambiente: durante la preparación de nuestro coloquio «Refugiados e inmigrantes de Europa Central en el movimiento antifascista y la Resistencia en Francia, 1933-1945», celebrado en París en octubre de 1986, el problema de la definición fue planteado concreta y «prácticamente». ¡Y hubo entonces un historiador eminente, para quién Alemania no formaría parte de Europa Central!.

  20. Central core disease

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    Jungbluth Heinz


    Full Text Available Abstract Central core disease (CCD is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown but the condition is probably more common than other congenital myopathies. CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle; orthopaedic complications are common and malignant hyperthermia susceptibility (MHS is a frequent complication. CCD and MHS are allelic conditions both due to (predominantly dominant mutations in the skeletal muscle ryanodine receptor (RYR1 gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1. Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanism(s. The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy; muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment. In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.

  1. Central immune alterations in passive strategy following chronic defeat stress. (United States)

    Joana, Perez-Tejada; Amaia, Arregi; Arantza, Azpiroz; Garikoitz, Beitia; Eneritz, Gomez-Lazaro; Larraitz, Garmendia


    The relationship between stress, mood disorders and immune disorders is known, but what remains to be resolved is why certain individuals are more susceptible than others to suffer different disorders, along with the biological mechanisms that underlie these differences. The objective of this study was to analyze the changes in the expression patterns of proinflammatory cytokines in the hypothalamus, hippocampus, amygdala and prefrontal cortex after chronic defeat, depending on the coping strategy used. The expression levels of α1b and α2a adrenergic receptors and cytokine-inducible nitric oxide synthase (iNOS) in the prefrontal cortex were also measured. The results indicated that subjects with a passive coping strategy showed high levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression in several cerebral structures in resting conditions after 21 days of chronic stress and increases in these cytokine levels in the hippocampus following an additional stress. Low expression levels of tumour necrosis factor-alpha (TNF-α) in the prefrontal cortex in active subjects at rest and in passive subjects after an additional defeat were detected. The iNOS expression levels were lower in the prefrontal cortex of the active group at rest. With respect to adrenergic receptor expression, there were no changes as a function of stress, but there were changes as a function of coping strategy. These results indicate differences in the variables studied in terms of the coping strategy adopted, with passive subjects having a biological profile that could be considered more vulnerable to the development of stress-related disorders.

  2. Central pain. (United States)

    Singh, Supreet


    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  3. central t

    Directory of Open Access Journals (Sweden)

    Manuel R. Piña Monarrez


    Full Text Available Dado que la Regresión Ridge (RR, es una estimación sesgada que parte de la solución de la regresión de Mínimos Cuadrados (MC, es vital establecer las condiciones para las que la distribución central t de Student que se utiliza en la prueba de hipótesis en MC, sea también aplicable a la regresión RR. La prueba de este importante resultado se presenta en este artículo.

  4. Increase in oxytocin and vasopressin concentration in the blood outflowing from sella turcica region after superior cervical ganglion stimulation in rat

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    Lipinska, S.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii


    The aim of the study was to investigate whether the stimulation of the superior cervical ganglion influences the oxytocin and vasopressin release into the blood in condition of the of the sella turcica integrity. The experiments were performed on male rats under urethane-chloralose anaesthesia. Four 0.7 ml samples of the blood from the sella turcica region flowing through a tube inserted in the maxillary interna vein were collected in the 30, 35, 60 and 90 min of the experiments. The animals were divided into three groups: 1) control, 2) after the exposition of superior cervical ganglion. 3) after the collection of the 1-st sample of the blood the superior cervical ganglion was electrically stimulated for 30 min with trains of pulses. Vasopressin (AVP) and oxytocin (OXY) were determined in the blood plasma by radioimmunoassay. Stimulation of the superior cervical ganglion evoked an significant increase of AVP and OXY release into the blood. The increase of AVP release occurred after 30 min longer latency than the increase of OXY release. (author). 32 refs, 2 figs.

  5. A novel splice site mutation of the arginine vasopressin-neurophysin II gene identified in a kindred with autosomal dominant familial neurohypophyseal diabetes insipidus. (United States)

    Tae, Hyun-Jung; Baek, Ki-Hyun; Shim, Sun-Mi; Yoo, Soon-Jib; Kang, Moo-Il; Cha, Bong-Yun; Lee, Kwang-Woo; Son, Ho-Young; Kang, Sung-Koo


    Autosomal dominant familial neurohypophyseal diabetes insipidus is an inherited deficiency of arginine vasopressin (AVP), and this is caused by mutations in the AVP-neurophysin II (AVP-NP II) gene. Most of these mutations have been located in the signal peptide or in the NP II moiety. In the present study, we have analyzed the AVP-NP II gene in a Korean family. Clinical and genetic studies were performed on three members of the family, and on a normal healthy unrelated individual. The diagnosis of neurohypophyseal diabetes insipidus was done by performing a fluid deprivation test and a vasopressin challenge. For genetic analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction (PCR). Clinical assessment of the affected individuals confirmed the diagnosis of neurohypophyseal diabetes insipidus. Genetic analysis of the AVP-NP II gene revealed a novel deletion mutation of a single nucleotide (guanine) within the splice acceptor site of intron 2 (IVS2 +1 delG). The affected individuals were heterozygous for this mutation. We also demonstrated through RT-PCR analysis of the mutant gene that this mutation resulted in the retention of intron 2 during pre-mRNA splicing. We concluded that a novel splicing mutation in the AVP-NP II gene causes neurohypophyseal diabetes insipidus in this family.

  6. In vivo biosynthesis of L-(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin: rapid estimation using reversed phase high pressure liquid chromatography. [Rats

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    Franco-Bourland, R.E.; Fernstrom, J.D.


    L(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin were purified from hypothalami and neurohypophyses 4 h after rats received L(/sup 35/S)Cys via the third ventricle. After acetic acid extraction, Sephadex G-25 filtration, and chemoadsorption to C18-silica (Sep-Pak cartridges), the labeled peptides were rapidly separated by gradient elution, reversed phase, high pressure liquid chromatography (HPLC). The identity and isotopic purity of the labeled peptides were determined by several reversed phase HPLC procedures in conjunction with chemical modification. The labeled peptide fractions were at least 50% radiochemically pure. Using this HPLC isolation procedure, incorporation of L-(/sup 35/S)Cys into each peptide was determined in hydrated and dehydrated rats. Label incorporation into arginine vasopressin and oxytocin in the hypothalamus and the neurohypophysis of dehydrated rats was 2-3 times greater than that in hydrated rats. Incorporation of label into hypothalamic and neurohypophyseal somatostatin was unaffected by the hydration state of the animal. This procedure thus provides a very rapid, but sensitive, set of techniques for studying the control of small peptide biosynthesis in the brain.

  7. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions. (United States)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  8. Variants in adjacent oxytocin/vasopressin gene region and associations with ASD diagnosis and other autism related endophenotypes

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    Sunday M. Francis


    Full Text Available Background: There has been increasing interest in oxytocin (peptide: OT, gene: OXT as a treatment pathway for neurodevelopmental disorders such as Autism Spectrum Disorder (ASD. Neurodevelopmental disorders affect functional, social, and intellectual abilities. With advances in molecular biology, research has connected multiple gene regions to the clinical presentation of ASD. Studies have also shown that the neuropeptide hormones OT and arginine vasopressin (AVP influence mammalian social and territorial behaviors and may have treatment potential for neurodevelopmental disorders. Published data examining molecular and phenotypic variation in ASD, such as cognitive abilities, are limited. Since most studies have focused on the receptors in the OT-AVP system, we investigated genetic variation within peptide genes for association with phenotypic ASD features that help identify subgroups within the spectrum.Methods: In this study, TDT analysis was carried out utilizing FBAT in 207 probands (156 trios and a European Ancestry (EA subsample (108 trios. The evolutionarily related and adjacent genes of OXT and AVP were studied for associations between the tagged single nucleotide polymorphisms and ASD diagnosis, social abilities, restrictive and repetitive behaviors, and IQ for cognitive abilities. Additionally, relationships with whole blood serotonin (WB5HT were explored because of the developmental relationships connecting plasma levels of OT and WB5HT within ASD.Results: Results indicate significant association between OXT rs6084258 (p=0.001 and ASD. Associations with several intermediate phenotypes were also noted: OXT rs6133010 was associated with IQ (full scale IQ, p=0.008; nonverbal IQ, p=0.010, verbal IQ, p=0.006; and OXT rs4813625 and OXT rs877172 were associated with WB5HT levels (EA, p=0.027 and p=0.033, respectively. Additionally, we measured plasma OT (pOT levels in a subsample (N=54. Results show the three polymorphisms, OXT rs6084258

  9. Small vessel disease and cognitive impairment : The relevance of central network connections

    NARCIS (Netherlands)

    Reijmer, Yael D.; Fotiadis, Panagiotis; Piantoni, Giovanni; Boulouis, Gregoire; Kelly, Kathleen E.; Gurol, Mahmut E.; Leemans, Alexander; O'Sullivan, Michael J.; Greenberg, Steven M.; Viswanathan, Anand


    Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network c

  10. Hydrogen peroxide centrally attenuates hyperosmolarity-induced thirst and natriuresis. (United States)

    Zanella, Regis C; Melo, Mariana Rosso; Furuya, Werner Issao; Colombari, Eduardo; Menani, José V; Colombari, Débora Simões Almeida


    Intragastric hypertonic NaCl that simulates the ingestion of osmotically active substances by food intake induces thirst, vasopressin and oxytocin release, diuresis and natriuresis. Reactive oxygen species (ROS) produced endogenously in central areas may act modulating autonomic and behavioral responses. In the present study, we investigated the effects of H2O2 injected centrally on water intake and renal responses induced by increasing plasma osmolality with intragastric (ig) administration of 2M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) with stainless steel cannula implanted in the lateral ventricle (LV) were used. Injections of H2O2 (2.5 μmol/1 μl) into the LV reduced ig 2M NaCl-induced water intake (3.1 ± 0.7, vs. PBS: 8.6 ± 1.0 ml/60 min, pnatriuresis (769 ± 93, vs. PBS: 1158 ± 168 μEq/120 min, pdiuresis (4.1 ± 0.5, vs. PBS: 5.0 ± 0.5 ml/120 min, pnatriuresis induced by hyperosmolarity and on meal-associated thirst.

  11. Music and Alterity Processes

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    Josep Martí


    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  12. Attention Alters Perceived Attractiveness. (United States)

    Störmer, Viola S; Alvarez, George A


    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another.

  13. Copeptin, a surrogate marker for arginine vasopressin secretion, is associated with higher glucose and insulin concentrations but not higher blood pressure in obese men

    DEFF Research Database (Denmark)

    Asferg, C L; Andersen, Ulrik Bjørn; Linneberg, A


    AIM: To explore the putative associations of plasma copeptin, the C-terminal portion of provasopressin and a surrogate marker for arginine vasopressin secretion, with obesity-related health problems, such as hyperlipidaemia, hyperinsulinaemia, hyperglycaemia, high blood pressure and an android fat...... blood pressure (r = 0.11, P = 0.29), 24-h diastolic blood pressure (r = 0.11, P = 0.28), BMI (r = 0.09, P = 0.37), total body fatness percentage (r = 0.10, P = 0.33), android fat mass percentage (r = 0.04, P = 0.66) or serum triglyceride concentrations (r = 0.04; P = 0.68). In contrast, plasma copeptin......, and is associated with abnormalities in glucose and insulin metabolism, but not with higher blood pressure or an android fat distribution in obese men....

  14. Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans. [Plasma Renin Activity and Plasma VasoPressin (United States)

    Kravik, S. E.; Keil, L. C.; Geelen, G.; Wade, C. E.; Barnes, P. R.


    The effects of lower body and abdominal pressure, produced by antigravity suit inflation, on blood pressure, pulse rate, fluid and electrolyte shift, plasma vasopressin and plasma renin activity in humans in upright postures were studied. Five men and two women stood upright for 3 hr with the suit being either inflated or uninflated. In the control tests, the suit was inflated only during the latter part of the trials. Monitoring was carried out with a sphygnomanometer, with sensors for pulse rates, and using a photometer and osmometer to measure blood serum characteristics. The tests confirmed earlier findings that the anti-g suit eliminates increases in plasma renin activity. Also, the headward redistribution of blood obtained in the tests commends the anti-g suit as an alternative to water immersion or bed rest for initial weightlessness studies.

  15. Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat. (United States)

    Anai, H; Ueta, Y; Serino, R; Nomura, M; Kabashima, N; Shibuya, I; Takasugi, M; Nakashima, Y; Yamashita, H


    The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.

  16. Early changes of endothelin,nitric oxide and arginine—vasopressin in patients with acute cerebral injury

    Institute of Scientific and Technical Information of China (English)

    杨云梅; 黄卫东; 等


    Objective:To ivvestigate the early changes and clinical significance of plasma endothelin(ET),nitric oxide(NO)and arginine-vasopressin(AVP)in patients wisth acute moderate or severe cerebral injury.Metods:The ealy(at24 hours after injury)plasma concentrations of ET,NOand AVP were measured with radionimmunoassay and Green technique in48cases of acute moderate(GCS≤8in27cases)or severe(GCS>8in21cases)cerebral injury(GroupA),in42cases of non-cerebral injury(GroupB)and in38normal individuals(GroupC),respectively,Results:The early plasma concentrations of ET(109.73ng/L±12.61ng/L),NO(92.82μmol/L013218.21μmol/L)andAVP(49.78ng/L±14.29ng/L)inGroup Awere higher than those in Group B(67。013211.33ng/L,52.66μmol/L±12.82μmol/Land29.93ng/L±12.11ng/L,respectiely,P<0.01)andGroupC(50.65ng/L±17.12ng/L,36.12μmol/L013212.16μmol/Land5.18ng/L±4.18ng/L,respectively,P<0.001).The amounts of ET,NOand AVPin patients with severe cerebral injury were 116.18ng/L±18.12ng/L,108.19μmol/L±13.28μmol/Land58.13ng/L±16.78ng/L,respectively,which were significantly higher than that of the patients with moderate cerebral injury(92.33ng/L±16.32ng/L,76.38μmol/L±12.71μmol/Land36.18ng/L±12.13ng/L respectively,P<0.01).The early levels of ET,NO and AVP in Group A were negatively related to the GCS scales.The amounts of ET,NO and AVP were126.23ng/L±15.23ng/L,118.18μmol/L±10.12μmol/Land63.49ng/L±14.36ng/Lrespectively in patients with subdural hematoma,which were significantly higher than those in patients with epidural hematoma(81.13ng/L±12.37ng/L,68.02μmol/L013213.18μmol/Land 45.63ng/L±12.41ng/L respectively,P<0.01).The plasma concentrations of ET,NO and AVP in stable duration(at336 hours after injury)in Group A and Group Bwere similar to those in GroupC.Conclusions:ET,NO and AVP were related to the pathophysiological process that occurs in the early stage of acute cerebral injury and the values of ET.NO and AVP correlate positively with the clinical manifestations,The changes

  17. Vasopressin and Breast Cancer (United States)


    hyperpolarizing pulses did not elicit an inward potassium rectifier current. Treatment with tetrodotoxin did not reveal the presence of an inward sodium current . The...potassium current or of a sodium current . of experimental solutions, as demonstrated by addition of a water-soluble dye. 4,4’.Diisothiocyanostilbene-2,2...detected, leading us to was stepped to various hyperpolarized potentials in physio- conclude that a voltage-gated sodium current is not present. logical

  18. Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping

    Directory of Open Access Journals (Sweden)

    Vito Salvador Hernandez


    Full Text Available The arginine-vasopressin (AVP-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs are known for their role in hydro-electrolytic balance control via their projections to neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula, and other brain regions, in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA. The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS, consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN and supraoptic (SON nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptors mRNA were not detected, using the same method. Water-deprivation for 24 hrs, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze test, and this effect was mimicked by bilateral microinfusion of VP into the CeA. Anxious behavior induced by either water deprivation or VP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of central amygdala inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

  19. Clinical efficacy observation of vasopressin and phentolamine in treatment for massive hemoptysis%垂体后叶素与酚妥拉明治疗大咯血疗效分析

    Institute of Scientific and Technical Information of China (English)



    目的:观察垂体后叶素,酚妥拉明两药单用和合用治疗大咯血的疗效。方法96例大咯血患者分3组:垂体后叶素组45例,采用注射垂体后叶素治疗;酚妥拉明组30例,注射酚妥拉明治疗;合用组21例:前二者同用,剂量稍减。比较3组患者治疗效果和不良反应情况。结果合用组总有效率为90.48%,高于垂体后叶素组和酚妥拉明组,与酚妥拉明组比较差异具有统计学意义(P<0.05);合用组不良反应率显著低于垂体后叶素组和酚妥拉明组(x2=4.7852、4.0728,P<0.05)。结论大咯血患者治疗中,后叶素与酚妥拉明合用优于单独使用治疗效果,并且具有较少的副反应。%Objective To investigate clinical effect of vasopressin and phentolamine in treatment for massive hemoptysis. Methods 96 cases of hemoptysis patients were divided into three groups: 45 cases of posterior pituitary vasopressin group, treated with injection of vasopressin; 30 cases of phentolamine group, treated with injection of phentolamine; 21 cases combined group, treated with both dose diminished. The therapeutic effect and adverse reactions of three groups were analyzed. Results After treatment, the total effective rate of combined group was 90.48%, higher than the vasopressin group and the phentolamine group, compared to phentolamine group with a significant difference (P < 0.05); The adverse reaction rate of combination group was significantly lower than that of the vasopressin group and phentolamine group (x2= 4.7852, 4.0728, P < 0.05). Conclusion The vasopressin combined with phentolamine in treatment of patients with massive hemoptysis has superior therapeutic effects and has fewer side effects.

  20. Ressourcenorientierte Diagnostik im Alter


    Forstmeier, Simon; Maercker, Andreas


    Trotz der im Alter zunehmenden körperlichen, kognitiven und sozialen Verlusten bleibt das subjektive Wohlbefinden relativ stabil. Dies weist auf die vielen Ressourcen älterer Menschen hin. Dieser Artikel stellt für die klinische Ressourcendiagnostik relevante Verfahren vor und erläutert die zugrunde liegenden Konzepte. Berücksichtigt werden Aktivitäten und Erlebnisse als Ressourcen, emotionale Ressourcen (positiver Affekt, Lebenszufriedenheit, Selbstwerterleben, Lebensqualität), motivationale...

  1. [Central nervous system malformations: neurosurgery correlates]. (United States)

    Jiménez-León, Juan C; Betancourt-Fursow, Yaline M; Jiménez-Betancourt, Cristina S


    Congenital malformations of the central nervous system are related to alterations in neural tube formation, including most of the neurosurgical management entities, dysraphism and craniosynostosis; alterations of neuronal proliferation; megalencefaly and microcephaly; abnormal neuronal migration, lissencephaly, pachygyria, schizencephaly, agenesis of the corpus callosum, heterotopia and cortical dysplasia, spinal malformations and spinal dysraphism. We expose the classification of different central nervous system malformations that can be corrected by surgery in the shortest possible time and involving genesis mechanisms of these injuries getting better studied from neurogenic and neuroembryological fields, this involves connecting innovative knowledge areas where alteration mechanisms in dorsal induction (neural tube) and ventral induction (telencephalization) with the current way of correction, as well as the anomalies of cell proliferation and differentiation of neuronal migration and finally the complex malformations affecting the posterior fossa and current possibilities of correcting them.

  2. 感染性休克复苏中血管活性药撤离对预后的影响%Effect of vasopressin withdrawal during early fluid resuscitation on prognosis in patients with septic ;shock

    Institute of Scientific and Technical Information of China (English)

    李家琼; 史载祥; 许继元; 张舟; 李琳; 卢飞; 莫逊; 李茂琴


    887)ml vs.(2326±568)ml;(4554±738)ml vs.(3847±454)ml],但第2天与第3天的液体复苏量比A组[(2289±376)ml vs.(2597±428)ml;(989±302)ml vs.(1438±313)ml]减少,3 d总液体复苏[(7648±815)ml vs.(7965±678)ml]明显减少(P<0.05)。(5)B组28 d生存率和无脏器衰竭时间有改善趋势但差异无统计学意义,28 d内脱离呼吸机时间[(16.3±9.2)d vs.(19.5±8.5)d]增加,住ICU时间缩短[(9.6±3.2)d vs.(8.4±3.1)d](P<0.05)。结论感染性休克复苏过程中严密监测下进行血管活性药撤离,能尽早充分复苏稳定循环,改善脏器灌注,并减少液体过负荷的风险,减少机械通气时间,缩短住ICU时间。%Objective To explore the effect of vasopressin withdrawal during early fluid resuscitation on tissue perfusion and prognosis in patients with septic shock. Methods Inclusion criteria:septic shock patients with APACHEII from 18 to 28 and GCS more than 7 when admitted to ICU. Exclusion criteria: patients with chronic history of heart, lung, liver and kidney dysfunction. 32 patients were given the EDGT protocol as group A from 2006 October to 2009 June; 30 patients were given vasopressin withdrawal during fluid resuscitation as group B from 2009 July to 2009 December. Norepinephrine (NE) and/or dobutamine were administrated to maintain mean arterial pressure (MAP)≥65 mmHg during EDGT progress in group A. Dose of vasopressors was adjusted according to experience of doctors. To maintain the MAP≥75 mmHg in group B, norepinephrine was administrated to adjust the systemic circulation peripheral vascular resistance index during 900 to 1 500 d·s·cm-5·(m2)-1;After MAP maintained stability for 1 h, dose of NE was dropped at 0.4 µg·kg-1·h-1 per 10 min. The dose of the last NE was injected when MAP was lower than 65 mmHg. Central venous oxygen saturation and lactate values were observed after 6 h. 3 d liquid balance and

  3. Hypothalamic Vasopressinergic Projections Innervate Central Amygdala GABAergic Neurons: Implications for Anxiety and Stress Coping (United States)

    Hernández, Vito S.; Hernández, Oscar R.; Perez de la Mora, Miguel; Gómora, María J.; Fuxe, Kjell; Eiden, Lee E.; Zhang, Limei


    The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA). The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS), consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptor mRNAs were not detected, using the same method. Water-deprivation (WD) for 24 h, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze (EPM) test, and this effect was mimicked by bilateral microinfusion of AVP into the CeA. Anxious behavior induced by either WD or AVP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of CeA inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala. PMID:27932956

  4. Neuropeptides and central control of sexual behaviour from the past to the present: a review. (United States)

    Argiolas, Antonio; Melis, Maria Rosaria


    Of the numerous neuropeptides identified in the central nervous system, only a few are involved in the control of sexual behaviour. Among these, the most studied are oxytocin, adrenocorticotropin, α-melanocyte stimulating hormone and opioid peptides. While opioid peptides inhibit sexual performance, the others facilitate sexual behaviour in most of the species studied so far (rats, mice, monkeys and humans). However, evidence for a sexual role of gonadotropin-releasing hormone, corticotropin releasing factor, neuropeptide Y, galanin and galanin-like peptide, cholecystokinin, substance P, vasoactive intestinal peptide, vasopressin, angiotensin II, hypocretins/orexins and VGF-derived peptides are also available. Corticotropin releasing factor, neuropeptide Y, cholecystokinin, vasopressin and angiotensin II inhibit, while substance P, vasoactive intestinal peptide, hypocretins/orexins and some VGF-derived peptide facilitate sexual behaviour. Neuropeptides influence sexual behaviour by acting mainly in the hypothalamic nuclei (i.e., lateral hypothalamus, paraventricular nucleus, ventromedial nucleus, arcuate nucleus), in the medial preoptic area and in the spinal cord. However, it is often unclear whether neuropeptides influence the anticipatory phase (sexual arousal and/or motivation) or the consummatory phase (performance) of sexual behaviour, except in a few cases (e.g., opioid peptides and oxytocin). Unfortunately, scarce information has been added in the last 15 years on the neural mechanisms by which neuropeptides influence sexual behaviour, most studied neuropeptides apart. This may be due to a decreased interest of researchers on neuropeptides and sexual behaviour or on sexual behaviour in general. Such a decrease may be related to the discovery of orally effective, locally acting type V phosphodiesterase inhibitors for the therapy of erectile dysfunction.

  5. Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models. (United States)

    Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F


    [V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of

  6. Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

    Directory of Open Access Journals (Sweden)

    Antunes V.R.


    Full Text Available In this study we investigated the effects of the injection into the supraoptic nucleus (SON of non-peptide AT1- and AT2-angiotensin II (ANG II receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP receptor antagonist d(CH25-Tyr(Me-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA. The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 ml over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P<0.01 and sodium intake (81%, N = 8, P<0.01 induced by the injection of ANG II (10 nmol into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. On the other hand, while there was a decrease in water intake (45%, N = 9, P<0.01, ANG II-induced sodium intake was significantly increased (70%, N = 8, P<0.01 following injection of the V1-type vasopressin antagonist d(CH25-Tyr(Me-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.

  7. Central bank Financial Independence


    J.Ramon Martinez-Resano


    Central bank independence is a multifaceted institutional design. The financial component has been seldom analysed. This paper intends to set a comprehensive conceptual background for central bank financial independence. Quite often central banks are modelled as robot like maximizers of some goal. This perspective neglects the fact that central bank functions are inevitably deployed on its balance sheet and have effects on its income statement. A financially independent central bank exhibits ...

  8. Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response. (United States)

    Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco


    Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

  9. Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin. (United States)

    Bernal, Antonio; Mahía, Javier; Puerto, Amadeo


    The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

  10. Neck muscle fatigue alters upper limb proprioception. (United States)

    Zabihhosseinian, Mahboobeh; Holmes, Michael W R; Murphy, Bernadette


    Limb proprioception is an awareness by the central nervous system (CNS) of the location of a limb in three-dimensional space and is essential for movement and postural control. The CNS uses the position of the head and neck when interpreting the position of the upper limb, and altered input from neck muscles may affect the sensory inputs to the CNS and consequently may impair the awareness of upper limb joint position. The purpose of this study was to determine whether fatigue of the cervical extensors muscles (CEM) using a submaximal fatigue protocol alters the ability to recreate a previously presented elbow angle with the head in a neutral position. Twelve healthy individuals participated. CEM activity was examined bilaterally using surface electromyography, and kinematics of the elbow joint was measured. The fatigue protocol included an isometric neck extension task at 70 % of maximum until failure. Joint position error increased following fatigue, demonstrating a significant main effect of time (F 2, 18 = 19.41, p ≤ 0.0001) for absolute error. No significant differences were found for variable error (F 2, 18 = 0.27, p = 0.76) or constant error (F 2, 18 = 1.16 of time, p ≤ 0.33). This study confirms that fatigue of the CEM can reduce the accuracy of elbow joint position matching. This suggests that altered afferent input from the neck subsequent to fatigue may impair upper limb proprioception.

  11. Effect of YM218, a nonpeptide vasopressin V(1A) receptor-selective antagonist, on rat mesangial cell hyperplasia and hypertrophy. (United States)

    Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Suzuki, Takeshi; Yatsu, Takeyuki; Shibasaki, Masayuki


    Mesangial cell growth constitutes a key feature of progressive glomerular injury. Vasopressin (AVP), a potent peptide vasoconstrictor, acts on mesangial cells through the V(1A) receptors, inducing contraction and cell proliferation. This study examined the effects of YM218, a nonpeptide AVP V(1A) receptor-selective antagonist, on the mitogenic and hypertrophic effects of AVP in rat mesangial cells. When added to mesangial cells whose growth was arrested, AVP concentration-dependently induced hyperplasia and hypertrophy. YM218 potently prevented AVP-induced hyperplasia and hypertrophy of these cells. Furthermore, AVP stimulated endothelin (ET)-1 secretion from mesangial cells in a concentration-dependent manner and this effect was potently inhibited by YM218. ET-1 also induced hyperplasia and hypertrophy in mesangial cells and this effect was completely abolished by ET(A) receptor-selective antagonist YM598. In addition, AVP-induced hyperplasia and hypertrophy were partly inhibited by YM598. These results suggest that AVP may modulate mesangial cell growth not only by its direct action but also through the stimulation of ET-1 secretion. YM218 displays high potency in inhibiting the AVP-induced physiologic responses of mesangial cells via the V(1A) receptors and is a potent pharmacologic probe for investigating the physiologic and pathophysiologic roles of AVP in several renal diseases.

  12. Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups (United States)

    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.


    The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

  13. Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network. (United States)

    Albers, H Elliott


    Arginine-vasotocin (AVT)/arginine vasopressin (AVP) are members of the AVP/oxytocin (OT) superfamily of peptides that are involved in the regulation of social behavior, social cognition and emotion. Comparative studies have revealed that AVT/AVP and their receptors are found throughout the "social behavior neural network (SBNN)" and display the properties expected from a signaling system that controls social behavior (i.e., species, sex and individual differences and modulation by gonadal hormones and social factors). Neurochemical signaling within the SBNN likely involves a complex combination of synaptic mechanisms that co-release multiple chemical signals (e.g., classical neurotransmitters and AVT/AVP as well as other peptides) and non-synaptic mechanisms (i.e., volume transmission). Crosstalk between AVP/OT peptides and receptors within the SBNN is likely. A better understanding of the functional properties of neurochemical signaling in the SBNN will allow for a more refined examination of the relationships between this peptide system and species, sex and individual differences in sociality.

  14. Effects of cysteamine administration on the in vivo incorporation of (/sup 35/S)cysteine into somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin in rat hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Cameron, J.L.; Fernstrom, J.D.


    The effect of cysteamine injection on the in vivo incorporation of (/sup 35/S)cysteine into somatostatin-14 (SRIF-14), SRIF-28, arginine vasopressin (AVP), and oxytocin (OXT) in rat hypothalamus was studied. (/sup 35/S)Cysteine was injected into the third ventricle 1 h, 4 h, or 1 week after cysteamine (300 mg/kg, sc) injection; animals were killed 4 h later. The drug was found to substantially reduce immunoreactive SRIF levels, but not OXT or AVP, 4 h after its injection. Cysteamine also caused large reductions in label incorporation into SRIF-14, SRIF-28, and OXT 1 and 4 h after drug injection. However, (/sup 35/S)cysteine incorporation into AVP was increased substantially at these time points, while that into acid-precipitable protein was normal. One week after cysteamine injection, label incorporation into all hypothalamic peptides was normal. Cysteine specific activity was also measured after (/sup 35/S)cysteine injection and was found to be similar in treatment and control groups. The results suggest that cysteamine inhibits the syntheses of SRIF-14, SRIF-28, and OXT and stimulates that of AVP.


    Irvine, Dexter R F; Fallon, James B; Kamke, Marc R


    The central auditory system retains into adulthood a remarkable capacity for plastic changes in the response characteristics of single neurons and the functional organization of groups of neurons. The most dramatic examples of this plasticity are provided by changes in frequency selectivity and organization as a consequence of either partial hearing loss or procedures that alter the significance of particular frequencies for the organism. Changes in temporal resolution are also seen as a consequence of altered experience. These forms of plasticity are likely to contribute to the improvements exhibited by cochlear implant users in the post-implantation period.


    Irvine, Dexter R. F.; Fallon, James B.; Kamke, Marc R.


    The central auditory system retains into adulthood a remarkable capacity for plastic changes in the response characteristics of single neurons and the functional organization of groups of neurons. The most dramatic examples of this plasticity are provided by changes in frequency selectivity and organization as a consequence of either partial hearing loss or procedures that alter the significance of particular frequencies for the organism. Changes in temporal resolution are also seen as a consequence of altered experience. These forms of plasticity are likely to contribute to the improvements exhibited by cochlear implant users in the post-implantation period. PMID:17572797

  17. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  18. Genetic Alterations in Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Bralten, Linda B. C.; French, Pim J., E-mail: [Department of Neurology, Erasmus University Medical Center, Erasmus University Rotterdam, Dr Molewaterplein 50, 3000 CA, Rotterdam (Netherlands)


    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes.

  19. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder. (United States)

    Gao, Shang-Feng; Lu, Yun-Rong; Shi, Li-Gen; Wu, Xue-Yan; Sun, Bo; Fu, Xin-Yan; Luo, Jian-Hong; Bao, Ai-Min


    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (Pdepression.

  20. NIDDK Central Repository (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  1. Central Neuropathic Pain Syndromes. (United States)

    Watson, James C; Sandroni, Paola


    Chronic pain is common in patients with neurologic complications of a central nervous system insult such as stroke. The pain is most commonly musculoskeletal or related to obligatory overuse of neurologically unaffected limbs. However, neuropathic pain can result directly from the central nervous system injury. Impaired sensory discrimination can make it challenging to differentiate central neuropathic pain from other pain types or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring recognition of its association with a past neurologic injury. This review focuses on unique clinical features that help distinguish central neuropathic pain. The most common clinical central pain syndromes-central poststroke pain, multiple sclerosis-related pain, and spinal cord injury-related pain-are reviewed in detail. Recent progress in understanding of the pathogenesis of central neuropathic pain is reviewed, and pharmacological, surgical, and neuromodulatory treatments of this notoriously difficult to treat pain syndrome are discussed.

  2. Central venous catheter - flushing (United States)

    ... during cancer treatment Bone marrow transplant - discharge Central venous catheter - dressing change Peripherally inserted central catheter - flushing Sterile technique Surgical wound care - open Review Date 9/22/2016 Updated by: ...

  3. Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study (United States)

    Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.


    Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

  4. Central serotonergic and noradrenergic receptors in functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    S O'Mahony; TG Dinan; PW Keeling; ASB Chua


    Functional dyspepsia is a symptom complex characterised by upper abdominal discomfort or pain, early satiety,motor abnormalities, abdominal bloating and nausea in the absence of organic disease. The central nervous system plays an important role in the conducting and processing of visceral signals. Alterations in brain processing of pain, perception and affective responses may be key factors in the pathogenesis of functional dyspepsia. Central serotonergic and noradrenergic receptor systems are involved in the processing of motor,sensory and secretory activities of the gastrointestinal tract. Visceral hypersensitivity is currently regarded as the mechanism responsible for both motor alterations and abdominal pain in functional dyspepsia. Some studies suggest that there are alterations in central serotonergic and noradrenergic systems which may partially explain some of the symptoms of functional dyspepsia. Alterations in the autonomic nervous system may be implicated in the motor abnormalities and increases in visceral sensitivity in these patients.Noradrenaline is the main neurotransmitter in the sympathetic nervous system and again alterations in the functioning of this system may lead to changes in motor function. Functional dyspepsia causes considerable burden on the patient and society. The pathophysiology of functional dyspepsia is not fully understood but alterations in central processing by the serotonergic and noradrenergic systems may provide plausible explanations for at least some of the symptoms and offer possible treatment targets for the future.

  5. Novel BRAF Alteration in a Sporadic Pilocytic Astrocytoma

    Directory of Open Access Journals (Sweden)

    Sonika Dahiya


    Full Text Available Pilocytic astrocytoma (PA is the most frequently encountered glial tumor (glioma or astrocytoma in children. Recent studies have identified alterations in the BRAF serine/threonine kinase gene as the likely causative mutation in these childhood brain tumors. The majority of these genetic changes involve chromosome 7q34 tandem duplication, resulting in aberrant BRAF fusion transcripts. In this paper, we describe a novel KIAA1549:BRAF fusion transcript in a sporadic PA tumor associated with increased ERK activation and review the spectrum of BRAF genetic alterations in this common pediatric low-grade central nervous system neoplasm.

  6. Neuropeptide Y in the arcuato-paraventricular pathway and diet selection in the vasopressin-deficient Brattleboro rat. (United States)

    Beck, Bernard; Max, Jean-Pierre


    Neuropeptide Y (NPY) is one of the most important brain peptides involved in feeding behavior. It influences both food choice and fluid homeostasis. The paraventricular and arcuate nuclei belong to the main pathway through which NPY stimulates carbohydrate intake. In this study, we measured NPY in various hypothalamic microdissected areas in Brattleboro di/di rats, a rat model of diabetes insipidus with specific dietary preferences. We confirmed that this rat is characterized by an increased fat intake (+10%; p<0.001) and a decreased carbohydrate intake (-10%; p<0.001) leading to a completely different dietary profile than that of di/+ controls. This profile was associated with a decrease in NPY in the paraventricular nucleus (-33%; p<0.005) and in the ventromedial nucleus (-24%; p<0.002). Intake of carbohydrate was negatively correlated with the gradient of NPY concentration between the arcuate and paraventricular nuclei. NPY could therefore contribute to the qualitative changes of feeding behavior in the Brattleboro rat through altered transport/release of the peptide and participate in the balance of neuropeptides that determines food choice in this strain of rat.

  7. 垂体后叶素与酚妥拉明联合治疗肺结核咯血的临床分析%Clinical Study on Vasopressin Combined With Phentolamine in Treatment of Tuberculosis Hemoptysis

    Institute of Scientific and Technical Information of China (English)



    目的:对垂体后叶素与酚妥拉明联合治疗肺结核咯血的临床疗效进行分析。方法选取2013年3月~2015年2月在我院接受治疗的52例肺结核咯血患者,将患者随机分为对照组和治疗组分别给予垂体后叶素与垂体后叶素联合酚妥拉明治疗,对两种治疗方法的效果进行比较。结果治疗组患者的治疗总有效率为92.3%,高于对照组的73.1%;治疗组患者的不良反应发生率为7.7%,低于对照组的30.8%,差异有统计学意义(P<0.05)。结论垂体后叶素与酚妥拉明联合治疗肺结核咯血的疗效显著,能够改善患者的咯血症状,并且不良反应少。%Objective Clinical effect of vasopressin combined with phentolamine in treatment of tuberculosis hemoptysis is to be studied.Methods Choose 52 patients of tuberculosis hemoptysis who were treated in hospital from March 2013 to February 2015 and separated them into control group and study group at random which were given vasopressin treatment and vasopressin combined with phentolamine treatment respectively,then compared patients’ treatment effects between two groups.Results Patients’ treatment efficacy in study group was 92.3%,while patients’ treatment efficacy in control group was 73.1%,and side-effect incidence in study group was 7.7%,which was much lower than 30.8% in control group,there was a treatment differential between two groups and such a differential had statistic value(P< 0.05).Conclusion Vasopressin combined with phentolamine is of efficacy in treatment of tuberculosis hemoptysis,it is conducive to improving patients’ clinical symptom of hemoptysis with few side effects.

  8. Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women. (United States)

    Chen, Xu; Hackett, Patrick D; DeMarco, Ashley C; Feng, Chunliang; Stair, Sabrina; Haroon, Ebrahim; Ditzen, Beate; Pagnoni, Giuseppe; Rilling, James K


    Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner's Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.

  9. Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, S.; Okada, K.; Saito, T.


    The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ((Ca2+)i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased (Ca2+) significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of (Ca2+)i depended on the intracellular Ca pool, since an AVP-induced rise in (Ca2+)i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased /sup 45/Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells.

  10. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors. (United States)

    Hashimoto, K; Makino, S; Hirasawa, R; Takao, T; Kageyama, J; Ogasa, T; Ota, Z


    We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  11. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors.

    Directory of Open Access Journals (Sweden)



    Full Text Available We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH, 1 micrograms/kg growth hormone releasing hormone (GRH, 500 micrograms thyrotropin-releasing hormone (TRH, 100 micrograms luteinizing hormone releasing hormone (LH-RH, and a relatively small dose (5 mU/kg of lysine vasopressin (LVP. In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH, prolactin (PRL and follicle-stimulating hormone (FSH responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  12. Effect of an increase in brain serotonin on the osmoregulatory response to a hypo- or hyperosmotic load in Wistar and vasopressin-deficient Brattleboro rats. (United States)

    Ivanova, L; Kochkaeva, L; Melidi, N


    Serotonin and its receptor agonists stimulate the release of arginine vasopressin (AVP) into peripheral blood under intraventricular injection. To test the hypothesis that brain serotonin can modulate the development of natural osmoregulatory responses, the effect of an increase in endogenous brain serotonin on the response to an intragastric hypo- or hyperosmotic loading was studied in Wistar and AVP-deficient Brattleboro rats. 5-Hydroxytryptophan (5-HTP), the rate-limiting serotonin biosynthesis precursor known to increase the brain level of serotonin, was injected intraperitoneally (5 mg/100 g body weight). The renal functional parameters (glomerular filtration rate [GFR], free water reabsorption, and urine flow rate) were monitored during the 4 h after intragastric infusion of water or a 2% NaCl solution (5% of body weight). Plasma AVP was measured by radioimmunoassay. In Wistar rats, intraperitoneal injection of 5-HTP at the same time as water loading prevented the development of the renal diuretic response: there was no increase in urine flow rate and GFR, and free water reabsorption remained at the high level. In AVP-deficient Brattleboro rats, unlike Wistar rats, 5-HTP treatment was without effect on the renal function parameters. In Wistar rats, injection of 5-HTP at the peak of water diuresis produced an abrogation of the diuretic response to water loading due to the increase in free water reabsorption. Plasma AVP increased from 1.2 +/- 0.4 to 4.2 +/- 1.6 pg/ml (n = 8 in each group, p HTP revealed no additive effect on plasma AVP and on free water reabsorption. We conclude that the 5-HTP-caused increase in brain serotonin contributed significantly to the dynamics of changes in the osmoregulatory response to the hypo-osmotic challenge due to stimulation of AVP secretion. 5-HTP had no additive effect on the osmoregulatory response to hyperosmotic loading. Peripherally injected 5-HTP had no effect on the renal function, being absent in AVP

  13. Central auditory function of deafness genes. (United States)

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd


    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  14. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)


    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  15. Epigenetic alterations in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    In-Seon CHOI; Tsung-Teh WU


    Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpG island methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesis and its relevance of clinical implications.

  16. Dry needling - peripheral and central considerations. (United States)

    Dommerholt, Jan


    Dry needling is a common treatment technique in orthopedic manual physical therapy. Although various dry needling approaches exist, the more common and best supported approach targets myofascial trigger points. This article aims to place trigger point dry needling within the context of pain sciences. From a pain science perspective, trigger points are constant sources of peripheral nociceptive input leading to peripheral and central sensitization. Dry needling cannot only reverse some aspects of central sensitization, it reduces local and referred pain, improves range of motion and muscle activation pattern, and alters the chemical environment of trigger points. Trigger point dry needling should be based on a thorough understanding of the scientific background of trigger points, the differences and similarities between active and latent trigger points, motor adaptation, and central sensitize application. Several outcome studies are included, as well as comments on dry needling and acupuncture.

  17. Central Laboratories Services (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  18. Complement Activation Alters Platelet Function (United States)


    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  19. Mephedrone alters basal ganglia and limbic dynorphin systems. (United States)

    German, Christopher L; Alburges, Mario E; Hoonakker, Amanda J; Fleckenstein, Annette E; Hanson, Glen R


    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D1 -like (SCH-23380) or D2 -like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  20. Central Pain Syndrome (United States)

    ... or hands. Central pain syndrome often begins shortly after the causative injury or damage, but may be delayed by months or even years, especially if it is related to post-stroke pain. × Definition Central pain syndrome is a neurological ...

  1. Central centrifugal cicatricial alopecia

    Directory of Open Access Journals (Sweden)

    Collin Blattner


    Full Text Available Central centrifugal cicatricial alopecia is a common cause of progressive permanent apical alopecia. This unique form of alopecia includes entities previously know as "hot comb alopecia," "follicular degeneration syndrome," "pseudopelade" in African Americans and "central elliptical pseudopelade" in Caucasians. The etiology appears to be multifactorial and the condition occurs in all races.

  2. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.


    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the opt

  3. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.


    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the opt

  4. Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats. (United States)

    Altinbas, Burcin; Yilmaz, Mustafa S; Savci, Vahide; Jochem, Jerzy; Yalcin, Murat


    Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

  5. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models (United States)



    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 μg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials. PMID:25846632

  6. Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells (United States)

    Pifano, Marina; Garona, Juan; Capobianco, Carla S.; Gonzalez, Nazareno; Alonso, Daniel F.; Ripoll, Giselle V.


    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects. Desmopressin (dDAVP) is a synthetic analog of AVP that acts as a selective agonist for the V2r, which shows antitumor properties in breast and colorectal cancer models. Recently, we developed a derivative of dDAVP named [V4Q5]dDAVP, which presents higher antitumor effects in a breast cancer model compared to the parental compound. The goal of present work was to explore the antitumor properties of the V2r agonist dDAVP and its novel analog [V4Q5]dDAVP on aggressive human lung (NCI-H82) and prostate cancer (PC-3) cell lines with neuroendocrine (NE) characteristics. We study the presence of specific NE markers (CgA and NSE) and V2r expression in NCI-H82 and PC-3. Both cell lines express high levels of NE markers NSE and CgA but then incubation with dDAVP diminished expression levels of both markers. DDAVP and [V4Q5]dDAVP significantly reduced proliferation, doubling time, and migration in both tumor cell cultures. [V4Q5]dDAVP analog showed a higher cytostatic effect than dDAVP, on cellular proliferation in the NCI-H82 cell line. Silencing of V2r using small interfering RNA significantly attenuated the inhibitory effects of [V4Q5]dDAVP on NCI-H82 cell proliferation. We, preliminarily, explored the in vivo effect of dDAVP and [V4Q5]dDAVP on NCI-H82 small cell lung cancer xenografts. Treated tumors (0.3 μg kg−1, thrice a week) grew slower in comparison to vehicle-treated animals. In this work, we demonstrated

  7. Central nervous system complications after liver transplantation. (United States)

    Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu


    We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology.

  8. [Neurocutaneous syndrome with hair alterations]. (United States)

    Camacho-Martínez, F


    There are multiple neurocutaneous syndromes that may show hair alterations such as the interglabellar peak or 'widow's peak', which is an alteration of the hair implantation, in addition to the genohypotrichosis, hypertrichosis and hair shaft dysplasias. In this chapter we will focus on the latter. Out of the unspecific hair shaft dysplasias the only ones showing neurological alterations are trichorrhexis invaginata, observed in the syndrome of Netherton. Among the specific dysplasias we would like to point out monilethrix, and very especially the moniliform hair syndrome, the trichorrhexis nodosa, the pili torti and trichotiodystrophy. The latter is actually a group of syndromes which associates a series of diverse symptoms that have in common hair brittleness, fertility problems and physical and mental retardation, and they constitute the basic syndrome know as 'BIDS syndrome.

  9. The central peak revisited

    Energy Technology Data Exchange (ETDEWEB)

    Shirane, G.


    The central peak in SrTiO{sub 3} was first observed by Riste and his collaborators in 1971. This was one of the key discoveries leading to an understanding of the dynamics of phase transitions. The most recent discovery of two length scales in SrTiO{sub 3} motivated a reinvestigation of the soft phonon and associated central peak by neutron scattering. These recent experiments shed new light on the nature of the central peak. It is now well established to be strongly sample dependent and it originates from defects in bulk crystals.

  10. Imaging central pain syndromes. (United States)

    Veldhuijzen, Dieuwke S; Greenspan, Joel D; Kim, Jong H; Coghill, Robert C; Treede, Rolf-Detlef; Ohara, Shinji; Lenz, Frederick A


    Anatomic, functional, and neurochemical imaging studies have provided new investigative tools in the study of central pain. High-resolution imaging studies allow for precise determination of lesion location, whereas functional neuroimaging studies measure pathophysiologic consequences of injury to the central nervous system. Additionally, magnetic resonance spectroscopy evaluates lesion-induced neurochemical changes in specific brain regions that may be related to central pain. The small number of studies to date precludes definitive conclusions, but the recent findings provide information that either supports or refutes current hypotheses and can serve to generate new ideas.

  11. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E;


    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities ...

  12. Central Asian Republic Info (United States)

    US Agency for International Development — CAR Info is designed and managed by the Central Asian Republic Mission to fill in the knowledge and reporting gaps in existing agency systems for that Mission. It...

  13. Central nervous system (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  14. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E


    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  15. "Central Station" Londonis

    Index Scriptorium Estoniae


    Londoni galeriis Milch seitsme läti, leedu ja eesti kunstniku projekt "Central Station". Kuraatorid Lisa Panting, Sally Tallant. Eestist osalevad Hanno Soans (Catarina Campinoga koostöös valminud video), Kiwa, Kai Kaljo

  16. Central Station Design Options

    DEFF Research Database (Denmark)


    The purpose of EDISON Work Package 4.1 is the evaluation of possible Central (charging) Stations design options for making possible the public charging of Electric Vehicles (EVs). A number of scenarios for EVs are assessed, with special emphasis on the options of Fast Charging and Battery Swapping....... The work identifies the architecture, sizing and siting of prospective Central Stations in Denmark, which can be located at shopping centers, large car parking lots or gas stations. Central Stations are planned to be integrated in the Danish distribution grid. The Danish island of Bornholm, where a high.......g. due to vandalism, the charge supply circuit is disconnected. More electrical vehicles on the market are capable today of quick charging up to 50 kW power level. The feasibility of Central Stations with fast charging/swapping option, their capacity, design, costs and grid impact, as well as battery...

  17. Altered cardiovascular reactivity and osmoregulation during hyperosmotic stress in adult rats developmentally exposed to polybrominated diphenyl ethers (PBDEs) (United States)

    Polybrominated diphenyl ethers (PBDEs) and the structurally similar chemicals polychlorinated biphenyls (PCBs) disrupt the function of multiple endocrine systems. PCBs and PBDEs disrupt the secretion of vasopressin (VP) from the hypothalamus during osmotic activation. Since the p...

  18. Gangs in Central America (United States)


    Citizen Security held in July 2008 indicated that Guatemala now has the second highest murder rate in Central America (roughly 45 per 100,000 regional security forces.48 In recent years, the U.S. Southern Command has taken a leading role in discussing the problem of citizen security in...the results CRS-19 51 “Memo: The Merida Initiative and Citizen Security in Mexico and Central America,” Washington Office on Latin America, March 2008

  19. Outsourcing central banking

    DEFF Research Database (Denmark)

    Khoury, Sarkis Joseph; Wihlborg, Clas


    The literature on Currency Boards (CB) stops at the water edge in terms of dealing with the totality of the functions of a central bank. Monetary policy, and banking supervisioncan be "outsourced" in an open economy with substantial foreign direct investment (FDI)in the banking sector if political...... the feasibility of, and constraints on, outsourcing of central bank functions. A brief discussion of the Argentinian experience is used for contrast.Key words: Currency Board, Foreign Banks, Supervision, Regional Integration,outsourcing....

  20. Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice. (United States)

    Zhang, Yue; Peti-Peterdi, János; Heiney, Kristina M; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K


    Lithium (Li) administration causes deranged expression and function of renal aquaporins and sodium channels/transporters resulting in nephrogenic diabetes insipidus (NDI). Extracellular nucleotides (ATP/ADP/UTP), via P2 receptors, regulate these transport functions. We tested whether clopidogrel bisulfate (CLPD), an antagonist of ADP-activated P2Y(12) receptor, would affect Li-induced alterations in renal aquaporins and sodium channels/transporters. Adult mice were treated for 14 days with CLPD and/or Li and euthanized. Urine and kidneys were collected for analysis. When administered with Li, CLPD ameliorated polyuria, attenuated the rise in urine prostaglandin E2 (PGE2), and resulted in significantly higher urinary arginine vasopressin (AVP) and aldosterone levels as compared to Li treatment alone. However, urine sodium excretion remained elevated. Semi-quantitative immunoblotting revealed that CLPD alone increased renal aquaporin 2 (AQP2), Na-K-2Cl cotransporter (NKCC2), Na-Cl cotransporter (NCC), and the subunits of the epithelial Na channel (ENaC) in medulla by 25-130 %. When combined with Li, CLPD prevented downregulation of AQP2, Na-K-ATPase, and NKCC2 but was less effective against downregulation of cortical α- or γ-ENaC (70 kDa band). Thus, CLPD primarily attenuated Li-induced downregulation of proteins involved in water conservation (AVP-sensitive), with modest effects on aldosterone-sensitive proteins potentially explaining sustained natriuresis. Confocal immunofluorescence microscopy revealed strong labeling for P2Y(12)-R in proximal tubule brush border and blood vessels in the cortex and less intense labeling in medullary thick ascending limb and the collecting ducts. Therefore, there is the potential for CLPD to be directly acting at the tubule sites to mediate these effects. In conclusion, P2Y(12)-R may represent a novel therapeutic target for Li-induced NDI.

  1. Art as Alterity in Education (United States)

    Zhao, Guoping


    In education, art has often been perceived as entertainment and decoration and is the first subject to go when there are budget cuts or test-score pressures. Drawing on Emmanuel Lévinas's idea of the primacy of radical alterity that breaks the totality of our being, enables self-transformation and ethics, and ensures community as a totality…

  2. School Reentry for Children with Acquired Central Nervous Systems Injuries (United States)

    Carney, Joan; Porter, Patricia


    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  3. Modelling glass alteration in an altered argillaceous environment (United States)

    Bildstein, O.; Trotignon, L.; Pozo, C.; Jullien, M.


    The long term behaviour of materials such as glass, steel and clay has been investigated in the context of deep geological disposal of radioactive wastes. The interactions between vitrified wastes, canister corrosion products (CPs) and clay are studied using a modified version of the reaction-transport code Crunch, especially looking at pH changes and possible cementation at the interface with the clayey materials. These perturbations may indeed affect the lifetime of glass matrix in deep repositories, e.g., high pH enhances the rate of glass alteration. This work focuses on the argillite of Bure. The calculations were performed at 323 K with a glass alteration rate switching from a high initial rate to a residual rate according to the sorption capacity of CPs. The time at which this sorption capacity is saturated is crucial to the system in terms of wastes package lifetime. The results show that the glass alteration imposes a high pH value at the interface with CPs and clay: up to a value of 9.2, compared to 7.3 which is the initial pH value in the argillite. Experimental data show that the rate of glass alteration is much higher in such pH conditions. For a R7T7-type glass, the rate is about five times higher at pH 9 than at pH 7. This pH perturbation migrates through the clayey domain as a result of the migration of mobile elements such as boron and sodium, and despite the existence of strong pH buffers in the argillite. The cementation of porosity at the interface between glass and clay is predicted by the model due to the massive precipitation of iron corrosion products and glass alteration products. At this point of the evolution of the system, the pH starts to decrease and the alteration rate of the glass could be significantly reduced. This porosity clogging effect is difficult to confirm by experiments especially since existing data on short term experiments tend to show a pervasive precipitation of silica in the domain instead of a localized precipitation


    Energy Technology Data Exchange (ETDEWEB)

    ROMINE, L.D.


    A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach to Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress.

  5. [Factors that alter taste perception]. (United States)

    Maffeis, E R; Silva-Netto, C R


    Dysfunction of taste perception is a significant problem for many individuals. Taste anomalies may affect health not only by directly affecting liquid and solid food intake, but also by creating a state of depression due to the loss of an important source of pleasure. Many factors alter taste perception, such as lesions of the oral mucosa, cigarette smoking, radiation, chemotherapy, renal disease, hepatitis, leprosy, hormones, nutrition, use of dentures, medications, and aging. Gum or ice chewing may temporarily help loss of taste. Patients should be encouraged to chew their food thoroughly, alternating the sides of the mouth, or alternating different foods. Unfortunately, in many cases there is no cure for this alteration, and patience is then the only possibility.

  6. The Naive Central Banker

    Directory of Open Access Journals (Sweden)

    Marcelo de Carvalho Griebeler


    Full Text Available There has been in some countries a trend of assigning other functions to central banks besides price stability. The most suggested function to be added to monetary authority’s obligations is to pursue economic growth or full employment. In this paper we characterize the behavior and analyse the optimal monetary policy of, what we call, a naive central banker. We describe the naive behavior as one that does face the inflation-unemployment trade-off, but it tries to minimize both variables simultaneously. Our findings, both under discretion and commitment, indicate that the naive central banker delivers lower expected inflation and inflation variance than the benchmark behavior whenever the economy is rigid enough. However, the degree of conservativeness also affects this result, such that the less conservative the naive policymaker, the more rigidity is necessary.

  7. SOCRATES Invades Central Europe

    Directory of Open Access Journals (Sweden)

    Joseph Slowinski


    Full Text Available The objective of this article is to explore the current reality faced by higher education students in Central and Eastern Europe and to draw out the implications of this current reality for policy makers in the future. In the article, I explore the influence of transnational corporations' training programs on education as it currently pertains to Central and Eastern European higher education and employment. In addition, multinational corporate entities exercise influence on European Union policy through the role of lobby organizations and activities. I explore the influence of these practices on education with an emphasis on the emerging importance of Western language skills. In addition, I focus on the European Union and its efforts to expand into Central and Eastern Europe in order to provide a focal point for analysis.

  8. [Central regulation of adenohypophyseal function]. (United States)

    Vigas, M


    The secretion of adenohypophyseal hormones is controlled by hypothalamic hypophysotropic hormones with stimulating (hormone releasing factors) or inhibitory (hormone release inhibiting factors) actions. The release of hypothalamic hormones is regulated by hierarchically higher nerve centres via neurons which liberate neurotransmitters at their endings. The secretion of growth hormone is controlled by hypothalamic hormones, somatotropin releasing factor and somatotropin release-inhibiting factor; of the neurotransmitters, the strongest effects have noradrenaline and dopamine. The release of ACTH is controlled by two stimulating hormones, the ACTH releasing factor and vasopressin, the effects of neurotransmitters are less marked, with the involvement of noradrenaline, serotonin, acetylcholine, gamma aminobutyric acid and other agents. Prolactin release is under the main inhibitory control of hypothalamic dopamine, no release-stimulating hypothalamic factor could be unequivocally demonstrated as yet; likely, several peptides are involved in this mechanism. The release of thyrotropic hormone is stimulated by thyrotropin releasing factor, whereas somatotropin release-inhibiting factor has an inhibitory action. Of the neurotransmitters, the inhibitory effect of dopamine is important; this agent however acts also at the hypophyseal level. External hypothalamic hormones and regulatory neurotransmitters are used in the diagnosis and treatment of neuroendocrine disorders.

  9. Effects of vasopressin and adrenaline on cerebral resuscitation in rats undergone cardiopulmonary resuscitation%血管加压素与肾上腺素对大鼠脑复苏效果的影响

    Institute of Scientific and Technical Information of China (English)

    杨伟伟; 彭鹏


    Objective To compare the effects of vasopressin and adrenaline on cerebral resuscitation in rats. Method Sixty male SD rats were used to set the animal model of cardiac arrest and were randomly (random number) divided into 4 groups (n = 15/group): sham operation group (sham-gro), negative control group (neg-gro), vasopressin group (vas-gro) and adrenaline group (adr-gro). Blood pressure was recorded, and brain tissue samples were obtained. Results There was no significant difference in the recovery rate between vas-gro and adr-gro 30 min after resuscitation (P <0.05). The mean blood pressure in vasgro was higher than that in adr-gro within 30 min (1,2, 5, 10, 20, 30 min) after restoration of spontaneous circulation. The measured MDA, SOD and GSH were significantly different (P < 0.05) between each two groups among vas-gro, sham-gro and adr-gro. Conclusions The recovery rate was similar between vasopressin group and adrenaline group during cardiopulmonary resuscitation in rats. However, vasopressin can to maintain the mean arterial pressure at a higher level after resuscitation, which can the increase the cerebral perfusion and reduce brain cell damage.%目的 比较血管加压素与肾上腺素对大鼠脑复苏效果的研究.方法 60只雄性SD大鼠建立心搏骤停模型,随机(随机数字法)分为4组(n=15/组):假手术组(sham operated group,shamgro)、阴性对照组(neg-gro)、血管加压素组(vas-gro)、肾上腺素组(adr-gro).分别记录血压变化,并取大鼠脑组织标本.结果 在复苏30 min后vas-gro与adr-gro复苏成功率差异无统计学意义(P>0.05);在自主循环恢复的30 min内(1,2,5,10,20,30 min)vas-gro的平均动脉压均高于adr-gro;测得MDA,SOD,GSH的量vas-gro,sham-gro,adr-gro互相之间差异有统计学意义(P<0.05).结论 血管加压素与肾上腺素在大鼠心肺复苏过程中成功率相近,但血管加压素能维持复苏后平均动脉压在较高水平,继而会更好的增加脑灌注,减轻脑细胞损伤.

  10. A molecular mechanics study of the effect of substitution in position 1 on the conformational space of the oxytocin/vasopressin ring (United States)

    Tarnowska, Monika; Liwo, Adam; Shenderovich, Mark D.; Liepiņa, Inta; Golbraikh, Alexander A.; Grzonka, Zbigniew; Tempczyk, Anna


    The effect of the substitution in position 1 on the low-energy conformations of the oxytocin/vasopressin 20-membered ring was investigated by means of molecular mechanics. Three representative substitutions were considered: β'-mercapto-β,β-dimethyl)propionic acid (Dmp), (β'-mercapto-β,β-cyclopentamethylene)propionic acid (Cpp), both forming strong antagonists, and (α,α-dimethyl-β-mercapto)propionic acid (α-Dmp), forming analogs of strongly reduced biological activity, with the β-mercaptopropionic (Mpa) residue taken as reference. Both ECEPP/2 (rigid valence geometry) and AMBER (flexible valence geometry) force fields were employed in the calculations. Three basic types of backbone conformations were taken into account which are distinguished by the type of β-turn at residues 3 and 4: β1/βIII, βII, and βI'/βIII', all types containing one or two intra-annular hydrogen bonds. The allowed (ring-closed) disulfide-bridge conformations were searched by an algorithm formulated in terms of scanning the disulfide-bridge torsional angle Cβ-S-S-Cβ. The ECEPP/2 and AMBER energies of the obtained conformations were found to be in reasonable agreement. Two of the low-energy conformers of the [Mpa1]-compound agreed very well with the cyclic part of the two conformers found in the crystal structure of [Mpa1]-oxytocin. An analysis of the effect of β-substitution on relative energies showed that the conformations with the N-C'-CH2-CH2 (ψ'1) and C'-CH2-CH2-S (ϰ'1) angles of the first residue around (-100°, 60°) and (100°, -60°) are not affected; this in most cases implies a left-handed disulfide bridge. In the case of α-substitution the allowed values of ψ'1 are close to ± 60°. This requirement, being in contradiction to the one concerning β-substitution, could explain the very low biological activity of the α-substituted analogs. The conformational preferences of substituted compounds can largely be explained by the analysis of local interactions

  11. Fantastic alterities and The Sandman



    This article explores the ways in which the comics medium enhances our understanding of literary models of the Fantastic. It examines the presence and depiction of multiple worlds in Neil Gaiman’s The Sandman, with specific reference to the role of the comics medium and its denial of mimesis when creating such alterities. \\ud \\ud It initially uses literature review to establish a contemporary working model of the Fantastic, taking as its basis the framework devised by Tzvetan Todorov, and inc...

  12. Buccal alterations in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Negrato Carlos


    Full Text Available Abstract Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: a increased concentration of mucin and glucose; b impaired production and/or action of many antimicrobial factors; c absence of a metalloprotein called gustin, that contains zinc and is responsible for the constant maturation of taste papillae; d bad taste; e oral candidiasis f increased cells exfoliation after contact, because of poor lubrication; g increased proliferation of pathogenic microorganisms; h coated tongue; i halitosis; and many others may occur as a consequence of chronic hyperglycaemia: a tongue alterations, generally a burning mouth; b periodontal disease; c white spots due to demineralization in the teeth; d caries; e delayed healing of wounds; f greater tendency to infections; g lichen planus; h mucosa ulcerations. Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present.

  13. Oral alterations among chemical dependents

    Directory of Open Access Journals (Sweden)

    Estela Vanessa COLODEL


    Full Text Available Introduction: It has been daily observed a significant increase ofchemical dependent individuals, as well as the lack of depth on thisissue in the dentistry area. Nevertheless many times the dentalclinicians are the first professionals to diagnose possible alterations,which appear due to the consumption of tobacco, alcohol and other illicit drugs. Objectives: To make a literature review of oral alterations and to identify them on a specific group of persons, which are addicted to different types of drugs. Material and methods: The clinical history of the selected individuals was added to the answers of a questionnaire,comprising the data of the present research. Results: Besides other minor soft tissue alterations, a high prevalence of caries and periodontal diseases were found in the studied population. Conclusion: It was concluded that the role of the dental clinician is very important to the health rehabilitation of drug addicts, individuals with physical and mental disorders that need specific oral care, which sometimes is neglected.

  14. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU


    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  15. Several Centuries of Centrality


    Roth, Dana L.


    As Carolyn Bertozzi mentioned in her inaugural editorial, the relationship of “Central Science” to “Chemistry” became popularized over 40 years ago with the publication of the first edition of Brown and LeMay’s Chemistry: The Central Science, now in its 13th edition. Yet as late as 2003, Prof. Sason Shaik at The Hebrew University claimed “popularization of chemistry remains scant.” He goes on to share [his] “own experience of popularizing chemistry by delivering the following universal messag...

  16. Glueballs A central mystery

    CERN Document Server

    Close, Francis Edwin


    Glueball candidates and qqbar mesons have been found to be produced with different momentum and angular dependences in the central region of pp collisions. This talk illustrates this phenomenon and explains the phi and t dependences of mesons with JPC = 0++,0-+, 1++, 2++ and 2-+. For production of 0++ and 2++ mesons the analysis reveals a systematic behaviour in the data that appears to distinguish between qqbar and non-qqbar or glueball candidates. An explanation is given for the absence of 0-+ glueball candidates in central production at present energies and the opportunity for their discovery at RHIC is noted.

  17. Efficacy of vasopressin combined with epinephrine during adult cardiopulmonary resuscitation:a meta-analysis%成人 CPR 中血管加压素联合肾上腺素疗效的 Meta分析

    Institute of Scientific and Technical Information of China (English)

    邹勤华; 钱会银; 徐波; 朱建良; 周保纯; 刘一韡; 朱凌霞; 刘励军


    目的:在成人心肺复苏术( CPR)中,血管加压素联合肾上腺素的应用是否优于肾上腺素尚未定论,本研究针对现有的临床研究资料进行荟萃分析。方法在Pub Med、万方数据库检索关于成人CPR联合或单独应用肾上腺素的所有随机对照临床研究。观察指标包括复苏后自主循环恢复( ROSC)率、入院存活率(或短期存活率)、出院存活率(或长期存活率)和神经功能预后。结果在检索到的191篇文献中,最终纳入分析的有8项随机对照研究(共5740例患者),其中5项为院外心脏骤停( OHCA,5172例患者)研究,3项为院内心脏骤停( IHCA,568例患者)研究。依据患者心脏骤停( CA)最初检测到的心律,分为室颤/室速( VF/VT),无脉性电活动和心室停顿进行亚组分析。结果表明,与单用肾上腺素组比较,血管加压素联合肾上腺素组能提高成人心脏骤停患者入院存活率(短期存活率)(RR=1.15,95%CI=1.01~1.32,P=0.04),而ROSC率、出院存活率及神经功能预后比较差异无统计学意义(P>0.05)。亚组分析发现,联合用药组对于IHCA患者ROSC率(RR 1.30,95%CI=1.11~1.51,P=0.001)及短期存活率(RR1.23,95%CI=1.05~1.44,P=0.01)效果优于肾上腺素组。结论血管加压素联合肾上腺素较单用肾上腺素可明显提高CA患者入院存活率(短期存活率);对于IHCA患者,联合应用可提高患者ROSC率和短期存活率。%Objective During adult cardiopulmonary resuscitation, the efficacy of vasopressin combined with epinephrine versus epinephrine alone remains controversial. This meta - analysis was conducted on the existing clinical research data. Methods PubMed and WANFANG databases were searched for randomized controlled clinical studies on the combination or the use of epinephrine alone during adult cardiopulmonary resuscitation. The observation outcomes included the return of spontaneous circulation (ROSC) after cardiopulmonary resuscitation, admission survival

  18. Central mechanism of the cardiovascular responses caused by L-proline microinjected into the paraventricular nucleus of the hypothalamus in unanesthetized rats. (United States)

    Lopes-Azevedo, Silvana; Busnardo, Cristiane; Corrêa, Fernando Morgan Aguiar


    Previously, we reported that microinjection of L-proline (L-Pro) into the paraventricular nucleus of the hypothalamus (PVN) caused vasopressin-mediated pressor responses in unanesthetized rats. In the present study, we report on the central mechanisms involved in the mediation of the cardiovascular effects caused by the microinjection of L-Pro into the PVN. Microinjection of increasing doses of L-Pro (3-100nmol/100nL) into the PVN caused dose-related pressor and bradycardic responses. No cardiovascular responses were observed after the microinjection of equimolar doses (33nmol/100nL) of its isomer D-Proline (D-Pro) or Mannitol. The PVN pretreatment with either a selective non-NMDA (NBQX) or selective NMDA (LY235959 or DL-AP7) glutamate receptor antagonists blocked the cardiovascular response to L-Pro (33nmol/100nL). The dose-effect curve for the pretreatment with increasing doses of LY235959 was located at the left in relation to the curves for NBQX and DL-AP7, showing that LY235959 is more potent than NBQX, which is more potent than DL-AP7 in inhibiting the cardiovascular response to L-Pro. The cardiovascular response to the microinjection of L-Pro into the PVN was not affected by local pretreatment with N(ω)-Propyl-l-arginine (N-Propyl), a selective inhibitor of the neuronal nitric oxide synthase (nNOS), suggesting that NO does not mediate the responses to L-Pro in the PVN. In conclusion, the results suggest that ionotropic receptors in the PVN, blocked by both NMDA and non-NMDA receptor antagonists, mediate the pressor response to L-Pro that results from activation of PVN vasopressinergic magnocellular neurons and vasopressin release into the systemic circulation.

  19. Retiring the central executive. (United States)

    Logie, Robert H


    Reasoning, problem solving, comprehension, learning and retrieval, inhibition, switching, updating, or multitasking are often referred to as higher cognition, thought to require control processes or the use of a central executive. However, the concept of an executive controller begs the question of what is controlling the controller and so on, leading to an infinite hierarchy of executives or "homunculi". In what is now a QJEP citation classic, Baddeley [Baddeley, A. D. (1996). Exploring the central executive. Quarterly Journal of Experimental Psychology, 49A, 5-28] referred to the concept of a central executive in cognition as a "conceptual ragbag" that acted as a placeholder umbrella term for aspects of cognition that are complex, were poorly understood at the time, and most likely involve several different cognitive functions working in concert. He suggested that with systematic empirical research, advances in understanding might progress sufficiently to allow the executive concept to be "sacked". This article offers an overview of the 1996 article and of some subsequent systematic research and argues that after two decades of research, there is sufficient advance in understanding to suggest that executive control might arise from the interaction among multiple different functions in cognition that use different, but overlapping, brain networks. The article concludes that the central executive concept might now be offered a dignified retirement.

  20. Central Nervous System Tuberculosis


    Bano, Shahina; Chaudhary, Vikas; Yadav, Sachchidanand


    Central nervous system tuberculosis is a rare presentation of active tuberculosis and accounts for about 1% of cases (1). The three clinical categories include meningitis, intracranial tuberculomas, and spinal tuberculous arachnoiditis. We report a case of a young man who presented with active pulmonary tuberculosis in addition to tuberculous meningitis and the presence of numerous intracranial tuberculomas.

  1. Central venous line - infants (United States)

    A central venous line (CVL) is a long, soft, plastic tube that is put into a large vein in the chest. WHY IS A CVL USED? A CVL is often put in when a baby cannot get a ... (MCC). A CVL can be used to give nutrients or medicines to a ...

  2. CMS Central Hadron Calorimeter


    Budd, Howard S.


    We present a description of the CMS central hadron calorimeter. We describe the production of the 1996 CMS hadron testbeam module. We show the results of the quality control tests of the testbeam module. We present some results of the 1995 CMS hadron testbeam.

  3. Ecodesign in Central America

    NARCIS (Netherlands)

    Crul, M.R.M.


    This PhD thesis describes and analyses the change process started by the Ecodesign project in Central America, executed between 1998 and 2002. The project started using the concept and praxis developed in Europe. Nine ecodesign projects were performed in industry, and ecodesign was introduced to cou

  4. Central nervous system tuberculosis. (United States)

    Torres, Carlos; Riascos, Roy; Figueroa, Ramon; Gupta, Rakesh K


    Tuberculosis (TB) has shown a resurgence in nonendemic populations in recent years and accounts for 8 million deaths annually in the world. Central nervous system involvement is one of the most serious forms of this infection, acting as a prominent cause of morbidity and mortality in developing countries. The rising number of cases in developed countries is mostly attributed to factors such as the pandemic of acquired immunodeficiency syndrome and increased migration in a globalized world. Mycobacterium TB is responsible for almost all cases of tubercular infection in the central nervous system. It can manifest in a variety of forms as tuberculous meningitis, tuberculoma, and tubercular abscess. Spinal infection may result in spondylitis, arachnoiditis, and/or focal intramedullary tuberculomas. Timely diagnosis of central nervous system TB is paramount for the early institution of appropriate therapy, because delayed treatment is associated with severe morbidity and mortality. It is therefore important that physicians and radiologists understand the characteristic patterns, distribution, and imaging manifestations of TB in the central nervous system. Magnetic resonance imaging is considered the imaging modality of choice for the study of patients with suspected TB. Advanced imaging techniques including magnetic resonance perfusion and diffusion tensor imaging may be of value in the objective assessment of therapy and to guide the physician in the modulation of therapy in these patients.

  5. Central Dogma Goes Digital. (United States)

    Lin, Yihan; Elowitz, Michael B


    In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology.

  6. Multicultural Central Asia. (United States)

    Boyle, Eric D.

    This article addresses the multicultural aspect of Central Asia in response to the discussion on diversity in U.S. classrooms. Many areas of the world are more diverse than the U.S., and these areas experience successes and failures with many of the same issues the U.S. is currently struggling with. Comparing the U.S. diversity debate with similar…

  7. Channeling the Central Dogma. (United States)

    Calabrese, Ronald L


    How do neurons and networks achieve their characteristic electrical activity, regulate this activity homeostatically, and yet show population variability in expression? In this issue of Neuron, O'Leary et al. (2014) address some of these thorny questions in this theoretical analysis that starts with the Central Dogma.

  8. Company activities - central region

    Energy Technology Data Exchange (ETDEWEB)

    Ayling, G.


    The first section of the article gives an overview of exploration and new developments in the field of gold, nickel, diamond and opal mining in central Queensland. The second part looks at coal, coal seam gas and petroleum exploration and development projects in the area. 1 fig.

  9. Testing for central symmetry

    NARCIS (Netherlands)

    Einmahl, John; Gan, Zhuojiong


    Omnibus tests for central symmetry of a bivariate probability distribution are proposed. The test statistics compare empirical measures of opposite regions. Under rather weak conditions, we establish the asymptotic distribution of the test statistics under the null hypothesis; it follows that they a

  10. Central areolar choroidal dystrophy.

    NARCIS (Netherlands)

    Boon, C.J.F.; Klevering, B.J.; Cremers, F.P.M.; Zonneveld-Vrieling, M.N.; Theelen, T.; Hollander, A.I. den; Hoyng, C.B.


    OBJECTIVE: To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD). DESIGN: Retrospective case series study. PARTICIPANTS: One hundred three patients with CACD from the Netherlands. METHODS

  11. Effects of passive heating on central blood volume and ventricular dimensions in humans

    DEFF Research Database (Denmark)

    Crandall, C.G.; Wilson, T.E.; Marving, J.;


    Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat...... plus central vasculature (17 +/- 2%), thorax (14 +/- 2%), inferior vena cava (23 +/- 2%) and liver (23 +/- 2%) (all P Udgivelsesdato: 2008/1/1...

  12. Induced, endogenous and exogenous centrality


    Everett, Martin G.; Stephen P. Borgatti


    Centrality measures are based upon the structural position an actor has within the network. Induced centrality, sometimes called vitality measures, take graph invariants as an overall measure and derive vertex level measures by deleting individual nodes or edges and examining the overall change. By taking the sum of standard centrality measures as the graph invariant we can obtain measures which examine how much centrality an individual node contributes to the centrality of the other nodes in...

  13. Do Central Banks Need Capital?


    Peter Stella


    Central banks may operate perfectly well without capital as conventionally defined. A large negative net worth, however, is likely to compromise central bank independence and interfere with its ability to attain policy objectives. If society values an independent central bank capable of effectively implementing monetary policy, recapitalization may become essential. Proper accounting practice in determining central bank profit or loss and rules governing the transfer of the central bank’s ope...

  14. Do Baryons Alter the Halos of Low Surface Brightness Galaxies?

    CERN Document Server

    de Naray, Rachel Kuzio


    High-quality observations of dark matter-dominated low surface brightness (LSB) galaxies indicate that, in contrast to the triaxial, centrally-concentrated cuspy halos formed in collisionless simulations of halo assembly, these galaxies reside in round, roughly constant density cored halos. In order to reconcile these data with galaxy formation in the context of LCDM, processes that alter the shape and density structure of the inner halo are required. We compile observational properties of LSB galaxies to evaluate the plausibility that a previously higher baryonic mass content and feedback from star formation can modify the dark matter halos of these galaxies. We also compare the properties of bulgeless disk galaxies formed in recent simulations to the LSB galaxy sample. We find that observational constraints on LSB galaxy star formation histories, structure, and kinematics make it difficult for baryonic physics to sphericalize and decrease the central density of the dark matter halos of LSB galaxies.

  15. Pesticide Exposures May Alter Mouth Bacteria (United States)

    ... fullstory_162249.html Pesticide Exposures May Alter Mouth Bacteria Study of Washington farm workers finds alterations persist ... News) -- Pesticide exposure may change the makeup of bacteria in the mouths of farm workers, a new ...

  16. A kernel version of multivariate alteration detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack


    Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations.......Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations....

  17. Central simple Poisson algebras

    Institute of Scientific and Technical Information of China (English)

    SU Yucai; XU Xiaoping


    Poisson algebras are fundamental algebraic structures in physics and symplectic geometry. However, the structure theory of Poisson algebras has not been well developed. In this paper, we determine the structure of the central simple Poisson algebras related to locally finite derivations, over an algebraically closed field of characteristic zero.The Lie algebra structures of these Poisson algebras are in general not finitely-graded.

  18. Central corneal abscess. (United States)

    van Bijsterveld, O P


    Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae.

  19. FNAL central email systems

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Jack; Lilianstrom, Al; Pasetes, Ray; Hill, Kevin; /Fermilab


    The FNAL Email System is the primary point of entry for email destined for an employee or user at Fermilab. This centrally supported system is designed for reliability and availability. It uses multiple layers of protection to help ensure that: (1) SPAM messages are tagged properly; (2) All mail is inspected for viruses; and (3) Valid mail gets delivered. This system employs numerous redundant subsystems to accomplish these tasks.

  20. Centrality Measures in Networks

    CERN Document Server

    Bloch, Francis; Tebaldi, Pietro


    We show that although the prominent centrality measures in network analysis make use of different information about nodes' positions, they all process that information in an identical way: they all spring from a common family that are characterized by the same simple axioms. In particular, they are all based on a monotonic and additively separable treatment of a statistic that captures a node's position in the network.

  1. Distributed Assessment of Network Centrality

    CERN Document Server

    Wehmuth, Klaus


    We propose a method for the Distributed Assessment of Network CEntrality (DANCE) in complex networks. DANCE attributes to each node a volume-based centrality computed using only localized information, thus not requiring knowledge of the full network topology. We show DANCE is simple, yet efficient, in assessing node centrality in a distributed way. Our proposal also provides a way for locating the most central nodes, again using only the localized information at each node. We also show that the node rankings based on DANCE's centrality and the traditional closeness centrality correlate very well. This is quite useful given the vast potential applicability of closeness centrality, which is however limited by its high computational costs. We experimentally evaluate DANCE against a state-of-the-art proposal to distributively assess network centrality. Results attest that DANCE achieves similar effectiveness in assessing network centrality, but with a significant reduction in the associated costs for practical ap...

  2. West and Central Africa. (United States)

    Lydie, N; Robinson, N J


    This article reviews scientific and other literature during the 1990s that links migration and mobility with the spread of sexually transmitted diseases (STDs), including HIV/AIDS. The focus is on key population groups linked to the spread of HIV and STDs in West and Central Africa: migrant laborers, truck drivers, itinerant traders, commercial sex workers (CSWs), and refugees. Countries with high emigration and immigration tend to have high levels of HIV infection, with the exception of Senegal. The main destination of immigrants are Senegal, Nigeria, and Cote d'Ivoire in West Africa and Cameroon, Congo, Gabon, and Congo in Central Africa. The risk of infection and the spread of HIV is variable among migrants. There is little in the literature that substantiates hypotheses about the strong association between migration and HIV-positive status. Information is needed on the duration, frequency of return visits, living conditions, sexual activities with multiple partners, and information before departure, along the routes, at final destination, and at the time of returns. Action-based research in five West African countries (Burkina Faso, Cote d'Ivoire, Mali, Niger, and Senegal) should produce results in late 1998. Comparable studies in Central Africa are unknown. Regional studies should be complemented by local studies. Prevention would benefit from studies on the relative size of these five population groups by geographic location.

  3. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis

    NARCIS (Netherlands)

    Gispen, W.H.; Duckers, H.J.; Dokkum, R.P. van; Verhaagen, J.; Luijtelaar, E.L.; Coenen, A.M.; Lopes da Silva, F.H.


    Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best de

  4. Central African Republic. (United States)


    Focus in this discussion of the Central African Republic is on: geography; the people; history and political conditions; government; the economy; foreign relations; and relations with the US. The population of the Central African Republic totaled 2.7 million in 1985 with an annual growth rate of 2.8%. The infant mortality rate is 134/1000 with life expectancy at 49 years. The Central African Republic is at almost the precise center of Africa, about 640 km from the nearest ocean. More than 70% of the population live in rural areas. There are more than 80 ethnic groups, each with its own language. The precolonial history of the area was marked by successive waves of migration, of which little is known. These migrations are responsible for the complex ethnic and linguistic patterns today. United with Chad in 1906, it formed the Oubangui-Chari-Chad colony. In 1910, it became 1 of the 4 territories of the Federation of French Equatorial Africa, along with Chad, Congo, and Gabon. After World War II, the French Constitution of 1946 inaugurated the first of a series of reforms that led eventually to complete independence for all French territories in western and equatorial Africa. The nation became an autonomous republic within the newly established French Community on December 1, 1958, and acceded to complete independence as the Central Africa Republic on August 13, 1960. The government is made up of the executive and the judicial branches. The constitution and legislature remain suspended. All executive and legislative powers, as well as judicial oversight, are vested in the chief of state. The Central African Republic is 1 of the world's least developed countries, with an annual per capita income of $310. 85% of the population is engaged in subsistence farming. Diamonds account for nearly 1/3 of export earnings; the industrial sector is limited. The US terminated bilateral assistance programs in 1979, due to the human rights violations of the Bokassa regime, but modest

  5. Small vessel disease and cognitive impairment: The relevance of central network connections. (United States)

    Reijmer, Yael D; Fotiadis, Panagiotis; Piantoni, Giovanni; Boulouis, Gregoire; Kelly, Kathleen E; Gurol, Mahmut E; Leemans, Alexander; O'Sullivan, Michael J; Greenberg, Steven M; Viswanathan, Anand


    Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network connections. Brain networks were reconstructed from diffusion-weighted MRI scans in 72 individuals (75 ± 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non-central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non-central network connections (r = 0.41 vs. r = 0.27; P 50%-10% connections). Higher SVD burden was associated with lower FA in central as well as non-central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): -0.15 (-0.35 to -0.02)]. The mediation effect was not observed for FA alterations in non-central network connections [-0.03 (-0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. Hum Brain Mapp 37:2446-2454, 2016. © 2016 Wiley Periodicals, Inc.

  6. Window to 'Clovis's' Altered Past (United States)


    This image taken by the Mars Exploration Rover Spirit shows a rock outcrop dubbed 'Clovis.' The rock was discovered to be softer than other rocks studied so far at Gusev Crater after the rover easily ground a hole (center) into it with its rock abrasion tool. An analysis of the interior of the hole with the rover's alpha particle X-ray spectrometer found higher concentrations of sulfur, bromine and chlorine compared to basaltic, or volcanic, rocks at Gusev. This might indicate that Clovis was chemically altered, and that fluids once flowed through the rock depositing these elements. Spirit's solar panels can be seen in the foreground. This image was taken by the rover's navigation camera on sol 205 (July 31, 2004).

  7. Epigenetic alterations underlying autoimmune diseases. (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein


    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  8. Epigenetic Alterations in Muscular Disorders

    Directory of Open Access Journals (Sweden)

    Chiara Lanzuolo


    Full Text Available Epigenetic mechanisms, acting via chromatin organization, fix in time and space different transcriptional programs and contribute to the quality, stability, and heritability of cell-specific transcription programs. In the last years, great advances have been made in our understanding of mechanisms by which this occurs in normal subjects. However, only a small part of the complete picture has been revealed. Abnormal gene expression patterns are often implicated in the development of different diseases, and thus epigenetic studies from patients promise to fill an important lack of knowledge, deciphering aberrant molecular mechanisms at the basis of pathogenesis and diseases progression. The identification of epigenetic modifications that could be used as targets for therapeutic interventions could be particularly timely in the light of pharmacologically reversion of pathological perturbations, avoiding changes in DNA sequences. Here I discuss the available information on epigenetic mechanisms that, altered in neuromuscular disorders, could contribute to the progression of the disease.

  9. Genetic alterations in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Schmid Roland M


    Full Text Available Abstract Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. In this article we describe major genetic alterations of pancreatic cancer, mutations in the proto-oncogene K-RAS and the tumor suppressors INK4A, TP53 and DPC4/SMAD4. The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and continuous growth. The knowledge of the underlying molecular mechanisms will offer new therapeutic and diagnostic options and hopefully improve the outcome of this aggressive disease.

  10. Self-alteration in HRI

    DEFF Research Database (Denmark)

    Yamazaki, Ryuji; Nørskov, Marco

    Humanlike androids are being developed with the ambition to be immersed into our daily life and meet us on an equal level in social interaction. The possibilities and limitations of these types of robots can potentially change societies and Human-Robot Interaction might affect the very way in which...... the ways in which our subjectivity can be innerly transformed, decentred, in other words, self-altered. In our trials so far, we have been investigating the potential of teleoperated androids, which are embodied telecommunication media with humanlike appearances. By conducting pilot studies in Japan...... and Denmark, we examine how Telenoid, a new type of teleoperated android robot designed as a minimalistic human, affect people in the real world. We introduce Telenoid to real-world as the fields of elderly care and child education by focusing on the social aspects of the android robot that might facilitate...

  11. Genetic alterations in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos


    The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

  12. Alcoholism with central pontine demyelination: a case report

    Directory of Open Access Journals (Sweden)

    Rohit Arora


    Full Text Available Central pontine myelinolysis is a non-inflammatory demyelinating disease characterized by loss of myelin with relative neuron sparing, associated with rapid correction of hyponatremia and sometimes hypernatremia or chronic alcoholism. We are reporting a case of 52 year old male patient who was chronic alcoholic from past 20 years, presented to us with complaints of altered sensorium and dysarthria of 5 days duration .He was investigated and diagnosed as case of central pontine myelinosis associated with chronic alcoholism. [Int J Basic Clin Pharmacol 2014; 3(1.000: 230-232

  13. Central venous catheter - dressing change (United States)

    ... during cancer treatment Bone marrow transplant - discharge Central venous catheter - flushing Peripherally inserted central catheter - flushing Sterile technique Surgical wound care - open Review Date 9/17/2016 Updated by: ...

  14. Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial.

    LENUS (Irish Health Repository)

    Lobo, Melvin D


    Hypertension contributes to cardiovascular morbidity and mortality. We assessed the safety and efficacy of a central iliac arteriovenous anastomosis to alter the mechanical arterial properties and reduce blood pressure in patients with uncontrolled hypertension.

  15. Central effects of fingolimod. (United States)

    Cruz, Vítor T; Fonseca, Joaquim


    Introduccion. El fingolimod, un modulador del receptor de la esfingosina-1-fosfato (S1P) dotado de un mecanismo de accion novedoso, fue el primer tratamiento oral aprobado para la esclerosis multiple remitente recurrente. Su union a los receptores S1P1 de los linfocitos promueve la retencion selectiva de los linfocitos T virgenes y de memoria central en los tejidos linfoides secundarios, lo que impide su salida hacia el sistema nervioso central (SNC). Asimismo, el fingolimod atraviesa con facilidad la barrera hematoencefalica, y diversos estudios le atribuyen un efecto neuroprotector directo en el SNC. Objetivo. Revisar la informacion disponible acerca de los efectos centrales del fingolimod. Desarrollo. El desequilibrio entre los procesos lesivos y reparadores constituye un reflejo de la desmielinizacion cronica, la degeneracion axonal y la gliosis, y parece contribuir a la discapacidad que la esclerosis multiple acarrea. La facilidad con la que el fingolimod atraviesa la barrera hematoencefalica le permite actuar directamente sobre los receptores S1P localizados en las celulas del SNC. Una vez en el interior del SNC, ocupa los receptores S1P de los oligodendrocitos y de sus celulas precursoras, de los astrocitos, los microgliocitos y las neuronas, fomentando la remielinizacion, la neuroproteccion y los procesos endogenos de regeneracion. La eficacia evidenciada en los ensayos clinicos concuerda con un mecanismo de accion que incluiria efectos directos sobre las celulas del SNC. Conclusiones. Los datos disponibles indican que la eficacia del fingolimod en el tratamiento de la esclerosis multiple se debe a su ambivalencia como molecula inmunomoduladora y moduladora directa de los receptores S1P del SNC. Tanto es asi que estudios recientes le atribuyen efectos neuroprotectores en varios modelos que suscitan expectativas en torno a su posible aplicacion terapeutica en la enfermedad de Alzheimer, el paludismo cerebral y el neuroblastoma, asi como en la neuroproteccion

  16. [Central anticholinergic syndrome]. (United States)

    Fernández Urretavizcaya, P; Cenoz Osinaga, J C; Jáuregui Garía, M L; Gállego Culleré, J


    Two new cases of anticolinergic central syndrome are described. The first case, a 8 year old girl, suffered a severe encefalopathy after topical application of mydriatic cholirio as an aid in a rutine study of ocular refraction. The second case, 67 year old man presented a severe neurological picture after accidental intake of a silvester plantground (Atropa belladonna). His neurological condition returned quickly to normal whith administration of physostigmine. Differents aspects of the etiology, clinical picture and diagnosis are discussed with special emphasis in patients with delirium or acute confusional states. Finally, attention is drawn in the necessity of a properly use of anticholinergic drugs overcoat in aged or children.

  17. Central osteosclerosis with trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Wakeling, Emma L.; Brady, Angela F. [North West Thames Regional Genetics Service, Kennedy-Galton Centre, Level 8 V, North West London Hospitals NHS Trust, Watford Road, HAI 3UJ, Harrow, Middlesex (United Kingdom); Cruwys, Michele [Department of Paediatrics, Hillingdon Hospital, Hillingdon, Middlesex (United Kingdom); Suri, Mohnish [Clinical Genetics Service, City Hospital, Nottingham (United Kingdom); Aylett, Sarah E. [Neurosciences Unit, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom); Hall, Christine [Department of Radiology, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom)


    Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder associated with defects in nucleotide excision repair. We report a 7-year-old boy with TTD due to mutation in the XPD gene. The patient has classic features of this condition, including brittle, sulphur-deficient hair, ichthyosis, growth retardation and developmental delay. In addition, he has radiological evidence of progressive central osteosclerosis. Although similar radiological findings have previously been reported in a small number of patients, this association is not widely recognised. We review the radiological findings in this and other similar cases and discuss the natural history of these bony changes. (orig.)

  18. Centralized vs. De-centralized Multinationals and Taxes

    DEFF Research Database (Denmark)

    Nielsen, Søren Bo; Raimondos-Møller, Pascalis; Schjelderup, Guttorm


    The paper examines how country tax differences affect a multinational enterprise's choice to centralize or de-centralize its decision structure. Within a simple model that emphasizes the multiple conflicting roles of transfer prices in MNEs - here, as a strategic pre-commitment device and a tax...... manipulation instrument -, we show that (de-)centralized decisions are more profitable when tax differentials are (small) large.Keywords: Centralized vs. de-centralized decisions, taxes, MNEs.JEL-Classification: H25, F23, L23....

  19. 感染性休克后期血管加压素分泌调节异常临床观察%Clinical analysis of decreased vasopressin modulation in the late phase of septic shock

    Institute of Scientific and Technical Information of China (English)

    周庆明; 王春玲; 杨秀芬; 孙静娜; 李栋梁; 王来


    目的:探讨感染性休克后期患者血管加压素( VP)分泌调节异常的规律及预后价值。方法选取2012年1月—2014年2月收治的感染性休克患者55例,测定其输注3%氯化钠溶液前后血钠及血清VP水平,以△VP/△Na≤0?.5 pg/mmol为无反应组,>0.5 pg/mmol为有反应组,比较2组患者血乳酸、C反应蛋白水平,应用血管活性药物的差异以及28 d病死率、(死亡患者)生存时间、(存活患者)住ICU时间。结果无反应组30例(54.5%),有反应组25例(45.5%)。2组患者性别、年龄、APACHE II评分、中心静脉压(CVP)、血压、血浆白蛋白水平、输注高渗盐水前后血钠水平差异均无统计学意义(分别为χ2=0.267, t =-0.563,-0.596,-0.712,0.779,1.306,0.257,0.233,均P >0.05),输注高渗盐水前后VP水平(ng/L)无反应组均低于有反应组(10.66±1.57 vs.17.13±5.12, t =6.091, P <0.01;11.65±1.74 vs.22.50±5.31, t =9.758, P <0.01)。无反应组的血乳酸、C反应蛋白水平及应用多巴胺或去甲肾上腺素剂量均高于有反应组(分别为t =-5.881,-4.143,-5.725,-5.625, P均<0.01)。28 d病死率无反应组高于有反应组(66.7%vs.40.0%,χ2=3.911, P <0.05);(死亡患者)生存时间2组无差异[(5.8±1.9)d vs.(6.1±2.3)d, t =0.384, P =0.704];(存活患者)住ICU时间无反应组高于有反应组[(9.9±2.3)d vs.(6.7±1.7)d, t =-4.044, P <0.01]。结论感染性休克后期患者基于渗透压调节的 VP分泌障碍有较高的发生率,对评价患者预后有一定价值。%Objective To investigate the abnormal regular pattern and prognostic value of vascular vasopressin ( VP) secretion in patients with late infection shock .Methods From 2012

  20. Diabetes insipidus in infants and children. (United States)

    Dabrowski, Elizabeth; Kadakia, Rachel; Zimmerman, Donald


    Diabetes insipidus, the inability to concentrate urine resulting in polyuria and polydipsia, can have different manifestations and management considerations in infants and children compared to adults. Central diabetes insipidus, secondary to lack of vasopressin production, is more common in children than is nephrogenic diabetes insipidus, the inability to respond appropriately to vasopressin. The goal of treatment in both forms of diabetes insipidus is to decrease urine output and thirst while allowing for appropriate fluid balance, normonatremia and ensuring an acceptable quality of life for each patient. An infant's obligate need to consume calories as liquid and the need for readjustment of medication dosing in growing children both present unique challenges for diabetes insipidus management in the pediatric population. Treatment modalities typically include vasopressin or thiazide diuretics. Special consideration must be given when managing diabetes insipidus in the adipsic patient, post-surgical patient, and in those undergoing chemotherapy or receiving medications that alter free water clearance.

  1. Central centrifugal cicatricial alopecia. (United States)

    Whiting, David A; Olsen, Elise A


    A progressive scarring alopecia of the central scalp is commonly seen in young to middle-aged females of African descent. It usually starts at the vertex or mid top of the scalp and gradually spreads centrifugally, hence, the unifying term of central centrifugal cicatricial alopecia. The clinical pattern is suggestive of female pattern alopecia, but a lack of follicular pores indicative of scarring is present. It can progress for years before slowly burning out. The etiology is unknown but genetic factors may be important. It is often associated with a history of traumatic hairstyling involving heat, traction, and chemicals. However, most patients of African descent without this disorder have similar styling habits. Nonetheless, avoidance of physical and chemical trauma to the scalp hair, the use of suitable shampoos and conditioners, and the encouragement of natural hairstyles may be helpful. Any infection should be treated. Topical or intralesional corticosteroids and systemic antibiotics may be useful and topical minoxidil should be tried with the hope of preventing further scarring and encouraging regrowth of recovering follicles. Current research into the etiology of this disorder will help to foster much-needed clinical trials of therapeutic agents.

  2. Central Sumatra enjoys success

    Energy Technology Data Exchange (ETDEWEB)

    Wongsosantiko, A.


    The Sihapas group contains the most prolific oil producing zones in the Central Sumatra Basin. It represents the transgressive, coarse clastic sequence deposited during the early Miocene. Some of these sandstone grade laterally into siltstones and shales of the Telisa Formation, believed to be a major source of rock for Central Sumatra oil. Recent exploratory wells drilled between the mountain front and coastal plain areas have provided more data for stratigraphic studies. These have resulted in subdivision of the lower Miocene transgressive sequence into discrete rock-stratigraphic units. The former Sihapas Formation has subsequently been elevated to group rank and now consists of several formations with the Duri Formation as the uppermost sand unit. This study covers Caltex's areas of operation, which includes the area between the Kampar River of the south, the Barumum River to the north, the Malacca Straits to the east, and the Barisan Mt. to the west. A basic map shows the regional scene, while a stratigraphic chart shows the lithology.

  3. en los pivotes centrales

    Directory of Open Access Journals (Sweden)

    Reynaldo Roque Rodés


    Full Text Available Se hace una revisión y comentarios sobre las ventajas y limitantes del empleo del LEPA (Low Enery Precision Aplication en los sistemas de riego de pivotes centrales. Estos sistemas o filosofía de manejo del agua para condiciones de escasez o mala calidad del líquido es una alternativa viable para la producción de alimentos. Introducida en la década del 80 en las planicies del sur de Texas, donde la alta evaporación del agua y la necesidad de regar grandes áreas con pivotes centrales obligaba a la búsqueda de una alternativa para incrementar al máximo la eficiencia de aplicación del riego. Aún en fase de estudio e introducción en Cuba para áreas específicas, puede ser una solución de incremento de los rendimientos de los cultivos, empleando menos agua y aguas con calidad limitada

  4. Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between. (United States)

    Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Reibold, Mathias; Bachner-Melman, Rachel; Granot, Roni; Bornstein, Gary; Knafo, Ariel; Yirmiya, Nurit; Ebstein, Richard P


    Converging evidence from both human and animal studies has highlighted the pervasive role of two neuropeptides, oxytocin (OXT) and arginine vasopressin (AVP), in mammalian social behaviours. Recent molecular genetic studies of the human arginine vasopressin 1a (AVPR1a) and oxytocin (OXTR) receptors have strengthened the evidence regarding the role of these two neuropeptides in a range of normal and pathological behaviours. Significant association between both AVPR1a repeat regions and OXTR single nucleotide polymorphisms (SNPs) with risk for autism has been provisionally shown which was mediated by socialization skills in our study. AVPR1a has also been linked to eating behaviour in both clinical and non-clinical groups, perhaps reflecting the social and ritualistic side of eating behaviour. Evidence also suggests that repeat variations in AVPR1a are associated with two other social domains in Homo sapiens: music and altruism. AVPR1a was associated with dance and musical cognition which we theorize as reflecting the ancient role of this hormone in social interactions executed by vocalization, ritual movement and dyadic (mother-offspring) and group communication. Finally, we have shown that individual differences in allocation of funds in the dictator game, a laboratory game of pure altruism, is predicted by length of the AVPR1a RS3 promoter-region repeat echoing the mechanism of this hormone's action in the vole model of affiliative behaviours and facilitation of positive group interactions. While still in its infancy, the current outlook for molecular genetic investigations of AVP-OXT continues to be fascinating. Future studies should profitably focus on pharmacogenomic and genomic imaging strategies facilitated by the ease and efficacy of manipulating AVP-OXT neurotransmission by intranasal administration. Importantly, physiological measures, behavioural paradigms and brain activation can be informed by considering between-group and also within-group individual

  5. A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder. (United States)

    Umbricht, Daniel; Del Valle Rubido, Marta; Hollander, Eric; McCracken, James T; Shic, Frederick; Scahill, Lawrence; Noeldeke, Jana; Boak, Lauren; Khwaja, Omar; Squassante, Lisa; Grundschober, Christophe; Kletzl, Heidemarie; Fontoura, Paulo


    The core symptoms of autism spectrum disorder (ASD) include impaired social communication, repetitive behaviors, and restricted interests. No effective pharmacotherapy for these core deficits exists. Within the domain of social communication, the vasopressin system is implicated in social cognition and social signaling deficits of ASD, and represents a potential therapeutic target. We assessed the effects of a single 20 mg intravenous dose of the arginine vasopressin receptor 1A (V1a) antagonist, RG7713, on exploratory biomarkers (eye tracking), behavioral and clinical measures of social cognition and communication (affective speech recognition (ASR), reading the mind in the eyes, olfactory identification, scripted interaction), and safety and tolerability in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 19 high-functioning adult male subjects with DSM-IV Autistic Disorder (age 18-45 years; full scale IQ >70; ABC-Irritability subscale ⩽13). Eye-tracking showed an increase in biological motion orienting preference with RG7713 (ES=0.8, p=0.047) and a non-significant improvement in the composite score (ES=0.2, p=0.29). RG7713 reduced ability to detect lust (ES=-0.8, p=0.03) and fear (ES=-0.7, p=0.07) in ASR. However, when all eight individual emotion subscales were combined into an overall ASR performance score, the reduction was non-significant (ES=-0.1, p=0.59). Thirteen adverse events were reported in 10 subjects; all were of mild (11/13) or moderate (2/13) severity. Although interpretation should be cautious due to multiple comparisons and small sample size, these results provide preliminary evidence from experimental and behavioral biomarkers, that blockade of the V1a receptor may improve social communication in adults with high-functioning ASD. identifier: NCT01474278 A Study of RO5028442 in Adult Male High-Functioning Autistic Patients. Available at:



    Nitesh Mishra; Manoj Kumar Sharma; Chandrasekhar, M.; Suresh, M; Ambareesha Kondam; Sanghishetty Vijay Prasad


    Obesity is a known risk factor for metabolic syndrome in adults. Metabolic syndrome includes agroup of cardiovascular disease risk factors namely impaired glucose tolerance, dyslipidaemia and hypertension.Central fat distribution, particularly intra-abdominal fat, is a greater risk factor than peripheral fat distribution.Anthropometric indices used to measure fat distribution have been shown to be associated with altered lipid profile.The objective of the present study was to compare the seru...

  7. Hindlimb unloading alters ligament healing (United States)

    Provenzano, Paolo P.; Martinez, Daniel A.; Grindeland, Richard E.; Dwyer, Kelley W.; Turner, Joanne; Vailas, Arthur C.; Vanderby, Ray Jr


    We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing, and hindlimb-suspended healing. Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals. After 3 or 7 wk, mechanical and/or morphological properties were measured in ligament, muscle, and bone. During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced. Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles. Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

  8. Epigenetic Alterations in Parathyroid Cancers (United States)

    Verdelli, Chiara; Corbetta, Sabrina


    Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile. PMID:28157158

  9. Pulmonary alterations in cocaine users

    Directory of Open Access Journals (Sweden)

    Mário Terra Filho

    Full Text Available CONTEXT: Brazilian researchers have recently recognized a marked increase in the number of people using abusable drugs and the consequences of this habit. It has become a major public health problem in a potentially productive segment of the general population. In the last few years, several medical articles have given special emphasis to pulmonary complications related to cocaine use. This review is based on this information and experience acquired with groups of cocaine users. OBJECTIVE: To present to physicians the pulmonary aspects of cocaine use and warn about the various effects this drug has on the respiratory system, stressing those related to long-term use. DESIGN: Narrative review. METHOD: Pulmonary complications are described. These may include infections (Staphylococcus aureus, pulmonary tuberculosis, acquired immunodeficiency syndrome/aids, etc., aspiration pneumonia, lung abscess, empyema, septic embolism, non-cardiogenic pulmonary edema, barotrauma, pulmonary granulomatosis, bronchiolitis obliterans and organizing pneumonia, pneumonitis and interstitial fibrosis, pneumonitis hypersensitivity, lung infiltrates and eosinophilia in individuals with bronchial hyperreactivity, diffuse alveolar hemorrhage, vasculitis, pulmonary infarction, pulmonary hypertension and alterations in gas exchange. It is concluded that physicians should give special attention to the various pulmonary and clinical manifestations related to cocaine use, particularly in young patients.

  10. Centrality Measures in Urban Networks

    CERN Document Server

    Crucitti, P; Porta, S; Crucitti, Paolo; Latora, Vito; Porta, Sergio


    Centrality has revealed crucial for understanding the structural order of complex relational networks. Centrality is also relevant for various spatial factors affecting human life and behaviors in cities. We present a comprehensive study of centrality distributions over geographic networks of urban streets. Four different measures of centrality, namely closeness, betweenness, straightness and information, are compared over eighteen 1-square-mile samples of different world cities. Samples are represented by primal geographic graphs, i.e. valued graphs defined by metric rather than topologic distance where intersections are turned into nodes and streets into edges. The spatial behavior of centrality indexes over the networks is investigated graphically by means of colour-coded maps. The results indicate that a spatial analysis, that we term Multiple Centrality Assessment(MCA), grounded not a single but on a set of different centrality indices, allows an extended comprehension of the city structure, nicely captu...

  11. Central diabetes insipidus: alert for dehydration in very low birth weight infants during the neonatal period. A case report

    Directory of Open Access Journals (Sweden)

    Maria Lúcia Silveira Ferlin

    Full Text Available CONTEXT: Central diabetes insipidus (CDI is a rare cause of hypernatremia during the neonatal period. The diagnosis is particularly difficult in very low birth weight (VLBW newborns. CASE REPORT: We report on a preterm newborn who presented CDI soon after birth. On the third day of life, signs of dehydration were present despite normal fluid supply. The diuresis rate was 4.4 ml/kg/h. Although the fluid supply was then increased, the dehydration continued, with hypernatremia, normal glycemia, diuresis of 7.4 ml/kg/h and urine density of 1005 mOsmol/l. Thus, a diagnostic hypothesis of diabetes insipidus was raised. A test with a nasal vasopressin analogue (dDAVP was performed and CDI was confirmed. Reduction of the fluid supply became possible through appropriate treatment. CONCLUSION: The diagnosis of CDI is rarely made during the neonatal period, especially in VLBW newborns, because of the difficulty in detecting elevated diuresis. Persistent hypernatremia, usually accompanied by hyperthermia despite abundant fluid supply, weight loss and low urine osmolality are important signs of alert.

  12. Orden monetario y bancos centrales Monetary order and Central Banks

    Directory of Open Access Journals (Sweden)

    Aglietta Michel


    Full Text Available Con el enfoque evolucionista e institucionalista de la economía de las convenciones francesa, este trabajo analiza el surgimiento histórico de la banca central y la creación institucional del 'arte de la banca central'. El artículo estudia los modelos formales del orden monetario, la banca libre y la banca central, y analiza los eventos históricos que llevaron a que el Banco de Inglaterra inventara el arte de manejar los bancos centrales en conjunción con el aprendizaje colectivo e institucional que lo hizo posible. Aglietta muestra que la banca central no es una creación del Estado sino una creación institucional endógena al sistema de mercado.With the evolutionist and institutionalist focus of the economics of the French conventions, this paper analyzes the historical rise of the central bank and the institutional creation of the 'art of the central bank'. The article studies formal models of the monetary order, free banking and the central bank, and analyzes the historie events that led to the Bank of England inventing the art of managing the central banks, in conjunction with the collective and institutional learning that made it possible. Aglietta shows that the central bank is not a creation of the State, but rather aninstitutional creation endogenous to the market system.

  13. Malnutrition alters the cardiovascular responses induced by central injection of tityustoxin in Fischer rats. (United States)

    Silva, Fernanda Cacilda Santos; Guidine, Patrícia Alves; Ribeiro, Mara Fernandes; Fernandes, Luciano Gonçalves; Xavier, Carlos Henrique; de Menezes, Rodrigo Cunha; Silva, Marcelo Eustáquio; Moraes-Santos, Tasso; Moraes, Márcio Flávio; Chianca, Deoclécio Alves


    Scorpion envenoming and malnutrition are considered two important public health problems in Brazil, involving mainly children. Both these conditions are more common among the economically stratified lower income portion of the population, thus suggesting that these factors should be analyzed concomitantly. It is known that cardiorespiratory manifestations, as cardiac arrhythmias, arterial hypertension and hypotension, pulmonary edema and circulatory failure are the main "causa mortis" of scorpion envenomation. Additionally, there are evidences in the literature that deficiencies in dietary intake endanger the CNS and modify the cardiovascular homeostasis. Then, the objective of this work is to evaluate the protein malnourished effect on cardiovascular responses induced by tityustoxin (TsTX, an α-type toxin extracted from the Tityus serrulatus scorpion venom). Fischer rats (n = 20) were injected i.c.v. with TsTX and divided in control and malnorished groups, which were, respectively, submitted to a control and a low-protein diet. Arterial pressure recordings were done until death of the animals. Although both groups presented an increased mean arterial pressure after TsTX injection, this increase was smaller and delayed in malnourished rats, when compared to control rats. In addition, heart rate increased only in rats from the control group. Finally, malnourished rats had an increase in survival time (9:9/13.5 vs. 15.5:10.5/18 min; p = 0.0009). In summary, our results suggest that the protein restriction attenuates the cardiovascular manifestations resulting from TsTX action on CNS.

  14. Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus.

    Directory of Open Access Journals (Sweden)

    Andrea S Lowe

    Full Text Available Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN paradigm to assess tinnitus in mice using the auditory brainstem response (ABR. We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS, which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2 to peak 1 (P1 and peak 4 (P4 to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.

  15. Adrenalectomy alters the sensitivity of the central nervous system melanocortin system

    NARCIS (Netherlands)

    Drazen, DL; Wortman, MD; Schwartz, MW; Clegg, DJ; van Dijk, G; Woods, SC; Seeley, RJ; Drazen, Deborah L.; Wortman, Matthew D.; Schwartz, Michael W.; Woods, Stephen C.; Seeley, Randy J.


    Removal of adrenal steroids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Thus, glucocorticoids appear to play a key role to promote positive energy balance in normal and pathological conditions

  16. Hydrothermal alteration studies of gabbros from northern central Indian ridge and their geodynamic implications

    Digital Repository Service at National Institute of Oceanography (India)

    Ray, Dwijesh; Mevel, C.; Banerjee, R.

    -magmatic phases directly crys- tallised from magma or formed by late-magmatic 668 Dwijesh Ray et al Figure 6. (a) Binary plot of Al (a.p.f.u) vs. Ti (a.p.f.u) of magmatic and vein Cpx, (b) Binary plot of MnO (wt%) vs. FeO t (wt%) of magmatic and porphyroclast... compo- sitions suggest evolutionary processes of present Figure 9. Representation of amphiboles in binary diagrams of Cl (wt%) vs. (a) Na (a.p.f.u) and (b) K (a.p.f.u). Filled circles represent vein amphibole and open squares represent amphiboles...

  17. Parasitic diseases of the central nervous system. (United States)

    Chacko, Geeta


    Parasitic infections, though endemic to certain regions, have over time appeared in places far removed from their original sites of occurrence facilitated probably by the increase in world travel and the increasing migration of people from their native lands to other, often distant, countries. The frequency of occurrence of some of these diseases has also changed based on a variety of factors, including the presence of intermediate hosts, geographic locations, and climate. One factor that has significantly altered the epidemiology of parasitic diseases within the central nervous system (CNS) is the HIV pandemic. In this review of the pathology of parasitic infections that affect the CNS, each parasite is discussed in the sequence of epidemiology, life cycle, pathogenesis, and pathology.

  18. UA1 central detector

    CERN Multimedia

    The UA1 central detector was crucial to understanding the complex topology of proton-antiproton events. It played a most important role in identifying a handful of Ws and Zs among billions of collisions. The detector was a 6-chamber cylindrical assembly 5.8 m long and 2.3 m in diameter, the largest imaging drift chamber of its day. It recorded the tracks of charged particles curving in a 0.7 Tesla magnetic field, measuring their momentum, the sign of their electric charge and their rate of energy loss (dE/dx). Atoms in the argon-ethane gas mixture filling the chambers were ionised by the passage of charged particles. The electrons which were released drifted along an electric field shaped by field wires and were collected on sense wires. The geometrical arrangement of the 17000 field wires and 6125 sense wires allowed a spectacular 3-D interactive display of reconstructed physics events to be produced.

  19. UA2 central calorimeter

    CERN Multimedia

    The UA2 central calorimeter measured the energy of individual particles created in proton-antiproton collisions. Accurate calibration allowed the W and Z masses to be measured with a precision of about 1%. The calorimeter had 24 slices like this one, each weighing 4 tons. The slices were arranged like orange segments around the collision point. Incoming particles produced showers of secondary particles in the layers of heavy material. These showers passed through the layers of plastic scintillator, generating light which was taken by light guides (green) to the data collection electronics. The amount of light was proportional to the energy of the original particle. The inner 23 cm of lead and plastic sandwiches measured electrons and photons; the outer 80 cm of iron and plastic sandwiches measured strongly interacting hadrons. The detector was calibrated by injecting light through optical fibres or by placing a radioactive source in the tube on the bottom edge.

  20. Altered mental status and endocrine diseases. (United States)

    Park, Elizabeth; Abraham, Michael K


    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with endocrine emergencies to facilitate the diagnosis and treatment in the emergency department.