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Sample records for oxytocin formulations analysis

  1. Pulmonary Delivery of an Ultra-Fine Oxytocin Dry Powder Formulation: Potential for Treatment of Postpartum Haemorrhage in Developing Countries

    PubMed Central

    Ibrahim, Jibriil P.; Bischof, Robert J.; Nassta, Gemma C.; Olerile, Livesey D.; Russell, Adrian S.; Meiser, Felix; Parkington, Helena C.; Coleman, Harold A.; Morton, David A. V.; McIntosh, Michelle P.

    2013-01-01

    Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 µm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 µm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world. PMID:24376618

  2. Pulmonary delivery of an ultra-fine oxytocin dry powder formulation: potential for treatment of postpartum haemorrhage in developing countries.

    PubMed

    Prankerd, Richard J; Nguyen, Tri-Hung; Ibrahim, Jibriil P; Bischof, Robert J; Nassta, Gemma C; Olerile, Livesey D; Russell, Adrian S; Meiser, Felix; Parkington, Helena C; Coleman, Harold A; Morton, David A V; McIntosh, Michelle P

    2013-01-01

    Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 µm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 µm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world. PMID:24376618

  3. Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation.

    PubMed

    Fabio, Karine; Curley, Kieran; Guarneri, Joseph; Adamo, Benoit; Laurenzi, Brendan; Grant, Marshall; Offord, Robin; Kraft, Kelly; Leone-Bay, Andrea

    2015-12-01

    In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control). PMID:25776985

  4. Neurofunctional maps of the 'maternal brain' and the effects of oxytocin: a multimodal voxel-based meta-analysis.

    PubMed

    Rocchetti, Matteo; Radua, Joaquim; Paloyelis, Yannis; Xenaki, Lida-Alkisti; Frascarelli, Marianna; Caverzasi, Edgardo; Politi, Pierluigi; Fusar-Poli, Paolo

    2014-10-01

    Several studies have tried to understand the possible neurobiological basis of mothering. The putative involvement of oxytocin, in this regard, has been deeply investigated. Performing a voxel-based meta-analysis, we aimed at testing the hypothesis of overlapping brain activation in functional magnetic resonance imaging (fMRI) studies investigating the mother-infant interaction and the oxytocin modulation of emotional stimuli in humans. We performed two systematic literature searches: fMRI studies investigating the neurofunctional correlates of the 'maternal brain' by employing mother-infant paradigms; and fMRI studies employing oxytocin during emotional tasks. A unimodal voxel-based meta-analysis was performed on each database, whereas a multimodal voxel-based meta-analytical tool was adopted to assess the hypothesis that the neurofunctional effects of oxytocin are detected in brain areas implicated in the 'maternal brain.' We found greater activation in the bilateral insula extending to the inferior frontal gyrus, basal ganglia and thalamus during mother-infant interaction and greater left insular activation associated with oxytocin administration versus placebo. Left insula extending to basal ganglia and frontotemporal gyri as well as bilateral thalamus and amygdala showed consistent activation across the two paradigms. Right insula also showed activation across the two paradigms, and dorsomedial frontal cortex activation in mothers but deactivation with oxytocin. Significant activation in areas involved in empathy, emotion regulation, motivation, social cognition and theory of mind emerged from our multimodal meta-analysis, supporting the need for further studies directly investigating the neurobiology of oxytocin in the mother-infant relationship. PMID:24734987

  5. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Francis, Sunday M.; Lee, Royce; de Wit, Harriet; Jacob, Suma

    2014-01-01

    MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its prosocial effects by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5 mg/kg), intranasal oxytocin (20 IU or 40 IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5 mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7 pg/ml at approximately 90–120 minutes, compared to 18.6 pg/ml after placebo. Intranasal oxytocin (40 IU, but not 20 IU) increased plasma oxytocin levels to 48.0 pg/ml, 30–60 min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., ‘High’ and ‘Like Drug’), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects. PMID:24882155

  6. Autism, oxytocin and interoception

    PubMed Central

    Quattrocki, E.; Friston, Karl

    2014-01-01

    Autism is a pervasive developmental disorder characterized by profound social and verbal communication deficits, stereotypical motor behaviors, restricted interests, and cognitive abnormalities. Autism affects approximately 1% of children in developing countries. Given this prevalence, identifying risk factors and therapeutic interventions are pressing objectives—objectives that rest on neurobiologically grounded and psychologically informed theories about the underlying pathophysiology. In this article, we review the evidence that autism could result from a dysfunctional oxytocin system early in life. As a mediator of successful procreation, not only in the reproductive system, but also in the brain, oxytocin plays a crucial role in sculpting socio-sexual behavior. Formulated within a (Bayesian) predictive coding framework, we propose that oxytocin encodes the saliency or precision of interoceptive signals and enables the neuronal plasticity necessary for acquiring a generative model of the emotional and social ‘self.’ An aberrant oxytocin system in infancy could therefore help explain the marked deficits in language and social communication – as well as the sensory, autonomic, motor, behavioral, and cognitive abnormalities – seen in autism. PMID:25277283

  7. Autism, oxytocin and interoception.

    PubMed

    Quattrocki, E; Friston, Karl

    2014-11-01

    Autism is a pervasive developmental disorder characterized by profound social and verbal communication deficits, stereotypical motor behaviors, restricted interests, and cognitive abnormalities. Autism affects approximately 1% of children in developing countries. Given this prevalence, identifying risk factors and therapeutic interventions are pressing objectives—objectives that rest on neurobiologically grounded and psychologically informed theories about the underlying pathophysiology. In this article, we review the evidence that autism could result from a dysfunctional oxytocin system early in life. As a mediator of successful procreation, not only in the reproductive system, but also in the brain, oxytocin plays a crucial role in sculpting socio-sexual behavior. Formulated within a (Bayesian) predictive coding framework, we propose that oxytocin encodes the saliency or precision of interoceptive signals and enables the neuronal plasticity necessary for acquiring a generative model of the emotional and social 'self.' An aberrant oxytocin system in infancy could therefore help explain the marked deficits in language and social communication—as well as the sensory, autonomic, motor, behavioral, and cognitive abnormalities—seen in autism. PMID:25277283

  8. The Social Salience Hypothesis of Oxytocin.

    PubMed

    Shamay-Tsoory, Simone G; Abu-Akel, Ahmad

    2016-02-01

    Oxytocin is a nonapeptide that also serves as a neuromodulator in the human central nervous system. Over the last decade, a sizeable body of literature has examined its effects on social behavior in humans. These studies show that oxytocin modulates various aspects of social behaviors such as empathy, trust, in-group preference, and memory of socially relevant cues. Several theoretical formulations have attempted to explain the effects of oxytocin. The prosocial account argues that oxytocin mainly enhances affiliative prosocial behaviors; the fear/stress theory suggests that oxytocin affects social performance by attenuating stress; and the in-/out-group approach proposes that oxytocin regulates cooperation and conflict among humans in the context of intergroup relations. Nonetheless, accumulating evidence reveals that the effects of oxytocin are dependent on a variety of contextual aspects and the individual's characteristics and can induce antisocial effects including aggression and envy. In an attempt to reconcile these accounts, we suggest a theoretical framework that focuses on the overarching role of oxytocin in regulating the salience of social cues through its interaction with the dopaminergic system. Crucially, the salience effect modulates attention orienting responses to external contextual social cues (e.g., competitive vs. cooperative environment) but is dependent on baseline individual differences such as gender, personality traits, and degree of psychopathology. This view could have important implications for the therapeutic applications of oxytocin in conditions characterized with aberrant social behavior. PMID:26321019

  9. Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors

    PubMed Central

    Yang, Xiao; Xi, Tao-Fang; Li, Yu-Xian; Wang, Hai-Hong; Qin, Ying; Zhang, Jie-Ping; Cai, Wen-Ting; Huang, Meng-Ting; Shen, Ji-Qiao; Fan, Xi-Min; Shi, Xuan-Zheng; Xie, Dong-Ping

    2014-01-01

    AIM: To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. METHODS: Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 °C, cold group) or room temperature (20-25 °C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. RESULTS: Colon transit was slower in the cold group than in the control group (P < 0.05). Colonic smooth muscle contractile response to oxytocin decreased, and the inhibitory effect of oxytocin on muscle contractility was enhanced by cold water intake (0.69 ± 0.08 vs 0.88 ± 0.16, P < 0.05). Atosiban and tetrodotoxin inhibited the effect of oxytocin on colonic motility. Oxytocin receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P < 0.05). Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 ± 83.72 pg/mL vs 100.56 ± 92.71 pg/mL, P < 0.05). However, in ovariectomized rats, estradiol treatment increased blood oxytocin, and the response of colonic muscle strips to oxytocin was attenuated. CONCLUSION: Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent. PMID:25152590

  10. A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

    PubMed Central

    Mitre, Mariela; Marlin, Bianca J.; Schiavo, Jennifer K.; Morina, Egzona; Norden, Samantha E.; Hackett, Troy A.; Aoki, Chiye J.

    2016-01-01

    Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent–infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. SIGNIFICANCE STATEMENT Oxytocin is an important peptide hormone involved in maternal behavior and social cognition, but it has been unclear what elements of neural circuits express oxytocin receptors due to the paucity of suitable antibodies. Here, we developed new antibodies to the mouse oxytocin receptor. Oxytocin receptors were found in discrete brain regions and at cortical synapses for modulating excitatory-inhibitory balance and plasticity. These antibodies should be useful for future studies of oxytocin and social behavior. PMID:26911697

  11. State-Space Formulation for Circuit Analysis

    ERIC Educational Resources Information Center

    Martinez-Marin, T.

    2010-01-01

    This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

  12. Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis

    PubMed Central

    Li, Jingguang; Zhao, Yajun; Li, Rena; Broster, Lucas S.; Zhou, Chenglin; Yang, Suyong

    2015-01-01

    A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen’s d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen’s d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders. PMID:26121678

  13. State-space formulations for flutter analysis

    NASA Technical Reports Server (NTRS)

    Weiss, S. J.; Tseng, K.; Morino, L.

    1976-01-01

    Various methods are presented and assessed for approximating the aerodynamic forces so that the State Space formulation and off-the-imaginary axis analysis are retained. The advantages of retaining these features are considerable, not only in simplifying the flutter analysis, but especially for more advanced applications such as optimal design of active control in which the flutter is merely a constraint to the optimization problem.

  14. Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies.

    PubMed

    Hofmann, Stefan G; Fang, Angela; Brager, Daniel N

    2015-08-30

    Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges' g=0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. PMID:26094200

  15. [Analysis of 39 cases of maternal deaths caused by incorrect use of oxytocin].

    PubMed

    Zheng, Q L; Zhang, X M

    1994-05-01

    Thirty-nine cases of maternal deaths directly caused by incorrect use of oxytocin in Fujian Province from 1986 to 1992 were analysed. The results showed that 90.00% of these deaths occurred in the rural and mountainous areas. The main reason was the ignorance of the birth attendents on the pros and cons of oxytocin administration and therefore the incorrect use. The causes of maternal deaths were ranged in the following order: uterine rupture, soft tissue injury of the birth canal and amniotic fluid embolism. All were emergent deaths with 79.49% dying in intrapartum period or within four hours after delivery and 28.20% at patients' home or on their way to hospital. PMID:7956550

  16. Oxytocin and appetite.

    PubMed

    Leng, Gareth; Onaka, Tatsushi; Caquineau, Celine; Sabatier, Nancy; Tobin, Vicky A; Takayanagi, Yuki

    2008-01-01

    Oxytocin has potent central effects on feeding behaviour, as well as on social and sexual behaviours, and one likely substrate for its anorectic effect is the ventromedial nucleus of the hypothalamus. This nucleus expresses a high density of oxytocin receptors, but contains very few oxytocin-containing fibres, hence it is a likely target of 'neurohormonal' actions of oxytocin, including possibly oxytocin released from the dendrites of magnocellular oxytocin neurones. As oxytocin release from dendrites is regulated independent of electrical activity and of secretion from the neurohypophysis, exactly how this release is regulated by metabolic and reproduction-related signals remains to be established fully. Intriguingly though, it looks as though this central release of oxytocin from magnocellular neurons might be instrumental in a fundamental shift in motivational behaviour - switching behaviour from being driven by the need to find and consume food, to the need to reproduce. PMID:18655879

  17. Oxytocin in Uniject Disposable Auto-Disable Injection System versus Standard Use for the Prevention of Postpartum Hemorrhage in Latin America and the Caribbean: A Cost-Effectiveness Analysis

    PubMed Central

    Pichon-Riviere, Andrés; Glujovsky, Demián; Garay, Osvaldo Ulises; Augustovski, Federico; Ciapponi, Agustin; Serpa, Magdalena; Althabe, Fernando

    2015-01-01

    Postpartum hemorrhage (PPH) is a leading cause of maternal death. Despite strong evidence showing the efficacy of routine oxytocin in preventing PPH, the proportion of women receiving it after delivery is still below 100%. The Uniject injection system prefilled with oxytocin (Uniject) has the potential advantage, due to its ease of use, to increase oxytocin utilization rates. We aimed to assess its cost-effectiveness in Latin America and the Caribbean (LAC). We used an epidemiological model to estimate: a) the impact of replacing oxytocin in ampoules with Uniject on the incidence of PPH, quality-adjusted life years (QALYs) and costs from a health care system perspective, and b) the minimum increment in oxytocin utilization rates required to make Uniject a cost-effective strategy. A consensus panel of LAC experts was convened to quantify the expected increase in oxytocin rates as a consequence of making Uniject available. Deterministic and probabilistic sensitivity analyses were performed. In the base case, the incremental cost of Uniject with respect to oxytocin in ampoules was estimated to be USD 1.00 (2013 US dollars). In the cost-effectiveness analysis, Uniject ranged from being cost-saving (in 8 out of 30 countries) to having an incremental cost-effectiveness ratio (ICER) of USD 8,990 per QALY gained. In most countries these ICERs were below one GDP per capita. The minimum required increment in oxytocin rates to make Uniject a cost-effective strategy ranged from 1.3% in Suriname to 16.2% in Haiti. Switching to Uniject could prevent more than 40,000 PPH events annually in LAC. Uniject was cost-saving or very cost-effective in almost all countries. Even if countries can achieve only small increases in oxytocin rates by incorporating Uniject, this strategy could be considered a highly efficient use of resources. These results were robust in the sensitivity analysis under a wide range of assumptions. PMID:26057930

  18. Oxytocin in Uniject Disposable Auto-Disable Injection System versus Standard Use for the Prevention of Postpartum Hemorrhage in Latin America and the Caribbean: A Cost-Effectiveness Analysis.

    PubMed

    Pichon-Riviere, Andrés; Glujovsky, Demián; Garay, Osvaldo Ulises; Augustovski, Federico; Ciapponi, Agustin; Serpa, Magdalena; Althabe, Fernando

    2015-01-01

    Postpartum hemorrhage (PPH) is a leading cause of maternal death. Despite strong evidence showing the efficacy of routine oxytocin in preventing PPH, the proportion of women receiving it after delivery is still below 100%. The Uniject injection system prefilled with oxytocin (Uniject) has the potential advantage, due to its ease of use, to increase oxytocin utilization rates. We aimed to assess its cost-effectiveness in Latin America and the Caribbean (LAC). We used an epidemiological model to estimate: a) the impact of replacing oxytocin in ampoules with Uniject on the incidence of PPH, quality-adjusted life years (QALYs) and costs from a health care system perspective, and b) the minimum increment in oxytocin utilization rates required to make Uniject a cost-effective strategy. A consensus panel of LAC experts was convened to quantify the expected increase in oxytocin rates as a consequence of making Uniject available. Deterministic and probabilistic sensitivity analyses were performed. In the base case, the incremental cost of Uniject with respect to oxytocin in ampoules was estimated to be USD 1.00 (2013 US dollars). In the cost-effectiveness analysis, Uniject ranged from being cost-saving (in 8 out of 30 countries) to having an incremental cost-effectiveness ratio (ICER) of USD 8,990 per QALY gained. In most countries these ICERs were below one GDP per capita. The minimum required increment in oxytocin rates to make Uniject a cost-effective strategy ranged from 1.3% in Suriname to 16.2% in Haiti. Switching to Uniject could prevent more than 40,000 PPH events annually in LAC. Uniject was cost-saving or very cost-effective in almost all countries. Even if countries can achieve only small increases in oxytocin rates by incorporating Uniject, this strategy could be considered a highly efficient use of resources. These results were robust in the sensitivity analysis under a wide range of assumptions. PMID:26057930

  19. Plasma oxytocin and personality traits in psychiatric outpatients.

    PubMed

    Bendix, Marie; Uvnäs-Moberg, Kerstin; Petersson, Maria; Gustavsson, Petter; Svanborg, Pär; Åsberg, Marie; Jokinen, Jussi

    2015-07-01

    The oxytocin system is regarded as being of relevance for social interaction. In spite of this, very few studies have investigated the relationship between oxytocin and personality traits in clinical psychiatric populations. We assessed the relationship between personality traits and plasma oxytocin levels in a population of 101 medication-free psychiatric outpatients (men = 37, women = 64). We used the Karolinska Scale of Personality (KSP) and diagnostic and symptomatic testing. Plasma oxytocin levels were analysed with a specific radioimmunoassay at inclusion and after one month for testing of stability. Plasma oxytocin levels were stable over time and did not differ between patients with or without personality disorders, nor were they related to severity of depressive or anxiety symptoms. The KSP factors Impulsiveness and Negative Emotionality were significant independent predictors of plasma oxytocin. A subscale analysis of these personality factors showed significant positive correlations between baseline plasma oxytocin and the KSP subscales monotony avoidance and psychic anxiety. The significant association between the KSP factor Impulsiveness and oxytocin levels observed at baseline was observed also one month later in men. These findings suggest that personality traits such as Impulsiveness and Negative emotionality which are linked to social functioning in several psychiatric disorders seem to be associated with endogenous plasma oxytocin levels. These variations in oxytocin levels might have an impact on social sensitivity or social motivation with possible gender differences. PMID:25910979

  20. [Transitory hyperbilirubinemia and oxytocin infusion].

    PubMed

    Quoss, I

    1978-01-01

    Serum bilirubin levels at 5th day of life was compared between 100 mature newborns with oxytocin infusion to the mother during labour and 100 mature newborns without oxytocin. Newborns, whose mothers received more than 5 IU oxytocin had significant higher bilirubin values than the controll group without oxytocin and the cases with oxytocin administration under 5 U. Hyperbilirubinaemie was also present in babies after vacuum extraction and oxytocin infusion. PMID:645287

  1. Efficacy and safety of oxytocin augmentation therapy for schizophrenia: an updated systematic review and meta-analysis of randomized, placebo-controlled trials.

    PubMed

    Oya, Kazuto; Matsuda, Yuki; Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao

    2016-08-01

    The aim of this study was to perform a systematic review and an updated and comprehensive meta-analysis of oxytocin augmentation therapy in patients with schizophrenia who received antipsychotic agents. Data published up to 07/11/2015 were obtained from PubMed, PsycINFO, and Cochrane Library databases. We conducted a systematic review and meta-analysis of patients' data from randomized controlled trials (RCTs) comparing oxytocin with placebo. Relative risk (RR), standardized mean difference (SMD), and 95 % confidence intervals (95 % CI) based on the random-effects model were calculated. We included seven RCTs; the total sample size was 206 patients. Oxytocin was superior to placebo for decreasing the Positive and Negative Syndrome Scale (PANSS) general subscale scores (SMD = -0.44, 95 % CI -0.82 to -0.06, p = 0.02, I (2) = 0 %, N = 4, n = 112); however, it was not different from placebo for total symptoms (SMD = -0.46, 95 % CI -1.20 to 0.28, p = 0.22, I (2) = 80 %, N = 6, n = 162), positive symptoms (SMD = -0.18, 95 % CI -0.87 to 0.51, p = 0.60, I (2) = 81 %, N = 6, n = 192), and negative symptoms (SMD = -0.34, 95 % CI -0.76 to 0.08, p = 0.12, I (2) = 55 %, N = 7, n = 214). However, a sensitivity analysis including only oxytocin administration on consecutive days studies was superior to placebo in negative symptoms (SMD = -0.44, 95 % CI -0.87 to -0.01, p = 0.04, I (2) = 51 %, N = 6 n = 192). There were no significant differences for all-cause discontinuation (RR = 1.02) and individual side effects such as headache and dizziness between oxytocin and placebo. Oxytocin may improve PANSS general subscale scores in schizophrenia and seems to be well tolerated. However, because the number of studies in the current analysis was small, further study will be required using larger sample sizes. PMID:26303414

  2. A Distributed Network for Social Cognition Enriched for Oxytocin Receptors.

    PubMed

    Mitre, Mariela; Marlin, Bianca J; Schiavo, Jennifer K; Morina, Egzona; Norden, Samantha E; Hackett, Troy A; Aoki, Chiye J; Chao, Moses V; Froemke, Robert C

    2016-02-24

    Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent-infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. PMID:26911697

  3. Analysis of bursting responses of oxytocin neurones in the rat in late pregnancy, lactation and after weaning.

    PubMed Central

    Jiang, Q B; Wakerley, J B

    1995-01-01

    1. Electrophysiological recordings were undertaken to compare bursting characteristics of oxytocin (OT) neurones at four reproductive stages: day 20 pregnancy, day 22 of pregnancy (expected day of parturition), day 7-11 of lactation, and day 5-6 after weaning. 2. Each OT neurone was recorded for 1 h of suckling, combined with cervico-vaginal probing at 5 min intervals as an additional stimulus for bursting. Intracerebroventricular (I.C.V.) oxytocin (2.2 ng) was given after 30 min to facilitate bursting responses. Bursts observed during suckling were classified as 'spontaneous' or 'probe-evoked'. 3. The percentage of cells displaying spontaneous and/or probe-evoked bursts during the recording was low in day 20 pregnant animals, high in lactators and intermediate in day 20 pregnant and weaner groups. These differences may relate to variation in the proportion of animals with a responsive milk-ejection reflex, as well as the relative size of the population of bursting OT neurones. 4. In the period before I.C.V. OT, overall burst frequency (including both spontaneous and probe-evoked bursts) was similar across groups. After I.C.V. OT, overall burst frequency was much higher in lactators compared with other groups. Similar results were obtained when spontaneous bursts were analysed separately. 5. Burst amplitude (action potentials per burst, including both spontaneous and probe-evoked bursts) prior to I.C.V. OT was similar between the day 20 pregnant, day 22 pregnant and lactating groups, but was lower in weaners. All groups showed an increase in burst amplitude after I.C.V. OT, but values in weaners remained lower than in other groups. In a separate analysis of spontaneous bursts, burst amplitude after I.C.V. OT was higher in lactators, and lower in weaners, than in pregnant animals. 6. Background firing rates of OT cells were higher in the day 20 and day 22 pregnant groups compared with lactators, and lower in weaners. Only OT cells in lactators showed a significant

  4. A formulation and analysis of combat games

    NASA Technical Reports Server (NTRS)

    Heymann, M.; Ardema, M. D.; Rajan, N.

    1984-01-01

    Combat which is formulated as a dynamical encounter between two opponents, each of whom has offensive capabilities and objectives is outlined. A target set is associated with each opponent in the event space in which he endeavors to terminate the combat, thereby winning. If the combat terminates in both target sets simultaneously, or in neither, a joint capture or a draw, respectively, occurs. Resolution of the encounter is formulated as a combat game; as a pair of competing event constrained differential games. If exactly one of the players can win, the optimal strategies are determined from a resulting constrained zero sum differential game. Otherwise the optimal strategies are computed from a resulting nonzero sum game. Since optimal combat strategies may frequently not exist, approximate or delta combat games are also formulated leading to approximate or delta optimal strategies. The turret game is used to illustrate combat games. This game is sufficiently complex to exhibit a rich variety of combat behavior, much of which is not found in pursuit evasion games.

  5. A formulation and analysis of combat games

    NASA Technical Reports Server (NTRS)

    Heymann, M.; Ardema, M. D.; Rajan, N.

    1985-01-01

    Combat is formulated as a dynamical encounter between two opponents, each of whom has offensive capabilities and objectives. With each opponent is associated a target in the event space in which he endeavors to terminate the combat, thereby winning. If the combat terminates in both target sets simultaneously or in neither, a joint capture or a draw, respectively, is said to occur. Resolution of the encounter is formulated as a combat game; namely, as a pair of competing event-constrained differential games. If exactly one of the players can win, the optimal strategies are determined from a resulting constrained zero-sum differential game. Otherwise the optimal strategies are computed from a resulting non-zero-sum game. Since optimal combat strategies frequencies may not exist, approximate of delta-combat games are also formulated leading to approximate or delta-optimal strategies. To illustrate combat games, an example, called the turret game, is considered. This game may be thought of as a highly simplified model of air combat, yet it is sufficiently complex to exhibit a rich variety of combat behavior, much of which is not found in pursuit-evasion games.

  6. Integrated Formulation of Beacon-Based Exception Analysis for Multimissions

    NASA Technical Reports Server (NTRS)

    Mackey, Ryan; James, Mark; Park, Han; Zak, Mickail

    2003-01-01

    Further work on beacon-based exception analysis for multimissions (BEAM), a method of real-time, automated diagnosis of a complex electromechanical systems, has greatly expanded its capability and suitability of application. This expanded formulation, which fully integrates physical models and symbolic analysis, is described. The new formulation of BEAM expands upon previous advanced techniques for analysis of signal data, utilizing mathematical modeling of the system physics, and expert-system reasoning,

  7. A simple way to improved formulation of {FE}^2 analysis

    NASA Astrophysics Data System (ADS)

    Šolinc, Urša; Korelc, Jože

    2015-11-01

    A new formulation of two-scale {FE}^2 analysis introduces symmetric stretch tensor as strain measure on macro level instead of asymmetric deformation gradient to determine boundary conditions on embedded microstructure. This significantly reduces computational cost of boundary conditions related sensitivity analysis of microstructure and with it the evaluation of local macroscopic stress tensors and tangent matrices. Various {FE}^2 formulations with isogeometric and standard finite element microanalysis are tested for consistency, accuracy and numerical efficiency on numerical homogenisation examples. Objective performance comparison of different {FE}^2 formulations is enabled with automation of all procedures in symbolic code generation system AceGen. The results obtained in numerical examples show reduced computational cost of the new {FE}^2 formulation without loss of accuracy and comparable numerical efficiency of higher order isogeometric and standard {FE}^2 formulations.

  8. Oxytocin for frontotemporal dementia

    PubMed Central

    MacKinley, Julia; Blair, Mervin; Oliver, Lindsay D.; Jesso, Sarah; Tartaglia, Maria C.; Borrie, Michael; Wells, Jennie; Dziobek, Isabel; Pasternak, Stephen; Mitchell, Derek G.V.; Rankin, Katherine; Kertesz, Andrew; Boxer, Adam

    2015-01-01

    Objective: To determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD). Methods: We conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects. Results: All 3 doses of intranasal oxytocin were safe and well tolerated. Conclusions: A multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD. Classification of evidence: This study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory. PMID:25503617

  9. Oxytocin promotes human ethnocentrism.

    PubMed

    De Dreu, Carsten K W; Greer, Lindred L; Van Kleef, Gerben A; Shalvi, Shaul; Handgraaf, Michel J J

    2011-01-25

    Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence. PMID:21220339

  10. Does acute, intense stimulation of oxytocin neurones in the supraoptic nucleus increase their content of oxytocin mRNA?

    PubMed

    Sumner, B E; Kawata, M; Russell, J A

    1989-06-12

    We investigated whether a sustained increase in oxytocin secretion, with or without enhanced electrical activity of the cell-bodies of oxytocin neurones, leads to a rapid increase in oxytocin mRNA content in these neurones. To stimulate oxytocin release, naloxone (2.5 mg/kg i.v. twice, 30 min apart) was given to urethane-anaesthetized female rats after intracerebroventricular (i.c.v.) morphine or vehicle infusion for 5 days; in the latter, naloxone acts on the neurohypophysis to increase oxytocin release without affecting the electrical activity of oxytocin neurone cell-bodies, but in the former, naloxone acts both on the neucohypophysis and on the cell-bodies to excite them electrically. Oxytocin content in peripheral plasma was measured intermittently by radioimmunoassay for 4 h after i.v. naloxone or vehicle, then the brain was removed and cryostat sections were cut through the supraoptic nucleus (SON). Oxytocin mRNA content in individual neurones (25-50 per rat) was measured semiquantitatively by in situ hybridisation histochemistry, using a tritiated synthetic cDNA 25-mer oligonucleotide probe, autoradiographical visualisation, and computer-assisted image-analysis to measure silver grain density. Nalaxone increased oxytocin content in plasma 7-fold for at least 40 min in i.c.v. vehicle-infused rats, and 40-fold for at least 40 min in i.c.v. morphine-infused rats. Naloxone had no significant effect on the oxytocin mRNA content in labelled cells in the SON, and no effect on the proportion of labelled cells, in either the i.c.v. morphine- or i.c.v. vehicle-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2743158

  11. Absence of oxytocin in the central nervous system of the snake Bothrops jararaca.

    PubMed

    Lazari, Maria Fatima Magalhaes; Alponti, Rafaela Fadoni; Freitas, Thalma Ariani; Breno, Maria Cristina; da Conceicao, Isaltino Marcelo; Silveira, Paulo Flavio

    2006-11-01

    We used four complementary techniques to investigate the presence of oxytocin peptide in the hypophysis and brain of the snake Bothrops jararaca. A high-pressure liquid chromatographic analysis failed to show oxytocin in extracts of hypophysial and brain tissues but provided estimative values of the amounts of vasotocin (12 ng/mg hypophysis and 0.5 ng/mg brain) and mesotocin (500 pg/mg hypophysis and 8 pg/mg brain). Western blots with a polyclonal anti-oxytocin antibody failed to detect oxytocin in both tissues but detected compounds with higher molecular weight than oxytocin, as well as a relatively weak cross-reactivity with mesotocin. The reverse transcription-polymerase chain reaction analysis failed to detect the expression of oxytocin gene transcript, but detected a transcript related to the mesotocin-neurophysin precursor in both tissues. Immunohistochemistry with the same anti-oxytocin antibody detected strong staining in the neurohypophysis and in few fibers in the inner zone of the median eminence, which was not abolished by pre-adsorption of this antibody with oxytocin, vasopressin, vasotocin or mesotocin and might not be attributed to oxytocin. In conclusion, our data demonstrate the absence of oxytocin in the central nervous system of the snake B. jararaca and underline the pitfalls that can result from the use of a single technique to investigate the presence of peptides in tissues. PMID:16838134

  12. Oxytocin Reduces Cocaine Seeking and Reverses Chronic Cocaine-Induced Changes in Glutamate Receptor Function

    PubMed Central

    Zhou, Luyi; Sun, Wei-Lun; Young, Amy B.; Lee, Kunhee; McGinty, Jacqueline F.

    2015-01-01

    Background: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. Methods: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Results: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. Conclusions: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. PMID:25539504

  13. Oxytocin for induction of labor.

    PubMed

    Smith, Jennifer G; Merrill, David C

    2006-09-01

    Oxytocin is the most common pharmacologic agent used for the induction and augmentation of labor. Oxytocin protocols can be divided into high-dose and low-dose protocols depending on the initial dose and the amount and rate of sequential increase in dose. Despite the frequency with which oxytocin in used in clinical practice, there is little consensus regarding which protocol is most appropriate. The purpose of this chapter is to review the most current data concerning recommendations for the use of oxytocin in the induction of labor, including cases of intrauterine fetal demise and vaginal birth after cesarean. PMID:16885666

  14. Validated HPTLC method of analysis for artemether and its formulations.

    PubMed

    Tayade, Nitin G; Nagarsenker, Mangal S

    2007-02-19

    A simple, sensitive, precise and rapid high-performance thin-layer chromatographic (HPTLC) method of analysis for artemether both as a bulk drug and in pharmaceutical formulations was developed and validated. The method employed TLC aluminum plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of toluene-ethyl acetate-formic acid (8:2:0.3, v/v/v) as mobile phase. Densitometric analysis of artemether was carried out in the reflectance mode at 565 nm. The system was found to give compact spots for artemether (R(f) value of 0.50+/-0.03). The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9904 in the concentration range 200-1000 ng per spot. The mean value of correlation coefficient, slope and intercept were 0.9904+/-0.011, 7.27+/-0.11 and 166.24+/-56.92, respectively. The method was validated for precision, accuracy, recovery and robustness. The limits of detection and quantitation were 65.91 and 197.74 ng per spot, respectively. The method has been successfully applied in the analysis of lipid based parenteral formulations and marketed oral solid dosage formulation. PMID:17045768

  15. Regulation of neuronal oxytocin mRNA by ovarian steroids in the mature and developing hypothalamus.

    PubMed Central

    Miller, F D; Ozimek, G; Milner, R J; Bloom, F E

    1989-01-01

    We have examined the changes in neuronal expression of oxytocin mRNA in the perinatal and mature female rat as a function of endogenous gonadal steroids. Northern blot analysis demonstrated a significant developmental increase in the abundance of oxytocin mRNA in the female brain concomitant with puberty. Ovariectomy of adult females decreased total brain oxytocin mRNA to significantly lower levels. In contrast, lactating mothers had increased levels of neuronal oxytocin mRNA. In situ hybridization analysis of neuronal oxytocin mRNA in adolescent, mature virgin, and ovariectomized virgin female brains demonstrated that the location and number of neurons expressing oxytocin mRNA was unchanged and that total brain oxytocin mRNA differences were attributable to amounts expressed per neuron. Differences in mRNA abundance were noted in oxytocin neurons throughout the hypothalamus, including those known to project as magnocellular neurons to the neurohypophysis and those of parvocellular origin thought to make wholly intracerebral connections. This developmental and dynamic regulation of oxytocin mRNA levels during gonadal maturation may coordinate the peripheral and central effects of this peptide on the reproductive biology of the female rat. Images PMID:2928343

  16. Ancient neuromodulation by vasopressin/oxytocin-related peptides

    PubMed Central

    Beets, Isabel; Temmerman, Liesbet; Janssen, Tom; Schoofs, Liliane

    2013-01-01

    Neuropeptidergic signaling is widely adopted by animals for the regulation of physiology and behavior in a rapidly changing environment. The vasopressin/oxytocin neuropeptide family originates from an ancestral peptide precursor in the antecedent of protostomian and deuterostomian animals. In vertebrates, vasopressin and oxytocin have both hormonal effects on peripheral target tissues, such as in the regulation of reproduction and water balance, and neuromodulatory actions in the central nervous system controlling social behavior and cognition. The recent identification of vasopressin/oxytocin-related signaling in C. elegans reveals that this peptidergic system is widespread among nematodes. Genetic analysis of the C. elegans nematocin system denotes vasopressin/oxytocin-like peptides as ancient neuromodulators of neuronal circuits involved in reproductive behavior and associative learning, whereas former invertebrate studies focused on conserved peripheral actions of this peptide family. Nematocin provides neuromodulatory input into the gustatory plasticity circuit as well as into distinct male mating circuits to generate a coherent mating behavior. Molecular interactions are comparable to those underlying vasopressin- and oxytocin-mediated effects in the mammalian brain. Understanding how the vasopressin/oxytocin family fine-tunes neuronal circuits for social behavior, learning and memory poses a major challenge. Functional conservation of these effects in nematodes and most likely in other invertebrates enables the development of future models to help answering this question. PMID:24058873

  17. Putting problem formulation at the forefront of GMO risk analysis.

    PubMed

    Tepfer, Mark; Racovita, Monica; Craig, Wendy

    2013-01-01

    When applying risk assessment and the broader process of risk analysis to decisions regarding the dissemination of genetically modified organisms (GMOs), the process has a tendency to become remarkably complex. Further, as greater numbers of countries consider authorising the large-scale dissemination of GMOs, and as GMOs with more complex traits reach late stages of development, there has been increasing concern about the burden posed by the complexity of risk analysis. We present here an improved approach for GMO risk analysis that gives a central role to problem formulation. Further, the risk analysis strategy has been clarified and simplified in order to make rigorously scientific risk assessment and risk analysis more broadly accessible to diverse stakeholder groups. PMID:23160540

  18. The oxytocin receptor gene (OXTR) localizes to human chromosome 3p25 by fluorescence in situ hybridization and PCR analysis of somatic cell hybrids

    SciTech Connect

    Simmons, C.F. Jr.; Clancy, T.E.; Quan, R.

    1995-04-10

    The human oxytocin receptor regulates parturition and myometrial contractility, breast milk let-down, and reproductive behaviors in the mammalian central nervous system. Kimura et al. recently identified a human oxytocin receptor cDNA by means of expression cloning from a human myometrial cDNA library. To elucidate further the molecular mechanisms that regulate oxytocin receptor gene expression and to define the expected Mendelian inheritance of possible human disease states, we must determine the number of genes, their localization, and their organization and structure. We summarize below our data indicating that the human oxytocin receptor gene is localized to 3p25 and exists as a single copy in the haploid genome. 9 refs., 2 figs.

  19. Aeroelastic analysis for propellers - mathematical formulations and program user's manual

    NASA Technical Reports Server (NTRS)

    Bielawa, R. L.; Johnson, S. A.; Chi, R. M.; Gangwani, S. T.

    1983-01-01

    Mathematical development is presented for a specialized propeller dedicated version of the G400 rotor aeroelastic analysis. The G400PROP analysis simulates aeroelastic characteristics particular to propellers such as structural sweep, aerodynamic sweep and high subsonic unsteady airloads (both stalled and unstalled). Formulations are presented for these expanded propeller related methodologies. Results of limited application of the analysis to realistic blade configurations and operating conditions which include stable and unstable stall flutter test conditions are given. Sections included for enhanced program user efficiency and expanded utilization include descriptions of: (1) the structuring of the G400PROP FORTRAN coding; (2) the required input data; and (3) the output results. General information to facilitate operation and improve efficiency is also provided.

  20. Oxytocin treatment in pediatric populations

    PubMed Central

    Taylor, Adrienne E.; Lee, Hsu-en; Buisman-Pijlman, Femke T. A.

    2014-01-01

    The role of endogenous oxytocin as neuromodulator of birth, lactation and social behaviors is well-recognized. Moreover, the use of oxytocin as a facilitator of social and other behaviors is becoming more and more accepted. Many positive effects have been attributed to intranasal oxytocin administration in animals and humans; with current research highlighting encouraging advances in its potential for use in mental health disorders. The new frontier will be investigating the effective use of oxytocin in pediatric populations. Limited animal data is available on this. Large-scale human studies focusing on autism are currently under way, but many other possibilities seem to lie in the future. However, we need to know more about the risks and effects of repeated use on the developing brain and body. This paper will provide an overview of the current understanding of the role of endogenous oxytocin and its related neuropeptide systems in influencing behaviors, in particular attachment, and will review (a) the literature on the use of intranasal oxytocin in young animals, children (age range birth-12 years) and adolescents (age range 13–19 years), (b) the expected benefits and risks based on the current research, and (c) the risks of oxytocin in children with severe psychopathology and early life trauma. The paper will conclude with a clinical perspective on these findings. PMID:25360094

  1. Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis.

    PubMed

    Rutigliano, Grazia; Rocchetti, Matteo; Paloyelis, Yannis; Gilleen, James; Sardella, Alberto; Cappucciati, Marco; Palombini, Erika; Dell'Osso, Liliana; Caverzasi, Edgardo; Politi, Pierluigi; McGuire, Philip; Fusar-Poli, Paolo

    2016-07-30

    A large array of studies have investigated peripheral oxytocin (OT) and vasopressin (ADH) as potential biomarkers of psychiatric disorders, with highly conflicting and heterogenous findings. We searched Web of KnowledgeSM and Scopus® for English original articles investigating OT and/or ADH levels in different biological fluids (plasma/serum, saliva, urine and cerebrospinal fluid) across several psychiatric disorders. Sixty-four studies were included. We conducted 19 preliminary meta-analyses addressing OT alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 7 psychiatric disorders and ADH alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 6 psychiatric disorders compared to controls. Hedge's g was used as effect size measure, together with heterogeneity analyses, test of publication biases and quality control. None of them (except serum OT in anorexia nervosa) revealed significant differences. There is no convincing evidence that peripheral ADH or OT might be reliable biomarkers in psychiatric disorders. However, the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies, which need to be validated and standardized. PMID:27183106

  2. Analysis of Transcription Factor mRNAs in Identified Oxytocin and Vasopressin Magnocellular Neurons Isolated by Laser Capture Microdissection

    PubMed Central

    Rodriguez-Canales, Jaime; Lubelski, Daniel; Rashid, Omar M.; Salinas, Yasmmyn D.; Shi, YiJun; Ponzio, Todd; Fields, Raymond; Emmert-Buck, Michael R.; Gainer, Harold

    2013-01-01

    The oxytocin (Oxt) and vasopressin (Avp) magnocellular neurons (MCNs) in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON), and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM), and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV) vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun) are differentially expressed in the Oxt and Avp MCNs. PMID:23894472

  3. Analysis of hematinic formulations available in the Indian market

    PubMed Central

    Karelia, B. N.; Buch, J. G.

    2012-01-01

    Objectives: To analyze the hematinic formulations available in Indian market for their varieties of dosage forms, iron salts used, content of elemental iron, frequency of administration, additional nutrients, and cost. Materials and Methods: Hematinic formulations listed in Indian Drug Review (2009) were analyzed for the iron salts contained and the elemental iron content. Preparations containing iron ± folic acid ± vitamin C were considered as ‘acceptable’ formulations. For proper comparison, cost of 100 mg elemental iron in each formulation was calculated. Acceptable oral formulations containing iron with folic acid were further classified according to iron salts, and the median cost of various iron salts was compared. We also identified oral solid formulations that required administration more than three times a day. Prices of ‘acceptable’ iron preparations were compared with that of ‘irrational’ formulations. Results: Out of 621 formulations, 365 were oral solid formulations, 232 were oral liquids, and 24 were for parenteral administration. Formulations containing iron salts like ferrous sulphate, ferrous sulphate (dried), carbonyl iron, and ferrous fumarate are cheaper than formulations containing other iron salts. Among the 365 oral (solid) iron formulations, we found 60 that would require administration more than three times a day to provide a therapeutic dosage of elemental iron. As compared to irrational formulations, the cost of acceptable formulations was in a significantly narrow range; however, the median cost of acceptable products was significantly higher than that of the irrational ones, except in case of the parenteral preparations. Conclusion: The drug regulation authorities should tune the drug price in such a way that rational formulations cost less than the irrational ones. PMID:22368414

  4. Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain.

    PubMed

    de Araujo, Aline Dantas; Mobli, Mehdi; Castro, Joel; Harrington, Andrea M; Vetter, Irina; Dekan, Zoltan; Muttenthaler, Markus; Wan, JingJing; Lewis, Richard J; King, Glenn F; Brierley, Stuart M; Alewood, Paul F

    2014-01-01

    Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general. PMID:24476666

  5. Opposing Oxytocin Effects on Intergroup Cooperative Behavior in Intuitive and Reflective Minds.

    PubMed

    Ma, Yina; Liu, Yi; Rand, David G; Heatherton, Todd F; Han, Shihui

    2015-09-01

    People often favor ingroup over outgroup members when choosing to cooperate. Such ingroup-favored cooperation is promoted by oxytocin-a neuropeptide shown to facilitate social cognition and that has emerged as a pharmacological target for treatments of social functioning deficits. The current study applied a dual-process model to investigate whether and how intuitive and reflective cognitive styles affect the oxytocin-motivated ingroup favoritism in cooperation. We examined oxytocin effects on ingroup favoritism in a double-blind, placebo-controlled between-subjects design where cognitive processing (intuition vs reflection) was experimentally manipulated in healthy Chinese males (n=150). We also supplemented this experimental manipulation with an individual difference analysis by assessing participants' inclination toward intuition or reflection in daily life. Intranasal administration of oxytocin (vs placebo) increased ingroup favoritism among participants primed to be intuitive or those who preferred intuition in daily life. In contrast, oxytocin decreased ingroup favoritism in participants primed to rely on reflective thinking or those who preferred reflective decision-making in daily life. Our results demonstrate that oxytocin has distinct functional roles when different cognitive styles (ie, intuition vs reflection) are promoted during social cooperation in a group situation. Our findings have implications for oxytocin pharmacotherapy of social dysfunction in that whether the effects of oxytocin on social functioning are facilitative, debilitative, or null, depends on an individual's cognitive style. PMID:25807529

  6. Plasma oxytocin explains individual differences in neural substrates of social perception.

    PubMed

    Lancaster, Katie; Carter, C Sue; Pournajafi-Nazarloo, Hossein; Karaoli, Themistoclis; Lillard, Travis S; Jack, Allison; Davis, John M; Morris, James P; Connelly, Jessica J

    2015-01-01

    The neuropeptide oxytocin plays a critical role in social cognition and behavior. A number of studies using intranasal administration have demonstrated that oxytocin improves social perception. However, little is known about the relationship between individual differences in endogenous levels of oxytocin and social cognition. In the current study, we assessed the relationship between endogenous oxytocin and brain activity during an animacy perception paradigm. Thirty-seven male participants underwent scanning and provided a blood sample for oxytocin analysis. In line with previous research, perception of animacy was associated with activations in superior temporal sulcus, inferior frontal gyrus, and medial prefrontal cortex (mPFC). Notably, participants' levels of plasma oxytocin robustly predicted activation in areas critical for social cognitive processes, such that higher oxytocin levels were related to increased activity in dorsal mPFC, ventral mPFC, dorsolateral PFC, superior temporal gyrus, and temporoparietal junction (TPJ), suggesting differential processing of social stimuli. Together these results show that stable variations in endogenous oxytocin levels explain individual differences in social perception. PMID:25852519

  7. Plasma oxytocin explains individual differences in neural substrates of social perception

    PubMed Central

    Lancaster, Katie; Carter, C. Sue; Pournajafi-Nazarloo, Hossein; Karaoli, Themistoclis; Lillard, Travis S.; Jack, Allison; Davis, John M.; Morris, James P.; Connelly, Jessica J.

    2015-01-01

    The neuropeptide oxytocin plays a critical role in social cognition and behavior. A number of studies using intranasal administration have demonstrated that oxytocin improves social perception. However, little is known about the relationship between individual differences in endogenous levels of oxytocin and social cognition. In the current study, we assessed the relationship between endogenous oxytocin and brain activity during an animacy perception paradigm. Thirty-seven male participants underwent scanning and provided a blood sample for oxytocin analysis. In line with previous research, perception of animacy was associated with activations in superior temporal sulcus, inferior frontal gyrus, and medial prefrontal cortex (mPFC). Notably, participants’ levels of plasma oxytocin robustly predicted activation in areas critical for social cognitive processes, such that higher oxytocin levels were related to increased activity in dorsal mPFC, ventral mPFC, dorsolateral PFC, superior temporal gyrus, and temporoparietal junction (TPJ), suggesting differential processing of social stimuli. Together these results show that stable variations in endogenous oxytocin levels explain individual differences in social perception. PMID:25852519

  8. Oxytocin and Maternal Brain Plasticity.

    PubMed

    Kim, Sohye; Strathearn, Lane

    2016-09-01

    Although dramatic postnatal changes in maternal behavior have long been noted, we are only now beginning to understand the neurobiological mechanisms that support this transition. The present paper synthesizes growing insights from both animal and human research to provide an overview of the plasticity of the mother's brain, with a particular emphasis on the oxytocin system. We examine plasticity observed within the oxytocin system and discuss how these changes mediate an array of other adaptations observed within the maternal brain. We outline factors that affect the oxytocin-mediated plasticity of the maternal brain and review evidence linking disruptions in oxytocin functions to challenges in maternal adaptation. We conclude by suggesting a strategy for intervention with mothers who may be at risk for maladjustment during this transition to motherhood, while highlighting areas where further research is needed. PMID:27589498

  9. Formulation for Simultaneous Aerodynamic Analysis and Design Optimization

    NASA Technical Reports Server (NTRS)

    Hou, G. W.; Taylor, A. C., III; Mani, S. V.; Newman, P. A.

    1993-01-01

    An efficient approach for simultaneous aerodynamic analysis and design optimization is presented. This approach does not require the performance of many flow analyses at each design optimization step, which can be an expensive procedure. Thus, this approach brings us one step closer to meeting the challenge of incorporating computational fluid dynamic codes into gradient-based optimization techniques for aerodynamic design. An adjoint-variable method is introduced to nullify the effect of the increased number of design variables in the problem formulation. The method has been successfully tested on one-dimensional nozzle flow problems, including a sample problem with a normal shock. Implementations of the above algorithm are also presented that incorporate Newton iterations to secure a high-quality flow solution at the end of the design process. Implementations with iterative flow solvers are possible and will be required for large, multidimensional flow problems.

  10. Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett’s Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium

    PubMed Central

    Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G.; Risch, Harvey A.; Shaheen, Nicholas J.; Bird, Nigel C.; Reid, Brian J.; Corley, Douglas A.; Hardie, Laura J.; Wu, Anna H.; Fitzgerald, Rebecca C.; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L.; MacGregor, Stuart; Whiteman, David; Westberg, Lars; Nyren, Olof; Lagergren, Jesper

    2015-01-01

    Background The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett’s oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. Methods This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Results Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Conclusion Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed. PMID:26406593

  11. Partial differential equation transform — Variational formulation and Fourier analysis

    PubMed Central

    Wang, Yang; Wei, Guo-Wei; Yang, Siyang

    2011-01-01

    Nonlinear partial differential equation (PDE) models are established approaches for image/signal processing, data analysis and surface construction. Most previous geometric PDEs are utilized as low-pass filters which give rise to image trend information. In an earlier work, we introduced mode decomposition evolution equations (MoDEEs), which behave like high-pass filters and are able to systematically provide intrinsic mode functions (IMFs) of signals and images. Due to their tunable time-frequency localization and perfect reconstruction, the operation of MoDEEs is called a PDE transform. By appropriate selection of PDE transform parameters, we can tune IMFs into trends, edges, textures, noise etc., which can be further utilized in the secondary processing for various purposes. This work introduces the variational formulation, performs the Fourier analysis, and conducts biomedical and biological applications of the proposed PDE transform. The variational formulation offers an algorithm to incorporate two image functions and two sets of low-pass PDE operators in the total energy functional. Two low-pass PDE operators have different signs, leading to energy disparity, while a coupling term, acting as a relative fidelity of two image functions, is introduced to reduce the disparity of two energy components. We construct variational PDE transforms by using Euler-Lagrange equation and artificial time propagation. Fourier analysis of a simplified PDE transform is presented to shed light on the filter properties of high order PDE transforms. Such an analysis also offers insight on the parameter selection of the PDE transform. The proposed PDE transform algorithm is validated by numerous benchmark tests. In one selected challenging example, we illustrate the ability of PDE transform to separate two adjacent frequencies of sin(x) and sin(1.1x). Such an ability is due to PDE transform’s controllable frequency localization obtained by adjusting the order of PDEs. The

  12. Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia.

    PubMed

    Shin, Na Young; Park, Hye Yoon; Jung, Wi Hoon; Park, Jin Woo; Yun, Je-Yeon; Jang, Joon Hwan; Kim, Sung Nyun; Han, Hyun Jung; Kim, So-Yeon; Kang, Do-Hyung; Kwon, Jun Soo

    2015-07-01

    Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion-recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double-blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia. PMID:25666311

  13. Analysis of a Commercial Marijuana e-Cigarette Formulation.

    PubMed

    Peace, Michelle R; Stone, Joseph W; Poklis, Justin L; Turner, Joseph B M; Poklis, Alphonse

    2016-06-01

    Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. With four states within the USA having legalized the cultivation, distribution and recreational use of marijuana and an additional 23 states plus the District of Columbia with laws that legalize marijuana in some form, it was inevitable that suppliers of legal marijuana would develop marijuana products for use in these electronic cigarettes. Presented is the analysis of one such marijuana electronic cigarette formulation sold under the brand name Liberty Reach. The cannabinoid concentrations in Liberty Reach as determined by high-performance liquid chromatography-triple quadrapole mass spectrometry (HPLC-MS-MS) were Δ9-tetrahydrocannabinol, 42.6% (w/v) and cannabidiol 0.5% (w/v). These concentrations were significantly lower than the labeled 69% Δ9-tetrahydrocannabinol and 1% cannabidiol. Furthermore, 4 cannabinoids, 13 marijuana terpenes, and propylene glycol were identified by a combination of Direct Analysis in Real Time-AccuTOF™ mass spectrometry (DART-MS), HPLC-MS-MS and gas chromatography-MS. PMID:27059691

  14. Slow Crack Growth of Brittle Materials With Exponential Crack-Velocity Formulation. Part 1; Analysis

    NASA Technical Reports Server (NTRS)

    Choi, Sung R.; Nemeth, Noel N.; Gyekenyesi, John P.

    2002-01-01

    Extensive slow-crack-growth (SCG) analysis was made using a primary exponential crack-velocity formulation under three widely used load configurations: constant stress rate, constant stress, and cyclic stress. Although the use of the exponential formulation in determining SCG parameters of a material requires somewhat inconvenient numerical procedures, the resulting solutions presented gave almost the same degree of simplicity in both data analysis and experiments as did the power-law formulation. However, the fact that the inert strength of a material should be known in advance to determine the corresponding SCG parameters was a major drawback of the exponential formulation as compared with the power-law formulation.

  15. Can magnetic resonance imaging predict the success of parturition in oxytocin-induced pregnant women?

    PubMed

    Sabir, N; Dicle, O; Yurdakul, B; Akkemik, B

    2000-01-01

    The aim of this study was to assess whether magnetic resonance imaging could predict the outcome of attempted vaginal delivery in a group of pregnant women whose parturition had to be induced by oxytocin. The signal intensity and morphology alterations in the cervix of 21 full-term pregnant women were analyzed before the induction of parturition. T2-weighted gradient echo sequences were utilized and signal intensity in the cervix was measured from the anterior and posterior lips of the cervix. An index indicating the brightness range of the cervix was formulated to overcome the effects of the individual intensity changes. Imaging features including the signal intensity and the evidence of effacement were correlated with the actual type of delivery performed. Images were also assessed visually by two independent radiologists. Statistical analysis of brightness indexes that were considered to have a predictive value as an indicator for possible delivery was not significant. However, visually assessed signal intensity of the cervix correlated strongly with the type of delivery. Effacement itself was the most reliable parameter in predicting the progress of the delivery. In conclusion, MR imaging seems to be useful for predicting normal parturition in full-term pregnant women who need oxytocin induction. However, the presence of effacement seems to be a more reliable and practical parameter that will be preferred in that prediction. PMID:10823630

  16. Intranasal inhalation of oxytocin improves face processing in developmental prosopagnosia.

    PubMed

    Bate, Sarah; Cook, Sarah J; Duchaine, Bradley; Tree, Jeremy J; Burns, Edwin J; Hodgson, Timothy L

    2014-01-01

    Developmental prosopagnosia (DP) is characterised by a severe lifelong impairment in face recognition. In recent years it has become clear that DP affects a substantial number of people, yet little work has attempted to improve face processing in these individuals. Intriguingly, recent evidence suggests that intranasal inhalation of the hormone oxytocin can improve face processing in unimpaired participants, and we investigated whether similar findings might be noted in DP. Ten adults with DP and 10 matched controls were tested using a randomized placebo-controlled double-blind within-subject experimental design (AB-BA). Each participant took part in two testing sessions separated by a 14-25 day interval. In each session, participants inhaled 24 IU of oxytocin or placebo spray, followed by a 45 min resting period to allow central oxytocin levels to plateau. Participants then completed two face processing tests: one assessing memory for a set of newly encoded faces, and one measuring the ability to match simultaneously presented faces according to identity. Participants completed the Multidimensional Mood Questionnaire (MMQ) at three points in each testing session to assess the possible mood-altering effects of oxytocin and to control for attention and wakefulness. Statistical comparisons revealed an improvement for DP but not control participants on both tests in the oxytocin condition, and analysis of scores on the MMQ indicated that the effect cannot be attributed to changes in mood, attention or wakefulness. This investigation provides the first evidence that oxytocin can improve face processing in DP, and the potential neural underpinnings of the findings are discussed alongside their implications for the treatment of face processing disorders. PMID:24074457

  17. Oxytocin and Social Motivation

    PubMed Central

    Gordon, Ilanit; Martin, Carina; Feldman, Ruth; Leckman, James F.

    2011-01-01

    Humans are fundamentally social creatures who are ‘motivated’ to be with others. In this review we examine the role of oxytocin (OT) as it relates to social motivation. OT is synthesized in the brain and throughout the body, including in the heart, thymus, gastrointestinal tract, as well as reproductive organs. The distribution of the OT receptor (OTR) system in both the brain and periphery is even more far-reaching and its expression is subject to changes over the course of development. OTR expression is also sensitive to changes in the external environment and the internal somatic world. The OT system functions as an important element within a complex, developmentally sensitive biobehavioral system. Other elements include sensory inputs, the salience, reward, and threat detection pathways, the hypothalamic-pituitary-gonadal axis, and the hypothalamic-pituitary-adrenal stress response axis. Despite an ever expanding scientific literature, key unresolved questions remain concerning the interplay of the central and peripheral components of this complex biobehavioral system that dynamically engages the brain and the body as humans interact with social partners over the course of development. PMID:21984889

  18. Elevated plasma oxytocin levels in children with Prader-Willi syndrome compared with healthy unrelated siblings.

    PubMed

    Johnson, Lisa; Manzardo, Ann M; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

    2016-03-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder associated with distinct abnormal behaviors including hyperphagia, profound social deficits, and obsessive-compulsive tendencies. PWS males showed reduced oxytocin receptor (OTR) gene expression and density in the hypothalamic paraventricular nucleus that may play a role in PWS psychopathology. Oxytocin is an anorexigenic neuropeptide similar to vasopressin that is associated with social cognition and obsessive-compulsive behavior. To evaluate oxytocin biology in PWS, we examined overnight fasting plasma oxytocin levels in 23 children with PWS (mean ± SD age: 8.2 ± 2.0 year) having genetic confirmation and 18 age matched healthy unrelated siblings without PWS (mean ± SD age: 8.2 ± 2.3 year) and a similar gender ratio under the same clinical assessments, specimen processing and laboratory conditions. Multiplex immune assays were carried out using the Milliplex Human Neuropeptide Magnetic panel and the Luminex system. Natural log-transformed oxytocin levels were analyzed using general linear model adjusting for diagnosis, gender, age and body mass index (BMI). Oxytocin plasma levels were significantly elevated in children with PWS (168 ± 121 pg/ml) compared with unrelated and unaffected siblings without the diagnosis of PWS (64.8 ± 83.8 pg/ml, F = 8.8, P < 0.01) and the diagnosis of PWS predicted oxytocin level (F = 9.5, P < 0.003) in controlled regression analysis with an overall model fit R(2) = 0.33 (P < 0.01). The symptoms of hyperphagia, anxiety and repetitive behaviors classically seen in PWS may be related to the disruption of oxytocin responsivity or feedback in the hypothalamic paraventricular nucleus possibly influencing vasopressin signaling. Further study is needed to characterize oxytocin function in PWS. PMID:26615966

  19. Vasopressin and oxytocin in stress.

    PubMed

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

    1995-12-29

    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. PMID:8597399

  20. Oxytocin and bone.

    PubMed

    Colaianni, Graziana; Sun, Li; Zaidi, Mone; Zallone, Alberta

    2014-10-15

    One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR(-/-) mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

  1. Capillary electrophoresis separation of the desamino degradation products of oxytocin

    PubMed Central

    Creamer, Jessica S.; Krauss, Shannon T.; Lunte, Susan M.

    2014-01-01

    Oxytocin is an endogenous and therapeutic hormone necessary for maternal health. It is also the subject of fast growing research in the field of behavioral science. This article describes a rapid capillary electrophoresis method using UV detection at 214 nm for the determination of the deamidation products of oxytocin. Deamidation is the most common degradation pathway of peptides and proteins and can lead to reduced therapeutic efficiency of biopharmaceuticals. To achieve a separation of the seven structurally similar desamino peptides from oxytocin, 11 mM sulfobutyl ether β-cyclodextrin and 10% v/v MeOH were added to a background electrolyte of 50 mM phosphate buffer at pH 6.0. The assay is linear within ≤5-100 μM for all species with a total analysis time of 12 min. The method was then applied to monitor the heat-stress degradation of oxytocin at 70°C, where all seven desamino species were observed over a 96 h period. PMID:24166826

  2. Mechanistic model and analysis of doxorubicin release from liposomal formulations.

    PubMed

    Fugit, Kyle D; Xiang, Tian-Xiang; Choi, Du H; Kangarlou, Sogol; Csuhai, Eva; Bummer, Paul M; Anderson, Bradley D

    2015-11-10

    Reliable and predictive models of drug release kinetics in vitro and in vivo are still lacking for liposomal formulations. Developing robust, predictive release models requires systematic, quantitative characterization of these complex drug delivery systems with respect to the physicochemical properties governing the driving force for release. These models must also incorporate changes in release due to the dissolution media and methods employed to monitor release. This paper demonstrates the successful development and application of a mathematical mechanistic model capable of predicting doxorubicin (DXR) release kinetics from liposomal formulations resembling the FDA-approved nanoformulation DOXIL® using dynamic dialysis. The model accounts for DXR equilibria (e.g. self-association, precipitation, ionization), the change in intravesicular pH due to ammonia release, and dialysis membrane transport of DXR. The model was tested using a Box-Behnken experimental design in which release conditions including extravesicular pH, ammonia concentration in the release medium, and the dilution of the formulation (i.e. suspension concentration) were varied. Mechanistic model predictions agreed with observed DXR release up to 19h. The predictions were similar to a computer fit of the release data using an empirical model often employed for analyzing data generated from this type of experimental design. Unlike the empirical model, the mechanistic model was also able to provide reasonable predictions of release outside the tested design space. These results illustrate the usefulness of mechanistic modeling to predict drug release from liposomal formulations in vitro and its potential for future development of in vitro - in vivo correlations for complex nanoformulations. PMID:26310713

  3. Lack of Association between Human Plasma Oxytocin and Interpersonal Trust in a Prisoner’s Dilemma Paradigm

    PubMed Central

    Christensen, James C.; Shiyanov, Pavel A.; Estepp, Justin R.; Schlager, John J.

    2014-01-01

    Expanding interest in oxytocin, particularly the role of endogenous oxytocin in human social behavior, has created a pressing need for replication of results and verification of assay methods. In this study, we sought to replicate and extend previous results correlating plasma oxytocin with trust and trustworthy behavior. As a necessary first step, the two most commonly used commercial assays were compared in human plasma via the addition of a known quantity of exogenous oxytocin, with and without sample extraction. Plasma sample extraction was found to be critical in obtaining repeatable concentrations of oxytocin. In the subsequent trust experiment, twelve samples in duplicate, from each of 82 participants, were collected over approximately six hours during the performance of a Prisoner’s Dilemma task paradigm that stressed human interpersonal trust. We found no significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed with careful consideration of methods and appropriate biofluids for analysis. PMID:25549255

  4. Oxytocin is associated with human trustworthiness.

    PubMed

    Zak, Paul J; Kurzban, Robert; Matzner, William T

    2005-12-01

    Human beings exhibit substantial interpersonal trust-even with strangers. The neuroactive hormone oxytocin facilitates social recognition in animals, and we examine if oxytocin is related to trustworthiness between humans. This paper reports the results of an experiment to test this hypothesis, where trust and trustworthiness are measured using the sequential anonymous "trust game" with monetary payoffs. We find that oxytocin levels are higher in subjects who receive a monetary transfer that reflects an intention of trust relative to an unintentional monetary transfer of the same amount. In addition, higher oxytocin levels are associated with trustworthy behavior (the reciprocation of trust). Absent intentionality, both the oxytocin and behavioral responses are extinguished. We conclude that perceptions of intentions of trust affect levels of circulating oxytocin. PMID:16109416

  5. Isogeometric analysis of Lagrangian hydrodynamics: Axisymmetric formulation in the rz-cylindrical coordinates

    NASA Astrophysics Data System (ADS)

    Bazilevs, Y.; Long, C. C.; Akkerman, I.; Benson, D. J.; Shashkov, M. J.

    2014-04-01

    A recent Isogeometric Analysis (IGA) formulation of Lagrangian shock hydrodynamics [4] is extended to the 3D axisymmetric case. The Euler equations of compressible hydrodynamics are formulated using the rz-cylindrical coordinates, and are discretized in the weak form using NURBS-based IGA. Artificial shock viscosity and internal energy projection are added to stabilize the formulation. The resulting discretization exhibits good accuracy and robustness properties. It also gives exact symmetry preservation on the appropriately constructed meshes. Several benchmark examples are computed to examine the performance of the proposed formulation.

  6. Micosoft Excel Sensitivity Analysis for Linear and Stochastic Program Feed Formulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sensitivity analysis is a part of mathematical programming solutions and is used in making nutritional and economic decisions for a given feed formulation problem. The terms, shadow price and reduced cost, are familiar linear program (LP) terms to feed formulators. Because of the nonlinear nature of...

  7. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study

    PubMed Central

    Kelly, Maria; Rutledge, Robb B.; Winston, Joel; Wright, Nicholas; Dolan, Raymond J.; Bahrami, Bahador

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants’ (unwarranted) reliance on their partners’ opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other’s performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration. PMID:27070542

  8. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

    PubMed

    Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration. PMID:27070542

  9. Positional FEM formulation for flexible multi-body dynamic analysis

    NASA Astrophysics Data System (ADS)

    Greco, M.; Coda, H. B.

    2006-03-01

    This paper presents a simple formulation to deal with flexible multi-body dynamic systems by the finite element method. The proposed methodology is based on the minimum potential energy theorem written regarding nodal positions. Velocity, acceleration and strain are achieved directly from positions, not displacements. A non-dimensional space is created and the relative curvature and fibers length are calculated for both reference and deformed configurations and used to calculate the strain energy at general points. The classical Newmark equations are used to integrate time. Damping is introduced into the mechanical system by a rheonomic energy functional. The final formulation has the advantage of being simple and easy to teach, when compared to classical counterparts. The behavior of a bench-mark problem (spin-up maneuver) is studied regarding the influence of mass representation on its overall transient and steady-state behavior. Three other examples are presented to show the applicability of the technique, namely, a flexible slider-crank mechanism, a flexible beam flight and a Peaucellier-type mechanism. The results are compared with other authors' numerical solutions.

  10. Dopamine-oxytocin interactions in penile erection.

    PubMed

    Baskerville, T A; Allard, J; Wayman, C; Douglas, A J

    2009-12-01

    Dopamine and oxytocin have established roles in the central regulation of penile erection in rats; however, the neural circuitries involved in a specific erectile context and the interaction between dopamine and oxytocin mechanisms remain to be elucidated. The medial preoptic area (MPOA), supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus may serve as candidate sites because they contain oxytocin cells, receive dopaminergic inputs and have been implicated in mediating masculine sexual behavior. Double immunofluorescence revealed that substantial numbers of oxytocin cells in the MPOA, SON and PVN possess dopamine D(2), D(3) and D(4) receptors. In anaesthetized rats, using intracavernous pressure as a physiological indicator of erection, blockade of lumbosacral oxytocin receptors (UK, 427843) reduced erectile responses to a nonselective dopamine agonist (apomorphine), suggesting that dopamine recruits a paraventriculospinal oxytocin pathway. In conscious males in the absence of a female, penile erection elicited by a D(2)/D(3) (Quinelorane) but not D(4) (PD168077) agonist was associated with activation of medial parvocellular PVN oxytocin cells. In another experiment where males were given full access to a receptive female, a D(4) (L-745870) but not D(2) or D(3) antagonist (L-741626; nafadotride) inhibited penile erection (intromission), and this was correlated with SON magnocellular oxytocin neuron activation. Together, the data suggest dopamine's effects on hypothalamic oxytocin cells during penile erection are context-specific. Dopamine may act via different parvocellular and magnocellular oxytocin subpopulations to elicit erectile responses, depending upon whether intromission is performed. This study demonstrates the potential existence of interaction between central dopamine and oxytocin pathways during penile erection, with the SON and PVN serving as integrative sites. PMID:20128851

  11. Changes in social functioning and circulating oxytocin and vasopressin following the migration to a new country.

    PubMed

    Gouin, Jean-Philippe; Pournajafi-Nazarloo, Hossein; Carter, C Sue

    2015-02-01

    Prior studies have reported associations between plasma oxytocin and vasopressin and markers of social functioning. However, because most human studies have used cross-sectional designs, it is unclear whether plasma oxytocin and vasopressin influences social functioning or whether social functioning modulates the production and peripheral release of these peptides. In order to address this question, we followed individuals who experienced major changes in social functioning subsequent to the migration to a new country. In this study, 59 new international students were recruited shortly after arrival in the host country and reassessed 2 and 5 months later. At each assessment participants provided information on their current social functioning and blood samples for oxytocin and vasopressin analysis. Results indicated that changes in social functioning were not related to changes in plasma oxytocin. Instead, baseline oxytocin predicted changes in social relationship satisfaction, social support, and loneliness over time. In contrast, plasma vasopressin changed as a function of social integration. Baseline vasopressin was not related to changes in social functioning over time. These results emphasize the different roles of plasma oxytocin and vasopressin in responses to changes in social functioning in humans. PMID:25446216

  12. 21 CFR 522.1680 - Oxytocin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytocin. 522.1680 Section 522.1680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin....

  13. Singularities in Dromo formulation. Analysis of deep flybys

    NASA Astrophysics Data System (ADS)

    Roa, Javier; Sanjurjo-Rivo, Manuel; Peláez, Jesús

    2015-08-01

    The singularities in Dromo are characterized in this paper, both from an analytical and a numerical perspective. When the angular momentum vanishes, Dromo may encounter a singularity in the evolution equations. The cancellation of the angular momentum occurs in very specific situations and may be caused by the action of strong perturbations. The gravitational attraction of a perturbing planet may lead to rapid changes in the angular momentum of the particle. In practice, this situation may be encountered during deep planetocentric flybys. The performance of Dromo is evaluated in different scenarios. First, Dromo is validated for integrating the orbit of Near Earth Asteroids. Resulting errors are of the order of the diameter of the asteroid. Second, a set of theoretical flybys are designed for analyzing the performance of the formulation in the vicinity of the singularity. New sets of Dromo variables are proposed in order to minimize the dependency of Dromo on the angular momentum. A slower time scale is introduced, leading to a more stable description of the flyby phase. Improvements in the overall performance of the algorithm are observed when integrating orbits close to the singularity.

  14. Oxytocin Enhances Social Persuasion during Hypnosis

    PubMed Central

    Bryant, Richard A.; Hung, Lynette

    2013-01-01

    It has long been argued that hypnosis cannot promote behaviors that people will not otherwise engage in. Oxytocin can enhance trust in others, and may promote the extent to which a hypnotized person complies with the suggestion of a hypnotist. This double-blind placebo study administered oxytocin or placebo to high hypnotizable participants (N = 28), who were then administered hypnotic suggestions for socially unorthodox behaviors, including swearing during the experiment, singing out loud, and dancing in response to a posthypnotic cue. Participants who received oxytocin were significantly more likely to swear and dance than those who received the placebo. This finding may be interpreted in terms of oxytocin increasing social compliance in response as a function of (a) increased trust in the hypnotist, (b) reduced social anxiety, or (c) enhanced sensitivity to cues to respond to experimental expectations. These results point to the potential role of oxytocin in social persuasion. PMID:23577153

  15. Oxytocin enhances social persuasion during hypnosis.

    PubMed

    Bryant, Richard A; Hung, Lynette

    2013-01-01

    It has long been argued that hypnosis cannot promote behaviors that people will not otherwise engage in. Oxytocin can enhance trust in others, and may promote the extent to which a hypnotized person complies with the suggestion of a hypnotist. This double-blind placebo study administered oxytocin or placebo to high hypnotizable participants (N = 28), who were then administered hypnotic suggestions for socially unorthodox behaviors, including swearing during the experiment, singing out loud, and dancing in response to a posthypnotic cue. Participants who received oxytocin were significantly more likely to swear and dance than those who received the placebo. This finding may be interpreted in terms of oxytocin increasing social compliance in response as a function of (a) increased trust in the hypnotist, (b) reduced social anxiety, or (c) enhanced sensitivity to cues to respond to experimental expectations. These results point to the potential role of oxytocin in social persuasion. PMID:23577153

  16. Dynamic thermal imaging analysis in the effectiveness evaluation of warming and cooling formulations.

    PubMed

    Koprowski, Robert; Wilczyński, Sławomir; Wróbel, Zygmunt; Błońska-Fajfrowska, Barbara

    2014-11-01

    Warming cosmetics and medicines are used to accelerate recovery from injuries whereas cooling preparations are used in the pains of muscles, joints, spine, bruises or edema. The paper verifies subjective heating or warming sensations with respect to the measured temperature changes. The influence of three formulations, labelled C1, C2, W1, on skin reaction was tested. The first two formulations (C1, C2) had a cooling effect while the formulation W1 had warming properties. Two hundred thermal images with a resolution of N×M=120×120 pixel were acquired with the Flir i7 infrared camera. The paper also shows how to analyse low resolution thermal images and their practical usefulness. For this purpose, a dedicated algorithm for image analysis and processing, which uses morphological operations, segmentation and area analysis, was applied. Application of both C1 and C2 resulted in subjective perception of feeling cold. Approximately 7min following application of the formulation C1, the skin temperature returned to baseline levels. The minimum skin temperature after using the formulation C1 was 27.5 °C and it was registered at the time of application. Application of W1, which by definition is a warming formulation, caused a sensation of coolness in the first minutes following the application. The perception of cool and warm sensations after the application of topical formulations is in no way correlated with the skin temperature assessed using a thermal imaging method. PMID:25240103

  17. An approach to probabilistic finite element analysis using a mixed-iterative formulation

    NASA Technical Reports Server (NTRS)

    Dias, J. B.; Nakazawa, S.

    1988-01-01

    An efficient algorithm for computing the response sensitivity of finite element problems based on a mixed-iterative formulation is proposed. This method does not involve explicit differentiation of the tangent stiffness array and can be used with formulations for which a consistent tangent stiffness is not readily available. The method has been successfully applied to probabilistic finite element analysis of problems using the proposed mixed formulation, and this exercise has provided valuable insights regarding the extension of the method to a more general class of problems to include material and geometric nonlinearities.

  18. Boundary formulations for sensitivity analysis without matrix derivatives

    NASA Technical Reports Server (NTRS)

    Kane, J. H.; Guru Prasad, K.

    1993-01-01

    A new hybrid approach to continuum structural shape sensitivity analysis employing boundary element analysis (BEA) is presented. The approach uses iterative reanalysis to obviate the need to factor perturbed matrices in the determination of surface displacement and traction sensitivities via a univariate perturbation/finite difference (UPFD) step. The UPFD approach makes it possible to immediately reuse existing subroutines for computation of BEA matrix coefficients in the design sensitivity analysis process. The reanalysis technique computes economical response of univariately perturbed models without factoring perturbed matrices. The approach provides substantial computational economy without the burden of a large-scale reprogramming effort.

  19. Post-buckling and Large Amplitude Free Vibration Analysis of Composite Beams: Simple Intuitive Formulation

    NASA Astrophysics Data System (ADS)

    Gunda, Jagadish Babu; Venkateswara Rao, Gundabathula

    2016-04-01

    Post-buckling and large amplitude free vibration analysis of composite beams with axially immovable ends is investigated in the present study using a simple intuitive formulation. Geometric nonlinearity of Von-Karman type is considered in the analysis which accounts for mid-plane stretching action of the beam. Intuitive formulation uses only two parameters: the critical bifurcation point and the axial stretching force developed due to membrane stretching action of the beam. Hinged-hinged, clamped-clamped and clamped-hinged boundary conditions are considered. Numerical accuracy of the proposed analytical closed-form solutions obtained from the intuitive formulation are compared to available finite element solutions for symmetric and asymmetric layup schemes of laminated composite beam which indicates the confidence gained on the present formulation.

  20. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

    PubMed

    Guastella, Adam J; Hickie, Ian B; McGuinness, Margaret M; Otis, Melissa; Woods, Elizabeth A; Disinger, Hannah M; Chan, Hak-Kim; Chen, Timothy F; Banati, Richard B

    2013-05-01

    A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans. PMID:23265311

  1. Sparse Canonical Correlation Analysis: New Formulation and Algorithm.

    PubMed

    Chu, Delin; Liao, Li-Zhi; Ng, Michael K; Zhang, Xiaowei

    2013-05-24

    In this paper, we study canonical correlation analysis (CCA), which has become a powerful tool in multivariate data analysis for finding the correlations between two sets of multidimensional variables. The main contributions of the paper are: (i) to reveal the equivalent relationship between a recursive formula and a trace formula for the multiple CCA problem; (ii) to obtain the explicit characterization of all solutions for the multiple CCA problem even the covariance matrices are singular; (iii) to develop a new sparse CCA algorithm; and (iv) to establish the equivalent relationship between the uncorrelated linear discriminant analysis and the CCA problem. We test several simulated and real world data sets in gene classification and cross-language document retrieval to demonstrate the effectiveness of the proposed algorithm. The performance of the proposed method is competitive with the state-of-the-art sparse CCA algorithms. PMID:23712996

  2. Sparse canonical correlation analysis: new formulation and algorithm.

    PubMed

    Chu, Delin; Liao, Li-Zhi; Ng, Michael K; Zhang, Xiaowei

    2013-12-01

    In this paper, we study canonical correlation analysis (CCA), which is a powerful tool in multivariate data analysis for finding the correlation between two sets of multidimensional variables. The main contributions of the paper are: 1) to reveal the equivalent relationship between a recursive formula and a trace formula for the multiple CCA problem, 2) to obtain the explicit characterization for all solutions of the multiple CCA problem even when the corresponding covariance matrices are singular, 3) to develop a new sparse CCA algorithm, and 4) to establish the equivalent relationship between the uncorrelated linear discriminant analysis and the CCA problem. We test several simulated and real-world datasets in gene classification and cross-language document retrieval to demonstrate the effectiveness of the proposed algorithm. The performance of the proposed method is competitive with the state-of-the-art sparse CCA algorithms. PMID:24136440

  3. Bedside Availability of Prepared Oxytocin and Rapid Administration After Delivery to Prevent Postpartum Hemorrhage: An Observational Study in Karnataka, India

    PubMed Central

    Moucheraud, Corrina; Gass, Jonathon; Lipsitz, Stuart; Spector, Jonathan; Agrawal, Priya; Hirschhorn, Lisa R; Gawande, Atul; Kodkany, Bhala

    2015-01-01

    Postpartum hemorrhage is a leading cause of maternal death worldwide. Rapid provision of uterotonics after childbirth is recommended to reduce the incidence and severity of postpartum hemorrhage. Data obtained through direct observation of childbirth practices, collected in a study of the World Health Organization’s Safe Childbirth Checklist in Karnataka, India, were used to measure if oxytocin prepared for administration and available at the bedside before birth was associated with decreased time to administration after birth. This was an observational study of provider behavior: data were obtained during a baseline assessment of health worker practices prior to introduction of the Safe Childbirth Checklist, representing behavior in the absence of any intervention. Analysis was based on 330 vaginal deliveries receiving oxytocin at any point postpartum. Oxytocin was prepared and available at bedside for approximately 39% of deliveries. We found that advance preparation and bedside availability of oxytocin was associated with increased likelihood of oxytocin administration within 1 minute after delivery (adjusted risk ratio = 4.89, 95% CI = 2.61, 9.16), as well as with decreased overall time to oxytocin administration after delivery (2.9 minutes sooner in adjusted models, 95% CI = -5.0, -0.9). Efforts to reduce postpartum hemorrhage should include recommendations and interventions to ensure advance preparation and bedside availability of oxytocin to facilitate prompt administration of the medicine after birth. PMID:26085025

  4. Maternal Care Effects on the Development of a Sexually Dimorphic Motor System: The Role of Spinal Oxytocin

    PubMed Central

    Lenz, Kathryn M.; Sengelaub, Dale R.

    2010-01-01

    Maternal licking in rats affects the development of the spinal nucleus of the bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile reflexes involved with copulation. Reduced maternal licking results in decreased motoneuron number, size, and dendritic length in the adult SNB, as well as deficits in adult male copulatory behavior. Our previous findings that licking-like tactile stimulation influences SNB dendritic development and upregulates Fos expression in the lumbosacral spinal cord suggest that afferent signaling is changed by differences in maternal stimulation. Oxytocin afferents from the hypothalamus are a possible candidate, given previous research that has shown oxytocin is released following sensory stimulation, oxytocin modulates excitability in the spinal cord, and is a pro-erectile modulator of male sex behavior. In this experiment, we used immunofluorescence and immediate early gene analysis to assess whether licking-like tactile stimulation of the perineum activated parvocellular oxytocinergic neurons in the hypothalamus in neonates. We also used enzyme immunoassay to determine whether this same stroking stimulation produced an increase in spinal oxytocin levels. We found that stroking increased Fos immunolabeling in small oxytocin-positive cells in the paraventricular nucleus of the hypothalamus, in comparison to unstroked or handled control pups. In addition, sixty seconds of licking-like perineal stimulation produced a transient 89% increase in oxytocin levels in the lumbosacral spinal cord. Together, these results suggest that oxytocin afferent activity may contribute to the effects of early maternal care on the masculinization of the SNB and resultant male copulatory behavior. PMID:20688065

  5. Bedside Availability of Prepared Oxytocin and Rapid Administration After Delivery to Prevent Postpartum Hemorrhage: An Observational Study in Karnataka, India.

    PubMed

    Moucheraud, Corrina; Gass, Jonathon; Lipsitz, Stuart; Spector, Jonathan; Agrawal, Priya; Hirschhorn, Lisa R; Gawande, Atul; Kodkany, Bhala

    2015-01-01

    Postpartum hemorrhage is a leading cause of maternal death worldwide. Rapid provision of uterotonics after childbirth is recommended to reduce the incidence and severity of postpartum hemorrhage. Data obtained through direct observation of childbirth practices, collected in a study of the World Health Organization's Safe Childbirth Checklist in Karnataka, India, were used to measure if oxytocin prepared for administration and available at the bedside before birth was associated with decreased time to administration after birth. This was an observational study of provider behavior: data were obtained during a baseline assessment of health worker practices prior to introduction of the Safe Childbirth Checklist, representing behavior in the absence of any intervention. Analysis was based on 330 vaginal deliveries receiving oxytocin at any point postpartum. Oxytocin was prepared and available at bedside for approximately 39% of deliveries. We found that advance preparation and bedside availability of oxytocin was associated with increased likelihood of oxytocin administration within 1 minute after delivery (adjusted risk ratio = 4.89, 95% CI = 2.61, 9.16), as well as with decreased overall time to oxytocin administration after delivery (2.9 minutes sooner in adjusted models, 95% CI = -5.0, -0.9). Efforts to reduce postpartum hemorrhage should include recommendations and interventions to ensure advance preparation and bedside availability of oxytocin to facilitate prompt administration of the medicine after birth. PMID:26085025

  6. A reference frame formulation for the analysis and design of steady manufacturing processes

    NASA Astrophysics Data System (ADS)

    Balagangadhar, Dinesh

    A reference frame formulation for large deformation steady state processes is proposed. The displacement and material state variables appear as the primary response fields in this mixed formulation. Unlike displacement based Lagrangian formulations, our formulation does not require a transient analysis to simulate a quasi-steady process and yields results that are free of numerical oscillations and which require considerably less computational effort. And unlike velocity based Eulerian methods, our formulation does not require free surface corrections or streamline integration algorithms. An iterative design environment for quasi-steady forming processes is developed from the computationally efficient reference frame formulation. The direct differentiation method is used to efficiently evaluate the response sensitivities. Select forming response measures and their sensitivities are combined with nonlinear programming methods to optimize the process. Three example problems are presented to demonstrate the efficiency of the proposed formulations: a laser surface treatment process is analyzed, a drawing process is analyzed and optimized and a multi-pass rolling process is analyzed and designed.

  7. The effects of vasopressin and oxytocin on methamphetamine-induced place preference behaviour in rats.

    PubMed

    Subiah, Cassandra O; Mabandla, Musa V; Phulukdaree, Alisa; Chuturgoon, Anil A; Daniels, Willie M U

    2012-09-01

    Methamphetamine is a highly addictive stimulant drug whose illicit use and resultant addiction has become an alarming global phenomenon. The mesolimbic dopaminergic pathway has been shown to be fundamental to the establishment of addictive behaviour. This pathway, as part of the reward system of the brain, has also been shown to be important in classical conditioning, which is a learnt response. Within the modulation of learning and memory, the neurohypophyseal hormones vasopressin and oxytocin have been reported to play a vital role, with vasopressin exerting a long- term facilitatory effect and oxytocin exerting an inhibitory effect. Therefore we adopted a conditioned place preference model to investigate whether vasopressin V1b receptor antagonist SSR 149415 or oxytocin treatment would cause a decrease in the seeking behaviour in a reinstatement paradigm. Behavioural findings indicated that methamphetamine induced a change in the place preference in the majority of our animals. This change in place preference was not seen when vasopressin was administered during the extinction phase. On the other hand the methamphetamine-induced change in place preference was enhanced during the reinstatement phase in the animals that were treated with oxytocin. Striatal dopamine levels were determined, as methamphetamine is known to increase dopamine transmission in this area. Significant changes in dopamine levels were observed in some of our animals. Rats that received both methamphetamine and oxytocin had significantly higher striatal dopamine than those that received oxytocin alone. Western blot analysis for hippocampal cyclic AMP response element binding protein (CREB) was also conducted as a possible indicator of glutamatergic NMDA receptor activity, a pathway that is important for learning and memory. The Western blot analysis showed no changes in hippocampal pCREB expression. Overall our data led us to conclude that methamphetamine treatment can change place preference

  8. Oxytocin improves emotion recognition for older males.

    PubMed

    Campbell, Anna; Ruffman, Ted; Murray, Janice E; Glue, Paul

    2014-10-01

    Older adults (≥60 years) perform worse than young adults (18-30 years) when recognizing facial expressions of emotion. The hypothesized cause of these changes might be declines in neurotransmitters that could affect information processing within the brain. In the present study, we examined the neuropeptide oxytocin that functions to increase neurotransmission. Research suggests that oxytocin benefits the emotion recognition of less socially able individuals. Men tend to have lower levels of oxytocin and older men tend to have worse emotion recognition than older women; therefore, there is reason to think that older men will be particularly likely to benefit from oxytocin. We examined this idea using a double-blind design, testing 68 older and 68 young adults randomly allocated to receive oxytocin nasal spray (20 international units) or placebo. Forty-five minutes afterward they completed an emotion recognition task assessing labeling accuracy for angry, disgusted, fearful, happy, neutral, and sad faces. Older males receiving oxytocin showed improved emotion recognition relative to those taking placebo. No differences were found for older females or young adults. We hypothesize that oxytocin facilitates emotion recognition by improving neurotransmission in the group with the worst emotion recognition. PMID:24856057

  9. Formulation of numerical procedures for dynamic analysis of spinning structures

    NASA Technical Reports Server (NTRS)

    Gupta, K. K.

    1986-01-01

    The paper presents the descriptions of recently developed numerical algorithms that prove to be useful for the solution of the free vibration problem of spinning structures. First, a generalized procedure for the computation of nodal centrifugal forces in a finite element owing to any specified spin rate is derived in detail. This is followed by a description of an improved eigenproblem solution procedure that proves to be economical for the free vibration analysis of spinning structures. Numerical results are also presented which indicate the efficacy of the currently developed procedures.

  10. Unified formulation for analysis of slopes with general slip surface

    SciTech Connect

    Espinoza, R.D.; Bourdeau, P.L. . School of Civil Engineering); Muhunthan, B. . Dept. of Civil and Environmental Engineering)

    1994-07-01

    The general availability of computers has provided efficient means of assessing the stability of slopes using several analytical methods. However, the increased use of computers coupled with a lack of unified presentation of the various methods sometimes leads to conflicting results. It is shown that the current analytical methods can be grouped into three categories based on the hypotheses used to describe the internal forces, namely: (1) the direction of the internal forces; (2) the height of the line of thrust; and (3) the shape of the distribution function of the internal shear forces. An analytical framework incorporating this idea is presented to facilitate and unify slope stability analysis with general slip surfaces. The study is a generalization of earlier work performed by Espinoza et al. for circular slip surfaces. The framework incorporates most current methods of analysis. The analytical model is implemented in a computer program. The program was used to study several case examples. On this basis, key issues associated with the influence of the internal shear forces on the factor of safety, for both circular and general slip failure surfaces, are discussed. It appears that for circular failure surfaces, even with heterogeneous soil stratigraphy the factor of safety is not affected by the choice of a particular hypothesis. On the contrary, for general slip surfaces this choice may significantly affect the results.

  11. Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications

    PubMed Central

    Freeman, Sara M.; Young, Larry J.

    2016-01-01

    In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site-specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition. However, despite the recent inundation of publications using intranasal oxytocin in humans, we still know very little about the neurophysiology of the oxytocin system in primates more broadly. Furthermore, the design and analysis of these human studies have remained largely uninformed of the potential neurobiological mechanisms underlying their findings. Although the methods available for studying the oxytocin and vasopressin systems in humans are incredibly limited as a result of practical and ethical considerations, there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning. Behavioural pharmacology and receptor autoradiography have been used to study the oxytocin and vasopressin systems in nonhuman primates, and there is now great potential to broaden our understanding of the neurobiology of these systems. In this review, we discuss comparative findings in receptor distributions in rodents and primates, with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades. We also identify specific ways that established technologies can be used to answer basic research questions in primates. Finally, we highlight areas of future research in nonhuman

  12. Exposure to synthetic oxytocin during delivery and its effect on psychomotor development.

    PubMed

    González-Valenzuela, María-José; López-Montiel, Dolores; González-Mesa, Ernesto Santiago

    2015-12-01

    The main objective is to examine the influence of oxytocin administration during delivery on psychomotor development at age five years. This was a retrospective cohort study involving two groups: children of mothers exposed vs. not exposed to oxytocin during labor. Of the 7,465 newborns registered in our maternity service during 2006 we randomly selected an initial sample of 400 children. Of these, 146 children were assessed using the motor scale of the Battelle Developmental Inventory. Other predictor variables that could potentially act as confounders and/or interact with the main relationship were also examined. The data were subjected to bivariate analysis, estimates of measures of strength of association, stratified analysis and multivariate binary logistic regression. The results indicate that exposure to synthetic oxytocin during delivery is an independent risk factor for a delay in gross and fine motor development. This was the case after controlling for the variables duration of labor and sex of the newborn, none of which modified the effect of oxytocin on gross and fine motor development. However, sex of the newborn were shown to be confounding gross motor development. In light of these results, and with the aim of preventing possible psychomotor alterations, further studies are now needed to analyze the effect that the oxytocin dose and the duration of perfusion may have on children's subsequent development. PMID:26011378

  13. Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes.

    PubMed

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

    2016-01-01

    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 (R(2) = 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. PMID:27599852

  14. Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes

    PubMed Central

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

    2016-01-01

    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. PMID:27599852

  15. [Oxytocin, the hormone that everyone uses and that few know].

    PubMed

    López-Ramírez, Cinthia Elizabeth; Arámbula-Almanza, Jaqueline; Camarena-Pulido, Eva Elizabet

    2014-07-01

    BACKGROUND. Oxytocin is a well known drug most commonly used in obstetrics for induction or augmentation of labor. Due to its essential role in labor, and the overall effect in the body, oxytocin must be deeply understood by all obstetricians who use it and prescribe it. There is relevant data listed about oxytocin and has reviewed the evidence in 31 full text articles of indexed journals between 1999 and 2013. In search engines like MEDLINE, MedicLatina, PUBMED, Wolters Kluwer Healt, with keywords like: oxytocin, oxytocin receptor, oxytocin vasopressin, oxytocin postpartum, oxytocin review, oxytocin labor, oxytocin release. The best evidence from the literature based on the methodology they used is included. The word oxytocin comes from the Greek words omega Chi upsilon xi, tau omicron Chi omicron chi xi, which means "swift birth". It is synthesized in the paraventricular and supraoptic nuclei of the hypotalamus is mainly released from the neurohypophysis and nerve terminals. It travels from the brain to the heart and the whole body, activating or modulating a wide range of functions and emotions. Mainly cause myometrial contractions and myoepithelial cells of the breast for milk ejection. Its adverse effects are dose-related. No one knows exactly the minumum and maximum dose of oxytocin. More research is needed about central and peripheral receptors, coupled with the use to which they currently gives to agonists and antagonists of oxytocin and its receptor. As of 2013, the documented adverse effects to date have been undervalued. PMID:25102673

  16. Phospholipid-based solid drug formulations for oral bioavailability enhancement: A meta-analysis.

    PubMed

    Fong, Sophia Yui Kau; Brandl, Martin; Bauer-Brandl, Annette

    2015-12-01

    Low bioavailability nowadays often represents a challenge in oral dosage form development. Solid formulations composed of drug and phospholipid (PL), which, upon contact with water, eventually form multilamellar liposomes (i.e. 'proliposomes'), are an emerging approach to solve such issue. Regarded as an 'improved' version of liposomes concerning storage stability, the potential and versatility of a range of such formulations for oral drug delivery have been extensively discussed. However, a systematic and quantitative analysis of the studies that applied solid PL for oral bioavailability enhancement is currently lacking. Such analysis is necessary for providing an overview of the research progress and addressing the question on how promising this approach can be on bioavailability enhancement. The current review performed a systematic search of references in three evidence-based English databases, Medline, Embase, and SciFinder, from the year of 1985 up till March 2015. A total of 112 research articles and 82 patents that involved solid PL-based formulations were identified. The majority of such formulations was intended for oral drug delivery (55%) and was developed to address low bioavailability issues (49%). A final of 54 studies that applied such formulations for bioavailability enhancement of 43 different drugs with poor water solubility and/or permeability were identified. These proof-of-concept studies with in vitro (n=31) and/or animal (n=23) evidences have been systematically summarized. Meta-analyses were conducted to measure the overall enhancement power (percent increase compared to control group) of solid PL formulations on drugs' solubility, permeability and oral bioavailability, which were found to be 127.4% (95% CI [86.1, 168.7]), 59.6% (95% CI [30.1, 89.0]), and 18.5% (95% CI [10.1, 26.9]) respectively. Correlations between the enhancement factors and in silico physiochemical properties of drugs were also performed to check if such approach can be

  17. Formulation of a dynamic analysis method for a generic family of hoop-mast antenna systems

    NASA Technical Reports Server (NTRS)

    Gabriele, A.; Loewy, R.

    1981-01-01

    Analytical studies of mast-cable-hoop-membrane type antennas were conducted using a transfer matrix numerical analysis approach. This method, by virtue of its specialization and the inherently easy compartmentalization of the formulation and numerical procedures, can be significantly more efficient in computer time required and in the time needed to review and interpret the results.

  18. Oxytocin promotes group-serving dishonesty.

    PubMed

    Shalvi, Shaul; De Dreu, Carsten K W

    2014-04-15

    To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group's outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker's focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption. PMID:24706799

  19. Oxytocin promotes group-serving dishonesty

    PubMed Central

    Shalvi, Shaul; De Dreu, Carsten K. W.

    2014-01-01

    To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group’s outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker’s focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption. PMID:24706799

  20. Oxytocin enhances the experience of attachment security.

    PubMed

    Buchheim, Anna; Heinrichs, Markus; George, Carol; Pokorny, Dan; Koops, Eva; Henningsen, Peter; O'Connor, Mary-Frances; Gündel, Harald

    2009-10-01

    Repeated interactions between infant and caregiver result in either secure or insecure relationship attachment patterns, and insecure attachment may affect individual emotion-regulation and health. Given that oxytocin enhances social approach behavior in animals and humans, we hypothesized that oxytocin might also promote the subjective experience of attachment security in humans. Within a 3-week interval, 26 healthy male students classified with an insecure attachment pattern were invited twice to an experimental session. At the beginning of each experiment, a single dose of oxytocin or placebo was administered intranasally, using a double-blind, placebo-controlled within-subject design. In both conditions, subjects completed an attachment task based on the Adult Attachment Projective Picture System (AAP). Thirty-two AAP picture system presentations depicted attachment-related events (e.g. illness, solitude, separation, and loss), and were each accompanied by four prototypical phrases representing one secure and three insecure attachment categories. In the oxytocin condition, a significant proportion of these insecure subjects (N=18; 69%) increased in their rankings of the AAP prototypical "secure attachment" phrases and decreased in overall ranking of the "insecure attachment" phrases. In particular, there was a significant decrease in the number of subjects ranking the pictures with "insecure-preoccupied" phrases from the placebo to the oxytocin condition. We find that a single dose of intranasally administered oxytocin is sufficient to induce a significant increase in the experience of attachment security in insecurely attached adults. PMID:19457618

  1. Oxytocin enhances the experience of attachment security

    PubMed Central

    Buchheim, Anna; Heinrichs, Markus; George, Carol; Pokorny, Dan; Koops, Eva; Henningsen, Peter; O’Connor, Mary-Frances; Gundel, Harald

    2011-01-01

    Summary Repeated interactions between infant and caregiver result in either secure or insecure relationship attachment patterns, and insecure attachment may affect individual emotion-regulation and health. Given that oxytocin enhances social approach behavior in animals and humans, we hypothesized that oxytocin might also promote the experience of attachment security in humans. Within a 3-week interval 26 healthy male students classified with an insecure attachment pattern were invited twice to an experimental session. Within each session, a single dose of oxytocin or placebo was administered, using a double-blind, placebo-controlled within-subject design. In both conditions, subjects completed an attachment task based on the Adult Attachment Projective Picture System (AAP). Thirty-two AAP picture system presentations depicted attachment-related events (e.g. illness, solitude, separation, loss), and were each accompanied by four prototypical phrases representing one secure and three insecure attachment categories. In the oxytocin condition, a significant proportion of these insecure subjects (N = 18; 69%) changed their rankings of “secure attachment” phrases towards the more appropriate for the AAP picture presentation, and the same subjects decreased in overall rating of the “insecure attachment” phrases. In particular, there was a significant decrease in the number of subjects ranking the pictures with “insecure-preoccupied” phrases from the placebo to the oxytocin condition. We find that a single dose of intranasally administered oxytocin is sufficient to induce a significant increase in the experience of attachment security in adults classified previously as insecure. PMID:19457618

  2. Peripheral oxytocin administration buffers autonomic but not behavioral responses to environmental stressors in isolated prairie voles.

    PubMed

    Grippo, Angela J; Pournajafi-Nazarloo, Hossein; Sanzenbacher, Lisa; Trahanas, Diane M; McNeal, Neal; Clarke, Deirdre A; Porges, Stephen W; Sue Carter, C

    2012-03-01

    Negative social experiences such as social stressors and isolation influence mental and physical illnesses, including affective disorders and heart disease. Studies focused on socially monogamous prairie voles can provide insight into neurobiological systems that underlie the consequences of negative social interactions. Female prairie voles were exposed to 28 days of social isolation or pairing with a female sibling (control). Voles were administered daily oxytocin [20 μg/50 μl, subcutaneous (sc)] or saline vehicle (50 μl, sc) for 14 days and exposed to two behavioral stressors [elevated plus maze (EPM) and resident-intruder test]. Brain tissue was collected for analysis of central peptide levels in the hypothalamic paraventricular nucleus (PVN). Isolation produced autonomic changes [increased heart rate (HR) and decreased HR variability) during both acute stressors and increased anxiety behaviors in the EPM. Oxytocin injection prevented the autonomic consequences of the acute stressors in isolated prairie voles, but did not affect the behaviors tested under the present conditions. Oxytocin had no effect on the behavioral or autonomic responsiveness in paired prairie voles. Oxytocin injection may exert a beneficial effect on autonomic responses to stressors in isolated animals through increasing the number of oxytocin-containing neurons and decreasing the number of corticotropin-releasing hormone-containing neurons in the PVN. Oxytocinergic mechanisms may serve to compensate for autonomic responses associated with chronic isolation and exposure to both social and non-social acute stressors. PMID:21854168

  3. A Sensitivity Analysis of the Nocturnal Boundary-Layer Properties to Atmospheric Emissivity Formulations

    NASA Astrophysics Data System (ADS)

    Siqueira, Mario B.; Katul, Gabriel G.

    2010-02-01

    A one-dimensional model for the mean potential temperature within the nocturnal boundary layer (NBL) was used to assess the sensitivity of three NBL properties (height, thermal stratification strength, and near-surface cooling) to three widely used atmospheric emissivity formulations. The calculations revealed that the NBL height is robust to the choice of the emissivity function, though this is not the case for NBL Richardson number and near-surface cooling rate. Rather than endorse one formulation, our analysis highlights the importance of atmospheric emissivity in modelling the radiative properties of the NBL especially for clear-sky conditions.

  4. Robust Maneuvering Envelope Estimation Based on Reachability Analysis in an Optimal Control Formulation

    NASA Technical Reports Server (NTRS)

    Lombaerts, Thomas; Schuet, Stefan R.; Wheeler, Kevin; Acosta, Diana; Kaneshige, John

    2013-01-01

    This paper discusses an algorithm for estimating the safe maneuvering envelope of damaged aircraft. The algorithm performs a robust reachability analysis through an optimal control formulation while making use of time scale separation and taking into account uncertainties in the aerodynamic derivatives. Starting with an optimal control formulation, the optimization problem can be rewritten as a Hamilton- Jacobi-Bellman equation. This equation can be solved by level set methods. This approach has been applied on an aircraft example involving structural airframe damage. Monte Carlo validation tests have confirmed that this approach is successful in estimating the safe maneuvering envelope for damaged aircraft.

  5. Paraventricular and supraoptic bursting oxytocin cells in rat are locally regulated by oxytocin and functionally related.

    PubMed

    Moos, F; Richard, P

    1989-01-01

    1. Oxytocin was pressure injected through a glass micropipette into a supraoptic (SON) or paraventricular nucleus (PVN) while recording the electrical activities of oxytocin cells in a contralateral nucleus, to see whether oxytocin acts locally in the magnocellular nuclei to control their bursting activity and whether the oxytocin cells of the four magnocellular nuclei were functionally interconnected during suckling. To test the rapidity of these relations, similar intranuclear injections were realized with acetylcholine, known to rapidly increase the background activity of oxytocin cells. The effects of intranuclear injections of oxytocin and acetylcholine were tested before and after interhemisphere sections of various dimensions. 2. Injecting oxytocin (1 ng in 100 nl) into a magnocellular nucleus (5 times into the PVN and 15 times into the SON) facilitated the occurrence and increased the amplitude of bursts of the oxytocin cells in both the contralateral PVN and SON. This facilitatory effect was similar to that induced by intraventricular injection of the same dose of oxytocin, though slightly delayed and lower. 3. Injecting acetylcholine (0.6 microgram in 100 nl) into the SON (7 times) induced a rapid and sustained increase in the background activity of oxytocin cells in both the contralateral PVN (2 times) and SON (5 times) within the same delay (less than 15 s). This excitatory effect was similar to that induced by an intraventricular injection of 5 micrograms acetylcholine. The effects on bursting activity were not considered in this study. 4. Neither the injections of oxytocin or acetylcholine outside but near the magnocellular nuclei (200-500 microns), nor the intranuclear injection of 100-200 nl of cerebrospinal fluid-like medium, modified the background activity, the frequency and amplitude of bursts of the oxytocin cells in the nucleus contralateral to the injection site. 5. After interhemisphere sections most oxytocin cells were silent, bursts

  6. Intranasal administration of oxytocin promotes social play in domestic dogs

    PubMed Central

    Romero, Teresa; Nagasawa, Miho; Mogi, Kazutaka; Hasegawa, Toshikazu; Kikusui, Takefumi

    2015-01-01

    In a recent paper,1 we examined whether oxytocin in the domestic dog modulates the maintenance of close social bonds in non-reproductive contexts. We found that exogenous oxytocin promotes positive social behaviors not only toward conspecifics, but also toward human partners. Here we examined in further detail the effect that oxytocin manipulation has on social play. When sprayed with oxytocin, subjects initiated play sessions more often and played for longer periods of time than when sprayed with saline. Furthermore, after oxytocin nasal intake dogs displayed play signals more often than after saline administration, suggesting that oxytocin enhances dogs' play motivation. To our knowledge, this study provides the first evidence that oxytocin promotes social play in the domestic dog. We use these results to hypothesize on the potential therapeutic use of oxytocin for promoting social behaviors and treating social deficits in the domestic dog. PMID:26478773

  7. Oxytocin enables maternal behaviour by balancing cortical inhibition.

    PubMed

    Marlin, Bianca J; Mitre, Mariela; D'amour, James A; Chao, Moses V; Froemke, Robert C

    2015-04-23

    Oxytocin is important for social interactions and maternal behaviour. However, little is known about when, where and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behaviour in female mice by enhancing auditory cortical pup call responses. Retrieval behaviour required the left but not right auditory cortex, was accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were preferentially expressed in the left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally precise excitatory and inhibitory responses in the left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing. PMID:25874674

  8. Oxytocin Enables Maternal Behavior by Balancing Cortical Inhibition

    PubMed Central

    Marlin, Bianca J.; Mitre, Mariela; D’amour, James A.; Chao, Moses V.; Froemke, Robert C.

    2015-01-01

    Oxytocin is important for social interactions and maternal behavior. However, little is known about when, where, and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behavior in female mice by enhancing auditory cortical pup call responses. Retrieval behavior required left but not right auditory cortex, was accelerated by oxytocin in left auditory cortex, and oxytocin receptors were preferentially expressed in left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally-precise excitatory and inhibitory responses in left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing. PMID:25874674

  9. An Analysis of Finite-Difference and Finite-Volume Formulations of Convervation Laws

    NASA Astrophysics Data System (ADS)

    Vinokur, Marcel

    1989-03-01

    Finite-difference and finite-volume formulations are analyzed in order to clear up the confusion concerning their application to the numerical solution of conservation laws. A new coordinate-free formulation of systems of conservation laws is developed, which clearly distinguishes the role of physical vectors from that of algebraic vectors which characterize the system. The analysis considers general types of equations-potential, Euler, and Navier-Stokes. Three-dimensional unsteady flows with time-varying grids are described using a single, consistent nomenclature for both formulations. Grid motion due to a non-inertial reference frame as well as flow adaptation is covered. In comparing the two formulations, it is found useful to distinguish between differences in numerical methods and differences in grid definition. The former plays a role for non-Cartesian grids and results in only cosmetic differences in the manner in which geometric terms are handled. The differences in grid definition for the two formulations is found to be more important, since it affects the manner in which boundary conditions, zonal procedures, and grid singularities are handled at computational boundaries. The proper interpretation of strong and weak conservation-law forms for quasi-one-dimensional and axisymmetric flows is brought out.

  10. An analysis of finite-difference and finite-volume formulations of conservation laws

    NASA Astrophysics Data System (ADS)

    Vinokur, Marcel

    1986-06-01

    Finite-difference and finite-volume formulations are analyzed in order to clear up the confusion concerning their application to the numerical solution of conservation laws. A new coordinate-free formulation of systems of conservation laws is developed, which clearly distinguishes the role of physical vectors from that of algebraic vectors which characterize the system. The analysis considers general types of equations--potential, Euler, and Navier-Stokes. Three-dimensional unsteady flows with time-varying grids are described using a single, consistent nomeclature for both formulations. Grid motion due to a non-inertial reference frame as well as flow adaptation is covered. In comparing the two formulations, it is found useful to distinguish between differences in numerical methods and differences in grid definition. The former plays a role for non-Cartesian grids, and results in only cosmetic differences in the manner in which geometric terms are handled. The differences in grid definition for the two formulations is found to be more important, since it affects the manner in which boundary conditions, zonal procedures, and grid singularities are handled at computational boundaries. The proper interpretation of strong and weak conservation-law forms for quasi-one-dimensional and axisymmetric flows is brought out.

  11. An analysis of finite-difference and finite-volume formulations of conservation laws

    NASA Technical Reports Server (NTRS)

    Vinokur, Marcel

    1986-01-01

    Finite-difference and finite-volume formulations are analyzed in order to clear up the confusion concerning their application to the numerical solution of conservation laws. A new coordinate-free formulation of systems of conservation laws is developed, which clearly distinguishes the role of physical vectors from that of algebraic vectors which characterize the system. The analysis considers general types of equations--potential, Euler, and Navier-Stokes. Three-dimensional unsteady flows with time-varying grids are described using a single, consistent nomeclature for both formulations. Grid motion due to a non-inertial reference frame as well as flow adaptation is covered. In comparing the two formulations, it is found useful to distinguish between differences in numerical methods and differences in grid definition. The former plays a role for non-Cartesian grids, and results in only cosmetic differences in the manner in which geometric terms are handled. The differences in grid definition for the two formulations is found to be more important, since it affects the manner in which boundary conditions, zonal procedures, and grid singularities are handled at computational boundaries. The proper interpretation of strong and weak conservation-law forms for quasi-one-dimensional and axisymmetric flows is brought out.

  12. An analysis of finite-difference and finite-volume formulations of conservation laws

    NASA Technical Reports Server (NTRS)

    Vinokur, Marcel

    1989-01-01

    Finite-difference and finite-volume formulations are analyzed in order to clear up the confusion concerning their application to the numerical solution of conservation laws. A new coordinate-free formulation of systems of conservation laws is developed, which clearly distinguishes the role of physical vectors from that of algebraic vectors which characterize the system. The analysis considers general types of equations: potential, Euler, and Navier-Stokes. Three-dimensional unsteady flows with time-varying grids are described using a single, consistent nomenclature for both formulations. Grid motion due to a non-inertial reference frame as well as flow adaptation is covered. In comparing the two formulations, it is found useful to distinguish between differences in numerical methods and differences in grid definition. The former plays a role for non-Cartesian grids, and results in only cosmetic differences in the manner in which geometric terms are handled. The differences in grid definition for the two formulations is found to be more important, since it affects the manner in which boundary conditions, zonal procedures, and grid singularities are handled at computational boundaries. The proper interpretation of strong and weak conservation-law forms for quasi-one-dimensional and axisymmetric flows is brought out.

  13. Complexity of oxytocin׳s effects in a chronic cocaine dependent population.

    PubMed

    Lee, Mary R; Glassman, Matthew; King-Casas, Brooks; Kelly, Deanna L; Stein, Elliot A; Schroeder, Jennifer; Salmeron, Betty Jo

    2014-09-01

    Behavioral and neuroplastic changes occurring in the development of addiction parallel those that occur in social bonding. This has led to speculation that drugs of abuse co-opt systems that subserve social attachment to shift attachment to drugs of abuse. Oxytocin, a neuropeptide that is important in social bonding, has been shown in rodents to decrease psychostimulant self-administration, locomotor activity, and conditioned place preference, it is unclear what role it may play in human drug addiction. In this double-blind, placebo-controlled crossover study, 23 cocaine-dependent inpatients in court-ordered treatment completed 4 task sessions measuring desire to use cocaine, cue-induced craving, monetary reward decisions and social cognition. Before each session, subjects administered 24 IU of intranasal oxytocin or placebo. Oxytocin increased desire to use cocaine and cue-induced excitability with no effect on cue-induced desire to use. Oxytocin also removed the effect of state anger on several measures of cue reactivity. Response to monetary reward increased under oxytocin and measures of social cognition worsened. The significant increase in the desire for drug and monetary reward as well as the significant decrease in measures of social cognition was small but warrant further study of the effect of oxytocin׳s effect in cocaine dependent subjects. The effect of oxytocin to modulate the relationship between state anger and cue reactivity should be explored further for potential therapeutic use of oxytocin in cocaine dependent patients. These findings are discussed in light of the human and rodent oxytocin literature. PMID:25044050

  14. Oxytocin Increases Generosity in Humans

    PubMed Central

    Zak, Paul J.; Stanton, Angela A.; Ahmadi, Sheila

    2007-01-01

    Human beings routinely help strangers at costs to themselves. Sometimes the help offered is generous—offering more than the other expects. The proximate mechanisms supporting generosity are not well-understood, but several lines of research suggest a role for empathy. In this study, participants were infused with 40 IU oxytocin (OT) or placebo and engaged in a blinded, one-shot decision on how to split a sum of money with a stranger that could be rejected. Those on OT were 80% more generous than those given a placebo. OT had no effect on a unilateral monetary transfer task dissociating generosity from altruism. OT and altruism together predicted almost half the interpersonal variation in generosity. Notably, OT had twofold larger impact on generosity compared to altruism. This indicates that generosity is associated with both altruism as well as an emotional identification with another person. PMID:17987115

  15. Fuel Plume Image Mixing Analysis Formulation With Proper Treatment of Non-Constant Velocity Flowfields

    NASA Technical Reports Server (NTRS)

    Mekkes, Gregory L.

    2000-01-01

    A previously developed technique allows an estimate of integral mixing to be obtained from an image of laser scattered light from particle seeded fuel in the hypervelocity flow through a scramjet combustor. This previous mixing analysis formulation contains an assumption of a constant velocity flowfield across the plane of the fuel plume image. For high-speed scramjet combustors, the velocity flowfield is quite uniform and an assumption of constant velocity works well. Applying this same mixing analysis technique to fuel plume images obtained from a mid-speed scramjet combustor makes it desirable to remove the constant velocity assumption. This is due to the non-uniform velocity flowfields present in mid-speed scramjet combustors. A new formulation of the mixing analysis methodology is developed and presented so that the technique can be applied to a mid-speed scramjet combustor without the need to assume a constant velocity flowfield.

  16. Oxytocin, testosterone, and human social cognition.

    PubMed

    Crespi, Bernard J

    2016-05-01

    I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint

  17. Pain modulation by intranasal oxytocin and emotional picture viewing — a randomized double-blind fMRI study

    PubMed Central

    Zunhammer, Matthias; Geis, Sandra; Busch, Volker; Eichhammer, Peter; Greenlee, Mark W.

    2016-01-01

    The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings. PMID:27546446

  18. Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

    PubMed

    Zunhammer, Matthias; Geis, Sandra; Busch, Volker; Eichhammer, Peter; Greenlee, Mark W

    2016-01-01

    The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings. PMID:27546446

  19. Stability Enhancing N-Terminal PEGylation of Oxytocin Exploiting Different Polymer Architectures and Conjugation Approaches.

    PubMed

    Collins, Jennifer; Kempe, Kristian; Wilson, Paul; Blindauer, Claudia A; McIntosh, Michelle P; Davis, Thomas P; Whittaker, Michael R; Haddleton, David M

    2016-08-01

    Oxytocin, a cyclic nine amino acid neurohypophyseal hormone therapeutic, is effectively used in the control of postpartum hemorrhaging (PPH) and is on the WHO List of Essential Medicines. However, oxytocin has limited shelf life stability in aqueous solutions, particularly at temperatures in excess of 25 °C and injectable aqueous oxytocin formulations require refrigeration (<8 °C). This is particularly problematic in the hot climates often found in many developing countries where daytime temperatures can exceed 40 °C and where reliable cold-chain storage is not always achievable. The purpose of this study was to develop N-terminal amine targeted PEGylation strategies utilizing both linear PEG and polyPEG "comb" polymers as an effective method for stabilizing solution formulations of this peptide for prolonged storage in the absence of efficient cold-chain storage. The conjugation chemistries investigated herein include irreversible amine targeted conjugation methods utilizing NHS ester and aldehyde reductive amination chemistry. Additionally, one reversible conjugation method using a Schiff base approach was explored to allow for the release of the native peptide, thus, ensuring that biological activity remains unaffected. The reversibility of this approach was investigated for the different polymer architectures, alongside a nonpolymer oxytocin analogue to monitor how pH can tune native peptide release. Elevated temperature degradation studies of the polymer conjugates were evaluated to assess the stability of the PEGylated analogues in comparison to the native peptide in aqueous formulations to mimic storage conditions in developing nations and regions where storage under appropriate conditions is challenging. PMID:27419537

  20. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    SciTech Connect

    Olszewski, Pawel K.; Fredriksson, Robert; Eriksson, Jenny D.; Mitra, Anaya; Radomska, Katarzyna J.; Gosnell, Blake A.; Solvang, Maria N.; Levine, Allen S.; Schioeth, Helgi B.

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  1. Oxytocin binding sites in bovine mammary tissue

    SciTech Connect

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressin binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.

  2. Oxytocin, Motivation and the Role of Dopamine

    PubMed Central

    Love, Tiffany M.

    2013-01-01

    The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded dramatically over the years from a simple peptide adept at inducing uterine contractions and milk ejection to a complex neuromodulator with a capacity to shape human social behavior. Decades of research have outlined oxytocin’s ability to enhance intricate social activities ranging from pair bonding, sexual activity, affiliative preferences, and parental behaviors. The precise neural mechanisms underlying oxytocin’s influence on such behaviors have just begun to be understood. Research suggests that oxytocin interacts closely with the neural pathways responsible for processing motivationally relevant stimuli. In particular, oxytocin appears to impact dopaminergic activity within the mesocorticolimbic dopamine system, which is crucial not only for reward and motivated behavior but also for the expression of affiliative behaviors. Though most of the work performed in this area has been done using animal models, several neuroimaging studies suggest similar relationships may be observed in humans. In order to introduce this topic further, this paper will review the recent evidence that oxytocin may exert some of its social-behavioral effects through its impact on motivational networks. PMID:23850525

  3. Effects of N-acetylimidazole on oxytocin binding in bovine mammary tissue

    SciTech Connect

    Zhao, X.; Gorewit, R.C.; Currie, W.B. )

    1990-01-01

    The effects of N-acetylimidazole on specific binding of oxytocin to microsomal fractions of bovine mammary gland were studied. N-acetylimidazole suppressed oxytocin binding, with time and concentration dependence. Decreased oxytocin binding activity appeared to be due to decreased affinity of the hormone for its receptor. Acetylation of oxytocin, rather than of oxytocin receptors, seemed to be responsible for the decreased binding.

  4. Oxytocin receptor DNA methylation in postpartum depression.

    PubMed

    Kimmel, Mary; Clive, Makena; Gispen, Fiona; Guintivano, Jerry; Brown, Tori; Cox, Olivia; Beckmann, Matthias W; Kornhuber, Johannes; Fasching, Peter A; Osborne, Lauren M; Binder, Elisabeth; Payne, Jennifer L; Kaminsky, Zachary

    2016-07-01

    The oxytocin receptor (OXTR) is a key regulator of stress and anxiety and may be regulated by both psychosocial risk factors and gonadal hormones, making it an attractive candidate for study in postpartum depression (PPD). The objective of this study was to investigate both serum hormone and PPD specific DNA methylation variation in the OXTR. Illumina HM450 microarray data generated in a prospective PPD cohort identified significant associations (P=0.014) with PPD in an intronic region in the OXTR located 4bp proximal to an estrogen receptor (ER) binding region. Pyrosequencing confirmed moderate evidence for an interaction of CpGs in the region with childhood abuse status to mediate PPD. These CpGs located on chr3 at positions 8810078 and 8810069 exhibited significant associations with postpartum depression scores from an independent cohort of 240 women with no prior psychiatric history. Hormone analysis suggested a PPD specific negative correlation of DNA methylation in the region with serum estradiol levels. Estradiol levels and OXTR DNA methylation exhibited a significant interaction to associate with the ratio of allopregnanolone to progesterone. Cumulatively, the data corroborate our previous hypotheses of a PPD specific increased sensitivity of epigenetic reprogramming at estrogen target genes and suggests that OXTR epigenetic variation may be an important mediator of mood relevant neuroactive steroid production. PMID:27108164

  5. Multi-pathway cellular analysis on crude natural drugs/herbs from Japanese Kampo formulations.

    PubMed

    Eshima, Shizuka; Yokoyama, Satoru; Abe, Takashi; Hayakawa, Yoshihiro; Saiki, Ikuo

    2015-01-01

    Kampo formulations comprise a number of crude natural drugs/herbs as constituents. The crude drugs/herbs have been traditionally classified by their traditional classifications or efficacies in Kampo medicines; however, it has been difficult to establish the scientific link between experimental evidence and traditional classifications in Kampo medicine. To clarify such traditional conceptions, we tested 112 crude drugs/herbs that are major components of Kampo formulations, in the multi-pathway analysis of 10 well-studied transcriptional activities including CREB, ERSF, HIF-1α, IRFs, MYC, NF-κB, p53, SMAD, SOX2, and TCF/LEF in A549 human lung cancer cells. By clustering the results of multi-pathway analysis with the Spearman rank-correlation coefficient and Ward linkage, three distinct traditional categories were significantly enriched in the major groupings, which are heat-clearing and dampness-drying herbs, acrid and warm exterior-resolving herbs, and acrid and cool exterior-resolving herbs. These results indicate that these crude drugs/herbs have similar effects on intracellular signaling and further imply that the traditional classifications of those enriched crude drugs/herbs can be supported by such experimental evidence. Collectively, our new in vitro multi-pathway analysis may be useful to clarify the mechanism of action of crude drugs/herbs and Kampo formulations. PMID:26035432

  6. Impact of influenza vaccine formulation with a detailed analysis of the cytokine response.

    PubMed

    Szyszko, E; Brokstad, K; Cox, R J; Hovden, A-O; Madhun, A; Haaheim, L R

    2006-11-01

    Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of two different influenza vaccine formulations on the resulting antibody and cytokine responses and compared these responses with influenza infection. Mice were vaccinated intramuscularly with one or two doses of whole or split virus vaccine or alternatively intranasally infected with influenza virus. Lymphocytes were isolated from spleen cells and stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene expression and at the protein level. Additionally, whole blood was collected and the serum antibody response investigated by haemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus vaccine induced higher antibody and cytokine responses and thus was more immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and a more mixed cytokine response after the second dose. Split virus vaccine induced a type 2 response, particularly after two vaccine doses. Our results show that two doses of vaccine (both vaccine formulation) were more effective in induction of Th2 type of cytokines and thus indicate that both the formulation and also the number of vaccine doses substantially influences the magnitude and quality of the immune response. PMID:17032238

  7. Using Time-Varying Sensitivity Analysis to Understand the Effects of Model Formulation on Model Behavior

    NASA Astrophysics Data System (ADS)

    Herman, J. D.; Reed, P. M.; Wagener, T.

    2012-12-01

    Lumped rainfall-runoff models are widely used for flow prediction, but a long-recognized need exists for diagnostic tools to determine whether the process-level behavior of a model aligns with the expectations inherent in its formulation. To this end, we develop a comprehensive exploration of dominant processes in the Hymod, HBV, and Sacramento Soil Moisture Accounting (SAC-SMA) model structures. Model controls are isolated using time-varying Sobol sensitivity analysis for twelve MOPEX watersheds in the eastern United States over a ten-year period. Sensitivity indices are visualized along gradients of observed precipitation and flow characteristics to identify key behavioral differences between the three models and to connect these back to the models' underlying assumptions. Results indicate that dominant processes strongly depend on time-varying hydroclimatic conditions. Parameters associated with surface processes generally dominate under dry conditions, while parameters associated with routing processes dominate under high flow conditions. The results highlight significant inter-model differences in dominant processes, even in models sharing the same process formulation (e.g., the soil moisture formulation in the Hymod and HBV models). The dominant processes identified are often counterintuitive; even these simple models represent complex, nonlinear systems, and the links between formulation and behavior are very difficult to discern a priori as complexity increases. Scrutinizing the links between model formulation and behavior becomes an important diagnostic approach, particularly in applications such as predictions under change where it is critical to identify how a model's dominant processes shift under hydrologic extremes. Sensitive parameters in the (a) Hymod, (b) SAC-SMA, and (c) HBV watershed models as conditions change from dry to wet. This is a qualitative summary of the time-varying sensitivity indices from twelve watersheds across a range of

  8. Analysis of munitions constituents in IMX formulations by HPLC and HPLC-MS.

    PubMed

    Russell, A L; Seiter, J M; Coleman, J G; Winstead, B; Bednar, A J

    2014-10-01

    The use of Insensitive Munitions eXplosives (IMX) is increasing as the Army seeks to replace certain conventional munitions constituents, such as 2,4,6-trinitrotolene (TNT), for improved safety. The IMX formulations are more stable and therefore less prone to accidental detonation while designed to match the performance of legacy materials. Two formulations, IMX 101 and 104 are being investigated as a replacement for TNT in artillery rounds and composition B Army mortars, respectively. The chemical formulations of IMX-101 and 104 are comprised of four constituents;2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), 1-nitroguanidine (NQ), and Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) which are mixed in various ratios to achieve the desired performance. The current work details the analysis of the IMX constituents by single column HPLC-UV-ESI-MS. Detection limits determined are in agreement with similar HPLC analysis of compounds, ranging from 7 to 9μg/L. Gradient mobile phases are used to allow separation of the 4 target compounds in more complex mixture of other concomitant compounds. Mass spectra are used to confirm analyte identity with chromatographic retention time. PMID:25059196

  9. Consistent linearization of the element-independent corotational formulation for the structural analysis of general shells

    NASA Technical Reports Server (NTRS)

    Rankin, C. C.

    1988-01-01

    A consistent linearization is provided for the element-dependent corotational formulation, providing the proper first and second variation of the strain energy. As a result, the warping problem that has plagued flat elements has been overcome, with beneficial effects carried over to linear solutions. True Newton quadratic convergence has been restored to the Structural Analysis of General Shells (STAGS) code for conservative loading using the full corotational implementation. Some implications for general finite element analysis are discussed, including what effect the automatic frame invariance provided by this work might have on the development of new, improved elements.

  10. Second-order cone programming formulation for consolidation analysis of saturated porous media

    NASA Astrophysics Data System (ADS)

    Zhang, Xue; Sheng, Daichao; Sloan, Scott W.; Krabbenhoft, Kristian

    2016-03-01

    In this paper, the incremental problem for consolidation analysis of elastoplastic saturated porous media is formulated and solved using second-order cone programming. This is achieved by the application of the Hellinger-Reissner variational theorem, which casts the governing equations of Biot's consolidation theory as a min-max optimisation problem. The min-max problem is then discretised using the finite element method and converted into a standard second-order cone programming problem that can be solved efficiently using modern optimisation algorithms (such as the primal-dual interior-point method). The proposed computational formulation is verified against a number of benchmark examples and also applied to simulate the construction of a road embankment on soft clay.

  11. Second-order cone programming formulation for consolidation analysis of saturated porous media

    NASA Astrophysics Data System (ADS)

    Zhang, Xue; Sheng, Daichao; Sloan, Scott W.; Krabbenhoft, Kristian

    2016-07-01

    In this paper, the incremental problem for consolidation analysis of elastoplastic saturated porous media is formulated and solved using second-order cone programming. This is achieved by the application of the Hellinger-Reissner variational theorem, which casts the governing equations of Biot's consolidation theory as a min-max optimisation problem. The min-max problem is then discretised using the finite element method and converted into a standard second-order cone programming problem that can be solved efficiently using modern optimisation algorithms (such as the primal-dual interior-point method). The proposed computational formulation is verified against a number of benchmark examples and also applied to simulate the construction of a road embankment on soft clay.

  12. Nonsocial functions of hypothalamic oxytocin.

    PubMed

    Yang, Hai-Peng; Wang, Liwei; Han, Liqun; Wang, Stephani C

    2013-01-01

    Oxytocin (OXT) is a hypothalamic neuropeptide composed of nine amino acids. The functions of OXT cover a variety of social and nonsocial activity/behaviors. Therapeutic effects of OXT on aberrant social behaviors are attracting more attention, such as social memory, attachment, sexual behavior, maternal behavior, aggression, pair bonding, and trust. The nonsocial behaviors/functions of brain OXT have also received renewed attention, which covers brain development, reproduction, sex, endocrine, immune regulation, learning and memory, pain perception, energy balance, and almost all the functions of peripheral organ systems. Coordinating with brain OXT, locally produced OXT also involves the central and peripheral actions of OXT. Disorders in OXT secretion and functions can cause a series of aberrant social behaviors, such as depression, autism, and schizophrenia as well as disturbance of nonsocial behaviors/functions, such as anorexia, obesity, lactation failure, osteoporosis, diabetes, and carcinogenesis. As more and more OXT functions are identified, it is essential to provide a general view of OXT functions in order to explore the therapeutic potentials of OXT. In this review, we will focus on roles of hypothalamic OXT on central and peripheral nonsocial functions. PMID:24967304

  13. Switching brain serotonin with oxytocin

    PubMed Central

    Mottolese, Raphaelle; Redouté, Jérôme; Costes, Nicolas; Le Bars, Didier; Sirigu, Angela

    2014-01-01

    Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human affect and sociality and in disorders like depression and autism. We asked whether these chemical messengers interact in the regulation of emotion-based behavior by administering OXT or placebo to 24 healthy subjects and mapping cerebral 5-HT system by using 2′-methoxyphenyl-(N-2′-pyridinyl)-p-[18F]fluoro-benzamidoethylpiperazine ([18F]MPPF), an antagonist of 5-HT1A receptors. OXT increased [18F]MPPF nondisplaceable binding potential (BPND) in the dorsal raphe nucleus (DRN), the core area of 5-HT synthesis, and in the amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the amygdala appears central in the regulation of 5-HT by OXT: [18F]MPPF BPND changes in the DRN correlated with changes in right amygdala, which were in turn correlated with changes in hippocampus, insula, subgenual, and orbitofrontal cortex, a circuit implicated in the control of stress, mood, and social behaviors. OXT administration is known to inhibit amygdala activity and results in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation have been associated with increased anxiety. The present study reveals a previously unidentified form of interaction between these two systems in the human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT signaling, which could lead to novel therapeutic strategies for mental disorders. PMID:24912179

  14. [Development of intranasal lactocin (oxytocin) drops technology].

    PubMed

    Klimas, Rimantas; Baranauskas, Algirdas; Gendrolis, Antanas

    2002-01-01

    Pure oxytocin substance was obtained from posterior part of cattle pituitary gland by high pressure liquid chromatography. Biological activity of the substance--450-500 IU/mg. Chromatographically pure Oxytocin substance was used in developing two different compositions of Lactocin intranasal drops (40 IU/ml). Stability evaluation was performed for 2 year period. The technical documentation was prepared on the basis of the research results. Lactocin is active preparation helping lactation and is indicated for lactostasis treatment and its prophylaxis after delivery. PMID:12474675

  15. Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness.

    PubMed

    Theodoridou, Angeliki; Rowe, Angela C; Penton-Voak, Ian S; Rogers, Peter J

    2009-06-01

    The neuropeptide oxytocin is involved in the development and maintenance of attachment behaviours in humans and other species. Little is known, however, about how it affects judgements of unfamiliar others. In a double-blind placebo-controlled study we investigated the effect of a single intranasal dose of oxytocin on judgements of facial trustworthiness and attractiveness. We found that oxytocin administration increased ratings of trustworthiness and attractiveness of male and female targets in raters of both sexes relative to control ratings, suggesting that higher levels of this neuropeptide may enhance affiliative behaviour towards unfamiliar others. Our results provide evidence in support of a general facilitative role of oxytocin in promoting positive trait judgements. PMID:19344725

  16. Taste masking analysis in pharmaceutical formulation development using an electronic tongue.

    PubMed

    Zheng, Jack Y; Keeney, Melissa P

    2006-03-01

    The purpose of this study is to assess the feasibility for taste masking and comparison of taste intensity during formulation development using a multichannel taste sensor system (e-Tongue). Seven taste sensors used in the e-Tongue were cross-selective for five basic tastes while having different sensitivity or responsibility for different tastes. Each of the individual sensors concurrently contributes to the detection of most substances in a complicated sample through the different electronic output. Taste-masking efficiency was evaluated using quinine as a bitter model compound and a sweetener, acesulfame K, as a bitterness inhibitor. In a 0.2 mM quinine solution, the group distance obtained from e-Tongue analysis was reduced with increasing concentration of acesulfame K. This result suggests that the sensors could detect the inhibition of bitterness by a sweetener and could be used for optimization of the sweetener level in a liquid formulation. In addition, the bitterness inhibition of quinine by using other known taste-masking excipients including sodium acetate, NaCl, Prosweet flavor, and Debittering powder or soft drinks could be detected by the e-Tongue. These results further suggest that the e-Tongue should be useful in a taste-masking evaluation study on selecting appropriate taste-masking excipients for a solution formulation or a reconstitution vehicle for a drug-in-bottle formulation. In another study, the intensity of the taste for several drug substances known to be bitter was compared using the e-Tongue. It was found that the group distance was 695 for prednisolone and 686 for quinine, which is much higher than that of caffeine (102). These results indicate that the taste of prednisolone and quinine is stronger or more bitter than that of caffeine as expected. Based on the group distance, the relative intensity of bitterness for these compounds could be ranked in the following order: ranitidine HCl>prednisolone Na>quinine HCl approximately

  17. Ontology representation and analysis of vaccine formulation and administration and their effects on vaccine immune responses

    PubMed Central

    2012-01-01

    Background A vaccine is a processed material that if administered, is able to stimulate an adaptive immune response to prevent or ameliorate a disease. A vaccination process may protect the host against subsequent exposure to an infectious agent and result in reduced disease or total prevention of the disease. Vaccine formulation and administration methods may affect vaccine safety and efficacy significantly. Results In this report, the detailed classification and definitions of vaccine components and vaccine administration processes are represented using OWL within the framework of the Vaccine Ontology (VO). Different use cases demonstrate how different vaccine formulations and routes of vaccine administration affect the protection efficacy, general immune responses, and adverse events following vaccination. For example, vaccinations of mice with Brucella abortus vaccine strain RB51 using intraperitoneal or intranasal administration resulted in different protection levels. As shown in the vaccine adverse event data provided by US FDA, live attenuated and nonliving vaccines are usually administered in different routes and have different local and systematic adverse effect manifestations. Conclusions Vaccine formulation and administration route can independently or collaboratively affect host response outcomes (positive protective immunity or adverse events) after vaccination. Ontological representation of different vaccine and vaccination factors in these two areas allows better understanding and analysis of the causal effects between different factors and immune responses. PMID:23256535

  18. Computational analysis of noise reduction devices in axial fans with stabilized finite element formulations

    NASA Astrophysics Data System (ADS)

    Corsini, A.; Rispoli, F.; Sheard, A. G.; Tezduyar, T. E.

    2012-12-01

    The paper illustrates how a computational fluid mechanic technique, based on stabilized finite element formulations, can be used in analysis of noise reduction devices in axial fans. Among the noise control alternatives, the study focuses on the use of end-plates fitted at the blade tips to control the leakage flow and the related aeroacoustic sources. The end-plate shape is configured to govern the momentum transfer to the swirling flow at the blade tip. This flow control mechanism has been found to have a positive link to the fan aeroacoustics. The complex physics of the swirling flow at the tip, developing under the influence of the end-plate, is governed by the rolling up of the jet-like leakage flow. The RANS modelling used in the computations is based on the streamline-upwind/Petrov-Galerkin and pressure-stabilizing/Petrov-Galerkin methods, supplemented with the DRDJ stabilization. Judicious determination of the stabilization parameters involved is also a part of our computational technique and is described for each component of the stabilized formulation. We describe the flow physics underlying the design of the noise control device and illustrate the aerodynamic performance. Then we investigate the numerical performance of the formulation by analysing the inner workings of the stabilization operators and of their interaction with the turbulence model.

  19. Analysis and antibacterial activity of Nigella sativa essential oil formulated in microemulsion system.

    PubMed

    Shaaban, Hamdy A; Sadek, Zainab; Edris, Amr E; Saad-Hussein, Amal

    2015-01-01

    The Essential oil (EO) of Nigella sativa (black cumin) was extracted from the crude oil and the volatile constituents were characterized using gas chromatographic analysis. The EO was formulated in water-based microemulsion system and its antibacterial activity against six pathogenic bacteria was evaluated using the agar well diffusion method. This activity was compared with two other well known biologically active natural and synthetic antimicrobials namely eugenol and Ceftriaxone(®). Results showed that N. sativa EO microemulsion was highly effective against S. aureus, B. cereus and S. typhimurium even at the lowest tested concentration of that EO in the microemulsion (100.0 μg/well). Interestingly, the EO microemulsion showed higher antibacterial activity than Ceftriaxone solution against S. typhimurium at 400.0 μg/well and almost comparable activity against E. coli at 500.0 μg/well. No activity was detected for the EO microemulsion against L. monocytogenes and P. aeruginosa. Eugenol which was also formulated in microemulsion was less effective than N. sativa EO microemulsion except against P. aeruginosa. The synthetic antibiotic (Ceftriaxone) was effective against most of the six tested bacterial strains. This work is the first report revealing the formulation of N. sativa EO in microemulsion system and investigating its antibacterial activity. The results may offer potential application of that water-based microemulsion in controlling the prevalence of some pathogenic bacteria. PMID:25748382

  20. Modeling and analysis of power processing systems: Feasibility investigation and formulation of a methodology

    NASA Technical Reports Server (NTRS)

    Biess, J. J.; Yu, Y.; Middlebrook, R. D.; Schoenfeld, A. D.

    1974-01-01

    A review is given of future power processing systems planned for the next 20 years, and the state-of-the-art of power processing design modeling and analysis techniques used to optimize power processing systems. A methodology of modeling and analysis of power processing equipment and systems has been formulated to fulfill future tradeoff studies and optimization requirements. Computer techniques were applied to simulate power processor performance and to optimize the design of power processing equipment. A program plan to systematically develop and apply the tools for power processing systems modeling and analysis is presented so that meaningful results can be obtained each year to aid the power processing system engineer and power processing equipment circuit designers in their conceptual and detail design and analysis tasks.

  1. Multidisciplinary High-Fidelity Analysis and Optimization of Aerospace Vehicles. Part 1; Formulation

    NASA Technical Reports Server (NTRS)

    Walsh, J. L.; Townsend, J. C.; Salas, A. O.; Samareh, J. A.; Mukhopadhyay, V.; Barthelemy, J.-F.

    2000-01-01

    An objective of the High Performance Computing and Communication Program at the NASA Langley Research Center is to demonstrate multidisciplinary shape and sizing optimization of a complete aerospace vehicle configuration by using high-fidelity, finite element structural analysis and computational fluid dynamics aerodynamic analysis in a distributed, heterogeneous computing environment that includes high performance parallel computing. A software system has been designed and implemented to integrate a set of existing discipline analysis codes, some of them computationally intensive, into a distributed computational environment for the design of a highspeed civil transport configuration. The paper describes the engineering aspects of formulating the optimization by integrating these analysis codes and associated interface codes into the system. The discipline codes are integrated by using the Java programming language and a Common Object Request Broker Architecture (CORBA) compliant software product. A companion paper presents currently available results.

  2. The many faces of oxytocin: implications for psychiatry.

    PubMed

    Zik, Jodi B; Roberts, David L

    2015-03-30

    Oxytocin is known as the 'love hormone' due its role in promoting mother-child and pair bonding. More recent research indicates that oxytocin may have broader pro-social effects on behavior and cognition, which points towards oxytocin's potential as an agent to help improve social cognition and functioning in psychiatric disorders such as schizophrenia and autism. However, new research on oxytocin has also uncovered a 'darker side', including oxytocin's possible role in social out-grouping and envy. Instead of a simple view of oxytocin as 'good' or 'bad', a more accurate depiction of oxytocin's role in social processing likely involves the presence of moderating factors. We review moderation effects in oxytocin and their implications for psychiatry. One implication is that, across diagnostic categories, oxytocin administration may have positive effects for patients with social cognitive deficits but negative effects for patients with social cognitive bias. We conclude that future intervention studies should use methods such as signal detection to measure both deficit and bias parameters of social cognition and to evaluate potential individual and contextual moderators both within and between psychiatric diagnoses in order to determine for whom oxytocin treatment may be beneficial and for whom it may actually be harmful. PMID:25619431

  3. Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach

    PubMed Central

    Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M

    2015-01-01

    Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917–rs2268498–rs4564970–rs237897–rs2268495–rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration. PMID:26506050

  4. Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach.

    PubMed

    Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M

    2015-01-01

    Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917-rs2268498-rs4564970-rs237897-rs2268495-rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration. PMID:26506050

  5. Oxytocin receptor ligands induce changes in cytoskeleton in neuroblastoma cells.

    PubMed

    Bakos, Jan; Strbak, Vladimir; Paulikova, Helena; Krajnakova, Lucia; Lestanova, Zuzana; Bacova, Zuzana

    2013-07-01

    Aim of the present study was to evaluate effects of ligands of oxytocin receptors on gene expression of neurofilament proteins (nestin and microtubule-associated protein 2 (MAP2)) associated with neuronal differentiation and growth factors (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) related to neuronal growth. Fluorescent staining of F-actin was used to observe morphology of cells. Co-treatment with oxytocin and oxytocin receptor antagonist--atosiban--resulted in significant increase of MAP2 gene expression in SK-N-SH cells. There was no effect of oxytocin on gene expression of growth factors BDNF and NGF. Surprisingly, oxytocin with atosiban significantly increased mRNA levels for both BDNF and NGF. Gene expression of vasopressin receptor (V1aR) significantly decreased in response to vasopressin. Atosiban decreased mRNA levels for oxytocin receptor (OXTR) and V1aR. Oxytocin significantly decreased OXTR and nestin mRNA levels and increased mRNA levels for BDNF and NGF in U-87 MG cells. The densest recruitment of F-actin filaments was observed in apical parts of filopodia in SK-N-SH cells incubated in oxytocin presence. Present data demonstrate complex role of ligands of oxytocin receptors in regulation of gene expression of intermediate filaments and thus, oxytocin might be considered as a growth factor in neuronal type of cells. PMID:23335033

  6. Time-varying sensitivity analysis clarifies the effects of watershed model formulation on model behavior

    NASA Astrophysics Data System (ADS)

    Herman, J. D.; Reed, P. M.; Wagener, T.

    2013-03-01

    Lumped rainfall-runoff models are widely used for flow prediction, but a long-recognized need exists for diagnostic tools to determine whether the process-level behavior of a model aligns with the expectations inherent in its formulation. To this end, we develop a comprehensive exploration of dominant parameters in the Hymod, HBV, and Sacramento Soil Moisture Accounting (SAC-SMA) model structures. Model controls are isolated using time-varying Sobol' sensitivity analysis for twelve MOPEX watersheds in the eastern United States over a 10 year period. Sensitivity indices are visualized along gradients of observed precipitation and streamflow to identify key behavioral differences between the three models and to connect these back to the models' underlying assumptions. Results indicate that the models' dominant parameters strongly depend on time-varying hydroclimatic conditions. Parameters associated with surface processes such as evapotranspiration and runoff generally dominate under dry conditions, when high evaporative fluxes are required for accurate simulation. Parameters associated with routing processes typically dominate under high-flow conditions, when performance depends on the timing of flow events. The results highlight significant inter-model differences in performance controls, even in cases where the models share similar process formulations. The dominant parameters identified can be counterintuitive; even these simple models represent complex, nonlinear systems, and the links between formulation and behavior are difficult to discern a priori as complexity increases. Scrutinizing the links between model formulation and behavior becomes an important diagnostic approach, particularly in applications such as predictions under change where dominant model controls will shift under hydrologic extremes.

  7. Stability-indicating HPLC method for the determination of the stability of oxytocin parenteral solutions prepared in polyolefin bags.

    PubMed

    Kaushal, G; Sayre, B E; Prettyman, T

    2012-02-01

    Oxytocin is very commonly used in clinical settings and is a nonapeptide hormone that stimulates the contraction of uterine smooth muscles. In this study the stability of extemporaneously compounded oxytocin solutions was investigated in polyolefin bags. The sterile preparations of oxytocin were compounded to the strength of 0.02 U/mL in accordance with United States Pharmacopeia (USP) <797> standards. In order to carry out the stability testing of these parenteral products, the solutions were stored under three different temperature conditions of -20°C (frozen), 2-6°C (refrigerated), and 22-25°C (room temperature). Three solutions from each temperature were withdrawn and were assessed for stability on days 0, 7, 15, 21, and 30 as per the USP guidelines. The assay of oxytocin was examined by an HPLC method at each time point. No precipitation, cloudiness or color change was observed during this study at all temperatures. The assay content by HPLC revealed that oxytocin retains greater than at least 90% of the initial concentrations for 21 days. There was no significant change in pH and absorbance values for 21 days under all the conditions of storage. Oxytocin parenteral solutions in the final concentration of 0.02 U/mL and diluted in normal saline are stable for at least 30 days under frozen and refrigerated conditions for 30 days. At the room temperature, the oxytocin solutions were stable for at least 21 days. The stability analysis results show that the shelf-life of 21 days observed in this study was far better than their recommended expiration dates. PMID:22460429

  8. Trace Analysis of Surfactants in Corexit Oil Dispersant Formulations and Seawater

    PubMed Central

    Place, Benjamin J.; Perkins, Matt J.; Sinclair, Ewan; Barsamian, Adam L.; Blakemore, Paul R.; Field, Jennifer A.

    2014-01-01

    After the April 2010 explosion on the Deepwater Horizon oil rig, and subsequent release of millions of barrels of oil, two Corexit oil dispersant formulations were used in unprecedented quantities both on the surface and sub-surface of the Gulf of Mexico. Although the dispersant formulations contain four classes of surfactants, current studies to date focus on the anionic surfactant, bis-(2-ethylhexyl) sulfosuccinate (DOSS). Factors affecting the integrity of environmental and laboratory samples for Corexit analysis have not been systematically investigated. For this reason, a quantitative analytical method was developed for the detection of all four classes of surfactants, as well as the hydrolysis products of DOSS, the enantiomeric mixture of α- and β-ethylhexyl sulfosuccinate (α-/β-EHSS). The analytical method was then used to evaluate which practices for sample collection, storage, and analysis resulted in high quality data. Large volume, direct injection of seawater followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) minimized analytical artifacts, analysis time, and both chemical and solid waste. Concentrations of DOSS in the seawater samples ranged from 71 – 13,000 ng/L, while the nonionic surfactants including Span 80, Tween 80, Tween 85 were detected infrequently (26% of samples) at concentrations from 840 – 9100 ng/L. The enantiomers α-/β-EHSS were detected in seawater, at concentrations from 200 – 1,900 ng/L, and in both Corexit dispersant formulations, indicating α-/β-EHSS were applied to the oil spill and may be not unambiguous indicator of DOSS degradation. Best practices are provided to ensure sample integrity and data quality for environmental monitoring studies and laboratory that require the detection and quantification of Corexit-based surfactants in seawater.

  9. Sniffing and Oxytocin: Effects on Olfactory Memories.

    PubMed

    Stoop, Ron

    2016-05-01

    In this issue of Neuron, Oettl et al. (2016) show how oxytocin can boost processing of olfactory information in female rats by a top-downregulation from the anterior olfactory nucleus onto the main olfactory bulb. As a result, interactions with juvenile conspecifics receive more attention and are longer memorized. PMID:27151635

  10. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  11. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  12. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  13. Severity of eating disorder symptoms related to oxytocin receptor polymorphisms in anorexia nervosa.

    PubMed

    Acevedo, Summer F; Valencia, Celeste; Lutter, Michael; McAdams, Carrie J

    2015-08-30

    Oxytocin is a peptide hormone important for social behavior and differences in psychological traits have been associated with variants of the oxytocin receptor gene in healthy people. We examined whether single nucleotide polymorphisms (SNPs) of the oxytocin receptor gene (OXTR) correlated with clinical symptoms in women with anorexia nervosa, bulimia nervosa, and healthy comparison (HC) women. Subjects completed clinical assessments and provided DNA for analysis. Subjects were divided into four groups: HC, subjects currently with anorexia nervosa (AN-C), subjects with a history of anorexia nervosa but in long-term weight recovery (AN-WR), and subjects with bulimia nervosa (BN). Five SNPs of the oxytocin receptor were examined. Minor allele carriers showed greater severity in most of the psychiatric symptoms. Importantly, the combination of having had anorexia and carrying either of the A alleles for two SNPS in the OXTR gene (rs53576, rs2254298) was associated with increased severity specifically for ED symptoms including cognitions and behaviors associated both with eating and appearance. A review of psychosocial data related to the OXTR polymorphisms examined is included in the discussion. OXTR polymorphisms may be a useful intermediate endophenotype to consider in the treatment of patients with anorexia nervosa. PMID:26106053

  14. Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

    PubMed

    Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Adám; Rónai, Zsolt; Kubinyi, Enikő

    2014-01-01

    The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system. PMID:24454713

  15. Oxytocin Receptor Gene Polymorphisms Are Associated with Human Directed Social Behavior in Dogs (Canis familiaris)

    PubMed Central

    Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Ádám; Rónai, Zsolt; Kubinyi, Enikő

    2014-01-01

    The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (−212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5′ and 3′ UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3′ and 5′ UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene–behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system. PMID:24454713

  16. Immunochromatographic removal of albumin in erythropoietin biopharmaceutical formulations for its analysis by capillary electrophoresis.

    PubMed

    Lara-Quintanar, Pilar; Lacunza, Izaskun; Sanz, Jesus; Diez-Masa, Jose Carlos; de Frutos, Mercedes

    2007-06-15

    Human serum albumin (HSA) is added to some pharmaceutical preparations as an excipient. This is the case for some of the commercial preparations of recombinant erythropoietin (rEPO). Differences in the number of the sialic acid moieties in the different rEPO glycoforms confer to these forms different net charges and different bioactivity. Knowledge of the isoforms present in each pharmaceutical product is then of interest. Differences in net charge of the rEPO forms make possible their separation by electrophoretical methods. However it has been observed in our laboratory that the amount of HSA usually present in these drug formulations interferes or even precludes separation of rEPO bands by capillary zone electrophoresis (CZE). In this work, an immunochromatographic method to remove HSA from rEPO biopharmaceutical formulations and a procedure to concentrate the sample that is needed to be performed prior to the analysis by CZE are developed. A home-made computer program to compare the percentage of correct assignments of electrophoretical bands provided by different migration parameters is used to study the effect of HSA remaining in samples on the accuracy of assignment of rEPO bands. When there exists a residual concentration of HSA in the sample (<2mg/ml) only the effective electrophoretic mobility is a reliable migration parameter to assign rEPO bands with a 100% of correct assignment. This parameter allows the correct assignment of bands of rEPO from pharmaceutical products formulated with HSA after immunochromatographic removal of HSA. Electrophoretical bands found in epoetin alpha, one of the commercial formulations of rEPO, are independent of the molecular mass of the excipients. The methodology used in this work for the analysis by CZE and the assignment of rEPO isoforms, as well as for the immunochromatographic HSA removal in the pharmaceutical products could be of high interest for the health authorities to control the quality of the product in

  17. Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior

    PubMed Central

    Ross, Heather E.; Young, Larry J.

    2009-01-01

    Oxytocin is produced in the hypothalamus and released into the circulation through the neurohypophyseal system. Peripherally released oxytocin facilitates parturition and milk ejection during nursing. Centrally released oxytocin coordinates the onset of maternal nurturing behavior at parturition and plays a role in mother-infant bonding. More recent studies have revealed a more general role for oxytocin in modulating affiliative behavior in both sexes. Oxytocin regulates alloparental care and pair bonding in female monogamous prairie voles. Social recognition in male and female mice is also modulated by oxytocin. In humans, oxytocin increases gaze to the eye region of human faces and enhances interpersonal trust and the ability to infer the emotions of others from facial cues. While the neurohypopheseal oxytocin system has been well characterized, less is known regarding the nature of oxytocin release within the brain. Here we review the role of oxytocin in the regulation prosocial interactions, and discuss the neuroanatomy of the central oxytocin system. PMID:19481567

  18. Analysis of Angular V-Cycle Multigrid Formulation for Three-Dimensional Discrete Ordinates Shielding Problems

    SciTech Connect

    Kucukboyaci, Vefa; Haghighat, Alireza

    2001-06-17

    New angular multigrid formulations have been developed, including the Simplified Angular Multigrid (SAM), Nested Iteration (NI), and V-Cycle schemes, which are compatible with the parallel environment and the adaptive differencing strategy of the PENTRAN three-dimensional parallel S{sub N} code. Through use of the Fourier analysis method for an infinite, homogeneous medium, the effectiveness of the V-Cycle scheme was investigated for different problem parameters including scattering ratio, spatial differencing weights, quadrature order, and mesh size. The theoretical analysis revealed that the V-Cycle scheme is effective for a large range of scattering ratios and is insensitive to mesh size. The effectiveness of the new schemes was also investigated for practical shielding applications such as the Kobayashi benchmark problem and the boiling water reactor core shroud problem.

  19. A formulation of rotor-airframe coupling for design analysis of vibrations of helicopter airframes

    NASA Technical Reports Server (NTRS)

    Kvaternik, R. G.; Walton, W. C., Jr.

    1982-01-01

    A linear formulation of rotor airframe coupling intended for vibration analysis in airframe structural design is presented. The airframe is represented by a finite element analysis model; the rotor is represented by a general set of linear differential equations with periodic coefficients; and the connections between the rotor and airframe are specified through general linear equations of constraint. Coupling equations are applied to the rotor and airframe equations to produce one set of linear differential equations governing vibrations of the combined rotor airframe system. These equations are solved by the harmonic balance method for the system steady state vibrations. A feature of the solution process is the representation of the airframe in terms of forced responses calculated at the rotor harmonics of interest. A method based on matrix partitioning is worked out for quick recalculations of vibrations in design studies when only relatively few airframe members are varied. All relations are presented in forms suitable for direct computer implementation.

  20. Coupled Ocean-Atmosphere 4D-Var: Formulation and Sensitivity Analysis Results

    NASA Astrophysics Data System (ADS)

    Ngodock, Hans; Carrier, Matthew; Xu, Liang; Amerault, Clark; Campbell, Tim; Rowley, Clark

    2016-04-01

    The US Navy is currently developing the first coupled ocean-atmosphere four-dimensional variational (4D-Var) data assimilation system to be used for short-term regional forecasting. This project merges the 4D-Var capabilities of the atmospheric component of the Coupled Ocean/Atmospheric Mesoscale Prediction System (COAMPS©) with the Navy Coastal Ocean Model (NCOM) through the Earth System Modeling Framework (ESMF). This will provide the coupled ocean-atmosphere forecast with a fully balanced analysis that accounts for all combined observations in both primary fluids (i.e. ocean and atmosphere). In this present work, the formulation of the system is presented in detail along with a series of adjoint sensitivity analysis results using the coupled ocean-atmosphere adjoint model. The sensitivity of the atmosphere (ocean) to each ocean (atmosphere) model variable is analyzed in detail in order to illustrate the usefulness of this approach in the coupled data assimilation system.

  1. Comparative analysis of several sediment transport formulations applied to dam-break flows over erodible beds

    NASA Astrophysics Data System (ADS)

    Cea, Luis; Bladé, Ernest; Corestein, Georgina; Fraga, Ignacio; Espinal, Marc; Puertas, Jerónimo

    2014-05-01

    Transitory flows generated by dam failures have a great sediment transport capacity, which induces important morphological changes on the river topography. Several studies have been published regarding the coupling between the sediment transport and hydrodynamic equations in dam-break applications, in order to correctly model their mutual interaction. Most of these models solve the depth-averaged shallow water equations to compute the water depth and velocity. On the other hand, a wide variety of sediment transport formulations have been arbitrarily used to compute the topography evolution. These are based on semi-empirical equations which have been calibrated under stationary and uniform conditions very different from those achieved in dam-break flows. Soares-Frazao et al. (2012) proposed a Benchmark test consisting of a dam-break over a mobile bed, in which several teams of modellers participated using different numerical models, and concluded that the key issue which still needs to be investigated in morphological modelling of dam-break flows is the link between the solid transport and the hydrodynamic variables. This paper presents a comparative analysis of different sediment transport formulations applied to dam-break flows over mobile beds. All the formulations analysed are commonly used in morphological studies in rivers, and include the formulas of Meyer-Peter & Müller (1948), Wong-Parker (2003), Einstein-Brown (1950), van Rijn (1984), Engelund-Hansen (1967), Ackers-White (1973), Yang (1973), and a Meyer-Peter & Müller type formula but with ad-hoc coefficients. The relevance of corrections on the sediment flux direction and magnitude due to the bed slope and the non-equilibrium hypothesis is also analysed. All the formulations have been implemented in the numerical model Iber (Bladé et al. (2014)), which solves the depth-averaged shallow water equations coupled to the Exner equation to evaluate the bed evolution. Two different test cases have been

  2. Separation Anxiety, Attachment and Inter-Personal Representations: Disentangling the Role of Oxytocin in the Perinatal Period

    PubMed Central

    Eapen, Valsamma; Dadds, Mark; Barnett, Bryanne; Kohlhoff, Jane; Khan, Feroza; Radom, Naomi; Silove, Derrick M.

    2014-01-01

    In this paper, we aimed to assess cross-sectionally and longitudinally associations between disturbances in maternal early attachment experiences, symptoms of separation anxiety and depression and oxytocin plasma levels. We examined a mediational model that tested the hypothesis that anxious attachment style arising from the mothers’ early bonding experiences with her own parents was associated with high levels of separation anxiety which, via its impact on depression, was associated with reduced levels of oxytocin in the postnatal period. Data is reported on a structured sample of 127 women recruited during pregnancy from a general hospital antenatal clinic and an initial follow up cohort of 57 women who were re-assessed at 3-months post-partum. We found an association between lower oxytocin level in the post partum period and symptoms of separation anxiety and depression during pregnancy, as well as maternal negative interpersonal representations, upbringing attributes and anxious attachment style. Further meditational analysis revealed that the unique association between anxious attachment and depression is mediated by separation anxiety and that depressed mood mediated the relationship between separation anxiety and oxytocin. In conjunction with evidence from the literature suggesting that lower oxytocin level is associated with bonding difficulties, our findings have significant implications for understanding the biological processes underpinning adverse attachment experiences, negative affect state, and mother-to-infant bonding difficulties. PMID:25229827

  3. Oxytocin Protects Hippocampal Memory and Plasticity from Uncontrollable Stress.

    PubMed

    Lee, Sun-Young; Park, Seong-Hae; Chung, ChiHye; Kim, Jeansok J; Choi, Se-Young; Han, Jung-Soo

    2015-01-01

    The hippocampus is vulnerable to uncontrollable stress and is enriched with oxytocin receptors, but their interactive influences on hippocampal functioning are unknown. This study aimed to determine the effects of intranasal oxytocin administration on stress-induced alterations in synaptic plasticity and spatial memory in male rats. While vehicle-administered stressed rats showed impairment in long-term potentiation, enhancement in long-term depression, and weakened spatial memory, these changes were not observed in oxytocin-administered stressed rats. To reveal the potential signaling mechanism mediating these effects, levels of phosphorylated extracellular signal-regulated kinases (pERK) in the hippocampus was examined. Western blotting showed that oxytocin treatment blocked stress-induced alterations of pERK. Additionally, the oxytocin receptor antagonist L-368,899 inhibited the oxytocin's protective effects on hippocampal memory to stress. Thus, intranasal administration of oxytocin reduced stress effects on hippocampal synaptic plasticity and memory in rats via acting on oxytocin receptors and regulating ERK activity. This study suggests that exogenous oxytocin may be a therapeutically effective means to counter the detrimental neurocognitive effects of stress. PMID:26688325

  4. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    PubMed

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. PMID:27237044

  5. Ageing and oxytocin: a call for extending human oxytocin research to ageing populations--a mini-review.

    PubMed

    Huffmeijer, Renske; van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2013-01-01

    Interest in oxytocin has increased rapidly over the last decades. Consequently, quite a number of studies have addressed the influence of oxytocin on social stress, perception, cognition, and decision making in healthy adults as well as in clinical samples characterized by some form of social disturbance. Surprisingly little research on oxytocin has focused on ageing populations. This is particularly striking in two areas of study: the role of oxytocin in grandparents' behavior toward and bonding with their grandchildren and the effects of oxytocin on the neurocognitive processing of socioemotional stimuli. The current mini-review offers an overview of the literature on the involvement of oxytocin in parental behavior and neurocognitive functioning, and discusses the relevance of these findings to ageing individuals. As the literature shows that oxytocin is profoundly involved in parenting and in bonding throughout life, it is highly likely that oxytocin plays a role in grandparenting and bonding between grandparents and grandchildren as well. However, results obtained with younger adults may not be directly applicable to older individuals in yet another type of relationship. The possibility that age-related changes occur in the oxytocin system (which is at present unclear) must be taken into account. In addition, ageing impairs neurocognitive processes that are profoundly affected by oxytocin (including some aspects of memory and emotion recognition) and is associated with alterations in both structure and function of the amygdala, which is prominently involved in mediating effects of oxytocin. Research investigating the ageing oxytonergic system and studies focusing on the involvement of oxytocin in socioemotional neurocognitive processes and social behavior in elderly individuals, including grandparents, are therefore urgently needed. PMID:22922544

  6. Mixed formulation for seismic analysis of composite steel-concrete frame structures

    NASA Astrophysics Data System (ADS)

    Ayoub, Ashraf Salah Eldin

    This study presents a new finite element model for the nonlinear analysis of structures made up of steel and concrete under monotonic and cyclic loads. The new formulation is based on a two-field mixed formulation. In the formulation, both forces and deformations are simultaneously approximated within the element through independent interpolation functions. The main advantages of the model is the accuracy in global and local response with very few elements while maintaining rapid numerical convergence and robustness even under severe cyclic loading. Overall four elements were developed based on the new formulation: an element that describes the behavior of anchored reinforcing bars, an element that describes the behavior of composite steel-concrete beams with deformable shear connectors, an element that describes the behavior of reinforced concrete beam-columns with bond-slip, and an element that describes the behavior of pretensioned or posttensioned, bonded or unbonded prestressed concrete structures. The models use fiber discretization of beam sections to describe nonlinear material response. The transfer of forces between steel and concrete is described with bond elements. Bond elements are modeled with distributed spring elements. The non-linear behavior of the composite element derives entirely from the constitutive laws of the steel, concrete and bond elements. Two additional elements are used for the prestressed concrete models, a friction element that models the effect of friction between the tendon and the duct during the posttensioning operation, and an anchorage element that describes the behavior of the prestressing tendon anchorage in posttensioned structures. Two algorithms for the numerical implementation of the new proposed model are presented; an algorithm that enforces stress continuity at element boundaries, and an algorithm in which stress continuity is relaxed locally inside the element. Stability of both algorithms is discussed. Comparison

  7. Development of simple thiol-reactive liposome formulations, one-step analysis and physicochemical characterization.

    PubMed

    Kaourma, E; Hatziantoniou, S; Georgopoulos, A; Kolocouris, A; Demetzos, C

    2005-04-01

    The aim of this study was to synthesize simple thiol-reactive conjugates from maleimide and lipoamines (stearylamine or oleylamine) and to develop a simple, fast and low-cost method for the preparation of lyophilized general-purpose thiol-reactive liposomes. A formulation of egg phosphatidylcholine-dipalmitoylphoshatidylglycerol (9:0.1 molar ratio) was developed and characterized. Freeze-drying methodology was established to produce a stock of liposomes and the physicochemical characteristics of the reconstituted liposomes were compared with those of the initial preparation. The physicochemical properties (size and zeta potential) of the new liposomal formulations were studied. High-performance thin-layer chromatography coupled to a flame ionization detector was applied for one-step analysis of the liposomal components and for determining the maleimide-lipoamine conjugates phospholipid molar ratio. The differences concerning the incorporation efficiency of the synthetic conjugates into liposomes were discussed on the basis of their conformational properties. The small difference in structure between the two thiol-reactive conjugates (i.e., the C18 alkyl chain double bond) causes a considerable difference in phospholipids packing of the resulting lipidic bilayers of the liposomes; the conformational bending of conjugate maleimide-oleylamine may contribute to the final architecture of liposomes. PMID:15831216

  8. Efficient modeling of flat and homogeneous acoustic treatments for vibroacoustic finite element analysis. Direct field formulations

    NASA Astrophysics Data System (ADS)

    Alimonti, L.; Atalla, N.

    2016-04-01

    This paper is concerned with the development of a simplified model for noise control treatments to speed up finite element analysis in vibroacoustic applications. The methodology relies on the assumption that the acoustic treatment is flat and homogeneous. Moreover, its finite lateral extent is neglected. This hypothesis is justified by short wavelength and large dissipation, which suggest that the reflected field emanating from the acoustic treatment lateral boundaries does not substantially affect its dynamic response. Under these circumstances, the response of the noise control treatment can be formally obtained by means of convolution integrals involving simple analytical kernels (i.e. Green functions). Such fundamental solutions can be computed efficiently by the transfer matrix method. However, some arbitrariness arises in the formulation of the mathematical model, resulting in different baffling conditions at the two ends of the treatment to be considered. Thus, the paper investigates the possibility of different formulations (i.e. baffling conditions) within the same hybrid finite element-transfer matrix framework, seeking for the best strategy in terms of tradeoff between efficiency and accuracy. Numerical examples are provided to show strengths and limitations of the proposed methodology.

  9. The Concentrations of Circulating Plasma Oxytocin and the Pattern of Oxytocin Release in Mare during Oestrus and after Ovulation

    NASA Astrophysics Data System (ADS)

    Bae, Sung Eun

    Mares susceptible to persistent mating-induced endometritis (PMIE) accumulate intrauterine fluid after mating. One of the factors causing delayed uterine clearance is thought to be impaired uterine contractility. Oxytocin is central in controlling myometrial contractility. The objective of the present study was to describe peripheral oxytocin release during estrus and in the early postovulatory period in reproductively-normal mares and to compare the baseline circulating oxytocin concentrations in reproductively-normal mares and mares with PMIE. Blood samples were collected from reproductively-normal mares (n=5) from day -5 of estrus to day 2 postovulation and every 5 min for 30 min from reproductively-normal mares (n=5) and mares with PMIE (n=5) on day 3 of estrus. Pulsatile secretion of oxytocin was observed in all mares. Mean plasma oxytocin concentrations were significantly higher (P<0.05) in estrus (day -5 to day -2) than on the day of ovulation (day 0). After ovulation, plasma oxytocin concentrations tended to increase. On day 3 of estrus, plasma oxytocin concentrations were significantly higher (P<0.01) in reproductively-normal mares than in mares with PMIE. The results showed there is a significant difference in plasma oxytocin concentrations between mares to PMIE. The low plasma oxytocin concentrations in mares with PMIE may contribute to predisposing factors in their poor uterine clearance in these mares.

  10. Brain oxytocin correlates with maternal aggression: link to anxiety.

    PubMed

    Bosch, Oliver J; Meddle, Simone L; Beiderbeck, Daniela I; Douglas, Alison J; Neumann, Inga D

    2005-07-20

    The oxytocinergic system is critically involved in the regulation of maternal behavior, which includes maternal aggression. Because aggression has been linked to anxiety, we investigated the maternal aggression and the role of brain oxytocin in lactating Wistar rats selectively bred for high anxiety-related behavior (HAB) or low anxiety-related behavior (LAB) during the 10 min maternal defense test. HAB dams displayed more maternal aggression against a virgin intruder compared with LAB dams, resulting in more defensive behavior and higher anxiety of HAB-defeated virgins. The different levels of aggression were accompanied by opposite oxytocin release patterns within the paraventricular nucleus (PVN; HAB, increase; LAB, decrease). Furthermore, oxytocin release was higher within the central nucleus of the amygdala (CeA) of HAB dams compared with LABs. A direct correlation between the offensive behavior displayed during the maternal defense test and local oxytocin release was found in both the PVN and CeA. Using retrodialysis, blockade of endogenous oxytocin action by infusion of an oxytocin receptor antagonist (des-Gly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT) into the PVN or CeA reduced maternal aggression of HAB dams, whereas infusion of synthetic oxytocin into the PVN tended to increase aggression toward the intruder in LAB dams. There were no significant differences in oxytocin receptor mRNA expression or oxytocin receptor binding between lactating HAB and LAB dams. Therefore, differences in intracerebral release patterns of oxytocin, rather than differences at the level of oxytocin receptors, are critical for the regulation of maternal aggressive behavior. PMID:16033890

  11. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats

    PubMed Central

    Zheng, Jun; Babygirija, Reji; Bülbül, Mehmet; Cerjak, Diana; Ludwig, Kirk

    2010-01-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression. PMID:20689056

  12. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats.

    PubMed

    Zheng, Jun; Babygirija, Reji; Bülbül, Mehmet; Cerjak, Diana; Ludwig, Kirk; Takahashi, Toku

    2010-10-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression. PMID:20689056

  13. Peripheral oxytocin administration reduces ethanol consumption in rats

    PubMed Central

    MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon; Wardley, Krystal; Deogan, Sumeet; Thomas, Cameron; Peris, Joanna

    2016-01-01

    The neuropeptide oxytocin interacts with mesolimbic dopamine neurons to mediate reward associated with filial behaviors, but also other rewarding behaviors such as eating or taking drugs of abuse. Based on its efficacy to decrease intake of other abused substances, oxytocin administration is implicated as a possible treatment for excessive alcohol consumption. We tested this hypothesis by measuring ethanol intake in male Sprague–Dawley rats injected with oxytocin or saline using two different ethanol self-administration paradigms. First, a dose–response curve was constructed for oxytocin inhibition of fluid intake using a modified drinking-in-the-dark model with three bottles containing .05% saccharine, 10% ethanol in saccharine, and 15% ethanol in saccharine. Doses of oxytocin tested were 0.05, 0.1, 0.3, and 0.5 mg/kg (I.P.). Next, rats received 0.3 mg/kg oxytocin preceding operant sessions in which they were trained to lever-press for either plain gelatin or ethanol gelatin in order to compare oxytocin inhibition of ethanol intake versus caloric intake. For the three-bottle choice study, rats consumed significantly less ethanol when treated with the three higher doses of oxytocin on the injection day. In the operant study, 0.3 mg/kg oxytocin significantly decreased ethanol gel consumption to a greater extent than plain gel consumption, both in terms of the amount of gel eaten and calories consumed. These data affirm oxytocin's efficacy for decreasing ethanol intake in rats, and confirm clinical studies suggesting oxytocin as a potential treatment for alcoholism. PMID:26519603

  14. Oxytocin: parallel processing in the social brain?

    PubMed

    Dölen, Gül

    2015-06-01

    Early studies attempting to disentangle the network complexity of the brain exploited the accessibility of sensory receptive fields to reveal circuits made up of synapses connected both in series and in parallel. More recently, extension of this organisational principle beyond the sensory systems has been made possible by the advent of modern molecular, viral and optogenetic approaches. Here, evidence supporting parallel processing of social behaviours mediated by oxytocin is reviewed. Understanding oxytocinergic signalling from this perspective has significant implications for the design of oxytocin-based therapeutic interventions aimed at disorders such as autism, where disrupted social function is a core clinical feature. Moreover, identification of opportunities for novel technology development will require a better appreciation of the complexity of the circuit-level organisation of the social brain. PMID:25912257

  15. Sources of Error and the Statistical Formulation of M S: m b Seismic Event Screening Analysis

    NASA Astrophysics Data System (ADS)

    Anderson, D. N.; Patton, H. J.; Taylor, S. R.; Bonner, J. L.; Selby, N. D.

    2014-03-01

    The Comprehensive Nuclear-Test-Ban Treaty (CTBT), a global ban on nuclear explosions, is currently in a ratification phase. Under the CTBT, an International Monitoring System (IMS) of seismic, hydroacoustic, infrasonic and radionuclide sensors is operational, and the data from the IMS is analysed by the International Data Centre (IDC). The IDC provides CTBT signatories basic seismic event parameters and a screening analysis indicating whether an event exhibits explosion characteristics (for example, shallow depth). An important component of the screening analysis is a statistical test of the null hypothesis H 0: explosion characteristics using empirical measurements of seismic energy (magnitudes). The established magnitude used for event size is the body-wave magnitude (denoted m b) computed from the initial segment of a seismic waveform. IDC screening analysis is applied to events with m b greater than 3.5. The Rayleigh wave magnitude (denoted M S) is a measure of later arriving surface wave energy. Magnitudes are measurements of seismic energy that include adjustments (physical correction model) for path and distance effects between event and station. Relative to m b, earthquakes generally have a larger M S magnitude than explosions. This article proposes a hypothesis test (screening analysis) using M S and m b that expressly accounts for physical correction model inadequacy in the standard error of the test statistic. With this hypothesis test formulation, the 2009 Democratic Peoples Republic of Korea announced nuclear weapon test fails to reject the null hypothesis H 0: explosion characteristics.

  16. Intermittent drinking, oxytocin and human health.

    PubMed

    Pruimboom, L; Reheis, D

    2016-07-01

    Looking at a waterhole, it is surprising that so many animals share the same space without visible signs of anxiety or aggression. Although waterholes are the preferred feeding locations of large carnivores, waterholes are shared by all type of herbivores of all sizes and shapes, including elephants. Recent research shows that the homeostatic disturbances leading to the "thirst feeling" not only activate specific substances regulating water and mineral household, but also the "trust and love" hormone oxytocin, while decreasing the production of the typical stress hormone cortisol. People using drugs, seem to be in search for oxytocin, as evidenced in studies with individuals on drugs such as ecstasy and gamma-hydroxybyturate. Hot environment, drought and increased sweating also activate specific oxytocin-producing parts of the hypothalamus, just as breastfeeding does in mother and infant. Water homeostasis is the only allostatic system activating trust neuro-anatomy and we suggest that this is due to the fact that all animals depend on water, whereas food type is species specific. Our hypothesis; regulating drinking behaviour through intermittent bulk drinking could increase oxytocin signalling, recover human trust and increase health by down-regulation of stress axis activity and inflammatory activity of the immune system. Intermittent bulk drinking should be defined as water (including tea and coffee) drinking up to a feeling of satiety and regulated by a mild feeling of thirst. This would mean that people would not drink less quantity but less frequently and that's how all animals, but also human newborns behave. It is the latter group, which is probably the only group of humans with a normal fluid homeostasis. PMID:27241263

  17. Factors Related to Intimidation During Oxytocin Administration.

    PubMed

    Beckmann, Claudia A; Cannella, Barbara L

    2015-01-01

    Patient's safety and quality are foremost issues in healthcare today and are often adversely influenced by communication and issues of perceived intimidation. Labor and delivery nurses are responsible for managing oxytocin infusions, but disagreements between providers and nurses related to the administration have been shown to cause tension and affect patient's care. The purpose of this study was to survey registered nurses in labor and delivery about perceived intimidation and how intimidation influenced actions and decisions. A total of 913 registered nurses who were members of the Association of Women's Health, Obstetric, and Neonatal Nurses and identified labor and delivery comprised the sample as their clinical focus. Nurses who met the inclusion criteria were invited to participate in the survey via e-mail invitation. An online survey assessing workplace intimidation by providers while managing oxytocin inductions, as well as demographic information was completed. Participants reported past issues with intimidation that influenced how they administered oxytocin. Nurses reported that past experiences with intimidation influenced their care and that they had been involved with medication errors where intimidation played a role. Organizational factors perceived supportive management, presence of an organizational code of conduct, and environment where collaboration was encouraged were associated with decreased reports of intimidation. PMID:26505847

  18. Developmental Perspectives on Oxytocin and Vasopressin

    PubMed Central

    Hammock, Elizabeth A D

    2015-01-01

    The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life. PMID:24863032

  19. Oxytocin Protects Hippocampal Memory and Plasticity from Uncontrollable Stress

    PubMed Central

    Lee, Sun-Young; Park, Seong-Hae; Chung, ChiHye; Kim, Jeansok J.; Choi, Se-Young; Han, Jung-Soo

    2015-01-01

    The hippocampus is vulnerable to uncontrollable stress and is enriched with oxytocin receptors, but their interactive influences on hippocampal functioning are unknown. This study aimed to determine the effects of intranasal oxytocin administration on stress-induced alterations in synaptic plasticity and spatial memory in male rats. While vehicle-administered stressed rats showed impairment in long-term potentiation, enhancement in long-term depression, and weakened spatial memory, these changes were not observed in oxytocin-administered stressed rats. To reveal the potential signaling mechanism mediating these effects, levels of phosphorylated extracellular signal-regulated kinases (pERK) in the hippocampus was examined. Western blotting showed that oxytocin treatment blocked stress-induced alterations of pERK. Additionally, the oxytocin receptor antagonist L-368,899 inhibited the oxytocin’s protective effects on hippocampal memory to stress. Thus, intranasal administration of oxytocin reduced stress effects on hippocampal synaptic plasticity and memory in rats via acting on oxytocin receptors and regulating ERK activity. This study suggests that exogenous oxytocin may be a therapeutically effective means to counter the detrimental neurocognitive effects of stress. PMID:26688325

  20. Evolution of oxytocin pathways in the brain of vertebrates

    PubMed Central

    Knobloch, H. Sophie; Grinevich, Valery

    2014-01-01

    The central oxytocin system transformed tremendously during the evolution, thereby adapting to the expanding properties of species. In more basal vertebrates (paraphyletic taxon Anamnia, which includes agnathans, fish and amphibians), magnocellular neurosecretory neurons producing homologs of oxytocin reside in the wall of the third ventricle of the hypothalamus composing a single hypothalamic structure, the preoptic nucleus. This nucleus further diverged in advanced vertebrates (monophyletic taxon Amniota, which includes reptiles, birds, and mammals) into the paraventricular and supraoptic nuclei with accessory nuclei (AN) between them. The individual magnocellular neurons underwent a process of transformation from primitive uni- or bipolar neurons into highly differentiated neurons. Due to these microanatomical and cytological changes, the ancient release modes of oxytocin into the cerebrospinal fluid were largely replaced by vascular release. However, the most fascinating feature of the progressive transformations of the oxytocin system has been the expansion of oxytocin axonal projections to forebrain regions. In the present review we provide a background on these evolutionary advancements. Furthermore, we draw attention to the non-synaptic axonal release in small and defined brain regions with the aim to clearly distinguish this way of oxytocin action from the classical synaptic transmission on one side and from dendritic release followed by a global diffusion on the other side. Finally, we will summarize the effects of oxytocin and its homologs on pro-social reproductive behaviors in representatives of the phylogenetic tree and will propose anatomically plausible pathways of oxytocin release contributing to these behaviors in basal vertebrates and amniots. PMID:24592219

  1. Maternal oxytocin response predicts mother-to-infant gaze

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The neuropeptide oxytocin is importantly implicated in the emergence and maintenance of maternal behavior that forms the basis of the mother–infant bond. However, no research has yet examined the specific association between maternal oxytocin and maternal gaze, a key modality through which the mothe...

  2. Hypothalamic oxytocin mediates social buffering of the stress response

    PubMed Central

    Smith, Adam S.; Wang, Zuoxin

    2013-01-01

    Background While stressful life events can enhance the risk of mental disorders, positive social interactions can propagate good mental health and normal behavioral routines. Still, the neural systems that promote these benefits are undetermined. Oxytocin is a hormone involved in social behavior and stress; thus, we focus on the impact that social buffering has on the stress response and the governing effects of oxytocin. Methods Female prairie voles (Microtus ochrogaster) were exposed to 1 hr immobilization stress then recovered alone or with their male partner to characterize the effect of social contact on the behavioral, physiological, and neuroendocrine stress response. In addition, we treated immobilized females recovering alone with oxytocin, or vehicle, and females recovering with their male partner with a selective oxytocin receptor antagonist, or vehicle. Group sizes varied from 6 to 8 voles (n = 98 total). Results We found that 1 hr immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in females recovering alone, but not the females recovering with their male partner. This social buffering by the male partner on biobehavioral responses to stress was accompanied by increased oxytocin release in the paraventricular nucleus (PVN) of the hypothalamus. Intra-PVN oxytocin injections reduced behavioral and corticosterone responses to immobilization whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering. Conclusions Together, our data demonstrate that PVN oxytocin mediates the social buffering effects on the stress response, and thus may be a target for treatment of stress-related disorders. PMID:24183103

  3. Intranasal administration of oxytocin increases human aggressive behavior.

    PubMed

    Ne'eman, R; Perach-Barzilay, N; Fischer-Shofty, M; Atias, A; Shamay-Tsoory, S G

    2016-04-01

    Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naïve to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. PMID:26862988

  4. Using plan analysis in psychotherapeutic case formulation of borderline personality disorder.

    PubMed

    Berthoud, Laurent; Kramer, Ueli; de Roten, Yves; Despland, Jean-Nicolas; Caspar, Franz

    2013-01-01

    A comprehensive understanding of the patient's problems is essential for a constructive therapeutic behaviour, especially in borderline personality disorder (BPD) where difficult interpersonal patterns are persistent. In these circumstances, the use of an integrative case formulation approach such as Plan Analysis, developed by K. Grawe and F. Caspar, can be of help for therapy planning. The focus here is on instrumental relations between behaviours and the hypothetical Plans and motives 'behind' those behaviours. The present qualitative study aimed at setting a prototypical Plan structure for n = 15 patients presenting a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of BPD using Plan Analysis. The first psychotherapeutic session of every outpatient was video-taped and evaluated according to the Plan Analysis procedure. Inter-rater reliability was established between two independent raters and was considered sufficient. The detailed prototypical Plan structure of BPD showed two main tendencies: first, the important presence of support-seeking among these patients and second, the will to be in control and to protect oneself. This study confirms the existence of several core similarities in the functioning of patients with BPD. These findings are in line with earlier studies and expand the latter with the aim of contributing to the understanding of BPD psychopathology. Clinical implications are discussed. PMID:21882297

  5. Thermoelastic Formulation of Stiffened, Unsymmetric Composite Panels for Finite Element Analysis of High Speed Aircraft

    NASA Technical Reports Server (NTRS)

    Collier, Craig S.

    2004-01-01

    An emerging technology need for capturing 3-D panel thermoelastic response with 2-D planar finite element models (FEMs) is aided with an equivalent plate stiffness and thermal coefficient formulation. The formulation is general and applies to all panel concepts. Included with the formulation is the ability to provide membrane-bending coupling of unsymmetric sections and calculation of all thermal expansion and bending responses from in-plane and through-the-thickness temperature gradients. Thermal residual strains for both the laminates and plies are included. The general formulation is defined and then applied to a hat-shaped, corrugated stiffened panel. Additional formulations are presented where required to include all of the hat's unique characteristics. Each formulation is validated independently with 3-D FEA.

  6. Oxytocin and Social Cognition in Affective and Psychotic Disorders

    PubMed Central

    Perez-Rodriguez, M. Mercedes; Mahon, Katie; Russo, Manuela; Ungar, Allison K.; Burdick, Katherine E.

    2014-01-01

    Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. PMID:25153535

  7. Oxytocin – A Multifunctional Analgesic for Chronic Deep Tissue Pain

    PubMed Central

    Goodin, Burel R.; Ness, Timothy J.; Robbins, Meredith T.

    2014-01-01

    The treatment of chronic pain arising from deep tissues is currently inadequate and there is need for new pharmacological agents to provide analgesia. The endogenous paracrine hormone/neurotransmitter oxytocin is intimately involved in the modulation of multiple physiological and psychological functions. Recent experiments have given clear evidence for a role of oxytocin in the modulation of nociception. The present article reviews the existent human and basic science data related to the direct and indirect effects of oxytocin on pain. Due to its analgesic, anxiolytic, antidepressant and other central nervous system effects, there is strong evidence that oxytocin and other drugs acting through the oxytocin receptor could act as multifunctional analgesics with unique therapeutic value. PMID:25345612

  8. Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Currently few evidence based interventions are available for the prevention of PTSD within the first weeks after trauma. Increased risk for PTSD development is associated with dysregulated fear and stress responses prior to and shortly after trauma, as well as with a lack of perceived social support early after trauma. Oxytocin is a potent regulator of these processes. Therefore, we propose that oxytocin may be important in reducing adverse consequences of trauma. The ‘BONDS’ study is conducted in order to assess the efficacy of an early intervention with intranasal oxytocin for the prevention of PTSD. Methods/Design In this multicenter double-blind randomized placebo-controlled trial we will recruit 220 Emergency Department patients at increased risk of PTSD. Trauma-exposed patients are screened for increased PTSD risk with questionnaires assessing peri-traumatic distress and acute PTSD symptoms within 7 days after trauma. Baseline PTSD symptom severity scores and neuroendocrine and psychophysiological measures will be collected within 10 days after trauma. Participants will be randomized to 7.5 days of intranasal oxytocin (40 IU) or placebo twice a day. Follow-up measurements at 1.5, 3 and 6 months post-trauma are collected to assess PTSD symptom severity (the primary outcome measure). Other measures of symptoms of psychopathology, and neuroendocrine and psychophysiological disorders are secondary outcome measures. Discussion We hypothesize that intranasal oxytocin administered early after trauma is an effective pharmacological strategy to prevent PTSD in individuals at increased risk, which is both safe and easily applicable. Interindividual and contextual factors that may influence the effects of oxytocin treatment will be considered in the analysis of the results. Trial registration Netherlands Trial Registry: NTR3190. PMID:24679046

  9. REVIEW: Oxytocin: Crossing the bridge between basic science and pharmacotherapy.

    PubMed

    Viero, Cedric; Shibuya, Izumi; Kitamura, Naoki; Verkhratsky, Alexei; Fujihara, Hiroaki; Katoh, Akiko; Ueta, Yoichi; Zingg, Hans H; Chvatal, Alexandr; Sykova, Eva; Dayanithi, Govindan

    2010-10-01

    Is oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein-coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo-pituitary-adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca²(+) in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy. PMID:20626426

  10. A hexahedron element formulation with a new multi-resolution analysis

    NASA Astrophysics Data System (ADS)

    Xia, YiMing; Chen, ShaoLin

    2015-01-01

    A multiresolution hexahedron element is presented with a new multiresolution analysis (MRA) framework. The MRA framework is formulated out of a mutually nesting displacement subspace sequence, whose basis functions are constructed of scaling and shifting on element domain of a basic node shape function. The basic node shape function is constructed from shifting to other seven quadrants around a specific node of a basic isoparametric element in one quadrant and joining the corresponding node shape functions of eight elements at the specific node. The MRA endows the proposed element with the resolution level (RL) to adjust structural analysis accuracy. As a result, the traditional 8-node hexahedron element is a monoresolution one and also a special case of the proposed element. The meshing for the monoresolution finite element model is based on the empiricism while the RL adjusting for the multiresolution is laid on the solid mathematical basis. The simplicity and clarity of shape function construction with the Kronecker delta property and the rational MRA enable the proposed element method to be more rational, easier and efficient in its implementation than the conventional mono-resolution solid element method or other MRA methods. The multiresolution hexahedron element method is more adapted to dealing with the accurate computation of structural problems.

  11. Demonstration of emulator-based Bayesian calibration of safety analysis codes: Theory and formulation

    SciTech Connect

    Yurko, Joseph P.; Buongiorno, Jacopo; Youngblood, Robert

    2015-05-28

    System codes for simulation of safety performance of nuclear plants may contain parameters whose values are not known very accurately. New information from tests or operating experience is incorporated into safety codes by a process known as calibration, which reduces uncertainty in the output of the code and thereby improves its support for decision-making. The work reported here implements several improvements on classic calibration techniques afforded by modern analysis techniques. The key innovation has come from development of code surrogate model (or code emulator) construction and prediction algorithms. Use of a fast emulator makes the calibration processes used here with Markov Chain Monte Carlo (MCMC) sampling feasible. This study uses Gaussian Process (GP) based emulators, which have been used previously to emulate computer codes in the nuclear field. The present work describes the formulation of an emulator that incorporates GPs into a factor analysis-type or pattern recognition-type model. This “function factorization” Gaussian Process (FFGP) model allows overcoming limitations present in standard GP emulators, thereby improving both accuracy and speed of the emulator-based calibration process. Calibration of a friction-factor example using a Method of Manufactured Solution is performed to illustrate key properties of the FFGP based process.

  12. Demonstration of emulator-based Bayesian calibration of safety analysis codes: Theory and formulation

    DOE PAGESBeta

    Yurko, Joseph P.; Buongiorno, Jacopo; Youngblood, Robert

    2015-05-28

    System codes for simulation of safety performance of nuclear plants may contain parameters whose values are not known very accurately. New information from tests or operating experience is incorporated into safety codes by a process known as calibration, which reduces uncertainty in the output of the code and thereby improves its support for decision-making. The work reported here implements several improvements on classic calibration techniques afforded by modern analysis techniques. The key innovation has come from development of code surrogate model (or code emulator) construction and prediction algorithms. Use of a fast emulator makes the calibration processes used here withmore » Markov Chain Monte Carlo (MCMC) sampling feasible. This study uses Gaussian Process (GP) based emulators, which have been used previously to emulate computer codes in the nuclear field. The present work describes the formulation of an emulator that incorporates GPs into a factor analysis-type or pattern recognition-type model. This “function factorization” Gaussian Process (FFGP) model allows overcoming limitations present in standard GP emulators, thereby improving both accuracy and speed of the emulator-based calibration process. Calibration of a friction-factor example using a Method of Manufactured Solution is performed to illustrate key properties of the FFGP based process.« less

  13. Three-dimensional Finite Element Formulation and Scalable Domain Decomposition for High Fidelity Rotor Dynamic Analysis

    NASA Technical Reports Server (NTRS)

    Datta, Anubhav; Johnson, Wayne R.

    2009-01-01

    This paper has two objectives. The first objective is to formulate a 3-dimensional Finite Element Model for the dynamic analysis of helicopter rotor blades. The second objective is to implement and analyze a dual-primal iterative substructuring based Krylov solver, that is parallel and scalable, for the solution of the 3-D FEM analysis. The numerical and parallel scalability of the solver is studied using two prototype problems - one for ideal hover (symmetric) and one for a transient forward flight (non-symmetric) - both carried out on up to 48 processors. In both hover and forward flight conditions, a perfect linear speed-up is observed, for a given problem size, up to the point of substructure optimality. Substructure optimality and the linear parallel speed-up range are both shown to depend on the problem size as well as on the selection of the coarse problem. With a larger problem size, linear speed-up is restored up to the new substructure optimality. The solver also scales with problem size - even though this conclusion is premature given the small prototype grids considered in this study.

  14. A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain.

    PubMed

    Baskin, Denis G; Kim, Francis; Gelling, Richard W; Russell, Brian J; Schwartz, Michael W; Morton, Gregory J; Simhan, Hyagriv N; Moralejo, Daniel H; Blevins, James E

    2010-09-01

    Evidence suggests that release of oxytocin in the nucleus tractus solitarius (NTS) of the hindbrain from descending projections that originate in the paraventricular nucleus can inhibit food intake by amplifying the satiety response to cholecystokinin (CCK). To further evaluate this mechanism in rats, we used a novel cytotoxin, saporin conjugated to oxytocin (OXY-SAP), a compound designed to destroy cells that express oxytocin receptors (OXYr). OXY-SAP was injected directly into the NTS to lesion neurons that express OXYr and that are implicated in potentiating CCK's satiety effects. The control consisted of injection of saporin conjugated to a nonsense peptide. We found that OXY-SAP was cytotoxic to human uterine smooth muscle cells in vitro, demonstrating that OXY-SAP can lesion cells that express OXYr. Using laser capture microdissection and real-time quantitative PCR, we demonstrated that OXYr mRNA levels were reduced in the NTS after OXY-SAP administration. Moreover, we found that OXY-SAP attenuated the efficacy of CCK-8 to reduce food intake and blocked the actions of an OXYr antagonist to stimulate food intake. The findings suggest that OXY-SAP is an effective neurotoxin for in vivo elimination of cells that express OXYr and is potentially useful for studies to analyze central nervous system mechanisms that involve the action of oxytocin on food intake and other physiological processes. PMID:20610562

  15. Yeast leavened banana-bread: formulation, processing, color and texture analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Banana powder (BP) was added to Hard Red Spring Wheat flour (HRSW) intended for yeast-leavened bread formulation. Five different formulations containing 10, 15, 20, 25, and 30% BP were prepared with varying amounts of base flour, while vital gluten was maintained at 25% in all blends. Based on the...

  16. Low oxytocin and melatonin levels and their possible role in the diagnosis and prognosis in Iraqi autistic children

    PubMed Central

    Abdulamir, Haidar A.; Abdul-Rasheed, Omar F.; Abdulghani, Emad A.

    2016-01-01

    Objectives: To test the possible association between oxytocin and melatonin levels with the severity of social and cognitive dysfunctions, and to study the correlation between these parameters in children with autism. Methods: A case-control study was carried out in the Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq. The study was performed on 60 male autistic patients recruited from the Pediatric Department of Al-Sader General Hospital, Baghdad, Iraq between November 2014 and April 2015. The levels of oxytocin and melatonin were measured in the serum of these autistic male patients, and categorized as mild, moderate, and severe (20 patients each), and was compared with 26 age- and gender-matched control subjects. Results: The data indicated that the levels of oxytocin (44.72 ± 36.1 µIU/mL) and melatonin in patients (23.08 ± 10.41 pg/mL) were significantly lower (p<0.05) than that of age-matched (102.1 ± 34.31 µIU/mL) and gender-matched controls (53.05 ± 38.38 pg/mL). These parameters were remarkably associated with the severity of the disease that was indicated by the significant decrease in the levels of oxytocin (47 ± 25.47 µIU/mL) and melatonin in moderate (20 ± 6.14 pg/mL), and patients with severe oxytocin (27.92 ± 10.23 µIU/mL) and patients with severe melatonin (21.69 ± 7.02 pg/mL) when compared with mild autistic patients with oxytocin (59.22 ± 27.32 µIU/mL) and melatonin (27.55 ± 14.71 pg/mL). These 2 parameters showed a significant positive correlation with each other in moderate (r=0.513; p=0.021), and severe patients (r=0.598; p=0.005). Conclusion: Receiver operating characteristic analysis revealed that oxytocin can be considered as a good diagnostic marker in severe autistic patients while melatonin can be considered as a good diagnostic marker in all autistic subgroups. This study proves the possibility of using oxytocin and melatonin in the diagnosis, and as markers of autism

  17. A methodology for formulating a minimal uncertainty model for robust control system design and analysis

    NASA Technical Reports Server (NTRS)

    Belcastro, Christine M.; Chang, B.-C.; Fischl, Robert

    1989-01-01

    In the design and analysis of robust control systems for uncertain plants, the technique of formulating what is termed an M-delta model has become widely accepted and applied in the robust control literature. The M represents the transfer function matrix M(s) of the nominal system, and delta represents an uncertainty matrix acting on M(s). The uncertainty can arise from various sources, such as structured uncertainty from parameter variations or multiple unstructured uncertainties from unmodeled dynamics and other neglected phenomena. In general, delta is a block diagonal matrix, and for real parameter variations the diagonal elements are real. As stated in the literature, this structure can always be formed for any linear interconnection of inputs, outputs, transfer functions, parameter variations, and perturbations. However, very little of the literature addresses methods for obtaining this structure, and none of this literature addresses a general methodology for obtaining a minimal M-delta model for a wide class of uncertainty. Since have a delta matrix of minimum order would improve the efficiency of structured singular value (or multivariable stability margin) computations, a method of obtaining a minimal M-delta model would be useful. A generalized method of obtaining a minimal M-delta structure for systems with real parameter variations is given.

  18. Quantitative HPLC Analysis of an Analgesic/Caffeine Formulation: Determination of Caffeine

    NASA Astrophysics Data System (ADS)

    Ferguson, Glenda K.

    1998-04-01

    A modern high performance liquid chromatography (HPLC) laboratory experiment which entails the separation of acetaminophen, aspirin, and caffeine and the quantitative assay of caffeine in commercial mixtures of these compounds has been developed. Our HPLC protocol resolves these compounds in only three minutes with a straightforward chromatographic apparatus which consists of a C-18 column, an isocratic mobile phase, UV detection at 254 nm, and an integrator; an expensive, sophisticated system is not required. The separation is both repeatable and rapid. Moreover, the experiment can be completed in a single three-hour period. The experiment is appropriate for any chemistry student who has completed a minimum of one year of general chemistry and is ideal for an analytical or instrumental analysis course. The experiment detailed herein involves the determination of caffeine in Goody's Extra Strength Headache Powders, a commercially available medication which contains acetaminophen, aspirin, and caffeine as active ingredients. However, the separation scheme is not limited to this brand of medication nor is it limited to caffeine as the analyte. With only minor procedural modifications, students can simultaneously quantitate all of these compounds in a commercial mixture. In our procedure, students prepare a series of four caffeine standard solutions as well as a solution from a pharmaceutical analgesic/caffeine mixture, chromatographically analyze each solution in quadruplicate, and plot relative average caffeine standard peak area versus concentration. From the mathematical relationship that results, the concentration of caffeine in the commercial formulation is obtained. Finally, the absolute standard deviation of the mean concentration is calculated.

  19. Is Oxytocin Application for Autism Spectrum Disorder Evidence-Based?

    PubMed Central

    Lee, Seung Yup; Lee, Ah Rah; Hwangbo, Ram; Han, Juhee; Hong, Minha

    2015-01-01

    Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD. PMID:26713079

  20. Oxytocin Reduces Reward-Driven Food Intake in Humans

    PubMed Central

    Ott, Volker; Finlayson, Graham; Lehnert, Hendrik; Heitmann, Birte; Heinrichs, Markus; Born, Jan; Hallschmid, Manfred

    2013-01-01

    Experiments in animals suggest that the neuropeptide oxytocin acts as an anorexigenic signal in the central nervous control of food intake. In humans, however, research has almost exclusively focused on the involvement of oxytocin in the regulation of social behavior. We investigated the effect of intranasal oxytocin on ingestion and metabolic function in healthy men. Food intake in the fasted state was examined 45 min after neuropeptide administration, followed by the assessment of olfaction and reward-driven snack intake in the absence of hunger. Energy expenditure was registered by indirect calorimetry, and blood was repeatedly sampled to determine concentrations of blood glucose and hormones. Oxytocin markedly reduced snack consumption, restraining, in particular, the intake of chocolate cookies by 25%. Oxytocin, moreover, attenuated basal and postprandial levels of adrenocorticotropic hormone and cortisol and curbed the meal-related rise in plasma glucose. Energy expenditure and hunger-driven food intake as well as olfactory function were not affected. Our results indicate that oxytocin, beyond its role in social bonding, regulates nonhomeostatic, reward-related energy intake, hypothalamic-pituitary-adrenal axis activity, and the glucoregulatory response to food intake in humans. These effects can be assumed to converge with the psychosocial function of oxytocin and imply possible applications in the treatment of metabolic disorders. PMID:23835346

  1. Synthetic oxytocin: looking beyond the benefits.

    PubMed

    Wickham, Sara

    2015-01-01

    While the notion of drug abuse tends to be applied more to substances used outside of medical settings, there is increased concern that synthetic oxytocin is being overused in maternity care settings. This article presents an overview of some of the issues that have been raised within this area, including the risks that have been cited by recent research, social scientists and childbirth commentators, the concerns that are being anecdotally discussed by midwives and, even more importantly, the experiences of women themselves. PMID:26310092

  2. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    ERIC Educational Resources Information Center

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  3. Proposed powered explicit guidance thrust integrals derivation/implementation. Mission planning, mission analysis and software formulation

    NASA Technical Reports Server (NTRS)

    Jaggers, R. F.

    1976-01-01

    A new exoatmospheric, powered explicit guidance (PEG) thrust integral formulation and a simple method of implementation are presented. The new thrust integral formulation is significantly simpler than that currently used in PEG. Preliminary estimates indicate a computer storage savings of 220 words, which is approximately 10 percent of the current PEG ascent program. Alternate methods of implementation that could produce even more savings are noted.

  4. Oxytocin and the augmentation of labor : Human and medical perspectives.

    PubMed

    Curtis, P

    1993-12-01

    At least a third of the women giving birth in the United States receive intravenous oxytocin for the induction and augmentation of labor. The problem of inactive or ineffective labor remains a major challenge for birth attendants, midwives, and physicians who practice obstetrics. Before the discovery of oxytocin, traditional approaches to augmentation ranged from magical and folk interventions to extensive bloodletting. Despite its wide use the effectiveness of oxytocin augmentation has not been well studied, and current research raises new questions about its effect on the brain. PMID:24214403

  5. A Double-Blind Randomized Controlled Trial of Oxytocin Nasal Spray and Social Cognition Training for Young People With Early Psychosis

    PubMed Central

    Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B.; Hickie, Ian B.; Scott, Elizabeth M.; Naismith, Sharon L.; Moore, Loretta; Alvares, Gail A.; Redoblado Hodge, Marie Antoinette; Guastella, Adam J.

    2015-01-01

    Social-cognitive deficits contribute to poor functional outcomes in early psychosis; however, no effective pharmacological treatments exist for these problems. This study was the first to investigate the efficacy of an extended treatment of oxytocin nasal spray combined with social cognition training (SCT) to improve social cognition, clinical symptoms, and social functioning in early psychosis. In a double-blind, randomized, placebo-controlled, between-subjects trial, 52 individuals (aged 16–35 years) diagnosed with an early psychosis schizophrenia-spectrum illness were recruited. Participants received oxytocin (24 International Units) or placebo nasal spray twice-daily for 6 weeks, combined with group SCT (2 × 1 hour weekly sessions for 6 weeks). An additional dose of oxytocin was administered before each weekly session. Assessments were conducted at baseline, post-treatment, and at 3-month follow-up. Primary outcomes included the Reading the Mind in the Eyes Test, the Scale for the Assessment of Positive and Negative Symptoms, and the Social Functioning Scale. Secondary outcomes included self-report and behavioral assessments of social cognition, symptom severity, and social functioning. Results showed that on all primary and secondary outcomes, there was no benefit of oxytocin nasal spray treatment in comparison to placebo. Exploratory post hoc analysis suggested that increased use of nasal spray was, however, associated with reductions in negative symptoms in the oxytocin condition only. This study represents the first evaluation of oxytocin treatment for early psychosis. Although results suggest no benefit of oxytocin treatment, results also highlight an urgent need to consider nasal spray delivery and dose-related variables for future clinical trials. PMID:24962607

  6. BEYOND LABOR: THE ROLE OF NATURAL AND SYNTHETIC OXYTOCIN IN THE TRANSITION TO MOTHERHOOD

    PubMed Central

    Bell, Aleeca F.; Erickson, Elise N.; Carter, C. Sue

    2013-01-01

    Endogenous oxytocin is a key component in the transition to motherhood affecting molecular pathways that buffer stress reactivity, support positive mood, and regulate healthy mothering behaviors (including lactation). Synthetic oxytocin is widely used throughout labor and postpartum care in modern obstetrics. Yet research on the implications beyond labor of maternal exposure to perinatal synthetic oxytocin is rare. In this article, we review oxytocin-related biological pathways and behaviors associated with the transition to motherhood, and evidence supporting the need for further research on potential effects of intrapartum oxytocin beyond labor. We include a primer on oxytocin at the molecular level. PMID:24472136

  7. The role of oxytocin in neuropsychiatric disorders.

    PubMed

    Marazziti, D; Catena Dell'osso, M

    2008-01-01

    Oxytocin (OT) is a neurohypophysial hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OT-like substances have been identified in all vertebrates, OT has been found only in mammals where it plays a major role in the onset and maintaining of behaviors which are typical of these animals, such as labour and lactation. Recently, several data have suggested the involvement of OT in the formation of infant attachment, maternal behavior, pair bonding and, more generally, in linking social signals with cognition, behaviors and reward. The aim of this paper was to review critically the role of OT in the regulation of different physiological functions and complex behaviors, as well as its possible involvement in the pathophysiology of some neuropsychiatric disorders. MEDLINE and PubMed (1972-2007) databases were searched for English language articles by using the following keywords: oxytocin, physiology, cognitive functions, attachment, psychopathology, psychiatric disorders. Papers were examined that addressed the following aspects of the OT system: synthesis and localization, receptors, physiology: In addition, latest findings showing abnormalities of OT and OT system in several neuropsychiatric disorders, including autism, obsessive-compulsive disorder, eating disorders, addiction, schizophrenia, post-traumatic stress disorder and Prader-Willy syndrome, will be also discussed together with the possible clinical use of OT or its analogues and/or antagonists. PMID:18336283

  8. Consistent formulation of solid dissipative effects in stability analysis of flow past a deformable solid

    NASA Astrophysics Data System (ADS)

    Giribabu, D.; Shankar, V.

    2016-07-01

    The linear stability of plane Couette flow past a deformable solid is analyzed in the creeping-flow limit with an objective towards elucidating the consequences of employing two widely different formulations for the dissipative stresses in the deformable solid. One of the formulations postulates that the dissipative stress is proportional to the strain-rate tensor based on the left Cauchy-Green tensor, while in the other the dissipative stress in the solid is proportional to the rate-of-deformation tensor. However, it is well known in continuum mechanics that the rate-of-deformation tensor obeys the fundamental principle of material-frame indifference while the strain-rate-tensor formulation does not and hence it is more appropriate to employ the rate-of-deformation tensor in the description of dissipative stresses in deformable solids. In this work we consider the specific context of stability of plane Couette flow past a deformable solid and demonstrate that the results concerning the stability of the system from both models differ drastically. In the rate-of-deformation formulation for the dissipative stress, there is a range of solid-fluid thickness ratios (between 1.21 and 1.46) wherein the system is always stable for nonzero values of solid viscosity, unlike the strain-rate-tensor formulation wherein the system is unstable at all values of solid thickness. Further, for a solid-fluid thickness ratio less than 1, incorporation of dissipative effects in the solid using the rate-of-deformation formulation shows that the flow is more unstable compared to a purely elastic neo-Hookean solid, while for strain-rate-tensor formulation the flow is stabilized with an increase in viscosity of the solid. Using the fundamentally correct dissipative stress formulation, we also address the stability of pressure-driven flow in a deformable channel, wherein previous work carried out for an elastic neo-Hookean solid has shown that only the short-wave instability (driven by the

  9. Modelling formulations using gene expression programming--a comparative analysis with artificial neural networks.

    PubMed

    Colbourn, E A; Roskilly, S J; Rowe, R C; York, P

    2011-10-01

    This study has investigated the utility and potential advantages of gene expression programming (GEP)--a new development in evolutionary computing for modelling data and automatically generating equations that describe the cause-and-effect relationships in a system--to four types of pharmaceutical formulation and compared the models with those generated by neural networks, a technique now widely used in the formulation development. Both methods were capable of discovering subtle and non-linear relationships within the data, with no requirement from the user to specify the functional forms that should be used. Although the neural networks rapidly developed models with higher values for the ANOVA R(2) these were black box and provided little insight into the key relationships. However, GEP, although significantly slower at developing models, generated relatively simple equations describing the relationships that could be interpreted directly. The results indicate that GEP can be considered an effective and efficient modelling technique for formulation data. PMID:21903163

  10. Oxytocin and the Biopsychology of Performance in Team Sports

    PubMed Central

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport. PMID:22997498

  11. Oxytocin and Social Cognitions in Schizophrenia: A Systematic Review.

    PubMed

    Bukovskaya, Oksana; Shmukler, Alexander

    2016-09-01

    Schizophrenia is a chronic multifactorial disorder. Over the last years, there has been a growing interest in cognitive deficits in schizophrenia, which is considered by many as the core abnormality of the disease. In the systematic review we focus on the social cognition and its correlation with the neuropeptide oxytocin, which is shown to be involved in the emotion recognizing processes, in the trust behavior and many other aspects of social functioning. The systematic review was performed in order to summarize the data on the liaison of oxytocin with the social cognition impairment in schizophrenia patients. Oxytocin is assumed to be a potential therapeutic agent for schizophrenia, with a special link to social cognitive functions. The oxytocinergic system is a promising neuromodulator of emotion recognition that may have the potential to normalize the social dysfunction seen in schizophrenia. Further studies are required to provide more data on the correlations between oxytocin and socialcognition as well as other schizophrenia symptoms. PMID:26689706

  12. Oxytocin binding by myoepithelial cell membranes from involuted mammary tissue.

    PubMed

    Ruberti, A; Olins, G M; Eakle, K A; Bremel, R D

    1983-04-29

    Oxytocin binding activity of myoepithelial cell membranes from mammary tissue was measured under a variety of different experimental conditions. Mammary tissue from non-lactating rats bound oxytocin with a Kd of 9.2 +/- 1.6 nM (+/- S.E.) and indicates that receptors are retained by the myoepithelial cells in a non-lactating state. Ovariectomy of non-lactating rats did not depress the binding activity of the membranes. Administration of the estrogenic compounds estradiol-17 beta and diethylstibestrol at doses which affect uterine weight and are known to increase uterine oxytocin binding did not influence the binding activity of the myoepithelial cells. This indicates that the oxytocin receptors of the mammary gland are not under the same endocrine control as the uterine receptors. PMID:6303330

  13. Oxytocin Increases Neurite Length and Expression of Cytoskeletal Proteins Associated with Neuronal Growth.

    PubMed

    Lestanova, Z; Bacova, Z; Kiss, A; Havranek, T; Strbak, V; Bakos, J

    2016-06-01

    Neuropeptide oxytocin acts as a growth and differentiation factor; however, its effects on neurite growth are poorly understood. The aims of the present study were (1) to evaluate time effects of oxytocin on expression of nestin and MAP2; (2) to measure the effect of oxytocin on gene expression of β-actin, vimentin, cofilin, and drebrin; and (3) to measure changes in neurite length and number in response to oxytocin/oxytocin receptor antagonist L-371,257. Exposure of SH-SY5Y cells to 1 μM oxytocin resulted in a significant increase in gene expression and protein levels of nestin after 12, 24, and 48 h. Oxytocin treatment induced no changes in gene expression of MAP2; however, a decrease of protein levels was observed in all time intervals. Gene expression of β-actin, vimentin, and drebrin increased in response to oxytocin. Oxytocin induced significant elongation of neurites after 12, 24, and 48 h. No change in neurite length was observed in the presence of the combination of retinoic acid and oxytocin receptor antagonist L-371,257. Oxytocin treatment for 12 h increased the number of neurites. Overall, the present data suggest that oxytocin contributes to the regulation of expression of cytoskeletal proteins associated with growth of neuronal cones and induces neurite elongation mediated by oxytocin receptors at least in certain types of neuronal cells. PMID:26474566

  14. Labor stimulation with oxytocin: effects on obstetrical and neonatal outcomes

    PubMed Central

    Hidalgo-Lopezosa, Pedro; Hidalgo-Maestre, María; Rodríguez-Borrego, María Aurora

    2016-01-01

    Abstract Objective: to evaluate the effects of labor stimulation with oxytocin on maternal and neonatal outcomes. Method: descriptive and analytical study with 338 women who gave birth at a tertiary hospital. Obstetric and neonatal variables were measured and compared in women submitted and non-submitted to stimulation with oxytocin. Statistics were performed using Chi-square test, Fisher exact test, Student t-test; and crude Odds Ratio with 95% confidence interval were calculated. A p < 0.05 was considered statistically significant. Results: stimulation with oxytocin increases the rates of cesarean sections, epidural anesthesia and intrapartum maternal fever in primiparous and multiparous women. It has also been associated with low pH values of umbilical cord blood and with a shorter duration of the first stage of labor in primiparous women. However, it did not affect the rates of 3rd and 4th degree perineal lacerations, episiotomies, advanced neonatal resuscitation, 5-minute Apgar scores and meconium. Conclusion: stimulation with oxytocin should not be used systematically, but only in specific cases. These findings provide further evidence to health professionals and midwives on the use of oxytocin during labor. Under normal conditions, women should be informed of the possible effects of labor stimulation with oxytocin. PMID:27463109

  15. Oxytocin, the peptide that bonds the sexes also divides them

    PubMed Central

    Gao, Shan; Becker, Benjamin; Luo, Lizhu; Geng, Yayuan; Zhao, Weihua; Yin, Yu; Hu, Jiehui; Gao, Zhao; Gong, Qiyong; Hurlemann, Rene; Yao, Dezhong; Kendrick, Keith M.

    2016-01-01

    Facilitation of social attraction and bonding by the evolutionarily conserved neuropeptide oxytocin is well-established in female mammals. However, accumulating behavioral evidence suggests that oxytocin may have evolved sex-specific functional roles in the domain of human social cognition. A critical question is how oxytocin differentially modulates neural processing of social information in men and women, leading to divergent behavioral responses. Here we show that intranasal oxytocin treatment produces sex- and valence-dependent increases in amygdala activation when women view individuals identified as praising others but in men those who criticize them. Women subsequently show increased liking for the faces of these individuals, whereas in men it is reduced. Thus, oxytocin may act differentially via the amygdala to enhance the salience of positive social attributes in women but negative ones in men. We hypothesize that oxytocin may have evolved different but complementary roles to help ensure successful reproduction by encouraging mothers to promote a prosocial rearing environment for offspring and fathers to protect against antisocial influences. PMID:27325780

  16. Oxytocin, the peptide that bonds the sexes also divides them.

    PubMed

    Gao, Shan; Becker, Benjamin; Luo, Lizhu; Geng, Yayuan; Zhao, Weihua; Yin, Yu; Hu, Jiehui; Gao, Zhao; Gong, Qiyong; Hurlemann, Rene; Yao, Dezhong; Kendrick, Keith M

    2016-07-01

    Facilitation of social attraction and bonding by the evolutionarily conserved neuropeptide oxytocin is well-established in female mammals. However, accumulating behavioral evidence suggests that oxytocin may have evolved sex-specific functional roles in the domain of human social cognition. A critical question is how oxytocin differentially modulates neural processing of social information in men and women, leading to divergent behavioral responses. Here we show that intranasal oxytocin treatment produces sex- and valence-dependent increases in amygdala activation when women view individuals identified as praising others but in men those who criticize them. Women subsequently show increased liking for the faces of these individuals, whereas in men it is reduced. Thus, oxytocin may act differentially via the amygdala to enhance the salience of positive social attributes in women but negative ones in men. We hypothesize that oxytocin may have evolved different but complementary roles to help ensure successful reproduction by encouraging mothers to promote a prosocial rearing environment for offspring and fathers to protect against antisocial influences. PMID:27325780

  17. Oxytocin induced oxidative stress in lactating Bubalis bubalis (Nili Ravi)

    PubMed Central

    2013-01-01

    Background Oxytocin has been reported for a wide range of adverse effects in different species of lactating animals. The present study was aimed to evaluate the adverse effects of oxytocin on biomarkers of oxidative stress in buffaloes. Lactating buffaloes (n = 40) were randomly selected from a commercial dairy farm located in the peri-urban area of district Faisalabad, Pakistan and divided into two equal groups viz. treatment and control groups, each containing 20 buffaloes. Buffaloes in treatment group were injected with oxytocin before each milking (morning and evening) for milk let down; whereas, animals in control group were milked naturally without oxytocin injection. Both the groups were assessed for oxidative stress biomarkers. Results Results showed significantly higher levels (P ≤ 0.05) of TOS, tHcy and ceruloplasmin oxidase activity in lactating buffaloes injected with oxytocin as compared to those of control group. On the other hand, serum levels of TAS, PON1 and arylesterase were significantly lower (P ≤ 0.05) in the buffaloes of treatment group. Conclusions Oxytocin injection in lactating buffaloes resulted in elevated oxidative stress by increasing the total homocysteine and ceruloplasmin oxidase activity and decreasing enzymatic activities of antioxidant enzymes including paraoxonase-1 and arylesterase; that might render the animals to poor productive and reproductive potential. PMID:23981231

  18. Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology

    PubMed Central

    Ait-Oudhia, Sihem; Mager, Donald E.; Straubinger, Robert M.

    2014-01-01

    Liposomal formulations of anticancer agents have been developed to prolong drug circulating lifetime, enhance anti-tumor efficacy by increasing tumor drug deposition, and reduce drug toxicity by avoiding critical normal tissues. Despite the clinical approval of numerous liposome-based chemotherapeutics, challenges remain in the development and clinical deployment of micro- and nano-particulate formulations, as well as combining these novel agents with conventional drugs and standard-of-care therapies. Factors requiring optimization include control of drug biodistribution, release rates of the encapsulated drug, and uptake by target cells. Quantitative mathematical modeling of formulation performance can provide an important tool for understanding drug transport, uptake, and disposition processes, as well as their role in therapeutic outcomes. This review identifies several relevant pharmacokinetic/pharmacodynamic models that incorporate key physical, biochemical, and physiological processes involved in delivery of oncology drugs by liposomal formulations. They capture observed data, lend insight into factors determining overall antitumor response, and in some cases, predict conditions for optimizing chemotherapy combinations that include nanoparticulate drug carriers. PMID:24647104

  19. Children and Databases: An Analysis of Data Entry and Query Formulation.

    ERIC Educational Resources Information Center

    Spavold, J.

    1989-01-01

    Describes study of 9- to 11-year-olds conducted in Great Britain that was designed to analyze the means by which elementary school children familiarized themselves with a large database. Types of error and frequency of occurrence are examined, query formulation is discussed, and the importance of keyboard skills is addressed. (nine references)…

  20. Analysis of ingredient functionality and formulation optimization of pasta supplemented with peanut flour.

    PubMed

    Howard, Brandy M; Hung, Yen-Con; McWatters, Kay

    2011-01-01

    The working peanut pasta formulation range determined from a previous study was used to determine the effects of varying ingredient quantities and processing conditions on the pasta's quality and consumer acceptance. The variables studied were percent peanut flour substituted for durum wheat flour (30%, 40%, and 50%), amount of carrageenan (2.4%, 2.65%, and 2.9%), and drying temperature (60, 74, and 88 °C) on the final cooked pasta quality. Properties measured include color, texture, moisture content, and cooking loss. A home-use sensory test was conducted to determine consumer preferences and the optimum range for variables studied. Color lightness values ranged from 43.53 to 65.02, decreasing (becoming darker) with increased peanut flour level and increased drying temperature. Maximum cutting force for cooked pasta ranged from 1.59 N to 3.22 N, with higher values only for pasta dried at 88 °C. Moisture content ranged from 57.35% to 69.38%, and values decreased as drying temperature increased. Cooking loss ranged from 5.14% to 7.99%, increasing with higher levels of peanut flour and decreasing with higher levels of carrageenan. When prepared with 30% peanut flour and dried at 60 °C, the pasta was lighter in color, higher in moisture, and softer in texture than the varieties dried at higher temperatures and made with higher levels of peanut flour. Response surface analysis of consumer test data revealed that the optimum peanut pasta should contain between 35% and 45% peanut flour and should be dried between 60 and 71 °C; however, the pasta with 30% peanut flour was also a popular sample in the "favorite" categories. Practical Application: Most non-gluten protein fortification studies in durum wheat pasta found decreased firmness of dry and cooked pasta, increased cooking loss, increased stickiness, and darker product color when compared to traditional pasta. Partially defatted peanut flour is a versatile food ingredient and has high protein content. Since the

  1. A comparative analysis of glove permeation resistance to paint stripping formulations.

    PubMed

    Stull, Jeffrey O; Thomas, Richard W; James, Lawrence E

    2002-01-01

    Although there is a wide variety of work gloves available to users of commercial paint stripping products, there are no published studies examining which type of gloves provide the best protection. To address this need, a multiphase study was undertaken to evaluate how several types of gloves resist multichemical-based paint stripping formulations. Due to the wide range of commercial paint stripping formulations available, seven categories of surrogate paint stripper formulations were created to evaluate glove performance initially. Twenty different glove types were identified for initial evaluation. Degradation resistance screening was carried out for each glove style and paint stripping formulation. Screening results were used to identify those glove styles least affected by the surrogate paint strippers. Those gloves were then evaluated for their resistance to permeation using continuous contact testing based on ASTM Test Method F 739. Glove styles showing extensive permeation with early breakthrough were then evaluated to see how they performed with only intermittent contact with the surrogate paint strippers using a modified form of ASTM Test Method F 1383. These results were used to select glove styles to be tested using commercially available paint stripping products. Gloves made of plastic laminate and butyl rubber were the most effective against the majority of paint strippers. More glove styles resisted permeation by N-methylpyrrolidone and dibasic ester-based paint strippers than conventional solvent products such as methylene chloride, methanol, isopropanol, acetone, and toluene. The study also found that decreased contact time caused relatively little change in permeation resistance and that the surrogate paint stripper data did not always accurately predict resistance to the commercial paint stripper formulations. PMID:11843429

  2. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    PubMed

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-01-01

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID:27552585

  3. A Heartfelt Response: Oxytocin Effects on Response to Social Stress in Men and Women

    PubMed Central

    Kubzansky, Laura D; Mendes, Wendy Berry; Appleton, Allison A.; Block, Jason; Adler, Gail K

    2012-01-01

    Background Animal research indicates that oxytocin is involved in social behavior, stress regulation, and positive physiologic adaptation. This study examines whether oxytocin enhances adaptive responses to social stress and compares effects between men and women. Methods Hypotheses were tested with a placebo-controlled, double-blind experiment. Social stress was induced. Changes in cardiovascular reactivity, affect, and behavior were assessed. Results Participants given oxytocin, relative to placebo, responded to social stress with a challenge orientation characterized by a benign pattern of cardiovascular reactivity. Gender differences emerged. Men given oxytocin reported less negative affect and had greater vagal rebound, while women given oxytocin reported more anger and had better math performance following social stress. Discussion Findings indicate oxytocin stimulates an approach-oriented cardiovascular profile during social stress, suggesting mechanisms by which oxytocin might improve physical health. However, before considering oxytocin as therapeutic or uniformly enhancing health, greater understanding of possible gender differences in effects is needed. PMID:22387929

  4. Oxytocin Treatment, Circuitry, and Autism: A Critical Review of the Literature Placing Oxytocin Into the Autism Context.

    PubMed

    Guastella, Adam J; Hickie, Ian B

    2016-02-01

    Observed impairment in reciprocal social interaction is a diagnostic hallmark of autism spectrum disorders. There is no effective medical treatment for these problems. Psychological treatments remain costly, time intensive, and developmentally sensitive for efficacy. In this review, we explore the potential of oxytocin-based therapies for social impairments in autism. Evidence shows that acute oxytocin administration improves numerous markers critical to the social circuitry underlying social deficits in autism. Oxytocin may optimize these circuits and enhance reward, motivation, and learning to improve therapeutic outcomes. Despite this, the current evidence of therapeutic benefit from extended oxytocin treatment remains very limited. We highlight complexity in crossing from the laboratory to the autism clinical setting in evaluation of this therapeutic. We discuss a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation. For the autism field, the therapeutic challenges will be resolved by a range of treatment strategies, including greater focus on specific interventions, such as oxytocin, that have a strong basis in the fundamental neurobiology of social behavior. More sophisticated and targeted clinical trials utilizing such approaches are now required, placing oxytocin into the autism context. PMID:26257243

  5. Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

    SciTech Connect

    Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J. )

    1989-01-01

    In transverse hippocampal slices from rat and guinea pig brains, the authors obtained unitary extracellular recordings from nonpyramidal neurones located in or near the stratum pyramidale in the CA1 field and in the transition region between the CA1 and the subiculum. In rats, these neurones responded to oxytocin at 50-1,000 nM by a reversible increase in firing rate. The oxytocin-induced excitation was suppressed by a synthetic structural analogue that acts as a potent, selective antioxytocic on peripheral receptors. Nonpyramidal neurones were also excited by carbachol at 0.5-10 {mu}M. The effect of this compound was postsynaptic and was blocked by the muscarinic antagonist atropine. In guinea pigs, by contrast, nonpyramidal neurones were unaffected by oxytocin, although they were excited by carbachol. Light microscopic autoradiography, carried out using a radioiodinated selective antioxytocic as a ligand, revealed labeling in the subiculum and in the CA1 area of the hippocampus of rats, whereas no oxytocin-binding sites were detected in the hippocampus of guinea pigs. The results indicate (i) that a hippocampal action of oxytocin is species-dependent and (ii) that a positive correlation exists between neuronal responsiveness to oxytocin and the presence in the hippocampus of high-affinity binding sites for this peptide.

  6. A multi-fidelity analysis selection method using a constrained discrete optimization formulation

    NASA Astrophysics Data System (ADS)

    Stults, Ian C.

    The purpose of this research is to develop a method for selecting the fidelity of contributing analyses in computer simulations. Model uncertainty is a significant component of result validity, yet it is neglected in most conceptual design studies. When it is considered, it is done so in only a limited fashion, and therefore brings the validity of selections made based on these results into question. Neglecting model uncertainty can potentially cause costly redesigns of concepts later in the design process or can even cause program cancellation. Rather than neglecting it, if one were to instead not only realize the model uncertainty in tools being used but also use this information to select the tools for a contributing analysis, studies could be conducted more efficiently and trust in results could be quantified. Methods for performing this are generally not rigorous or traceable, and in many cases the improvement and additional time spent performing enhanced calculations are washed out by less accurate calculations performed downstream. The intent of this research is to resolve this issue by providing a method which will minimize the amount of time spent conducting computer simulations while meeting accuracy and concept resolution requirements for results. In many conceptual design programs, only limited data is available for quantifying model uncertainty. Because of this data sparsity, traditional probabilistic means for quantifying uncertainty should be reconsidered. This research proposes to instead quantify model uncertainty using an evidence theory formulation (also referred to as Dempster-Shafer theory) in lieu of the traditional probabilistic approach. Specific weaknesses in using evidence theory for quantifying model uncertainty are identified and addressed for the purposes of the Fidelity Selection Problem. A series of experiments was conducted to address these weaknesses using n-dimensional optimization test functions. These experiments found that model

  7. Oxytocin-dependent consolation behavior in rodents

    PubMed Central

    Burkett, J. P.; Andari, E.; Johnson, Z. V.; Curry, D. C.; de Waal, F. B. M.; Young, L. J.

    2016-01-01

    Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human. PMID:26798013

  8. Oxytocin-dependent consolation behavior in rodents.

    PubMed

    Burkett, J P; Andari, E; Johnson, Z V; Curry, D C; de Waal, F B M; Young, L J

    2016-01-22

    Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human. PMID:26798013

  9. Analysis of protamine peptides in insulin pharmaceutical formulations by capillary electrophoresis.

    PubMed

    Lamalle, Caroline; Servais, Anne-Catherine; Demelenne, Alice; Crommen, Jacques; Fillet, Marianne

    2016-03-01

    Protamines are a group of highly basic peptides that are sometimes added to insulin formulations to prolong the pharmacological action. In this study, different methods were investigated to identify protamine in insulin formulations. Capillary electrophoresis in aqueous and non-aqueous media was tested to separate these peptides with very close amino acid sequences. Different buffers (phosphate or formate, both acidified) and various additives (principally negatively charged and neutral surfactants) were investigated to optimize peptide separation. Finally, a micellar electrokinetic capillary chromatography method using a capillary of 120 cm effective length and an aqueous background electrolyte made up of 100 mM phosphate buffer (pH 2) and 50 mM Thesit® gave the best results, providing the separation of the four major protamine peptides within 25 min. PMID:26829340

  10. Formulation and numerical analysis of nonisothermal multiphase flow in porous media

    SciTech Connect

    Martinez, M.J.

    1995-06-01

    A mathematical formulation is presented for describing the transport of air, water and energy through porous media. The development follows a continuum mechanics approach. The theory assumes the existence of various average macroscopic variables which describe the state of the system. Balance equations for mass and energy are formulated in terms of these macroscopic variables. The system is supplemented with constitutive equations relating fluxes to the state variables, and with transport property specifications. Specification of various mixing rules and thermodynamic relations completes the system of equations. A numerical simulation scheme, employing the method of lines, is described for one-dimensional flow. The numerical method is demonstrated on sample problems involving nonisothermal flow of air and water. The implementation is verified by comparison with existing numerical solutions.

  11. Oxytocin decreases sweet taste sensitivity in mice

    PubMed Central

    Sinclair, Michael S.; Perea-Martinez, Isabel; Abouyared, Marianne; St. John, Steven J.; Chaudhari, Nirupa

    2015-01-01

    Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10 mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300 mM), citric acid (20 mM), quinine (0.3 mM), saccharin (10 mM), and a mix of MSG and IMP (100 mM and 0.5 mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1 mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3 M sucrose, and overall shifted the sucrose concentration – behavioral response curves rightward (mean EC50saline = 0.362 M vs. EC50OXT = 0.466 M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. PMID:25554481

  12. Oxytocin and social affiliation in humans.

    PubMed

    Feldman, Ruth

    2012-03-01

    A conceptual model detailing the process of bio-behavioral synchrony between the online physiological and behavioral responses of attachment partners during social contact is presented as a theoretical and empirical framework for the study of affiliative bonds. Guided by an ethological behavior-based approach, we suggest that micro-level social behaviors in the gaze, vocal, affective, and touch modalities are dynamically integrated with online physiological processes and hormonal response to create dyad-specific affiliations. Studies across multiple attachments throughout life are presented and demonstrate that the extended oxytocin (OT) system provides the neurohormonal substrate for parental, romantic, and filial attachment in humans; that the three prototypes of affiliation are expressed in similar constellations of social behavior; and that OT is stable over time within individuals, is mutually-influencing among partners, and that mechanisms of cross-generation and inter-couple transmission relate to coordinated social behavior. Research showing links between peripheral and genetic markers of OT with concurrent parenting and memories of parental care; between administration of OT to parent and infant's physiological readiness for social engagement; and between neuropeptides and the online synchrony of maternal and paternal brain response in social-cognitive and empathy networks support the hypothesis that human attachment develops within the matrix of biological attunement and close behavioral synchrony. The findings have conceptual implications for the study of inter-subjectivity as well as translational implications for the treatment of social disorders originating in early childhood, such as autism spectrum disorders, or those associated with disruptions to early bonding, such as postpartum depression or child abuse and neglect. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID:22285934

  13. Oxytocin differentially affects sucrose taking and seeking in male and female rats.

    PubMed

    Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2015-04-15

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens. PMID:25647756

  14. Oxytocin Differentially Affects Sucrose Taking and Seeking in Male and Female Rats

    PubMed Central

    Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2015-01-01

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3 mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens. PMID:25647756

  15. Marketing Mix Formulation for Higher Education: An Integrated Analysis Employing Analytic Hierarchy Process, Cluster Analysis and Correspondence Analysis

    ERIC Educational Resources Information Center

    Ho, Hsuan-Fu; Hung, Chia-Chi

    2008-01-01

    Purpose: The purpose of this paper is to examine how a graduate institute at National Chiayi University (NCYU), by using a model that integrates analytic hierarchy process, cluster analysis and correspondence analysis, can develop effective marketing strategies. Design/methodology/approach: This is primarily a quantitative study aimed at…

  16. Performance Analysis and Design Synthesis (PADS) computer program. Volume 1: Formulation

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The program formulation for PADS computer program is presented. It can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general-purpose branched trajectory optimization program. In the former use, it has the Space Shuttle Synthesis Program as well as a simplified stage weight module for optimally sizing manned recoverable launch vehicles. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent; the second employs the method of quasilinearization, which requires a starting solution from the first trajectory module.

  17. An efficient formulation based on the Lagrangian method for contact-impact analysis of flexible multi-body system

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Liu, Jin-Yang; Hong, Jia-Zhen

    2016-04-01

    In this paper, an efficient formulation based on the Lagrangian method is presented to investigate the contact-impact problems of flexible multi-body systems. Generally, the penalty method and the Hertz contact law are the most commonly used methods in engineering applications. However, these methods are highly dependent on various non-physical parameters, which have great effects on the simulation results. Moreover, a tremendous number of degrees of freedom in the contact-impact problems will influence the numerical efficiency significantly. With the consideration of these two problems, a formulation combining the component mode synthesis method and the Lagrangian method is presented to investigate the contact-impact problems in flexible multi-body system numerically. Meanwhile, the finite element meshing laws of the contact bodies will be studied preliminarily. A numerical example with experimental verification will certify the reliability of the presented formulation in contact-impact analysis. Furthermore, a series of numerical investigations explain how great the influence of the finite element meshing has on the simulation results. Finally the limitations of the element size in different regions are summarized to satisfy both the accuracy and efficiency.

  18. Broadband Noise Prediction When Turbulence Simulation Is Available - Derivation of Formulation 2B and Its Statistical Analysis

    NASA Technical Reports Server (NTRS)

    Farassat, Fereidoun; Casper, Jay H.

    2012-01-01

    We show that a simple modification of Formulation 1 of Farassat results in a new analytic expression that is highly suitable for broadband noise prediction when extensive turbulence simulation is available. This result satisfies all the stringent requirements, such as permitting the use of the exact geometry and kinematics of the moving body, that we have set as our goal in the derivation of useful acoustic formulas for the prediction of rotating blade and airframe noise. We also derive a simple analytic expression for the autocorrelation of the acoustic pressure that is valid in the near and far fields. Our analysis is based on the time integral of the acoustic pressure that can easily be obtained at any resolution for any observer time interval and digitally analyzed for broadband noise prediction. We have named this result as Formulation 2B of Farassat. One significant consequence of Formulation 2B is the derivation of the acoustic velocity potential for the thickness and loading terms of the Ffowcs Williams-Hawkings (FW-H) equation. This will greatly enhance the usefulness of the Fast Scattering Code (FSC) by providing a high fidelity boundary condition input for scattering predictions.

  19. Formulation and Analysis of Compliant Grouted Waste Forms for SHINE Waste Streams

    SciTech Connect

    Ebert, William; Pereira, Candido; Heltemes, Thad A.; Youker, Amanda; Makarashvili, Vakhtang; Vandegrift, George F.

    2014-01-01

    Optional grouted waste forms were formulated for waste streams generated during the production of 99Mo to be compliant with low-level radioactive waste regulations. The amounts and dose rates of the various waste form materials that would be generated annually were estimated and used to determine the effects of various waste processing options, such as the of number irradiation cycles between uranium recovery operations, different combinations of waste streams, and removal of Pu, Cs, and Sr from waste streams for separate disposition (which is not evaluated in this report). These calculations indicate that Class C-compliant grouted waste forms can be produced for all waste streams. More frequent uranium recovery results in the generation of more chemical waste, but this is balanced by the fact that waste forms for those waste streams can accommodate higher waste loadings, such that similar amounts of grouted waste forms are required regardless of the recovery schedule. Similar amounts of grouted waste form are likewise needed for the individual and combined waste streams. Removing Pu, Cs, and Sr from waste streams lowers the waste form dose significantly at times beyond about 1 year after irradiation, which may benefit handling and transport. Although these calculations should be revised after experimentally optimizing the grout formulations and waste loadings, they provide initial guidance for process development.

  20. Assessment of formulation robustness for nano-crystalline suspensions using failure mode analysis or derisking approach.

    PubMed

    Nakach, Mostafa; Authelin, Jean-René; Voignier, Cecile; Tadros, Tharwat; Galet, Laurence; Chamayou, Alain

    2016-06-15

    The small particle size of nano-crystalline suspensions can be responsible for their physical instability during drug product preparation (downstream processing), storage and administration. For that purpose, the commercial formulation needs to be sufficiently robust to various triggering conditions, such as ionic strength, shear rate, wetting/dispersing agent desorption by dilution, temperature and pH variation. In our previous work we described a systematic approach to select the suitable wetting/dispersant agent for the stabilization of nano-crystalline suspension. In this paper, we described the assessment of the formulation robustness (stabilized using a mixture of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone (PVP) and) by measuring the rate of perikinetic (diffusion-controlled) and orthokinetic (shear-induced) aggregation as a function of ionic strength, temperature, pH and dilution. The results showed that, using the SDS/PVP system, the critical coagulation concentration is about five times higher than that observed in the literature for suspension colloidaly stable at high concentration. The nano-suspension was also found to be very stable at ambient temperature and at different pH conditions. Desorption test confirmed the high affinity between API and wetting/dispersing agent. However, the suspension undergoes aggregation at high temperature due to the desorption of the wetting/dispersing agent and disaggregation of SDS micelles. Furthermore, aggregation occurs at very high shear rate (orhokinetic aggregation) by overcoming the energy barrier responsible for colloidal stability of the system. PMID:27102992

  1. Formulation and in vitro absorption analysis of Rhizoma paridis steroidal saponins.

    PubMed

    Liu, Zhen; Wang, Jieyin; Gao, Wenyuan; Man, Shuli; Guo, Huimin; Zhang, Jingze; Liu, Changxiao

    2013-01-30

    Rhizoma paridis steroidal saponins (RPS) have been prepared and identified as the active compounds for antitumor activity in our previous study. However, the low oral bioavailability of the steroidal saponins restricted its using. In the present research, solid dispersion (SD) and phytosome (PHY) formulation of RPS were prepared, and the physicochemical parameters as well as the intestinal absorption in rat everted gut sac model were investigated. Seven agents were selected as the carriers of SD, and poloxamer 407 (P 407) was the most suitable one. SD reduced the particle size of saponins in the water solution, enhanced the solubility of the saponins by about 3.5 folds, and significantly improved the absorption transport of saponins from 48 to 104 μg in everted gut sac of the rat system. PHY significantly enhanced the hydrophilic of saponins but showed little effect on the absorption in small intestine. Jejunum and ileum part absorbed more absolute contents of total saponins than duodenum parts. Six saponins, the main contents of RPS, used as the index of comparing the three forms, were also further investigated in the physico-chemical properties and the absorption tests. n-Octanol/water partition coefficients of the six saponins ordered in RPS, SD and PHY were Chonglouoside H>Dioscin>Polyphyllin D>Gracillin>Paris-VII>Formosanin C. All the saponins possessed the higher absorptive characteristics in SD formulation. The absorption rate of diosgenyl saponins in intestine was more than the pennogenyl saponins. PMID:23107795

  2. Fingerprint analysis and synthetic adulterant search in Hedera helix formulations by capillary electrophoresis.

    PubMed

    Cianchino, V; Ortega, C; Acosta, G; Martínez, L D; Gomez, M R

    2007-04-01

    A high-performance capillary electrophoretic (CE) method has been developed for obtaining electropherograms of various extracts and the commercial formulation (fingerprints) of Hedera helix L used in Argentina as a cough's treatment. Also, a capillary zone electrophoresis (CZE) method was developed for the search, identification and determination of some possible adulterants. These likely adulterants are common synthetic drugs used in respiratory diseases (antitussive, decongestant and bronchodilator agents). Under optimum conditions, the analytes (ephedrine, codeine, diphenhydramine and constituents of H. helix formulations) were separated within less than 10 min in 20 mM sodium tetraborate buffer (pH 9.0). The present procedure was validated with respect to selectivity, linearity range, limits of detection (LOD) and quantification (LOQ), precision (repeatability and intermediate precision), solution stability and accuracy; the results obtained were satisfactory. Good linearity was obtained over two orders of magnitude and detection limits (S/N = 3) were better than 1.2 microg ml(-1) for all analytes. The CE methodology was successfully applied to the search and subsequent determination of ephedrine, codeine and diphenhydramine in H. helix extracts and its phytopharmaceutical products. PMID:17484280

  3. Effects of intranasal oxytocin on 'compassion focused imagery'.

    PubMed

    Rockliff, Helen; Karl, Anke; McEwan, Kirsten; Gilbert, Jean; Matos, Marcela; Gilbert, Paul

    2011-12-01

    This study explored the effects of oxytocin on Compassion Focused Imagery (CFI), that is, imagining another "mind" being deeply compassionate to oneself, and the interaction of these effects with self-criticism and feeling socially safe with others. Forty-four healthy participants (29 men and 15 women) completed self-report measures of self-criticism, attachment style, and social safeness before taking part in a double-blind randomized placebo controlled study. They attended two imagery sessions, receiving oxytocin in one and a placebo in the other. Positive affect was measured before and after each imagery session, and "imagery experience" was assessed after each session. Overall, oxytocin increased the ease of imagining compassionate qualities but there were important individual differences in how CFI was experienced. Participants higher in self-criticism, lower in self-reassurance, social safeness, and attachment security had less positive experiences of CFI under oxytocin than placebo, indicating that the effects of oxytocin on affiliation may depend on attachment and self-evaluative styles. PMID:21707149

  4. Does oxytocin affect mind-reading? A replication study.

    PubMed

    Radke, Sina; de Bruijn, Ellen R A

    2015-10-01

    One of the most well-known findings in human oxytocin research is its beneficial effect on "mind-reading", i.e., inferring others' mental states just from the eye region in the Reading the Mind in the Eyes Test (RMET). Previous studies have partially confirmed these improvements and have further shown that they depend both on baseline social-emotional abilities and on specific item characteristics such as difficulty. Following the original design of Domes et al. (2007), the aim of the current study was to replicate and extend previous findings by thoroughly investigating the impact of oxytocin administration on RMET performance. We tested for potential moderation effects involving item difficulty, valence, intensity, sex of poser as well as individual differences in trait empathy measured with the Empathy Quotient (EQ) for a general score and the Interpersonal Reactivity Index (IRI) for a multidimensional assessment of cognitive and emotional empathy. Oxytocin did not affect mind-reading, neither in general nor when considering specific item characteristics. An association between oxytocin-induced changes in RMET performance and emotional empathy (the empathic concern scale of the IRI) was evident, with individuals low in emotional empathy showing greater improvement after oxytocin administration compared to placebo. The reproducibility and variability of these and prior findings needs to be addressed in future experiments. As true effects may not replicate across different studies for various reasons, this should not discourage, but encourage further research. PMID:26142239

  5. Oxytocin increases the likeability of physically formidable men

    PubMed Central

    Mayer, Jennifer; Mussweiler, Thomas; Heinrichs, Markus

    2015-01-01

    Physical size and strength are associated with dominance and threat. The current study tested (i) whether men’s evaluations of male strangers would be negatively influenced by cues indicating physical formidability, and (ii) whether these evaluations would be influenced by oxytocin, a neuropeptide that mediates social behavior and reduces social anxiety. In a placebo-controlled double-blind design, we administered either oxytocin (24 I.U.) or placebo intranasally to 100 healthy males and assessed their responses to an image of either a physically formidable (strong) or physically non-formidable (weak) male peer. Whereas participants receiving placebo expressed dislike and avoidance of the strong male relative to the weak male, oxytocin selectively improved social evaluation of the strong male. These results provide first evidence that oxytocin regulates social evaluation of peers based on body features indicating strength and formidability. We discuss the possibility that oxytocin may promote the expansion of social networks by increasing openness toward potentially threatening individuals. PMID:25193946

  6. Endocannabinoid signaling mediates oxytocin-driven social reward.

    PubMed

    Wei, Don; Lee, DaYeon; Cox, Conor D; Karsten, Carley A; Peñagarikano, Olga; Geschwind, Daniel H; Gall, Christine M; Piomelli, Daniele

    2015-11-10

    Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions. PMID:26504214

  7. Endocannabinoid signaling mediates oxytocin-driven social reward

    PubMed Central

    Wei, Don; Lee, DaYeon; Cox, Conor D.; Karsten, Carley A.; Peñagarikano, Olga; Geschwind, Daniel H.; Gall, Christine M.; Piomelli, Daniele

    2015-01-01

    Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions. PMID:26504214

  8. The herding hormone: oxytocin stimulates in-group conformity.

    PubMed

    Stallen, Mirre; De Dreu, Carsten K W; Shalvi, Shaul; Smidts, Ale; Sanfey, Alan G

    2012-01-01

    People often conform to others with whom they associate. Surprisingly, however, little is known about the possible hormonal mechanisms that may underlie in-group conformity. Here, we examined whether conformity toward one's in-group is altered by oxytocin, a neuropeptide often implicated in social behavior. After administration of either oxytocin or a placebo, participants were asked to provide attractiveness ratings of unfamiliar visual stimuli. While viewing each stimulus, participants were shown ratings of that stimulus provided by both in-group and out-group members. Results demonstrated that on trials in which the ratings of the in-group and out-group were incongruent, the ratings of participants given oxytocin conformed to the ratings of their in-group but not of their out-group. Participants given a placebo did not show this in-group bias. These findings indicate that administration of oxytocin can influence subjective preferences, and they support the view that oxytocin's effects on social behavior are context dependent. PMID:22991128

  9. Exploring dissociation and oxytocin as pathways between trauma exposure and trauma-related hyperemesis gravidarum: a test-of-concept pilot.

    PubMed

    Seng, Julia; Miller, Janis; Sperlich, Mickey; van de Ven, Cosmas J M; Brown, Stephanie; Carter, C Sue; Liberzon, Israel

    2013-01-01

    Posttraumatic stress disorder (PTSD) is associated with gastrointestinal and genitourinary comorbidities. These map onto the somatization disorder symptoms in the Diagnostic and Statistical Manual of Mental Disorders ( American Psychiatric Association, 1994 ) and the dissociative (conversion) disorders symptoms in the International Classification of Diseases taxonomy ( World Health Organization, 2007 ). Hyperemesis gravidarum (HG) is one of these symptoms and a gastrointestinal comorbidity of PTSD occurring in pregnancy. It is an idiopathic condition defined as severe vomiting with dehydration, metabolic imbalance, wasting, and hospital care seeking. HG is more severe than the normative phenomenon of nausea and vomiting of pregnancy. This test-of-concept pilot (N = 25) explored the hypothesis that there is a trauma-related subtype of HG characterized by (a) high levels of dissociative symptoms and (b) altered plasma concentrations of oxytocin. This hypothesis is informed by a theory of posttraumatic oxytocin dysregulation that posits altered oxytocin function as a mechanism of gut smooth muscle peristalsis dysfunction. A 4-group analysis compared controls with nausea and vomiting of pregnancy (NV only) and cases with HG only, NV and PTSD, or HG and PTSD. Oxytocin was correlated with the nausea and vomiting symptom severity score (r = .464, p = .019) and with the dissociation symptom score (r = .570, p = .003). Women in the group with both PTSD and HG (the trauma-related HG subtype) had the highest levels of dissociation and the highest levels of oxytocin. A linear regression model indicated that the independent association of the trauma-related HG subtype with oxytocin level was mediated by high levels of dissociative symptoms. PMID:23282046

  10. The effect of a single oxytocin or carbetocin treatment on uterine contractility in early postpartum dairy cows.

    PubMed

    Bajcsy, Arpád Csaba; Szenci, Ottó; van der Weijden, Gijsbert C; Doornenbal, Arie; Maassen, Francesca; Bartyik, János; Taverne, Marcel A M

    2006-01-20

    The uterotonic characteristics and effectiveness of a single treatment with either oxytocin or carbetocin were quantified in early postpartum dairy cows after normal, uncomplicated calvings. Both the short-term (within 4 h), and the long-term effects (between 12 and 36 h) of the two treatments were compared. Between 14 and 16 h after parturition, 27 multiparous Holstein-Friesian dairy cows, without fetal membrane retention, were selected and divided into three groups. The first group (n = 9) was administered 50 IU oxytocin intramuscularly, the second group (n = 10) received 0.35 mg carbetocin, while animals of the third group (n = 8), serving as a control, were administered 5 mL saline solution. A transcervically introduced open tip catheter system was used for the non-invasive acquisition of the intrauterine pressure (IUP) recording. After digitalization, the signals were analyzed, using a specially adapted graphical software program. A significant short-term effect was found both in the oxytocin and carbetocin treated groups from the analysis of the contraction frequencies (FREQ) and of the total area under the curve (TAUC). After significant peaking during the first post-treatment hour, the values of the parameters for these two groups remained higher during the second hour, returning to the initial levels again during the third hour and reaching the level of the control group by the 12th hour. Mean amplitude (AMP), duration (DUR) and area under the curve (AUC) of pressure cycles were not significantly affected by any of the treatments. Although mean FREQ and TAUC significantly declined from the initial values to 12, 24 and 36 h in all groups, mean AMP and AUC in the oxytocin and carbetocin treated groups, and mean DUR only in the carbetocin treated group to 12 and 36 h, the long-term analysis revealed no significant treatment differences for any IUP parameters. Because treatment with either oxytocin, or carbetocin elicited similar uterotonic effects in healthy