Science.gov

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

    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.

  2. 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).

  3. A sniff of trust: meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group.

    PubMed

    Van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2012-03-01

    The neuropeptide oxytocin has a popular reputation of being the 'love' hormone. Here we test meta-analytically whether experiments with intranasal administration of oxytocin provide support for the proposed effects of oxytocin. Three psychological effects were subjected to meta-analysis: facial emotion recognition (13 effect sizes, N=408), in-group trust (8 effect sizes, N=317), and out-group trust (10 effect sizes; N=505). We found that intranasal oxytocin administration enhances the recognition of facial expressions of emotions, and that it elevates the level of in-group trust. The hypothesis that out-group trust is significantly decreased in the oxytocin condition was not supported. It is concluded that a sniff of oxytocin can change emotion perception and behavior in trusting relationships. PMID:21802859

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

    PubMed

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

    2014-08-01

    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 pro-social 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 1.5mg/kg), intranasal oxytocin (20IU or 40IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7pg/ml at approximately 90-120min, compared to 18.6pg/ml after placebo. Intranasal oxytocin (40IU, but not 20IU) increased plasma oxytocin levels to 48.0pg/ml, 30-60min 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.

  5. Oxytocin Injection

    MedlinePlus

    ... oxytocin, a hormone, to stimulate contractions of the uterus and smooth muscle tissue. The drug will be ... infection, eclampsia, cervical cancer, previous uterine surgery, prolapsed uterus, breech position, placenta previa, or other abnormal position ...

  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. 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

  8. 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

  9. Pitocin and autism: An analysis of oxytocin receptor desensitization in the fetus.

    PubMed

    Gottlieb, Mark M

    2016-02-01

    The risk of Pitocin as a cause of autism attributable to oxytocin receptor desensitization in the brain of the fetus is evaluated in terms of a mathematical model. A composite unit, D, for oxytocin receptor desensitization levels is established with the form ((IU-h)/ml)E-3, where IU is the international unit for oxytocin. The desensitization values for oxytocin receptor desensitization at a concentration of 10 nmol of oxytocin per liter for 3, 4.2 and 6h corresponding to 0%, 50% and 100% desensitization are calculated to be 15 D, 21 D, and 30 D, respectively. The permeability of the blood-brain barrier in the fetus to oxytocin is discussed, and the upper limit of the concentration of Pitocin in the placenta, and its possible diffusion into the blood and brain of the fetus, is calculated for a routine dose of 6 milli U per minute of Pitocin over a 12h labor. This dose of Pitocin is shown to result in a desensitization value in units of D that is more than a factor of 10 below the 0% desensitization value of 15 D. This indicates that routine doses of Pitocin are not a significant cause of autism attributable to oxytocin receptor desensitization. This is consistent with the findings of a major epidemiological study of the association of Pitocin with autism in Denmark entitled, "Oxytocin-augmented labor and risk for males", Behavioral Brain Research, May 1, 2015; 284:207-212, which found no association between the use of Pitocin during labor and the incidence of autism for females, and a modest association for males.

  10. 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…

  11. Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies

    PubMed Central

    Wigton, Rebekah; Radua, Jocham; Allen, Paul; Averbeck, Bruno; Meyer-Lindenberg, Andreas; McGuire, Philip; Shergill, Sukhi S.; Fusar-Poli, Paolo

    2015-01-01

    Background Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. Methods We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. Results We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. Limitations This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. Conclusion Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration. PMID:25520163

  12. 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

  13. 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

  14. A sociability gene? Meta-analysis of oxytocin receptor genotype effects in humans.

    PubMed

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

    2014-04-01

    Variation in the oxytocin receptor (OXTR) gene may partly explain individual differences in oxytocin-related social behavior. Two single nucleotide polymorphisms (SNPs) have been suggested as promising candidates: rs53576 and rs2254298, although the results of studies were not consistent. We carried out meta-analyses for these two SNPs, covering five domains of outcomes: (a) biology, (b) personality, (c) social behavior, (d) psychopathology, and (e) autism, on the basis of 82 pertinent effect sizes, 48 for OXTR rs53576 (N=17 559) and 34 for OXTR rs2254298 (N=13 547). Combined effect sizes did not differ from zero in any of the domains, nor for all domains combined. Clinical status, age, and sex did not moderate the effect sizes. Minor allele frequency was related to ethnicity, with significantly lower minor allele frequencies in samples with predominantly Caucasian participants. The domain of biological functioning seemed most promising, but comprised few studies. We conclude that so far two of the most intensively studied OXTR SNPs (rs53576 and rs2254298) failed to explain a significant part of human social behavior.

  15. 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.

  16. Titration of intravenous synthetic oxytocin post vaginal birth following induction or augmentation.

    PubMed

    Lewis, Lucy; Hauck, Yvonne L; Pemberton, Alissa; Crichton, Caroline; Conwell, Marion

    2016-10-01

    Evidence exists for titration of intravenous oxytocin during induction and augmentation, whereas no evidence was identified for titration of intravenous oxytocin following vaginal birth, where management excluded oxytocin for postpartum haemorrhage (PPH). This retrospective cohort study explored this issue through patient case notes and computerised perinatal data. Analysis included 335 women comparing induction (n = 226, 67%) to augmentation (n = 109, 33%). The two groups differed in terms of: parity; oxytocin dosage; length of time on intravenous oxytocin; and the length of first and second stage labour. They had similar rates of PPH and titration of intravenous oxytocin following birth was rarely recorded.

  17. Titration of intravenous synthetic oxytocin post vaginal birth following induction or augmentation.

    PubMed

    Lewis, Lucy; Hauck, Yvonne L; Pemberton, Alissa; Crichton, Caroline; Conwell, Marion

    2016-10-01

    Evidence exists for titration of intravenous oxytocin during induction and augmentation, whereas no evidence was identified for titration of intravenous oxytocin following vaginal birth, where management excluded oxytocin for postpartum haemorrhage (PPH). This retrospective cohort study explored this issue through patient case notes and computerised perinatal data. Analysis included 335 women comparing induction (n = 226, 67%) to augmentation (n = 109, 33%). The two groups differed in terms of: parity; oxytocin dosage; length of time on intravenous oxytocin; and the length of first and second stage labour. They had similar rates of PPH and titration of intravenous oxytocin following birth was rarely recorded. PMID:27634662

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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,

  3. Oxytocin and the maternal brain.

    PubMed

    Leng, Gareth; Meddle, Simone L; Douglas, Alison J

    2008-12-01

    Oxytocin released within the brain from both magnocellular and parvocellular systems of the hypothalamus has diverse effects on behavior. When oxytocin is released within the brain, its effects are to diminish fearfulness; this not only encourages social investigation of newcomers, but also may enhance a tendency to express aggression toward an intruder. Oxytocin supports social recognition, redirects behavior away from feeding directed behavior toward sexual behavior, and facilitates the formation of social bonds. This system, which depends not only upon release of oxytocin but also on oxytocin receptor distribution within the brain, becomes particularly important at parturition, when a bond is first formed between mother and offspring.

  4. 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

  5. Multivariate analysis of identity of imported technical PCN formulation.

    PubMed

    Falandysz, J; Chudzyński, K; Takekuma, M; Yamamoto, T; Noma, Y; Hanari, N; Yamashita, N

    2008-10-01

    Chloronaphthalenes form a class of compounds consisting of 8 CN homologue groups and altogether of 75 congeners, which used have been most extensively in 1930--1950. An investigation have been performed on the possible origin of unidentified by name technical chloronaphthalene formulation unlawfully imported recently from the United Kingdom to Japan. Principal component analysis (PCA) and Cluster Analysis of chloronaphthalene congener isomer-specific and homologue classes' compositional HRGC/HRMS data of imported CN formulation and of certain brands of technical CN formulation called Halowax (Halowax 1000, 1001 and 1031) enabled to identify that unnamed product is not Halowax 1001. A less accurate multivariate examination based on CN homologue classes patter did indicate on large similarity between unlawfully imported technical CN formulation and Halowax 1001 (manufactured by the Koppers Ind. Co., USA), while a more accurate based on CN congeners pattern differentiated them as to of various origin mixtures. Based on chlorine content of imported CN formulation (50-52%) and its no similarity to Halowax 1001 it seems reasonable to conclude that unnamed CN mixture examined could be a sample of stockpiled Seekay wax R93.

  6. Analysis of the Low and List Drop-Breakup Formulation.

    NASA Astrophysics Data System (ADS)

    Brown, Philip S., Jr.

    1986-03-01

    An analysis of the Low and List drop-breakup formulation has uncovered several computational problems that arise in calculating both the fragment distribution function and the Bleck expansion coefficients that appear in the discrete coalcacence/breakup equation. Special procedures have been developed to deal effectively with these problems. The discrete coalescence/breakup equation has been solved using the Low and List breakup formulation and the earlier List and Gillespie formulation. Comparison shows that the Low and List model solutions approach equilibrium more slowly than do the earlier model solutions; moreover, the Low and List equilibrium drop spectra exhibit a bimodality in the small-drop end of the spectrum. The longer time constants associated with the Low and List equations ease somewhat the severe computational stability problem associated with List and Gillespie equations.

  7. Oxytocin administration enhances controlled social cognition in patients with schizophrenia

    PubMed Central

    Woolley, J.D.; Chuang, B.; Lam, O.; Lai, W.; O’Donovan, A.; Rankin, K.P.; Mathalon, D.H.; Vinogradov, S.

    2014-01-01

    Summary Background Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. Methods We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. Results Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58) = 8.75; p = 0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. Discussion Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of

  8. 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

  9. Comparative analysis of oxytocin receptor density in the nucleus accumbens: an adaptation for female and male alloparental care?

    PubMed

    Olazábal, Daniel E

    2014-01-01

    Parental behavior is commonly displayed by progenitors. However, other individuals, genetically related (e.g. siblings, aunts, uncles) or not with the newborns, also display parental behavior (commonly called alloparental, or adoptive behavior). I hypothesize that species that live in family or social groups where other non-reproductive members (males and females) take care of infants, have brain adaptations to promote or facilitate that behavioral response. The present work revises the evidence supporting the hypothesis that high density of oxytocin receptors (OXTR) in the nucleus accumbens (NA) is one of those adaptations. All species known to have high NA OXTR show not only female, but also male alloparental care. Therefore, I predict that high NA OXTR could be present in all species in which juvenile and adult male alloparental behavior have been observed. Strategies to test this and other alternative working hypothesis and its predictions are presented. PMID:25446893

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: a meta-analysis.

    PubMed

    Shahrestani, Sara; Kemp, Andrew H; Guastella, Adam J

    2013-09-01

    Many studies have highlighted the potential of oxytocin (OT) to enhance facial affect recognition in healthy humans. However, inconsistencies have emerged with regard to the influence of OT on the recognition of specific emotional expressions (happy, angry, fear, surprise, disgust, and sadness). In this study, we conducted a meta-analysis of seven studies comprising 381 research participants (71 females) examining responses to the basic emotion types to assess whether OT enhances the recognition of emotion from human faces and whether this was influenced by the emotion expression and exposure time of the face. Results showed that intranasal OT administration enhances emotion recognition of faces overall, with a Hedges g effect size of 0.29. When analysis was restricted to facial expression types, significant effects of OT on recognition accuracy were specifically found for the recognition of happy and fear faces. We also found that effect sizes increased to moderate when exposure time of the photograph was restricted to early phase recognition (< 300 ms) for happy and angry faces, or later phase recognition for fear faces (> 300 ms). The results of the meta-analysis further suggest that OT has potential as a treatment to improve the recognition of emotion in faces, allowing individuals to improve their insight into the intentions, desires, and mental states of others.

  15. Calorimetric analysis of cryopreservation and freeze-drying formulations.

    PubMed

    Sun, Wendell Q

    2015-01-01

    Differential scanning calorimetry (DSC) is a commonly used thermal analysis technique in cryopreservation and freeze-drying research. It has been used to investigate crystallization, eutectic formation, glass transition, devitrification, recrystallization, melting, polymorphism, molecular relaxation, phase separation, water transport, thermochemistry, and kinetics of complex reactions (e.g., protein denaturation). Such information can be used for the optimization of protective formulations and process protocols. This chapter gives an introduction to beginners who are less familiar with this technique. It covers the instrument and its basic principles, followed by a discussion of the methods as well as examples of specific applications.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Re-analysis procedure based on the mixed formulation

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Peters, Jeanne M.

    1987-01-01

    An analysis procedure is presented for large-scale structural systems, with large numbers of degrees of freedom and design variables. The procedure uses a mixed formulation with the fundamental unknowns consisting of both stress and displacement parameters. Other elements of the procedure include: (1) lumping the design variables into a single tracing parameter; (2) operator splitting or additive decomposition of different arrays in the finite element equations into the corresponding arrays of the original structure plus correction terms; and (3) application of a reduction method through the use of the finite element method and the classical Bubnov-Galerkin technique. The re-analysis procedure is applied to the linear static and free vibration problems of plate and shell structures.

  4. Perturbational formulation of principal component analysis in molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Koyama, Yohei M.; Kobayashi, Tetsuya J.; Tomoda, Shuji; Ueda, Hiroki R.

    2008-10-01

    Conformational fluctuations of a molecule are important to its function since such intrinsic fluctuations enable the molecule to respond to the external environmental perturbations. For extracting large conformational fluctuations, which predict the primary conformational change by the perturbation, principal component analysis (PCA) has been used in molecular dynamics simulations. However, several versions of PCA, such as Cartesian coordinate PCA and dihedral angle PCA (dPCA), are limited to use with molecules with a single dominant state or proteins where the dihedral angle represents an important internal coordinate. Other PCAs with general applicability, such as the PCA using pairwise atomic distances, do not represent the physical meaning clearly. Therefore, a formulation that provides general applicability and clearly represents the physical meaning is yet to be developed. For developing such a formulation, we consider the conformational distribution change by the perturbation with arbitrary linearly independent perturbation functions. Within the second order approximation of the Kullback-Leibler divergence by the perturbation, the PCA can be naturally interpreted as a method for (1) decomposing a given perturbation into perturbations that independently contribute to the conformational distribution change or (2) successively finding the perturbation that induces the largest conformational distribution change. In this perturbational formulation of PCA, (i) the eigenvalue measures the Kullback-Leibler divergence from the unperturbed to perturbed distributions, (ii) the eigenvector identifies the combination of the perturbation functions, and (iii) the principal component determines the probability change induced by the perturbation. Based on this formulation, we propose a PCA using potential energy terms, and we designate it as potential energy PCA (PEPCA). The PEPCA provides both general applicability and clear physical meaning. For demonstrating its power, we

  5. 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... Oxytocin injection. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b... 10 to 20. Sows 0.25 to 1.0 5 to 20. (2) Indications for use. Oxytocin may be used as a...

  6. 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

  7. Adiponectin selectively inhibits oxytocin neurons of the paraventricular nucleus of the hypothalamus

    PubMed Central

    Hoyda, Ted D; Fry, Mark; Ahima, Rexford S; Ferguson, Alastair V

    2007-01-01

    Adiponectin is an adipocyte derived hormone which acts in the brain to modulate energy homeostasis and autonomic function. The paraventricular nucleus of the hypothalamus (PVN) which plays a key role in controlling pituitary hormone secretion has been suggested to be a central target for adiponectin actions. A number of hormones produced by PVN neurons have been implicated in the regulation of energy homeostasis including oxytocin, corticotropin releasing hormone and thyrotropin releasing hormone. In the present study we investigated the role of adiponectin in controlling the excitability of magnocellular (MNC – oxytocin or vasopressin secreting) neurons within the PVN. Using RT-PCR techniques we have shown expression of both adiponectin receptors in the PVN. Patch clamp recordings from MNC neurons in hypothalamic slices have also identified mixed (27% hyperpolarization, 42% depolarization) effects of adiponectin in modulating the excitability of the majority of MNC neurons tested. These effects are maintained when cells are placed in synaptic isolation using tetrodotoxin. Additionally we combined electrophysiological recordings with single cell RT-PCR to examine the actions of adiponectin on MNC neurons which expressed oxytocin only, vasopressin only, or both oxytocin and vasopressin mRNA and assess the profile of receptor expression in these subgroups. Adiponectin was found to hyperpolarize 100% of oxytocin neurons tested (n = 6), while vasopressin cells, while all affected (n = 6), showed mixed responses. Further analysis indicates oxytocin neurons express both receptors (6/7) while vasopressin neurons express either both receptors (3/8) or one receptor (5/8). In contrast 6/6 oxytocin/vasopressin neurons were unaffected by adiponectin. Co-expressing oxytocin and vasopressin neurons express neither receptor (4/6). The results presented in this study suggest that adiponectin plays specific roles in controlling the excitability oxytocin secreting neurons, actions

  8. 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.

  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. Elliptical vortices in shear: Hamiltonian moment formulation and Melnikov analysis

    SciTech Connect

    Ngan, K.; Meacham, S.; Morrison, P.J.

    1995-07-01

    The equations of motion for interacting, elliptical vortices in a background shear flow are derived using a Hamiltonian moment formulation. The equations reduce to the 6th order system of Melander et al. [J. Fluid Mech. 167, 95 (1986)] when a pair of vortices is considered and shear is neglected. The equations for a pair of identical vortices axe analyzed with a number of methods, with particular emphasis on the basic interactions and on the implications for vortex merger. The splitting distance between the stable and unstable manifolds connecting the hyperbolic fixed points of the intercentroidal motion-the separatrix splitting-is estimated with a Melnikov analysis. This analysis differs from the standard time-periodic Melnikov analysis on two counts: (a) the ``periodic`` perturbation arises from a second degree of freedom in the system which is not wholly independent of the first degree of freedom, the intercentroidal motion; (b) this perturbation has a faster time scale than the intercentroidal motion. The resulting Melnikov integral appears to be exponentially small in the perturbation as the latter goes to zero. Numerical simulations, notably Poincare sections, provide a global view of the dynamics and indicate that there are two modes of merger. The effect of the shear on chaotic motion and on chaotic scattering is also discussed.

  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. 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.

  13. Newborn Analgesia Mediated by Oxytocin during Delivery

    PubMed Central

    Mazzuca, Michel; Minlebaev, Marat; Shakirzyanova, Anastasia; Tyzio, Roman; Taccola, Giuliano; Janackova, Sona; Gataullina, Svetlana; Ben-Ari, Yehezkel; Giniatullin, Rashid; Khazipov, Rustem

    2011-01-01

    The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth. PMID:21519396

  14. 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.

  15. 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

  16. Oxytocin and social motivation.

    PubMed

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

    2011-10-01

    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.

  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. 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.

  19. Basal salivary oxytocin level predicts extra- but not intra-personal dimensions of emotional intelligence.

    PubMed

    Koven, Nancy S; Max, Laura K

    2014-06-01

    A wealth of literature suggests that oxytocin is an important mediator of social cognition, but much of the research to date has relied on pharmaceutical administration methods that can raise oxytocin to artificially high levels. The present study builds upon previous work by examining whether basal oxytocin level predicts intra- and extra-personal (i.e., self- and other-focused) elements of emotional intelligence (EI), independent of shared variance with current mood. The sample included 71 healthy young adults (46 women). Assessment measures included the Mayer-Salovey-Caruso Emotional Intelligence Test Version 2.0 (MSCEIT), the Trait Meta-Mood Scale, and the Profile of Mood States. Peripheral oxytocin levels were examined with enzyme-linked immunosorbent assay from saliva after solid phase extraction. Oxytocin level was unrelated to TMMS scores but was positively associated with performance in the Experiential EI domain of the MSCEIT. However, total mood disturbance was positively related to MSCEIT scores. Hierarchical regression analysis indicated that oxytocin level added unique variance to the prediction of MSCEIT performance beyond that of current mood. These results confirm an association between endogenous levels of oxytocin in healthy adults and a subset of EI abilities, including extra-personal emotion recognition and the channeling of emotions to enhance social proficiency. PMID:24767616

  20. Basal salivary oxytocin level predicts extra- but not intra-personal dimensions of emotional intelligence.

    PubMed

    Koven, Nancy S; Max, Laura K

    2014-06-01

    A wealth of literature suggests that oxytocin is an important mediator of social cognition, but much of the research to date has relied on pharmaceutical administration methods that can raise oxytocin to artificially high levels. The present study builds upon previous work by examining whether basal oxytocin level predicts intra- and extra-personal (i.e., self- and other-focused) elements of emotional intelligence (EI), independent of shared variance with current mood. The sample included 71 healthy young adults (46 women). Assessment measures included the Mayer-Salovey-Caruso Emotional Intelligence Test Version 2.0 (MSCEIT), the Trait Meta-Mood Scale, and the Profile of Mood States. Peripheral oxytocin levels were examined with enzyme-linked immunosorbent assay from saliva after solid phase extraction. Oxytocin level was unrelated to TMMS scores but was positively associated with performance in the Experiential EI domain of the MSCEIT. However, total mood disturbance was positively related to MSCEIT scores. Hierarchical regression analysis indicated that oxytocin level added unique variance to the prediction of MSCEIT performance beyond that of current mood. These results confirm an association between endogenous levels of oxytocin in healthy adults and a subset of EI abilities, including extra-personal emotion recognition and the channeling of emotions to enhance social proficiency.

  1. 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

  2. Oxytocin and bone

    PubMed Central

    Sun, Li; Zaidi, Mone; Zallone, Alberta

    2014-01-01

    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

  3. Intravenous oxytocin alone for cervical ripening and induction of labour

    PubMed Central

    Alfirevic, Zarko; Kelly, Anthony J; Dowswell, Therese

    2014-01-01

    Background Oxytocin is the commonest induction agent used worldwide. It has been used alone, in combination with amniotomy or following cervical ripening with other pharmacological or non-pharmacological methods. Objectives To determine the effects of oxytocin alone for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour or placebo/no treatment. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (January 2009) and bibliographies of relevant papers. Selection criteria Randomised and quasi-randomised trials comparing intravenous oxytocin with placebo or no treatment, or with prostaglandins (vaginal or intracervical) for third trimester cervical ripening or labour induction. Data collection and analysis Two review authors independently assessed eligibility and carried out data extraction. Main results Sixty-one trials (12,819 women) are included. When oxytocin inductions were compared with expectant management, fewer women failed to deliver vaginally within 24 hours (8.4% versus 53.8%, risk ratio (RR) 0.16, 95% confidence interval (CI) 0.10 to 0.25). There was a significant increase in the number of women requiring epidural analgesia (RR 1.10, 95% CI 1.04 to 1.17). Fewer women were dissatisfied with oxytocin induction in the one trial reporting this outcome (5.9% versus 13.7%, RR 0.43, 95% CI 0.33 to 0.56). Compared with vaginal prostaglandins, oxytocin increased unsuccessful vaginal delivery within 24 hours in the two trials reporting this outcome (70% versus 21%, RR 3.33, 95% CI 1.61 to 6.89). There was a small increase in epidurals when oxytocin alone was used (RR 1.09, 95% CI 1.01 to 1.17). Most of the studies included women with ruptured membranes, and there was some evidence that vaginal prostaglandin increased infection in mothers (chorioamnionitis RR 0.66, 95% CI 0.47 to 0.92) and babies (use of antibiotics RR 0.68, 95% CI 0.53 to 0.87). These data should be

  4. 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

  5. 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

  6. 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

  7. Aspartate analysis in formulations using a new enzyme sensor.

    PubMed

    Campanella, L; Aturki, Z; Sammartino, M P; Tomassetti, M

    1995-04-01

    A biosensor has been developed for the purpose of directly analysing aspartate in pharmaceutical formulations and aspartame in sweeteners. This biosensor consists of an ammonia-sensitive gas-diffusion electrode and the enzyme L-aspartase immobilized by means of polyazetidine on a dialysis membrane.

  8. Spectroscopic analysis of phenolic compounds for food and feed formulations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenolic compounds exhibit several bioactive properties including anti-oxidant, anti-microbial, and anti-fungal characteristics with potential applications as additives in functional food and feed formulations. Phenolic compounds occur in plants as secondary metabolites and may be recovered as a co-...

  9. 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.

  10. 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

  11. 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

  12. 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...

  13. A new strategy to stabilize oxytocin in aqueous solutions: I. The effects of divalent metal ions and citrate buffer.

    PubMed

    Avanti, Christina; Amorij, Jean-Pierre; Setyaningsih, Dewi; Hawe, Andrea; Jiskoot, Wim; Visser, Jan; Kedrov, Alexej; Driessen, Arnold J M; Hinrichs, Wouter L J; Frijlink, Henderik W

    2011-06-01

    In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na(+) and K(+)) and divalent metal ions (Ca(2+), Mg(2+), and Zn(2+)) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl(2), MgCl(2), or ZnCl(2) and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca(2+), Mg(2+), or Zn(2+), while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions.

  14. 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.

  15. 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

  16. 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

  17. LC method for the analysis of Oxiconazole in pharmaceutical formulations.

    PubMed

    Milano, Julie; Morsch, Lisoni M; Cardoso, Simone Gonçalves

    2002-09-01

    A LC method has been developed for the quantitative determination of Oxiconazole (Ox) in bulk form, lotion and cream pharmaceutical formulations. The method validation yielded good results including the range, linearity, precision, accuracy, recovery, specificity, robustness, limit of quantitation and limit of detection. The LC separation was carried by reversed phase chromatography using a LiChrocart C(8) column (125 mm x 4.0 mm i.d., 5 microm particle size). The mobile phase was composed of methanol-0.02 M ammonium acetate buffer (85:15 v/v), pumped isocratically at flow rate 1 ml min(-1). The detection was carried out on UV detector at 254 nm. The calibration curve for Ox was linear from 40.0-140.0 microg ml(-1) range. The precision of this method, calculated as the relative standard deviation (R.S.D.) was 1.57% for lotion and 0.71% for cream. The R.S.D. values for intra- and inter-day precision studies were 0.57 and 1.34%, respectively. The recovery of the drug ranged between 98.84-102.2% (lotion) and 100.54-101.59% (cream). The stability indicating capability of the assays was proved using forced degradation. Chromatograms showed Ox well resolved from the degradation product.

  18. 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.

  19. 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.

  20. 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.

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

    PubMed

    Freeman, Sara M; Young, Larry J

    2016-04-01

    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

  2. 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

  3. Oxytocin in the cardiovascular responses to stress.

    PubMed

    Wsol, A; Cudnoch-Jedrzejewska, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L

    2008-12-01

    The present study was designed to determine the role of central oxytocin (OXY) in regulation of the cardiovascular responses to the alarming stress. Three groups of male, normotensive Sprague Dawley rats, received intracerebroventricular (i.c.v.) infusion of one of the following: 1) vehicle, 2) OXY or 3) OXY antagonist (OXANT). Mean arterial blood pressure (MABP) and heart rate (HR) were recorded at rest, during and after application of the alarming stressor (air jet). Under resting conditions the i.c.v. infusions of vehicle, OXY or OXYANT did not influence the cardiovascular parameters. The alarming stressor evoked significant increases in MABP and HR that were significantly greater in the rats receiving i.c.v. infusion of oxytocin antagonist than in those receiving vehicle or OXY. The study provides evidence that stimulation of the brain oxytocin receptors by endogenous oxytocin plays significant role in inhibition of cardiovascular responses to stress.

  4. 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

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Chemical analysis and biological properties of two different formulations of white portland cements.

    PubMed

    Ahmed, Hany Mohamed Aly; Luddin, Norhayati; Kannan, Thirumulu Ponnuraj; Mokhtar, Khairani Idah; Ahmad, Azlina

    2016-07-01

    White Portland cement (WPC) has generated research interests in the field of endodontics. This study compared between the properties of two formulations of white Portland cement (WPC) of different origin (Malaysia [MA] and Egypt [EG]). WPCs with and without calcium chloride dihydrate were prepared. Scanning electron microscope (SEM), energy dispersive X-ray micro-analysis, and X-ray diffraction were used for surface morphology evaluation, elemental, and phase analysis, respectively. After the preparation of optimized serial dilutions, the cytotoxicity was evaluated on human periodontal ligament fibroblasts (HPLFs) and dental pulp stem cells (DPSCs) using methyl-thiazol-diphenyltetrazolium assay after 24 and 72 h. Cell attachment properties were examined under SEM after 24 and 72 h. Results showed that the surface morphology and chemical composition of both formulations demonstrated detectable variations. The cytotoxicity evaluation showed different cellular responses of HPLFs compared to DSPCs. Both formulations favored the viability of HPLFs. However, the fast set formulations demonstrated severe cytotoxicity on DPSCs. Significant differences between EGWPC and MAWPC were identified (p < 0.05). The cell attachment properties were favorable; however, HPLFs attached and spread over the samples better than DPSCs. In conclusion, WPC of different origin may show differences in chemical and biological properties. The addition of CaCl2 ·2H2 O to WPC can affect its properties. Human cell types may react differently towards different formulations of WPCs. SCANNING 38:303-316, 2016. © 2015 Wiley Periodicals, Inc. PMID:26382064

  12. Oxytocin in the Treatment of Dystocia in Mice

    PubMed Central

    Narver, Heather L

    2012-01-01

    Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research. PMID:22330862

  13. Oxytocin links mothering received, mothering bestowed and adult stress responses.

    PubMed

    Pedersen, Cort A; Boccia, Maria L

    2002-12-01

    We review recent discoveries that implicate oxytocin in the intergenerational transmission of similar levels of maternal behavior and acute stress responses in female rats. First, ICV-infused oxytocin antagonist decreased the display by nursing dams of pup-licking (PL) and arched-back nursing (ABN), but not other components of maternal behavior, and increased maternal self-grooming suggesting that oxytocin may shift the balance of oral grooming by dams away from themselves and toward pups. Second, oxytocin receptor concentrations in areas of the adult brain where oxytocin stimulates maternal behavior or diminishes anxiety and adrenal axis responses to acute stress were positively related to PL-ABN received during infancy. Third, oxytocin and oxytocin antagonist treatments of pups on postnatal days 2-10, respectively increased and decreased PL by the treated rats when adult and themselves nursing dams. This indicates that oxytocin activity in female pups, which may be regulated by PL-ABN received from their mothers, influences their adult levels of PL. These three lines of evidence suggest that oxytocin selectively enhances PL-ABN by rat dams, which then increases oxytocin activity in female pups and, thereby, facilitates their expression of central oxytocin receptors (and perhaps other aspects of central oxytocin systems) and, consequently, their adult PL-ABN frequencies and acute stress responses.

  14. Oxytocin/vasopressin-related peptides have an ancient role in reproductive behavior.

    PubMed

    Garrison, Jennifer L; Macosko, Evan Z; Bernstein, Samantha; Pokala, Navin; Albrecht, Dirk R; Bargmann, Cornelia I

    2012-10-26

    Many biological functions are conserved, but the extent to which conservation applies to integrative behaviors is unknown. Vasopressin and oxytocin neuropeptides are strongly implicated in mammalian reproductive and social behaviors, yet rodent loss-of-function mutants have relatively subtle behavioral defects. Here we identify an oxytocin/vasopressin-like signaling system in Caenorhabditis elegans, consisting of a peptide and two receptors that are expressed in sexually dimorphic patterns. Males lacking the peptide or its receptors perform poorly in reproductive behaviors, including mate search, mate recognition, and mating, but other sensorimotor behaviors are intact. Quantitative analysis indicates that mating motor patterns are fragmented and inefficient in mutants, suggesting that oxytocin/vasopressin peptides increase the coherence of mating behaviors. These results indicate that conserved molecules coordinate diverse behavioral motifs in reproductive behavior.

  15. 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

  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. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. The role of oxytocin in cardiovascular regulation

    PubMed Central

    Gutkowska, J.; Jankowski, M.; Antunes-Rodrigues, J.

    2014-01-01

    Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions. PMID:24676493

  6. Pulsatile secretion of oxytocin during parturition in the pig: temporal relationship with fetal expulsion.

    PubMed Central

    Gilbert, C L; Goode, J A; McGrath, T J

    1994-01-01

    1. To assess changes in oxytocin release as they occur in relation to the rapid progress of events at fetal expulsion, continuous automated blood withdrawals (3 ml min-1) from an indwelling jugular catheter and intramammary pressure recordings were obtained from nine primiparous pigs (190-220 kg). Data were acquired over 16 h of normal parturition, during which thirty-five piglets were born. 2. Oxytocin secretion during parturition, when measured by radioimmunoassay (RIA) in blood collected and pooled every minute, showed a baseline secretion (19.8-88.37 pg ml-1) that was raised relative to preterm values. Analysis of individual secretion profiles revealed significant fluctuations or peaks of concentration superimposed on this baseline, with a slow periodicity of 4-12 min. These substantial peaks in secretion were not temporally related to fetal expulsion or visible abdominal contractions. 3. A small (13%) but significant increase in plasma oxytocin was also seen when assay data from the minutes coinciding with a birth were meaned and compared with the following minutes. This rise did not persist into further minutes. 4. Intramammary pressure recordings revealed a highly repeatable and characteristic phenomenon in that fetal expulsion was followed after 33.74 +/- 1.31 s (mean +/- S.E.M. time from emergence of fetus to peak pressure rise) in thirty-three of thirty-five instances by a distinctive and rapid bolus release of oxytocin. These 'postpartum oxytocin pulses' could be closely mimicked by injections of exogenous oxytocin (0.03-1.0 ng kg-1; lag time from jugular injection to peak pressure rise, 20.44 +/- 0.99 s). The timing of this event coincided with the small postpartum pulse measurable by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8189385

  7. 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.

  8. 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.

  9. Nonlinear consider covariance analysis using a sigma-point filter formulation

    NASA Technical Reports Server (NTRS)

    Lisano, Michael E.

    2006-01-01

    The research reported here extends the mathematical formulation of nonlinear, sigma-point estimators to enable consider covariance analysis for dynamical systems. This paper presents a novel sigma-point consider filter algorithm, for consider-parameterized nonlinear estimation, following the unscented Kalman filter (UKF) variation on the sigma-point filter formulation, which requires no partial derivatives of dynamics models or measurement models with respect to the parameter list. It is shown that, consistent with the attributes of sigma-point estimators, a consider-parameterized sigma-point estimator can be developed entirely without requiring the derivation of any partial-derivative matrices related to the dynamical system, the measurements, or the considered parameters, which appears to be an advantage over the formulation of a linear-theory sequential consider estimator. It is also demonstrated that a consider covariance analysis performed with this 'partial-derivative-free' formulation yields equivalent results to the linear-theory consider filter, for purely linear problems.

  10. [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

  11. 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

  12. Convergence and attractors of augmented Lagrangian formulations in the dynamic analysis of multibody systems

    NASA Astrophysics Data System (ADS)

    Bustamante, D. A.; Kurdila, A. J.; Menon, R. G.

    1993-04-01

    The augmented Lagrangian formulation used in the dynamic analysis of multibody systems under holonomic constraints is presently found to exhibit fixed-step convergence, so that the approximate accelerations and Lagrange multipliers at a fixed time interval approach the exact accelerations and multipliers as the number of iterations becomes large. Also noted are a fixed time-interval rate of convergence inequality for the Lagrange multipliers, and corroborating empirical evidence for these analytical developments.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 21 CFR 522.1680 - Oxytocin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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. (a.... It will contract smooth muscle cells of the mammary gland for milk letdown if the udder is in...

  19. 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

  20. 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.

  1. 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.

  2. Applications of Quantum Cascade Laser Spectroscopy in the Analysis of Pharmaceutical Formulations.

    PubMed

    Galán-Freyle, Nataly J; Pacheco-Londoño, Leonardo C; Román-Ospino, Andrés D; Hernandez-Rivera, Samuel P

    2016-09-01

    Quantum cascade laser spectroscopy was used to quantify active pharmaceutical ingredient content in a model formulation. The analyses were conducted in non-contact mode by mid-infrared diffuse reflectance. Measurements were carried out at a distance of 15 cm, covering the spectral range 1000-1600 cm(-1) Calibrations were generated by applying multivariate analysis using partial least squares models. Among the figures of merit of the proposed methodology are the high analytical sensitivity equivalent to 0.05% active pharmaceutical ingredient in the formulation, high repeatability (2.7%), high reproducibility (5.4%), and low limit of detection (1%). The relatively high power of the quantum-cascade-laser-based spectroscopic system resulted in the design of detection and quantification methodologies for pharmaceutical applications with high accuracy and precision that are comparable to those of methodologies based on near-infrared spectroscopy, attenuated total reflection mid-infrared Fourier transform infrared spectroscopy, and Raman spectroscopy.

  3. 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.

  4. Surface integral equation formulation for the analysis of left-handed metamaterials.

    PubMed

    Rivero, J; Taboada, J M; Landesa, L; Obelleiro, F; García-Tuñón, I

    2010-07-19

    A surface integral equation (SIE) formulation is applied to the analysis of electromagnetic problems involving three-dimensional (3D) piecewise homogenized left-handed metamaterials (LHM). The resulting integral equations are discretized by the well-known method of moments (MoM) and solved via an iterative process. The unknowns are defined only on the interfaces between different media, avoiding the discretization of volumes and surrounding space, which entails a drastic reduction in the number of unknowns arising in the numerical discretization of the equations. Besides, the SIE-MoM formulation inherently includes the radiation condition at infinity, so it is not necessary to artificially include termination absorbing boundary conditions. Some 3D numerical examples are presented to confirm the validity and versatility of this approach on dealing with LHM, also providing some intuitive verifications of the singular properties of these amazing materials. PMID:20720970

  5. 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

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

    PubMed Central

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

    2015-01-01

    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 small 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

  7. The effect of low-dose oxytocin infusion on cerebral hemodynamics in pregnant women.

    PubMed

    van Veen, Teelkien R; Belfort, Michael A; Zeeman, Gerda G

    2011-08-01

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive, nonsmoking patients undergoing induction of labor. No vasoactive drugs were used before or during the study period. Measurements were made at baseline and 15, 30, 60, and 120 minutes after oxytocin initiation. Mean arterial pressure, cerebral perfusion pressure, resistance index, resistance area product, and cerebral flow index at different times were calculated and compared using one-way analysis of variance (ANOVA) for repeated measures or Friedman repeated-measures ANOVA as appropriate, with P<0.05 regarded as significant. No significant systemic or cerebrovascular changes were noted after oxytocin initiation, and there was no correlation between the dosage administered and any hemodynamic parameter. Induction-dose oxytocin does not significantly affect selected cerebral hemodynamic parameters in the first 2 hours after initiation.

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

    PubMed Central

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

    2015-01-01

    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 small 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

  9. 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.

  10. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates.

    PubMed

    Minakata, Hiroyuki

    2010-07-01

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

  11. Behavioral consequences of intracerebral vasopressin and oxytocin: focus on learning and memory.

    PubMed

    Engelmann, M; Wotjak, C T; Neumann, I; Ludwig, M; Landgraf, R

    1996-01-01

    Since the pioneering work of David de Wied and his colleagues, the neuropeptides arginine vasopressin and oxytocin have been thought to play a pivotal role in behavioral regulation in general, and in learning and memory in particular. The present review focuses on the behavioral effects of intracerebral arginine vasopressin and oxytocin, with particular emphasis on the role of these neuropeptides as signals in interneuronal communication. We also discuss several methodological approaches that have been used to reveal the importance of these intracerebral neuropeptides as signals within signaling cascades. The literature suggests that arginine vasopressin improves, and oxytocin impairs, learning and memory. However, a critical analysis of the subject indicates the necessity for a revision of this generalized concept. We suggest that, depending on the behavioral test and the brain area under study, these endogenous neuropeptides are differentially involved in behavioral regulation; thus, generalizations derived from a single behavioral task should be avoided. In particular, recent studies on rodents indicate that socially relevant behaviors triggered by olfactory stimuli and paradigms in which the animals have to cope with an intense stressor (e.g., foot-shock motivated active or passive avoidance) are controlled by both arginine vasopressin and oxytocin released intracerebrally.

  12. 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

  13. 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.

  14. 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.

  15. HPLC analysis and standardization of Brahmi vati – An Ayurvedic poly-herbal formulation

    PubMed Central

    Mishra, Amrita; Mishra, Arun K.; Tiwari, Om Prakash; Jha, Shivesh

    2013-01-01

    Objectives The aim of the present study was to standardize Brahmi vati (BV) by simultaneous quantitative estimation of Bacoside A3 and Piperine adopting HPLC–UV method. BV very important Ayurvedic polyherbo formulation used to treat epilepsy and mental disorders containing thirty eight ingredients including Bacopa monnieri L. and Piper longum L. Materials and methods An HPLC–UV method was developed for the standardization of BV in light of simultaneous quantitative estimation of Bacoside A3 and Piperine, the major constituents of B. monnieri L. and P. longum L. respectively. The developed method was validated on parameters including linearity, precision, accuracy and robustness. Results The HPLC analysis showed significant increase in amount of Bacoside A3 and Piperine in the in-house sample of BV when compared with all three different marketed samples of the same. Results showed variations in the amount of Bacoside A3 and Piperine in different samples which indicate non-uniformity in their quality which will lead to difference in their therapeutic effects. Conclusion The outcome of the present investigation underlines the importance of standardization of Ayurvedic formulations. The developed method may be further used to standardize other samples of BV or other formulations containing Bacoside A3 and Piperine. PMID:24396246

  16. 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

  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. 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.

  19. 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.

  20. A hybrid-mixed finite element formulation for the geometrically exact analysis of three-dimensional framed structures

    NASA Astrophysics Data System (ADS)

    Santos, H. A. F. A.; Pimenta, P. M.; Almeida, J. P. M.

    2011-11-01

    This paper addresses the development of a hybrid-mixed finite element formulation for the quasi-static geometrically exact analysis of three-dimensional framed structures with linear elastic behavior. The formulation is based on a modified principle of stationary total complementary energy, involving, as independent variables, the generalized vectors of stress-resultants and displacements and, in addition, a set of Lagrange multipliers defined on the element boundaries. The finite element discretization scheme adopted within the framework of the proposed formulation leads to numerical solutions that strongly satisfy the equilibrium differential equations in the elements, as well as the equilibrium boundary conditions. This formulation consists, therefore, in a true equilibrium formulation for large displacements and rotations in space. Furthermore, this formulation is objective, as it ensures invariance of the strain measures under superposed rigid body rotations, and is not affected by the so-called shear-locking phenomenon. Also, the proposed formulation produces numerical solutions which are independent of the path of deformation. To validate and assess the accuracy of the proposed formulation, some benchmark problems are analyzed and their solutions compared with those obtained using the standard two-node displacement/ rotation-based formulation.

  1. 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. PMID:27594772

  2. Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats

    PubMed Central

    De Melo, Vitor U.; Saldanha, Rayssa R. M.; Dos Santos, Carla R.; De Campos Cruz, Josiane; Lira, Vitor A.; Santana-Filho, Valter J.; Michelini, Lisete C.

    2016-01-01

    The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic) neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN). Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry) within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation. PMID:27790154

  3. 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

  4. Separation anxiety, attachment and inter-personal representations: disentangling the role of oxytocin in the perinatal period.

    PubMed

    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

  5. Separation anxiety, attachment and inter-personal representations: disentangling the role of oxytocin in the perinatal period.

    PubMed

    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.

  6. 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.

  7. 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.

  8. 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

  9. Peripheral oxytocin administration reduces ethanol consumption in rats.

    PubMed

    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 0.5mg/kg (I.P.). Next, rats received 0.3mg/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, 0.3mg/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.

  10. 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

  11. 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

  12. Oxytocin Facilitates Pavlovian Fear Learning in Males.

    PubMed

    Eckstein, Monika; Scheele, Dirk; Patin, Alexandra; Preckel, Katrin; Becker, Benjamin; Walter, Annika; Domschke, Katharina; Grinevich, Valery; Maier, Wolfgang; Hurlemann, René

    2016-03-01

    In human evolution, social group living and Pavlovian fear conditioning have evolved as adaptive mechanisms promoting survival and reproductive success. The evolutionarily conserved hypothalamic peptide oxytocin is a key modulator of human sociality, but its effects on fear conditioning are still elusive. In the present randomized controlled study involving 97 healthy male subjects, we therefore employed functional magnetic resonance imaging and simultaneous skin conductance response (SCR) measures to characterize the modulatory influence of intranasal oxytocin (24 IU) on Pavlovian fear conditioning. We found that the peptide strengthened conditioning on both the behavioral and neural levels. Specifically, subjects exhibited faster task-related responses and enhanced SCRs to fear-associated stimuli in the late phase of conditioning, which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function. This speaks against amygdalocentric views of oxytocin having pure anxiolytic-like effects. Instead, it suggests that the peptide enables extremely rapid and flexible adaptation to fear signals in social contexts, which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Nonlinear dynamic analysis of multi-base seismically isolated structures with uplift potential I: formulation

    NASA Astrophysics Data System (ADS)

    Tsopelas, Panos C.; Roussis, Panayiotis C.; Constantinou, Michael C.

    2009-09-01

    The complexity of modern seismically isolated structures requires the analysis of the structural system and the isolation system in its entirety and the ability to capture potential discontinuous phenomena such as isolator uplift and their effects on the superstructures and the isolation hardware. In this paper, an analytical model is developed and a computational algorithm is formulated to analyze complex seismically isolated superstructures even when undergoing highly-nonlinear phenomena such as uplift. The computational model has the capability of modeling various types of isolation devices with strong nonlinearities, analyzing multiple superstructures (up to five separate superstructures) on multiple bases (up to five bases), and capturing the effects of lateral loads on bearing axial forces, including bearing uplift. The model developed herein has been utilized to form the software platform 3D-BASIS-ME-MB, which provides the practicing engineering community with a versatile tool for analysis and design of complex structures with modern isolation systems.

  18. 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...

  19. Evolution of oxytocin pathways in the brain of vertebrates.

    PubMed

    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

  20. 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

  1. 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

  2. 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

  3. Applications of Quantum Cascade Laser Spectroscopy in the Analysis of Pharmaceutical Formulations.

    PubMed

    Galán-Freyle, Nataly J; Pacheco-Londoño, Leonardo C; Román-Ospino, Andrés D; Hernandez-Rivera, Samuel P

    2016-09-01

    Quantum cascade laser spectroscopy was used to quantify active pharmaceutical ingredient content in a model formulation. The analyses were conducted in non-contact mode by mid-infrared diffuse reflectance. Measurements were carried out at a distance of 15 cm, covering the spectral range 1000-1600 cm(-1) Calibrations were generated by applying multivariate analysis using partial least squares models. Among the figures of merit of the proposed methodology are the high analytical sensitivity equivalent to 0.05% active pharmaceutical ingredient in the formulation, high repeatability (2.7%), high reproducibility (5.4%), and low limit of detection (1%). The relatively high power of the quantum-cascade-laser-based spectroscopic system resulted in the design of detection and quantification methodologies for pharmaceutical applications with high accuracy and precision that are comparable to those of methodologies based on near-infrared spectroscopy, attenuated total reflection mid-infrared Fourier transform infrared spectroscopy, and Raman spectroscopy. PMID:27558366

  4. Oxytocin and social cognition in affective and psychotic disorders.

    PubMed

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

    2015-02-01

    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.

  5. 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

  6. Human Neuroimaging of Oxytocin and Vasopressin in Social Cognition

    PubMed Central

    Zink, Caroline F; Meyer-Lindenberg, Andreas

    2012-01-01

    The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using “pharmacological fMRI” and “imaging genetics”, respectively. PMID:22326707

  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. 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

  9. Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy

    PubMed Central

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

    2010-01-01

    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. Isolation and simultaneous LC analysis of thiram and its less toxic transformation product in DS formulation.

    PubMed

    Walia, Suresh; Sharma, Rajendra Kumar; Parmar, Balraj S

    2009-09-01

    A simple and sensitive high pressure liquid chromatographic method has been developed for the simultaneous determination of Thiram and its transformation product using isocratic mixture of methanol-water (65:35) at flow rates of 0.75 mL min(-1), PDA detector using UV absorbance (lambda(max)) at 217 nm for Thiram and 265.5 nm for the transformation product. The transformation product was isolated from the commercial DS formulation and has been tentatively assigned the structure by (1)H NMR and ESI-MS spectral data. The separation is dependent on the nature of the mobile phase, its flow rate and the nature of the HPLC column. The detection limit (signal/noise; S/N = 3) for both Thiram and its transformation product was 0.2 ppm. The method has been successfully applied to analysis of soil and soybean samples spiked with Thiram, its transformation product and a commercial sample containing these products.

  11. Shear banding analysis of plastic models formulated for incompressible viscous flows

    NASA Astrophysics Data System (ADS)

    Lemiale, V.; Mühlhaus, H.-B.; Moresi, L.; Stafford, J.

    2008-12-01

    We investigate shear band orientations for a simple plastic formulation in the context of incompressible viscous flow. This type of material modelling has been introduced in literature to enable the numerical simulation of the deformation and failure of the lithosphere coupled with the mantle convection. In the present article, we develop a linear stability analysis to determine the admissible shear band orientations at the onset of bifurcation. We find that the so-called Roscoe angle and Coulomb angle are both admissible solutions. We present numerical simulations under plane strain conditions using the hybrid particle-in-cell finite element code Underworld. The results both in compressional and extensional stress conditions show that the variation of the numerical shear bands angle with respect to the internal friction angle follows closely the evolution of the Coulomb angle.

  12. A nonlinear solid shell element formulation for analysis of composite panels under blast wave pressure loading

    NASA Astrophysics Data System (ADS)

    Park, Hun

    A comprehensive methodology to accurately predict the dynamic response of composite panels under blast wave pressure loading has been successfully developed for the first time. It includes the modeling of geometrically nonlinear dynamic effect, progressive failure and strain-rate effect on constitutive equation and strength. For dynamic analysis, a nonlinear solid shell element formulation is combined with the trapezoidal rule for numerical integration in time. The progressive damage incorporates the effect of the material failure, such as fiber failure, matrix cracking and fiber-matrix shearing failure on the stiffness and strength. Material degradation models based on the rule of mixtures are proposed for each failure mode. To implement the strain-rate effect on the constitutive equation of the material, a viscoplastic model is adopted. In this model, three material parameters are determined by conducting uniaxial tension tests on off-axis specimen. The effect of strain rates on material strength is implemented via the linear least square fit of the test data. A key ingredient of the analysis is a geometrically nonlinear solid shell element based on the assumed strain formulation to alleviate element locking. In this approach, the composite shell is treated as a three-dimensional solid. Accordingly, the change of shell thickness is allowed and the kinematics of deformation is described by six vector components at a point on the shell midsurface. The mass matrix always remains constant during the analysis. Example problems under static and dynamic loadings are solved to investigate the behavior of composite panels undergoing large deformation while experiencing material damage. The analysis results are compared with the test data available. Results of the numerical analysis show that the effect of the progressive failure and strain-rates on structural responses are considerable. For a composite plate under static pressure loadings, maximum displacement and

  13. Rapid analysis of liquid formulations containing sodium chloride using laser-induced breakdown spectroscopy.

    PubMed

    St-Onge, Louis; Kwong, Elizabeth; Sabsabi, Mohamad; Vadas, Elizabeth B

    2004-10-29

    The purpose of this work was to demonstrate the possibilities offered by laser-induced breakdown spectroscopy (LIBS) for the direct and rapid analysis of pharmaceutical liquid formulations. Sodium chloride in solution was chosen as a model compound. A pulsed Nd:YAG laser (1064 nm) was used to produce a gaseous plasma from the liquid sample. The ensuing plasma emission was spectrally analysed, and the intensity of an atomic line from sodium was used to quantitate the sodium chloride. Using surface analysis of a flowing solution, the precision (%R.S.D.) of a measurement lasting 50 s (average of 50 laser shots at 1 shot/s) was approximately 0.5% for isotonic solutions. On a non-flowing solution, a 50 s measurement had an R.S.D. of 1.8%. Direct analysis in closed (transparent) bottles was possible but more complex, requiring the superimposition of two sequential laser sparks. Using a surface procedure, common commercial isotonic products (including injectable, bacteriostatic injectable, and nasal solutions) were analysed. Their sodium content (corresponding to 0.9% sodium chloride) was accurately determined in all cases, demonstrating the capabilities of LIBS for the rapid analysis of liquid pharmaceutical products.

  14. 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.

  15. Oxytocin specifically enhances valence-dependent parasympathetic responses.

    PubMed

    Gamer, Matthias; Büchel, Christian

    2012-01-01

    The evolutionarily highly conserved neuropeptide oxytocin seems to be involved in the regulation of complex forms of social behavior. It enhances the processing of positive social stimuli, reduces behavioral and neuroendocrine stress responses and modulates amygdala activity in humans. Moreover, it has been proposed that oxytocin dampens sympathetic nervous system activity. This hypothesis was tested in a double-blind, placebo-controlled study with 38 men either receiving 24 IU oxytocin intranasally or a placebo spray. While accomplishing an emotion classification task, electrodermal responses were measured as an index of sympathetic activity. Moreover, heart rate changes were recorded that are additionally mediated by the parasympathetic nervous system. Oxytocin enhanced differential heart rate responses to facial expressions as a function of the emotional valence, but had no effect on electrodermal activity or tonic measures of physiological arousal. These results indicate that oxytocin specifically modulates phasic activity of the parasympathetic nervous system which potentially reflects an increased motivational value of facial expressions following oxytocin treatment. Findings suggest that anxiolytic effects of oxytocin are not reflected in short-term sympathetic responses and may even be a consequence of rather than a prerequisite for improved social information processing. PMID:21641726

  16. 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

  17. Limit analysis and homogenization of porous materials with Mohr–Coulomb matrix. Part I: Theoretical formulation

    NASA Astrophysics Data System (ADS)

    Anoukou, K.; Pastor, F.; Dufrenoy, P.; Kondo, D.

    2016-06-01

    The present two-part study aims at investigating the specific effects of Mohr-Coulomb matrix on the strength of ductile porous materials by using a kinematic limit analysis approach. While in the Part II, static and kinematic bounds are numerically derived and used for validation purpose, the present Part I focuses on the theoretical formulation of a macroscopic strength criterion for porous Mohr-Coulomb materials. To this end, we consider a hollow sphere model with a rigid perfectly plastic Mohr-Coulomb matrix, subjected to axisymmetric uniform strain rate boundary conditions. Taking advantage of an appropriate family of three-parameter trial velocity fields accounting for the specific plastic deformation mechanisms of the Mohr-Coulomb matrix, we then provide a solution of the constrained minimization problem required for the determination of the macroscopic dissipation function. The macroscopic strength criterion is then obtained by means of the Lagrangian method combined with Karush-Kuhn-Tucker conditions. After a careful analysis and discussion of the plastic admissibility condition associated to the Mohr-Coulomb criterion, the above procedure leads to a parametric closed-form expression of the macroscopic strength criterion. The latter explicitly shows a dependence on the three stress invariants. In the special case of a friction angle equal to zero, the established criterion reduced to recently available results for porous Tresca materials. Finally, both effects of matrix friction angle and porosity are briefly illustrated and, for completeness, the macroscopic plastic flow rule and the voids evolution law are fully furnished.

  18. Formulation and analysis of food-grade mineral hydrocarbons in toxicology studies.

    PubMed

    Walters, D G; Sherrington, K V; Worrell, N; Riley, R A

    1994-06-01

    Methods are presented for the formulation and rapid determination of mineral hydrocarbons (MHCs) in animal diet and tissue. Food grade white oils and low melting point waxes are mixed as liquids with powdered diet. Higher melting point waxes are first powdered using a novel atomization technique before dry mixing with diet. MHCs sufficiently soluble in carbon tetrachloride (CCl4) are determined in diet by ultrasonic solvent extraction, adsorption of polar material on Florisil and analysis of the residue by quantitative Fourier Transform Infra Red (FT-IR) spectroscopy. Quantification in tissue is achieved by aqueous saponification, followed by extraction, clean-up and FT-IR analysis as for diet samples. A 10-fold increase in sensitivity over previous methods is achieved, below 0.002% (w/w) in diet and 0.1 mg/g in tissue. Over 80% of the CCl4 used can be recovered and recycled. Control diet seems to contain approximately 0.003% (w/w) background MHC. The method was modified for one powdered wax, only sparingly soluble in CCl4, high concentrations being extracted from diet by flotation in aqueous cetrimide and determined gravimetrically with a limit of detection of 0.1% (w/w) in diet. Application of these methods to 90-day feeding studies is described, and future developments due to the phasing out of CCl4 are discussed.

  19. 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.

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

    DOE PAGES

    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

  1. 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.

  2. Limit analysis and homogenization of porous materials with Mohr-Coulomb matrix. Part I: Theoretical formulation

    NASA Astrophysics Data System (ADS)

    Anoukou, K.; Pastor, F.; Dufrenoy, P.; Kondo, D.

    2016-06-01

    The present two-part study aims at investigating the specific effects of Mohr-Coulomb matrix on the strength of ductile porous materials by using a kinematic limit analysis approach. While in the Part II, static and kinematic bounds are numerically derived and used for validation purpose, the present Part I focuses on the theoretical formulation of a macroscopic strength criterion for porous Mohr-Coulomb materials. To this end, we consider a hollow sphere model with a rigid perfectly plastic Mohr-Coulomb matrix, subjected to axisymmetric uniform strain rate boundary conditions. Taking advantage of an appropriate family of three-parameter trial velocity fields accounting for the specific plastic deformation mechanisms of the Mohr-Coulomb matrix, we then provide a solution of the constrained minimization problem required for the determination of the macroscopic dissipation function. The macroscopic strength criterion is then obtained by means of the Lagrangian method combined with Karush-Kuhn-Tucker conditions. After a careful analysis and discussion of the plastic admissibility condition associated to the Mohr-Coulomb criterion, the above procedure leads to a parametric closed-form expression of the macroscopic strength criterion. The latter explicitly shows a dependence on the three stress invariants. In the special case of a friction angle equal to zero, the established criterion reduced to recently available results for porous Tresca materials. Finally, both effects of matrix friction angle and porosity are briefly illustrated and, for completeness, the macroscopic plastic flow rule and the voids evolution law are fully furnished.

  3. An analysis of cytotoxic botanical formulations used in the traditional medicine of ancient Persia as abortifacients.

    PubMed

    Madari, Hamta; Jacobs, Robert S

    2004-08-01

    We report here an analysis of plants used by traditional healers of ancient Persia to induce abortions. Six herbal formulations that contain 39 different species from 21 plant families with their vernacular names, English names, amounts used, and their methods of preparation are reported. Our initial objective of this ethnobotanical analysis was to evaluate the validity and the efficacy of the plants used by (1) comparing other reported uses of these plants in traditional medicine, (2) investigating the medical and pharmacological literature on the medicinal properties of the plant species used, and (3) investigating the reported cytotoxic effects of compounds prevalent in these plants. Previous phytochemical analyses have shown that a number of plant species are rich in coumarin compounds that have potential antineoplastic or cytotoxic activities. Our results indicate a correlation between the reported use of these plants as abortifacients and their cytotoxic (antineoplastic) effects. In addition, we discuss the process in which this ethnobotanical investigation led to the discovery of dicoumarol (a coumarin anticoagulant) as a potential chemotherapeutic agent.

  4. 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…

  5. 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...

  6. Clinical observations on the course of oxytocin- or prostaglandin E2/oxytocin-induced parturition in mares.

    PubMed

    Witkowski, M; Witkowski, M; Pawłowski, K

    2014-01-01

    The objective of this study was to compare the course of parturitions induced with sole oxytocin with those induced with the combination of intracervical prostaglandin E2 jelly and oxytocin. For this purpose 13 mares in advanced pregnancy were allocated to the groups pretreated with either intracervical PGE2 (experimental group) or saline (control group) two hours before intravenous oxytocin (5 IU) administration. The mares were compared with respect to cervical dilation diameter (CDD) 20 min. after oxytocin injection. Time intervals from the first oxytocin dose to: the first external signs of parturition, the chorioallantois rupture, the delivery of a foal and time interval from the delivery of a foal to the placenta separation were measured. Cervical dilatation diameter as well as proportion of mares with cervical dilatation > 20 cm were significantly higher in the group of PGE2 treated mares comparing with control group (p = 0.0115 and p = 0.0490, respectively). All time intervals measured were statistically insignificant for both groups of mares, however time intervals from the first oxytocin dose to the first external signs of parturition, to the allantochorion rupture and to the delivery of a foal, were very close to the significance level (alpha = 0.05). To conclude, PGE/oxytocin combination has positive influence on the preparation of the uterine cervix to parturition. Moreover, it seems that PGE2 pretreatment reduced total oxytocin dose for successful parturition induction and shortened time elapsing between the first oxytocin dose and the delivery of a foal what is crucial for foal's safety.

  7. Screening of monoclonal antibody formulations based on high-throughput thermostability and viscosity measurements: design of experiment and statistical analysis.

    PubMed

    He, Feng; Woods, Christopher E; Trilisky, Egor; Bower, Keith M; Litowski, Jennifer R; Kerwin, Bruce A; Becker, Gerald W; Narhi, Linda O; Razinkov, Vladimir I

    2011-04-01

    The purpose of this study was to demonstrate the utility of combining a design of experiment (DOE) approach with high-throughput formulation screening to identify the main factors affecting protein thermostability and solution viscosity. The optimization of buffer compositions was guided by statistical analysis of the data to obtain the targeted combination of low viscosity and high thermostability. Different monoclonal antibody (mAb) formulation variables were evaluated in the study to achieve optimization of two parameters: (i) thermostability characterized by temperature of hydrophobic exposure and (ii) viscosity. High-throughput measurements were employed to characterize both parameters. The significance of each factor and the two-way interactions between them was studied by multivariable regression analysis. An experimental design was used to estimate the significance of all factors, including interaction effects. The range of optimal buffer compositions that maximized thermostability and minimized viscosity of a mAb formulation was determined. The described high-throughput methods are well suited for characterization of multiple protein formulation compositions with minimized resources such as time and material. The DOE approach can be successfully applied to the screening of mAb formulations early in the development lifecycle.

  8. Oxytocin's role in anxiety: a critical appraisal.

    PubMed

    MacDonald, Kai; Feifel, David

    2014-09-11

    A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety states, anxiety-related traits, and moreover, that this system may be a target for the development of novel anxiolytic treatments. However, studies of OT's acute and chronic effects on various aspects of anxiety have produced mixed results. In this forward-looking review, we discuss the myriad phenomena to which the term "anxiety" is applied in the OT literature and the problem this presents developing a coherent picture of OT's role in anxiety. We then survey several different fields of research that support the role of the OT system in human anxiety, including evolutionary perspectives, translational and neuroimaging research, genetic studies, and clinical trials of intranasal OT. As an outgrowth of this data, we propose a "bowtie" model of OT's role at the interface of social attachment and anxiety. We next direct attention to understudied brain regions and neural circuits which may be important to study in OT experiments in humans anxiety disorders. Finally, we conclude by proposing questions and priorities for studying both the clinical potential of OT in anxiety, as well as mechanisms that may underlie this potential. Crucially, these priorities include targeted proof-of-concept clinical trials of IN OT in certain anxiety disorders, including investigations of individual moderators of OT's anxiolytic effects (i.e. sex, genetic factors, and early experience). This article is part of a Special Issue entitled Oxytocin and Social Behav.

  9. Sense and sensibility: Swedish midwives' ambiguity to the use of synthetic oxytocin for labour augmentation.

    PubMed

    Ekelin, Maria; Svensson, Judith; Evehammar, Susanne; Kvist, Linda J

    2015-03-01

    The use of intravenous artificial oxytocin for augmentation of labour is very common in midwifery care in Sweden. Studies have shown that oxytocin is often administered to women in labour who have no signs of labour dystocia. It was the aim of this study to examine Swedish midwives' views on and experiences of labour augmentation in the context of normal labour. Individual interviews were carried out with 15 midwives from southern Sweden. The material was analysed using qualitative content analysis, which resulted in one theme: sense and sensibility and four main categories: permissible situations, motivating the decision, intervening in the birth process and iatrogenic awareness. The results showed that midwives expressed ambiguity about augmentation of labour. They were of the opinion that oxytocin was used very often and sometimes unnecessarily. There is awareness that interventions to augment labour can result in undesirable effects on the birth process. Despite this, deeper discussion of this problem was avoided in the interviews. Further research should focus on the process involved when midwives weigh pros and cons when deciding to augment labour. More knowledge is also needed about the barriers for optimal care in labour that are inherent in health-care systems.

  10. The effect of intranasal oxytocin versus placebo treatment on the autonomic responses to human sounds in autism: a single-blind, randomized, placebo-controlled, crossover design study

    PubMed Central

    2014-01-01

    Background Many individuals with autism spectrum disorders (ASD) have difficulty with verbal communication, which might be due to a lack of spontaneous orientation toward social auditory stimuli. Previous studies have shown that a single dose of oxytocin improves speech comprehension in autism. The primary aim of this study was to investigate whether the orientation behaviors toward human sounds are different for neurotypical (NT) adults and adults with ASD and whether oxytocin has an effect on their orientation behaviors toward human sounds. Methods This was a randomized, placebo-controlled, within-subject, crossover design study of intranasal oxytocin versus placebo in 13 NT adults and 16 adults with ASD. Subjects were randomized to 24 IU intranasal oxytocin or placebo on different days, and they were blind to the treatment. The participants then listened passively to human and non-human affective sounds while their skin conductance responses (SCRs) and the changes in peripheral blood vessel constriction were monitored as an indicator of spontaneous orientation. The monitored data were analyzed by a mixed-design ANOVA. Results Oxytocin enhanced the difference between the SCRs to human and non-human sounds in both the NT and ASD groups (F(1,56) = 6.046, p = 0.017). Further correlation coefficient analysis showed significant correlations between this SCR difference and the scores in the autism spectrum quotient ‘attention to detail’ and ‘social skill’ subscales and interpersonal reactivity index and social functioning scale in the ASD group. Oxytocin was well tolerated, and no serious adverse effects were reported. Conclusions The difference in SCRs implies that oxytocin nasal spray may enhance orientation behaviors toward human sounds in the presence of other environmental sounds in both ASD and NT adults. Trial registration UMIN-CTR Clinical Trial, Unique trial number: UMIN000005809 PMID:24576333

  11. 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.

  12. 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.

  13. Sustained delivery of intact drug to the colon: mesalamine formulation and temporal gastrointestinal transit analysis.

    PubMed

    Chuong, Monica C; Christensen, J Mark; Ayres, James W

    2009-01-01

    The goal was to use temporal gastrointestinal transit simulations and formulation to predict and provide sustained input of target-site directed oral drug delivery exclusively into the colon. Using mesalamine as the model drug for formulation coupled with stomach emptying rates (fed and unfed) plus intestinal transit times demonstrates concepts and provides a specific example for treatment in ulcerative colitis. Formulation involved extrusion and spheronization into beads which were then coated with aqueous Eudragit S. Drug is released only at colonic pH and gastrointestinal transit predicts sustained drug input into the colon, especially when food effects are included. PMID:18821272

  14. [Postpartal serum bilirubin levels in the newborn after induction of labour with "prostaglandin cap" or oxytocin (author's transl)].

    PubMed

    Grünberger, W; Coradello, H; Huber, J; Husslein, P

    1981-04-01

    In the course of a prospective study the development of Serum bilirubine levels was controlled in 90 neonates. In 30 cases labour had been induced by means of intravenous oxytocin infusion, in a further 30 cases by means of local peri-cervical prostaglandine E2 (PGE2)-application. The control group consisted of 30 children, with spontaneous onset of labour. Anamnesis, duration of gravidity, course of labour and method of delivery were the same in all groups; the neonates were all treated the same. The serum bilirubine was determined fotometrically with the Greiner Selective Analyzer GSA II on the 1st, 3rd and 5th post partum day and the results assessed by the multivariant analysis according to Newman-Keuls. No differences were found between the PGE2- and the control group, the bilirubine values of the oxytocin groups were significantly higher (p less than 0.001). Icteric neonates with serum bilirubine values of greater than 12 mg% were found more than double as often in the oxytocin group than in the PGE2- group (7:3). The results indicate, that for labour induction by pharmaceuticals, local application of PGE2 by means of a portio cap should be favored over intravenous oxytocin administration.

  15. [Oxytocin: evidence for a therapeutic potential of the social neuromodulator].

    PubMed

    Eckstein, M; Hurlemann, R

    2013-11-01

    Only few substances have achieved such a great prominence in recent years as the hypothalamic neuropeptide oxytocin, which is also widely known as the love hormone. Oxytocin is a potent neuromodulator which can improve social cognitive functions including empathy, trust, cooperation and social learning. However, oxytocin can also promote negative social behavior and increase poor memory and feelings of fear in social situations. Positive data from initial clinical trials give rise to the hope that oxytocin will prove to be a substance which is suitable for targeted treatment of poor social-cognitive behavior in neuropsychiatric diseases. This review article summarizes the most important recent preclinical and clinical human studies and discusses the findings presented with respect to current concepts of personal and contextual influences. PMID:24190030

  16. 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

  17. 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

  18. Hypnosis, attachment, and oxytocin:an integrative perspective (1.).

    PubMed

    Zelinka, Vladimir; Cojan, Yann; Desseilles, Martin

    2014-01-01

    This article considers links between clinical hypnosis, attachment theory, and oxytocin. First, it proposes that commonalities between clinical hypnosis and attachment theory may improve our understanding of the hypnotherapeutic process. Then, it suggests that an integrative model unifying clinical hypnosis and attachment theory may constitute a link between clinical hypnosis and a neurobiological factor such as oxytocin. Finally, it discusses the implications of these hypotheses for clinical practice and future researches.

  19. A qualitative analysis of the elements used by palliative care clinicians when formulating a survival estimate

    PubMed Central

    Clarkson, Rose; Selby, Debbie; Myers, Jeff

    2013-01-01

    Objective For patients with advanced and/or incurable disease, clinicians are often called upon to formulate and communicate an estimate of likely survival duration. The objective of this study was to gain a deeper appreciation of this process by identifying and exploring the specific elements that may inform and/or impact a clinician's estimate of survival (CES). Methods Semistructured interviews were conducted among a group of palliative care clinicians in the setting of a tertiary academic health sciences centre. Qualitative data were subsequently analysed using a grounded theory approach. Results Five major themes were identified as being central to the process of CES formulation: use of objective patient-specific elements, strength of the patient-clinician relationship, purpose and context of an individual CES, perceived role of hope and the overall likelihood of CES inaccuracy. Conclusions For any given patient, several elements have the potential to inform and/or impact the process of CES formulation. Study participants were aware of objective clinical factors known to correlate with actual survival duration and likely integrate this information when formulating a CES. Formulation occurs within a larger context comprised of a number of elements that may influence individual estimates. These elements exist against a background of awareness of the overall likelihood of CES inaccuracy. Clinicians are encouraged to develop a personalised and standardised approach to CES formulation whereby an awareness of the menu of potentially impacting elements is consciously integrated into an individual process. PMID:24644752

  20. 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

  1. 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

  2. The effect of intranasal administration of oxytocin on fear recognition.

    PubMed

    Fischer-Shofty, M; Shamay-Tsoory, S G; Harari, H; Levkovitz, Y

    2010-01-01

    The oxytocinergic system has recently been placed amongst the most promising targets for various psychiatric treatments due to its role in prosocial behavior and anxiety reduction. Although recent studies have demonstrated a general effect of administration of oxytocin on emotion recognition, no study to date has examine the effect of oxytocin on each emotion separately. In the present study, a double-blind placebo-controlled crossover design was used in a dynamic facial expression task, in order to assess the effects of administration of oxytocin on emotion recognition. A single dose of oxytocin or a placebo was administered intranasally to 27 healthy male subjects 45 min prior to task performance. The results showed that a single intranasal administration of oxytocin, as opposed to the placebo, improved the subjects' ability to recognize fear, but not other emotions. These results suggest a specific role for oxytocin in fear recognition, which could be relevant for clinical disorders that manifest deficits in processing emotional facial expressions, particularly fear. PMID:19747930

  3. 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

  4. Molluscicidal efficacies of different formulations of niclosamide: result of meta-analysis of Chinese literature.

    PubMed

    Yang, Guo-Jing; Li, Wei; Sun, Le-Ping; Wu, Feng; Yang, Kun; Huang, Yi-Xin; Zhou, Xiao-Nong

    2010-09-07

    The control efforts on Oncomelania hupensis, the intermediate snail host of Schistosoma japonicum, cannot be easily excluded from the integrated approach of schistosomiasis control in China. Application of chemical compounds, molluscicides, in snail habitats is a common method for snail control in addition to environmental modification. We conducted a systematic review and meta-analysis to assess the molluscicidal effects of the currently recommended 50% niclosamide ethanolamine salt wettable powder and a new 4% niclosamide ethanolamine salt powder developed by Chinese researchers. Literature was searched from three Chinese databases, i.e. Chinese Biomedical Database, VIP Database and Wanfang Database, on field mollusciciding trials of niclosamide in China (from January 1, 1990 to April 1, 2010). Molluscicidal effects on reduction of snail population of the 50% or 4% niclosamide formulations in field trial were evaluated 3 days, 7 days or 15 days post-application. Out of 90 publications, 20 papers were eventually selected for analysis. Publication bias and heterogeneity tests indicated that no publication bias existed but heterogeneity between studies was present. Meta-analysis in a random effect model showed that the snail mortality of 3, 7 and 15 days after spraying the 50% niclosamide ethanolamine salt wettable powder were 77% [95%CI: 0.68-0.86], 83% [95%CI: 0.77-0.89], and 88% [95%CI: 0.82-0.92], respectively. For the 4% niclosamide ethanolamine salt powder, the snail mortality after 3, 7 and 15 days were 81% [95%CI: 0.65-0.93], 90% [95%CI: 0.83-0.95] and 94% [95%CI: 0.91-0.97], respectively. Both are good enough to be used as molluscicides integrated with a schistosomiasis control programme. The 4% niclosamide ethanolamine salt powder can be applied in the field without water supply as the surrogate of the current widely used 50% niclosamide ethanolamine salt wettable powder. However, to consolidate the schistosomiasis control achievement gained, it is

  5. Stability-indicating micellar electrokinetic chromatography method for the analysis of sumatriptan succinate in pharmaceutical formulations.

    PubMed

    Al Azzam, Khaldun M; Saad, Bahruddin; Tat, Chai Yuan; Mat, Ishak; Aboul-Enein, Hassan Y

    2011-12-15

    A micellar electrokinetic chromatography method for the determination of sumatriptan succinate in pharmaceutical formulations was developed. The effects of several factors such as pH, surfactant and buffer concentration, applied voltage, capillary temperature, and injection time were investigated. Separation took about 5 min using phenobarbital as internal standard. The separation was carried out in reversed polarity mode at 20 °C, 26 kV and using hydrodynamic injection for 10s. Separation was achieved using a bare fused-silica capillary 50 μm×40 cm and background electrolyte of 25 mM sodium dihydrogen phosphate-adjusted with concentrated phosphoric acid to pH 2.2, containing 125 mM sodium dodecyl sulfate and detection was at 226 nm. The method was validated with respect to linearity, limits of detection and quantification, accuracy, precision and selectivity. The calibration curve was linear over the range of 100-2000 μg mL(-1). The relative standard deviations of intra-day and inter-day precision for migration time, peak area, corrected peak area, ratio of corrected peak area and ratio of peak area were less than 0.68, 3.48, 3.28, 2.97 and 2.83% and 2.01, 5.50, 4.46, 4.92 and 4.07%, respectively. The proposed method was successfully applied to the determinations of the analyte in tablet. Forced degradation studies were conducted by introducing a sample of sumatriptan succinate standard solution to different forced degradation conditions using neutral (water), basic (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H(2)O(2)) and photolytic (exposure to UV light at 254 nm for 2 h). It is concluded that the stability-indicating method for sumatriptan succinate can be used for the analysis of the drug in various samples.

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

    PubMed Central

    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

  7. 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

  8. Central administration of oxytocin differentially increases yawning, penile erections and scratching in high- (HY) and low-yawning (LY) sublines of Sprague-Dawley rats.

    PubMed

    Eguibar, Jose R; Cortes, Carmen; Isidro, O; Ugarte, A

    2015-07-01

    Central administration of oxytocin has been shown to induce yawning, penile erection, grooming and scratching. Yawning and penile erections are due to activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus. We selectively bred two sublines from Sprague-Dawley rats, one with a high-yawning frequency (HY) of 20yawns/h, and one with a low-yawning (LY) frequency of 2yawns/h. The aim of the current study was to analyze the behavioral effects of centrally-administered oxytocin [15ng-10μg; intracerebroventricularly (i.c.v.)] on yawning, penile erections, grooming and scratching in adult male rats from both sublines. Oxytocin produced a dose-dependent increase in yawning and penile erection frequencies and this effect was significantly higher in the HY, compared to the LY, subline. However, the number of oxytocin-induced scratching bouts was significantly higher in the LY, compared to the HY group. In conclusion, these sublines represent a suitable model for detailed analysis of behavior induced by oxytocin and other neuropeptides in animals with different spontaneous expression of behavioral traits.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Oxytocin decreases sweet taste sensitivity in mice.

    PubMed

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

    2015-03-15

    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 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM 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 (0.1mg/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 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). 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.

  16. 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

  17. 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.

  18. Spectral analysis of pharmaceutical formulations prepared according to ancient recipes in comparison with old museum remains.

    PubMed

    Gamberini, M Cristina; Baraldi, C; Freguglia, G; Baraldi, P

    2011-10-01

    A study of the composition of the remains of ancient ointments from museums was undertaken to enable understanding of the preparation techniques. Comparison of ancient recipes from different historical periods and spectroscopic characteristics of inorganic and/or organic remains recovered in museum vessels enabled preparation of ancient pharmaceutical-cosmetic formulations. Farmacopea Augustana by Occo was one the most important books studied for the 14 formulations prepared in the laboratory. Three formulations are discussed in detail and raw materials and new preparations were proposed for ozone ageing. The most important micro Raman results are discussed. The spectra of the raw materials lipids, beeswax, and resins are discussed; beeswax and pig suet (axŭngia) Raman spectra were found to be similar, but different from those of the aged oils. SERS was applied to ancient ointments and galbanum and the Raman spectra are reported and discussed for the first time.

  19. Multivariate analysis of phenol in freeze-dried and spray-dried insulin formulations by NIR and FTIR.

    PubMed

    Maltesen, Morten Jonas; Bjerregaard, Simon; Hovgaard, Lars; Havelund, Svend; van de Weert, Marco; Grohganz, Holger

    2011-06-01

    Dehydration is a commonly used method to stabilise protein formulations. Upon dehydration, there is a significant risk the composition of the formulation will change especially if the protein formulation contains volatile compounds. Phenol is often used as excipient in insulin formulations, stabilising the insulin hexamer by changing the secondary structure. We have previously shown that it is possible to maintain this structural change after drying. The aim of this study was to evaluate the residual phenol content in spray-dried and freeze-dried insulin formulations by Fourier transform infrared (FTIR) spectroscopy and near infrared (NIR) spectroscopy using multivariate data analysis. A principal component analysis (PCA) and partial least squares (PLS) projections were used to analyse spectral data. After drying, there was a difference between the two drying methods in the phenol/insulin ratio and the water content of the dried samples. The spray-dried samples contained more water and less phenol compared with the freeze-dried samples. For the FTIR spectra, the best model used one PLS component to describe the phenol/insulin ratio in the powders, and was based on the second derivative pre-treated spectra in the 850-650 cm(-1) region. The best PLS model based on the NIR spectra utilised three PLS components to describe the phenol/insulin ratio and was based on the standard normal variate transformed spectra in the 6,200-5,800 cm(-1) region. The root mean square error of cross validation was 0.69% and 0.60% (w/w) for the models based on the FTIR and NIR spectra, respectively. In general, both methods were suitable for phenol quantification in dried phenol/insulin samples.

  20. Oxytocin action at the lactotroph is required for prolactin surges in cervically stimulated ovariectomized rats

    PubMed Central

    McKee, De'Nise T.; Poletini, Maristela O.; Bertram, Richard; Freeman, Marc E.

    2007-01-01

    Cervical stimulation induces two daily rhythmic prolactin surges, nocturnal and diurnal, which persist for several days. We have shown that a bolus injection of oxytocin initiates a similar prolactin rhythm, which persists despite low levels of oxytocin following injection. This suggests that oxytocin may trigger the cervical stimulated-induced rhythmic prolactin surges. To investigate this hypothesis, we infused an oxytocin antagonist that does not cross the blood brain barrier for 24h before and after cervical stimulation and measured serum prolactin. We also measured dopaminergic neuronal activity, since mathematical modeling predicted that this activity would be low in the presence of the oxytocin antagonist. We thus tested this hypothesis by measuring dopaminergic neuronal activity in the tuberoinfundibular, periventricular hypophyseal, and tuberohypophyseal dopaminergic neurons. Infusion of oxytocin antagonist before cervical stimulation abolished prolactin surges and infusion of oxytocin antagonist after cervical stimulation abolished the diurnal and significantly decreased the nocturnal surges of prolactin. The rhythmic prolactin surges returned after the clearance of the oxytocin antagonist. Hypothalamic dopaminergic activity was elevated in anti-phase with prolactin surges and the anti-phase elevation was abolished by the oxytocin antagonist in the tuberoinfundibular and tuberohypophyseal dopaminergic neurons, consistent with the mathematical model. These findings suggest that oxytocin is a physiologically relevant prolactin-releasing factor. However, the cervical stimulated-induced prolactin surges are maintained even in the absence of oxytocin actions at the lactotroph which strongly suggests the maintenance of prolactin surges are not dependent upon oxytocin actions at the pituitary gland. PMID:17615142

  1. Analysis of a non-linear structure by considering two non-linear formulations

    NASA Astrophysics Data System (ADS)

    Majed, R.; Raynaud, J. L.

    2003-03-01

    In recent years, modal synthesis methods have been extended for solving non-linear dynamic problems subjected to harmonic excitation. These methods are based on the notion of non-linear or linearized modes and exploited in the case of structures affected by localized non-linearity. Actually, the experimental tests executed on non-linear structures are time consuming, particularly when repeated experimental tests are needed. It is often preferable to consider new non-linear methods with a view to decrease significantly the number of attempts during prototype tests and improving the accuracy of the dynamic behaviour. This article describes two fundamental non-linear formulations based on two different strategies. The first formulation exploits the eigensolutions of the associated linear system and the dynamics characteristics of each localized non-linearity. The second formulation is based on the exploitation of the linearized eigensolutions obtained using an iterative process. This article contains a numerical and an experimental study which examines the non-linear behaviour of the structure affected by localized non-linearities. The study is intended to validate the numerical algorithm and to evaluate the problems arising from the introduction of non-linearities. The complex responses are evaluated using the iterative Newton-Raphson method and for a series of discrete frequencies. The theory has been applied to a bi-dimensional structure and consists of evaluating the harmonic responses obtained using the proposed formulations by comparing measured and calculated transfer functions.

  2. 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

  3. An elasto-viscoplastic constitutive formulation for dry powder compression analysis using finite elements

    NASA Astrophysics Data System (ADS)

    Mittal, Bhavishya

    The aim of this research was to measure, analyze, model, and predict the rate-dependent mechanical behavior of dry powders undergoing compression in a die. Mechanical properties of two ceramic powders (MZF and alumina) were studied up to 14 MPa using a medium pressure flexible boundary cubical triaxial tester (CTT). The powders were subjected to undrained tests along two stress paths and three compression rates of 0.62, 6.21, and 20.7 MPa/minute. Based on test results from compression and shear stress paths, a new elasto-viscoplastic constitutive model (PSU-EVP) was developed for studying the dry powder compression process. The PSU-EVP model was formulated using the critical state theory, the modified Cam-clay model, and the Adachi and Oka model as the basis. Unlike the modified Cam-clay model, the PSU-EVP model explicitly accounts for the work done in the volumetric compression of pore air or gas during dry powder compression. This key feature of the PSU-EVP model helps in isolating the effect of entrapped pore air (or gas) on the mechanical properties of powders. Based on the PSU-EVP constitutive model back-prediction results and sensitivity analysis, it was concluded that the model gave fairly good results for most CTT test data collected at 0.62 MPa/minute and 6.21 MPa/minute. However, the back-prediction results obtained at 20.7 MPa/minute had high average relative difference values (>20%). Overall, the PSU-EVP model can be considered to be the first step towards the development of a more robust and accurate constitutive model for the predicting stress distributions in a dry powder during compression process. A 3D finite element prediction tool (PSU-FEM v2.0 software) was developed to model the powder compression process in an elastic die. The PSU-FEM v2.0 contained a fast iterative solver based on the multigrid method. The results obtained from the multigrid solver were compared with a conventional Gauss-Siedel iterative method, conjugate gradient, and ABAQUS

  4. 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

  5. Mathematical Analysis of Continuum Electrodynamics: Implications for the Kinetic Formulation of Light

    NASA Astrophysics Data System (ADS)

    Sheppard, Cheyenne J.

    Optical momentum within material media has been studied for a century. Although great strides have been made towards understanding photon momenta, there is still a question regarding the correct momentum of light. This is due to the many mathematical interpretations of Maxwell's unification of electromagnetism, yielding many independent views of classical electrodynamic quantities. Within this correspondence, the optical momentum controversy is studied via mathematical principles of continuum relativistic electrodynamics. The electromagnetic wave momentum is studied via moving contribution, where a framework for moving media is developed. Application of the framework with respect to independent formulations of electrodynamics are shown to be consistent with conservation of energy and momentum. In doing this, thought experiments are employed to test each approach and demonstrate the electrodynamic forces with respect to each formulation. This is first applied to two moving perfect reflector submerged in a dielectric medium such that both Abraham and Minkowski momenta are derived. Second, a moving slab of moving magneto-dielectric material is studied expanding the arguments into time average and time varying calculations. Each approach is consistent with electromagnetic wave theory and demonstrates the mathematical methods for deriving the both Abraham and Minkowski momentum models. The kinetic subsystem is studied by use of established physical principles, namely the Lagrangian. The field energy density and momentum density are used to derive the force expressions of electromagnetic fields. This formulates the respective system of equations, forming Maxwell's equations in terms of the field energy and momentum density. By use of the relativistic principle of virtual power, the Maxwell field stress tensor and kinetic momentum density are derived uniquely, disproving specific electrodynamic formulations as the kinetic formulation.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Method-of-moments formulation for the analysis of plasmonic nano-optical antennas.

    PubMed

    Taboada, José M; Rivero, Javier; Obelleiro, Fernando; Araújo, Marta G; Landesa, Luis

    2011-07-01

    We present a surface integral equation (SIE) to model the electromagnetic behavior of metallic objects at optical frequencies. The electric and magnetic current combined field integral equation considering both tangential and normal equations is applied. The SIE is solved by using a method-of-moments (MoM) formulation. The SIE-MoM approach is applied only on the material boundary surfaces and interfaces, avoiding the cumbersome volumetric discretization of the objects and the surrounding space required in differential-equation formulations. Some canonical examples have been analyzed, and the results have been compared with analytical reference solutions in order to prove the accuracy of the proposed method. Finally, two plasmonic Yagi-Uda nanoantennas have been analyzed, illustrating the applicability of the method to the solution of real plasmonic problems. PMID:21734731

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

    PubMed

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

    2014-02-01

    Oxytocin (OT) 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 CE method using UV detection at 214 nm for the determination of the deamidation products of OT. 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 OT, 11 mM sulfobutyl ether β-CD and 10% v/v MeOH were added to a BGE 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 OT at 70°C, where all seven desamino species were observed over a 96 h period.

  13. Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies.

    PubMed

    Kumru, Ozan S; Joshi, Sangeeta B; Smith, Dawn E; Middaugh, C Russell; Prusik, Ted; Volkin, David B

    2014-09-01

    Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.

  14. Gravity-induced coating flows of vaginal gel formulations: in vitro experimental analysis.

    PubMed

    Kieweg, Sarah L; Geonnotti, Anthony R; Katz, David F

    2004-12-01

    Efficacy of topical microbicidal drug delivery formulations against HIV depends in part on their coating distributions and retention on vaginal epithelium. This study focused on gravity-induced coating flows of vaginal gels, and effects of formulation composition and surface wettability on coating. We hypothesized that presence of a yield stress, and surface wettability, affect coating. Experiments imaged and analyzed coating flows of gels on inclined model hydrophilic or hydrophobic surfaces. The in vitro wettability conditions bracket those believed to exist on vaginal epithelium in vivo. Six commercial vaginal gels were studied: three polyacrylic acid-based (PAA) and three cellulose-based. Our research group uses these gels in complementary human in vivo studies and other in vitro experimental analyses; this study is a first step in linking the in vivo and in vitro measurements. Coating by PAA gels was different from cellulose-based gels: the former exhibited yield stresses, which prevented initial gel shape from deforming during sliding. Coating flows of cellulose gels depended upon surface wettability. The slipping rates of the PAA gels ranked inversely with fitted yield stress values. The coating flow rates of the cellulose gels (hydrophilic surface) did not correlate with consistency index, but ranked inversely with the shear-thinning index. This study introduces a simple methodology for comparing trial formulations and relating their flows to gel constituents and physical properties. It also suggests differences in coating by current commercial gels.

  15. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

    PubMed

    Nagasawa, Miho; Mitsui, Shouhei; En, Shiori; Ohtani, Nobuyo; Ohta, Mitsuaki; Sakuma, Yasuo; Onaka, Tatsushi; Mogi, Kazutaka; Kikusui, Takefumi

    2015-04-17

    Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment. PMID:25883356

  16. A novel strategy for quantitative analysis of the formulated complex system using chromatographic fingerprints combined with some chemometric techniques.

    PubMed

    Zhong, Xuan; Yan, Jun; Li, Yan-Chun; Kong, Bo; Lu, Hong-Bing; Liang, Yi-Zeng

    2014-11-28

    In this work, a novel strategy based on chromatographic fingerprints and some chemometric techniques is proposed for quantitative analysis of the formulated complex system. Here, the formulated complex system means a formulated type of complicated analytical system containing more than one kind of raw material under some concentration composition according to a certain formula. The strategy is elaborated by an example of quantitative determination of mixtures consist of three essential oils. Three key steps of the strategy are as follows: (1) remove baselines of the chromatograms; (2) align retention time; (3) conduct quantitative analysis using multivariate regression with entire chromatographic profiles. Through the determination of concentration compositions of nine mixtures arranged by uniform design, the feasibility of the proposed strategy is validated and the factors that influence the quantitative result are also discussed. This strategy is proved to be viable and the validation indicates that quantitative result obtained using this strategy mainly depends on the efficiency of the alignment method as well as chromatographic peak shape of the chromatograms. Previously, chromatographic fingerprints were only used for identification and/or recognition of some products. This work demonstrates that with the assistance of some effective chemometric techniques, chromatographic fingerprints are also potential and promising in solving quantitative problems of complex analytical systems.

  17. Symbolic Formulation of Large-scale Open-loop Multibody Systems for Vibration Analysis Using Absolute Joint Coordinates

    NASA Astrophysics Data System (ADS)

    Jiang, Wei; Chen, Xuedong; Luo, Xin; Huang, Qingjiu

    A novel symbolic formulation is presented to model dynamics of large-scale open-loop holonomic multibody systems, by using absolute joint coordinates and via matrix transformation, instead of solving constraint equations. The resulting minimal set of second-order linear ordinary differential equations (ODEs) can be used for linear vibration analysis and control directly. The ODEs are generated in three steps. Firstly, a set of linearized ODEs are formulated in terms of absolute coordinates without considering any constraint. Secondly, an overall transform matrix representing constraint topology for the entire constrained system is generated. Finally, matrices for a minimal set of ODEs for the open-loop holonomic multibody system are obtained via matrix transformation. The correctness and efficiency of the presented algorithm are verified by numerical experiments on various cases of holonomic multibody systems with different open-loop topologies, including chain topology and tree topology. It is indicated that the proposed method can significantly improve efficiency without losing computational accuracy.

  18. Myometrial oxytocin receptor mRNA concentrations at preterm and term delivery - the influence of external oxytocin.

    PubMed

    Liedman, Ragner; Hansson, Stefan Rocco; Igidbashian, Sarah; Akerlund, Mats

    2009-03-01

    The hormonal system for induction of term and preterm labour is not fully understood. Therefore, we investigated myometrial gene expressions for neurohypophyseal hormones and their receptors, prostaglandin F(2alpha) and ovarian steroid receptors in women delivered by Caesarean section. Myometrial tissue for real time PCR was collected from 39 women delivered at term before and after the onset of labour and preterm. Women delivered electively at term had significantly higher oxytocin receptor mRNA expressions (2.52 +/- 0.37 oxytocin receptor/actin; median +/- SEM) than those delivered with ongoing labour at term (1.01 +/- 0.34; p = 0.015) and those at preterm (1.08 +/- 0.25; p = 0.004). Sub-analyses revealed that the difference at term pregnancies solely was related to patients receiving oxytocin during labour (p = 0.007). These patients had higher oxytocin peptide mRNA levels than those without labour at term (p = 0.009). PGF(2alpha) receptor mRNA concentrations were 27.80 +/- 3.55, 11.46 +/- 2.87 and 19.54 +/- 5.52 PGF receptor/actin, respectively, for the groups. Women without labour at term had higher concentration than those with labour (p = 0.005). Our results suggest that oxytocin, its receptor and the PGF(2alpha) receptor are involved in the regulation of labour through a paracrine mechanism.

  19. Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

    PubMed Central

    Ayers, Luke W; Missig, Galen; Schulkin, Jay; Rosen, Jeffrey B

    2011-01-01

    Oxytocin is known to have anti-anxiety and anti-stress effects. Using a fear-potentiated startle paradigm in rats, we previously demonstrated that subcutaneously administered oxytocin suppressed acoustic startle following fear conditioning compared with startle before fear conditioning (termed background anxiety), but did not have an effect on cue-specific fear-potentiated startle. The findings suggest oxytocin reduces background anxiety, an anxious state not directly related to cue-specific fear, but sustained beyond the immediate threat. The goal of the present study was to compare the effects of centrally and peripherally administered oxytocin on background anxiety and cue-specific fear. Male rats were given oxytocin either subcutaneously (SC) or intracerebroventricularly (ICV) into the lateral ventricles before fear-potentiated startle testing. Oxytocin doses of 0.01 and 0.1 μg/kg SC reduced background anxiety. ICV administration of oxytocin at doses from 0.002 to 20 μg oxytocin had no effect on background anxiety or cue-specific fear-potentiated startle. The 20 μg ICV dose of oxytocin did reduce acoustic startle in non-fear conditioned rats. These studies indicate that oxytocin is potent and effective in reducing background anxiety when delivered peripherally, but not when delivered into the cerebroventricular system. Oxytocin given systemically may have anti-anxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in many anxiety and mental health disorder patients. PMID:21796104

  20. Investigation of Oxytocin Secretion in Anorexia Nervosa and Bulimia Nervosa: Relationships to Temperament Personality Dimensions.

    PubMed

    Monteleone, Alessio Maria; Scognamiglio, Pasquale; Volpe, Umberto; Di Maso, Virginia; Monteleone, Palmiero

    2016-01-01

    Published studies suggested an implication of oxytocin in some temperament characteristics of personality. Therefore, we measured oxytocin secretion in 23 women with anorexia nervosa (AN), 27 with bulimia nervosa (BN) and 19 healthy controls and explored the relationships between circulating oxytocin and patients' personality traits. Plasma oxytocin levels were significantly reduced in AN women but not in BN ones. In healthy women, the attachment subscale scores of the reward dependence temperament and the harm avoidance (HA) scores explained 82% of the variability in circulating oxytocin. In BN patients, plasma oxytocin resulted to be negatively correlated with HA, whereas no significant correlations emerged in AN patients. These findings confirm a dysregulation of oxytocin production in AN but not in BN and show, for the first time, a disruption of the associations between hormone levels and patients' temperament traits, which may have a role in certain deranged behaviours of eating disorder patients.

  1. The role of oxytocin in familiarization-habituation responses to social novelty

    PubMed Central

    Tops, Mattie; Huffmeijer, Renske; Linting, Mariëlle; Grewen, Karen M.; Light, Kathleen C.; Koole, Sander L.; Bakermans-Kranenburg, Marian J.; van IJzendoorn, Marinus H.

    2013-01-01

    Stress or arousal responses to novel social contexts ease off when individuals get familiar with the social context. In the present study we investigated whether oxytocin is involved in this process of familiarization-habituation as oxytocin is known to increase trust and decrease anxiety. Fifty-nine healthy female subjects took part in the same experimental procedure in two sessions separated by 4 weeks. In the first (novelty) session state trust scores were significantly positively correlated with salivary oxytocin levels while in the second (familiarity) session state trust scores were significantly negatively correlated with salivary oxytocin levels. In a path model oxytocin was associated with increased trust in the novelty session and trust was associated with decreased oxytocin levels in the familiarity session. The results are consistent with the idea that oxytocin decreases stress-to-novelty responses by promoting familiarization to novel social contexts. PMID:24151482

  2. Oxytocin Increases the Influence of Public Service Advertisements

    PubMed Central

    Lin, Pei-Ying; Grewal, Naomi Sparks; Morin, Christophe; Johnson, Walter D.; Zak, Paul J.

    2013-01-01

    This paper presents a neurophysiologic model of effective public service advertisements (PSAs) and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH) and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs. PMID:23460821

  3. Cognitive bias in rats is not influenced by oxytocin

    PubMed Central

    McGuire, Molly C.; Williams, Keith L.; Welling, Lisa L. M.; Vonk, Jennifer

    2015-01-01

    The effect of oxytocin on cognitive bias was investigated in rats in a modified conditioned place preference paradigm. Fifteen male rats were trained to discriminate between two different cue combinations, one paired with palatable foods (reward training), and the other paired with unpalatable food (aversive training). Next, their reactions to two ambiguous cue combinations were evaluated and their latency to contact the goal pot recorded. Rats were injected with either oxytocin (OT) or saline with the prediction that rats administered OT would display a shorter average latency to approach on ambiguous trials. There was no significant difference between latencies to approach on ambiguous trials compared to reward trials, but the rats were significantly slower on the aversive compared to the ambiguous conditions. Oxytocin did not affect approach time; however, it was unclear, after follow-up testing, whether the OT doses tested were sufficient to produce the desired effects on cognitive bias. Future research should consider this possibility. PMID:26388811

  4. PA01.73. A retrospective analysis of efficacy of various ayurvedic formulations in psychiatric diseases

    PubMed Central

    Deole, Yogesh; Chaudhuri, Kundan; Chandola, H M; Murthy, A.R.V.

    2012-01-01

    Purpose: Mental disorders are high on rise in India. Epidemiological studies conducted in India on mental and behavioural disorders report varying prevalence rates, ranging from 9.5 to 370 per 1000 population. The overall DALYs burden for mental disorders is projected to increase to 15 per cent by the year 2020 and this increase is proportionately larger than that for cardiovascular diseases. Ayurveda bears great responsibility in preventing and treating the mental disorders. Medhya Rasayana is the treatment perspective to prevent and manage psychiatric disorders. In Ayurveda, Rasayana therapy has been stated as a unique therapy in curing mental diseases. It can promote memory and intelligence and can increase immunity against disease and promote strength and vitality as well as it can control ageing process by serving as anti oxidant agent. A review of various studies carried out in Ayurveda is made to enlist the best effective treatment measures in promoting and preventing mental disorders. Method: Available research works carried out at Institute for Post Graduate Teaching & Research in Ayurveda, Jamnagar from the year 2001 to 2012 are screened and referred with relation to mental disorders. The treatments are reviewed and enlisted for assessing the efficacy. Result: On reviewing the researches, it was found that nearly 15 works found suitable are carried out in relation to mental disorders. The data shows that Ayurvedic formulations like Aamalakyadi and Medhya Rasayana Ghrita (in Alzheimer's disease), Rasayana Ghana tablets (in stress), Rasona tablets, Brahmi ghrita, flax seed capsules and Ashwagandharishta (in depression), Shirodhara (in insomnia), Saraswatarishta (in perimenopausal syndrome) are effective in psychiatric diseases. Conclusion: Researches show that Ayurvedic formulations are effective in moderate manner in treating the psychiatric diseases. Ayurvedic Medhya Rasayana formulations can be used for preventing and managing psychiatric disorders.

  5. Oxytocin and vasopressin modulate risk-taking.

    PubMed

    Patel, Nilam; Grillon, Christian; Pavletic, Nevia; Rosen, Dana; Pine, Daniel S; Ernst, Monique

    2015-02-01

    The modulation of risk-taking is critical for adaptive and optimal behavior. This study examined how oxytocin (OT) and arginine vasopressin (AVP) influence risk-taking in function of three parameters: sex, risk-valence, and social context. Twenty-nine healthy adults (14 males) completed a risk-taking task, the Stunt task, both in a social-stress (evaluation by unfamiliar peers) and non-social context, in three separate drug treatment sessions. During each session, one of three drugs, OT, AVP, or placebo (PLC), was administered intra-nasally. OT and AVP relative to PLC reduced betting-rate (risk-averse effect). This risk-averse effect was further qualified: AVP reduced risk-taking in the positive risk-valence (high win-probability), and regardless of social context or sex. In contrast, OT reduced risk-taking in the negative risk-valence (low win-probability), and only in the social-stress context and men. The reduction in risk-taking might serve a role in defensive behavior. These findings extend the role of these neuromodulators to behaviors beyond the social realm. How the behavioral modulation of risk-taking maps onto the function of the neural targets of OT and AVP may be the next step in this line of research. PMID:25446228

  6. Oxytocin facilitates social approach behavior in women

    PubMed Central

    Preckel, Katrin; Scheele, Dirk; Kendrick, Keith M.; Maier, Wolfgang; Hurlemann, René

    2014-01-01

    In challenging environments including both numerous threats and scarce resources, the survival of an organism depends on its ability to quickly escape from dangers and to seize opportunities to gain rewards. The phylogenetically ancient neurohormonal oxytocin (OXT) system has been shown to influence both approach and avoidance (AA) behavior in men, but evidence for comparable effects in women is still lacking. We thus conducted a series of pharmacological behavioral experiments in a randomized double-blind study involving 76 healthy heterosexual women treated with either OXT (24 IU) or placebo intranasally. In Experiment 1, we tested how OXT influenced the social distance subjects maintained between themselves and either a female or male experimenter. In Experiment 2, we applied a reaction time based AA task. In Experiment 3 we investigated effects on peri-personal space by measuring the lateral attentional bias in a line bisection task. We found that OXT specifically decreased the distance maintained between subjects and the male but not the female experimenter and also accelerated approach toward pleasant social stimuli in the AA task. However, OXT did not influence the size of peri-personal space, suggesting that it does not alter perception of personal space per se, but rather that a social element is necessary for OXT's effects on AA behavior to become evident. Taken together, our results point to an evolutionarily adaptive mechanism by which OXT in women selectively promotes approach behavior in positive social contexts. PMID:24904342

  7. The neuropeptide oxytocin modulates consumer brand relationships.

    PubMed

    Fürst, Andreas; Thron, Jesko; Scheele, Dirk; Marsh, Nina; Hurlemann, René

    2015-01-01

    Each year, companies invest billions of dollars into marketing activities to embellish brands as valuable relationship partners assuming that consumer brand relationships (CBRs) and interpersonal relationships rest upon the same neurobiological underpinnings. Given the crucial role of the neuropeptide oxytocin (OXT) in social bonding, this study tests whether OXT-based mechanisms also determine the bond between consumers and brands. We conducted a randomized, placebo-controlled study involving 101 subjects and analyzed the effect of intranasal OXT on consumers' attribution of relationship qualities to brands, brands paired with human celebrity endorsers, and familiar persons. OXT indeed promoted the attribution of relationship qualities not only in the case of social and semi-social stimuli, but also brands. Intriguingly, for subjects scoring high on autistic-like traits, the effect of OXT was completely reversed, evident in even lower relationship qualities across all stimulus categories. The importance of OXT in a CBR context is further corroborated by a three-fold increase in endogenous release of OXT following exposure to one's favorite brand and positive associations between baseline peripheral OXT concentrations and brand relationship qualities. Collectively, our findings indicate that OXT not only plays a fundamental role in developing interpersonal relationships, but also enables relationship formation with objects such as brands. PMID:26449882

  8. Social vocalizations can release oxytocin in humans

    PubMed Central

    Seltzer, Leslie J.; Ziegler, Toni E.; Pollak, Seth D.

    2010-01-01

    Vocalizations are important components of social behaviour in many vertebrate species, including our own. Less well-understood are the hormonal mechanisms involved in response to vocal cues, and how these systems may influence the course of behavioural evolution. The neurohormone oxytocin (OT) partly governs a number of biological and social processes critical to fitness, such as attachment between mothers and their young, and suppression of the stress response after contact with trusted conspecfics. Rodent studies suggest that OT's release is contingent upon direct tactile contact with such individuals, but we hypothesized that vocalizations might be capable of producing the same effect. To test our hypothesis, we chose human mother–daughter dyads and applied a social stressor to the children, following which we randomly assigned participants into complete contact, speech-only or no-contact conditions. Children receiving a full complement of comfort including physical, vocal and non-verbal contact showed the highest levels of OT and the swiftest return to baseline of a biological marker of stress (salivary cortisol), but a strikingly similar hormonal profile emerged in children comforted solely by their mother's voice. Our results suggest that vocalizations may be as important as touch to the neuroendocrine regulation of social bonding in our species. PMID:20462908

  9. Oxytocin and cardioprotection in diabetes and obesity.

    PubMed

    Jankowski, Marek; Broderick, Tom L; Gutkowska, Jolanta

    2016-01-01

    Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs. PMID:27268060

  10. Oxytocin mediates social neuroprotection after cerebral ischemia

    PubMed Central

    Karelina, Kate; Stuller, Kathleen A.; Jarrett, Brant; Zhang, Ning; Wells, Jackie; Norman, Greg J.; DeVries, A. Courtney

    2011-01-01

    Background and Purpose The reduced incidence, morbidity and mortality of stroke among humans with strong social support have been well-documented; however, the mechanisms underlying this socially mediated phenomenon remain unknown, but may involve oxytocin (OT), a hormone that modulates some aspects of social behavior in humans and other animals. Methods In the present study, adult male mice were socially isolated (housed individually) or socially paired (housed with an ovariectomized female); social pairing increased hypothalamic OT gene expression. To determine whether a causal relationship exists between increased OT and improved stroke outcome, mice were treated with exogenous OT or OT receptor antagonist (OTA) beginning one week prior to induction of experimental stroke via middle cerebral artery occlusion (MCAO). Results Relative to social isolation, social housing attenuated infarct size, neuroinflammation, and oxidative stress following experimental stroke; the neuroprotective effect of social housing was eliminated by OTA treatment. In contrast, administration of OT to socially isolated mice reproduced the neuroprotection conferred by social housing. We further report evidence for a direct suppressive action of OT on cultured microglia, which is a key instigator in the development of neuroinflammation after cerebral ischemia. Conclusions These findings support the hypothesis that OT mediates the neuroprotective effect of social interaction on stroke outcome. PMID:21960564

  11. The neuropeptide oxytocin modulates consumer brand relationships

    PubMed Central

    Fürst, Andreas; Thron, Jesko; Scheele, Dirk; Marsh, Nina; Hurlemann, René

    2015-01-01

    Each year, companies invest billions of dollars into marketing activities to embellish brands as valuable relationship partners assuming that consumer brand relationships (CBRs) and interpersonal relationships rest upon the same neurobiological underpinnings. Given the crucial role of the neuropeptide oxytocin (OXT) in social bonding, this study tests whether OXT-based mechanisms also determine the bond between consumers and brands. We conducted a randomized, placebo-controlled study involving 101 subjects and analyzed the effect of intranasal OXT on consumers’ attribution of relationship qualities to brands, brands paired with human celebrity endorsers, and familiar persons. OXT indeed promoted the attribution of relationship qualities not only in the case of social and semi-social stimuli, but also brands. Intriguingly, for subjects scoring high on autistic-like traits, the effect of OXT was completely reversed, evident in even lower relationship qualities across all stimulus categories. The importance of OXT in a CBR context is further corroborated by a three-fold increase in endogenous release of OXT following exposure to one’s favorite brand and positive associations between baseline peripheral OXT concentrations and brand relationship qualities. Collectively, our findings indicate that OXT not only plays a fundamental role in developing interpersonal relationships, but also enables relationship formation with objects such as brands. PMID:26449882

  12. Social vocalizations can release oxytocin in humans.

    PubMed

    Seltzer, Leslie J; Ziegler, Toni E; Pollak, Seth D

    2010-09-01

    Vocalizations are important components of social behaviour in many vertebrate species, including our own. Less well-understood are the hormonal mechanisms involved in response to vocal cues, and how these systems may influence the course of behavioural evolution. The neurohormone oxytocin (OT) partly governs a number of biological and social processes critical to fitness, such as attachment between mothers and their young, and suppression of the stress response after contact with trusted conspecfics. Rodent studies suggest that OT's release is contingent upon direct tactile contact with such individuals, but we hypothesized that vocalizations might be capable of producing the same effect. To test our hypothesis, we chose human mother-daughter dyads and applied a social stressor to the children, following which we randomly assigned participants into complete contact, speech-only or no-contact conditions. Children receiving a full complement of comfort including physical, vocal and non-verbal contact showed the highest levels of OT and the swiftest return to baseline of a biological marker of stress (salivary cortisol), but a strikingly similar hormonal profile emerged in children comforted solely by their mother's voice. Our results suggest that vocalizations may be as important as touch to the neuroendocrine regulation of social bonding in our species.

  13. Oxytocin facilitates the sensation of social stress.

    PubMed

    Eckstein, Monika; Scheele, Dirk; Weber, Kristina; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René

    2014-09-01

    Essentially all social species experience social stress which can be a catalyst for detriments in mental and physical health. The neuropeptide oxytocin (OXT) has been shown to produce anxiolytic and antistress effects, thereby qualifying the OXT system as a promising drug target in the treatment of stress-related disorders. However, recently it has been shown that OXT can have anxiogenic effects as well. In the present study, we used functional magnetic resonance imaging to scan the brains of 60 healthy men while they were exposed to social stress after they received either intranasal OXT (24 IU) or placebo treatment. Although OXT administration did not alter salivary cortisol levels as a surrogate marker of stress axis activity, our participants initially reported an increment in perceived social stress. This behavioral effect was paralleled on the neural level by increased activity in the precuneus and cingulate cortex. Taken together, our results support the hypothesis that OXT can induce a self-referential processing bias which facilitates the sensation of social stress in the absence of altered endocrine responses.

  14. Oxytocin and cardioprotection in diabetes and obesity.

    PubMed

    Jankowski, Marek; Broderick, Tom L; Gutkowska, Jolanta

    2016-06-07

    Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs.

  15. Oxytocin: the Great Facilitator of Life

    PubMed Central

    Lee, Heon-Jin; Macbeth, Abbe H.; Pagani, Jerome; Young, W. Scott

    2009-01-01

    Oxytocin (Oxt) is a nonapeptide hormone best known for its role in lactation and parturition. Since 1906 when its uterine-contracting properties were described until 50 years later when its sequence was elucidated, research focused on its peripheral roles in reproduction. Only over the past several decades have researchers focused on what functions Oxt might have in the brain, the subject of this review. Immunohistochemical studies revealed that magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei are the neurons of origin for the Oxt released from the posterior pituitary. Smaller cells in various parts of the brain, as well as release from magnocellular dendrites, provide the Oxt responsible for modulating various behaviors at its only identified receptor. Although Oxt is implicated in a variety of “non-social” behaviors, such as learning, anxiety, feeding and pain perception, it is Oxt’s roles in various social behaviors that have come to the fore recently. Oxt is important for social memory and attachment, sexual and maternal behavior, and aggression. Recent work implicates Oxt in human bonding and trust as well. Human disorders characterized by aberrant social interactions, such as autism and schizophrenia, may also involve Oxt expression. Many, if not most, of Oxt’s functions, from social interactions (affiliation, aggression) and sexual behavior to eventual parturition, lactation and maternal behavior, may be viewed as specifically facilitating PMID:19482229

  16. Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus

    PubMed Central

    Nissenson, R.; Flouret, G.; Hechter, O.

    1978-01-01

    Estradiol-17β administration to young (10- to 12-week-old) rabbits to produce the “estrogen-dominated” uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In “progesterone-dominated” uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [3H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [3H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [3H]oxytocin binding; the concentration of specific [3H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon

  17. Oxytocin may mediate the benefits of positive social interaction and emotions.

    PubMed

    Uvnäs-Moberg, K

    1998-11-01

    During breastfeeding or suckling, maternal oxytocin levels are raised by somatosensory stimulation. Oxytocin may, however, also be released by nonnoxious stimuli such as touch, warm temperature etc. in plasma and in cerebrospinal fluid. Consequently, oxytocin may be involved in physiological and behavioral effects induced by social interaction in a more general context. In both male and female rats oxytocin exerts potent physiological antistress effects. If daily oxytocin injections are repeated over a 5-day period, blood pressure is decreased by 10-20 mmHg, the withdrawal latency to heat stimuli is prolonged, cortisol levels are decreased and insulin and cholecystokinin levels are increased. These effects last from 1 to several weeks after the last injection. After repeated oxytocin treatment weight gain may be promoted and the healing rate of wounds increased. Most behavioral and physiological effects induced by oxytocin can be blocked by oxytocin antagonists. In contrast, the antistress effects can not, suggesting that unidentified oxytocin receptors may exist. The prolonged latency in the tail-flick test can be temporarily reversed by administration of naloxone, suggesting that endogenous opioid activity has been increased by the oxytocin injections. In contrast, the long-term lowering of blood pressure and of cortisol levels as well as the sedative effects of oxytocin have been found to be related to an increased activity of central alpha 2-adrenoceptors. Positive social interactions have been related to health-promoting effects. Oxytocin released in response to social stimuli may be part of a neuroendocrine substrate which underlies the benefits of positive social experiences. Such processes may in addition explain the health-promoting effects of certain alternative therapies. Because of the special properties of oxytocin, including the fact that it can become conditioned to psychological state or imagery, oxytocin may also mediate the benefits attributed to

  18. 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.

  19. 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.

  20. 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…

  1. 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.

  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. Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

    PubMed

    Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

    2015-08-01

    In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR). PMID:26159838

  4. 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

  5. Sensitive spectrofluorimetric method of analysis for venlafaxine in spiked rat plasma and formulations.

    PubMed

    Shahnawaz, Sheikh; Siddiqui, Zaki; Hoda, Quaisul

    2010-07-01

    A simple, sensitive, accurate and affordable spectrofluorimetric method was developed and validated for the determination of venlafaxine, both in marketed preparations as well as in spiked rat plasma. Venlafaxine depicted strong native fluorescence property in freshly prepared 0.05 M sulphuric acid. The excitation and emission wavelengths were found to be 237.0 nm and 301.0 respectively. Effect of variations in pH, temperature, concentration, change in molarities of different solvents, and effect of excipients were studied. The calibration graph in case of dosage forms and in spiked plasma was found to be rectilinear in the concentrations of 15-600 ng/ml and 20-650 ng/ml respectively. The intra- day and inter-day accuracy measurements of VEN in formulations ranged from 0.29 to 0.44% and 0.27 to 0.49%, respectively. The intra-day and inter-day accuracy in measurement of VEN in plasma ranged from 0.062 to 2.26% and 0.52 to 2.32%, respectively. The limit of detection (LOD) was found to be 6.0 ng/mL and 4.0 ng/mL in plasma and formulations respectively. The mean recovery of VEN from plasma was 97.46. PMID:20191378

  6. 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.

  7. Improved formulation of global QCD analysis with zero-mass hard cross sections

    SciTech Connect

    Nadolsky, Pavel M.; Tung, W.-K.

    2009-06-01

    The zero-mass (ZM) parton formalism is widely used in high-energy physics because of its simplicity and historical importance, even while massive quarks (c,b,t) are playing an increasingly prominent role in particle phenomenology, including global QCD analyses of parton distributions based on the more precise general-mass (GM) QCD formalism. In view of this dichotomy, we show how the obvious inconsistencies of the conventional implementation of the ZM formalism can be corrected, while preserving the simplicity of its hard matrix elements. The resulting intermediate-mass (IM) scheme for perturbative QCD calculation can be considered either as improved ZM formulation with realistic treatment of heavy-flavor kinematics; or as a simplified GM formulation with approximate ZM hard cross sections. Phenomenologically, global analyses based on IM calculations can effectively reproduce, within the present estimated uncertainty bands, the more correct GM results on parton distributions, as well as their predictions for a wide range of collider processes of current interest.

  8. Main rotor free wake geometry effects on blade air loads and response for helicopters in steady maneuvers. Volume 1: Theoretical formulation and analysis of results

    NASA Technical Reports Server (NTRS)

    Sadler, S. G.

    1972-01-01

    A mathematical model and computer program were implemented to study the main rotor free wake geometry effects on helicopter rotor blade air loads and response in steady maneuvers. The theoretical formulation and analysis of results are presented.

  9. Mixed variational formulations of finite element analysis of elastoacoustic/slosh fluid-structure interaction

    NASA Technical Reports Server (NTRS)

    Felippa, Carlos A.; Ohayon, Roger

    1991-01-01

    A general three-field variational principle is obtained for the motion of an acoustic fluid enclosed in a rigid or flexible container by the method of canonical decomposition applied to a modified form of the wave equation in the displacement potential. The general principle is specialized to a mixed two-field principle that contains the fluid displacement potential and pressure as independent fields. This principle contains a free parameter alpha. Semidiscrete finite-element equations of motion based on this principle are displayed and applied to the transient response and free-vibrations of the coupled fluid-structure problem. It is shown that a particular setting of alpha yields a rich set of formulations that can be customized to fit physical and computational requirements. The variational principle is then extended to handle slosh motions in a uniform gravity field, and used to derive semidiscrete equations of motion that account for such effects.

  10. Spectroscopic analysis of pharmaceutical formulations through the use of chemometric tools

    NASA Astrophysics Data System (ADS)

    Ornelas-Soto, N.; Barbosa-García, O.; Meneses-Nava, M.; Ramos-Ortíz, G.; Pichardo-Molina, J.; Maldonado, J. L.; Contreras, U.; López-Martínez, L.; López-de-Alba, P.; López-Barajas, F.

    2009-09-01

    In this work, fast and reliable spectroscopic methods in combination with chemometric tools were developed for simultaneous determination of Acetylsalicylic Acid, Acetaminophen and Caffeine in commercial formulations. For the first-order multivariate calibration method (PLS-1), calibration and validation sets were constructed with 23 and 10 samples respectively according to a central composite design. The Micro-Raman, FTIR-HATR and UV absorption spectra in the region of 100-2000 cm-1, 400-4400 cm-1 and 200-350 nm, respectively, were recorded. The % REP's (Percentage of relative error of prediction) was less than 18 for all used spectroscopic techniques. Subsequently, commercial pharmaceutical samples were analyzed with percentage of recovery between 90 and 117% for the three compounds.

  11. Formulation and numerical analysis of diatomic molecular dissociation using Boltzmann kinetic equation

    NASA Astrophysics Data System (ADS)

    Yano, Ryosuke; Suzuki, Kojiro; Kuroda, Hisayasu

    2007-01-01

    The direct description of chemical reactions by the Boltzmann equation still involves some difficulties in the kinetic theory. In this paper, we describe diatomic molecular dissociation due to transitions of vibrational quantum states resulting from inelastic collisions. These can be described by the Wang Chang-Uhlenbeck (WCU) equation. To avoid direct evaluation of the strong nonlinear collision kernel of the WCU equation, we used a kinetic equation. For accurate description of the dissociation process, we describe improvements we made to the conventional inelastic collision model (the so-called Morse model). Combining this inelastic collision model with the gas mixture model by Oguchi, we formulated a model for representing diatomic molecular dissociations. We validated this model by simulating a hypersonic shock layer with diatomic molecular dissociation.

  12. Analysis of TJ-II experimental data with neoclassical formulations of the radial electric field

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Tapia, C.; Martinell, J. J.; López-Bruna, D.; Melnikov, A. V.; Eliseev, L.; Rodríguez, C.; Ochando, M. A.; Castejón, F.; García, J.; van Milligen, B. P.; Fontdecaba, J. M.

    2015-11-01

    Neoclassical theory provides usable expressions for studying transport in toroidal plasmas and computing the associated radial electric field. An algebraic and three semi-analytical models are used here to study the radial electric field in TJ-II plasmas and compare it with experimental data from a heavy ion beam probe (HIBP) and with DKES calculations. Good qualitative agreement as well as reasonable quantitative agreement is found which allows us to validate the models for describing TJ-II radial electric fields. Furthermore, a simple algebraic formulation (2005 Plasma Phys. Rep. 31 14) provides physical insight for the interpretation of experimental data from the TJ-II heliac in spite of its complicated geometry, like the place of the transition from the electron to the ion root of the radial electric field, which occurs at the maximum value of collisionality, for example.

  13. Mixed variational formulation of finite element analysis of acoustoelastic/slosh fluid-structure interaction

    NASA Technical Reports Server (NTRS)

    Felippa, C. A.; Ohayon, R.

    1990-01-01

    A general three-field variational principle is obtained for the motion of an acoustic fluid enclosed in a rigid or flexible container by the method of canonical decomposition applied to a modified form of the wave equation in the displacement potential. The general principle is specialized to a mixed two-field principle that contains the fluid displacement potential and pressure as independent fields. This principle contains a free parameter alpha. Semidiscrete finite-element equations of motion based on this principle are displayed and applied to the transient response and free-vibrations of the coupled fluid-structure problem. It is shown that a particular setting of alpha yields a rich set of formulations that can be customized to fit physical and computational requirements. The variational principle is then extended to handle slosh motions in a uniform gravity field, and used to derived semidiscrete equations of motion that account for such effects.

  14. The Peptide Oxytocin Antagonist F-792, When Given Systemically, Does Not Act Centrally in Lactating Rats.

    PubMed

    Leng, G; Russell, J A

    2016-04-01

    Oxytocin secreted by nerve terminals in the posterior pituitary has important actions for ensuring a successful outcome of pregnancy: it stimulates uterine contractions that lead to birth and it is essential in the milk-ejection reflex, enabling milk to be expelled from the mammary glands into the mouths of suckling young. Oxytocin also has important actions in the brain: released from dendrites of neurones that innervate the posterior pituitary, oxytocin auto-excites the neurones to fire action potentials in co-ordinated bursts, causing secretion of pulses of oxytocin. Central oxytocin actions are blocked by an oxytocin antagonist given into the brain and, consequently, milk transfer stops. Systemic peptide oxytocin antagonist (atosiban) treatment is used clinically in management of pre-term labour, a major obstetric problem. Hence, it is important to know whether an oxytocin antagonist given peripherally can enter the brain and interfere with central oxytocin actions. In the present study, we tested F792, a peptide oxytocin antagonist. In urethane-anaesthetised suckled rats, we show that the mammary gland responsiveness to oxytocin is blocked by i.v. injections of 7 μg/kg of F792, and the milk-ejection reflex is blocked when F792 is given directly into the brain at a dose of 0.2 μg. To critically test whether F792 given systemically can enter the brain, we recorded the suckling- and oxytocin-induced burst-firing of individual antidromically identified oxytocin neurones in the paraventricular nucleus. Given systemically at 100 μg/kg i.v., F792 acted only peripherally, blocking the milk-ejecting actions of oxytocin, but not the burst-firing of oxytocin neurones during suckling (n = 5 neurones in five rats). Hence, this peptide oxytocin antagonist does not enter the brain from the circulation to interfere with an essential oxytocin function in the brain. Furthermore, the functions of oxytocin in the brain evidently cannot be explored with a systemic peptide

  15. Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

    PubMed Central

    Peñagarikano, Olga; Lázaro, María T.; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A.; Peles, Elior; Maidment, Nigel T.; Murphy, Niall P.; Yang, X. William; Golshani, Peyman; Geschwind, Daniel H.

    2015-01-01

    Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homologue of CNTNAP2, in which mutant forms cause Cortical Dysplasia and Focal Epilepsy syndrome (CDFE), displays many features parallel to the human disorder. Since CDFE has high penetrance for autism spectrum disorder (ASD) we performed an in vivo screen for drugs that treat abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment. PMID:25609168

  16. Oxytocin modulates GABAAR subunits to confer neuroprotection in stroke in vitro

    PubMed Central

    Kaneko, Yuji; Pappas, Colleen; Tajiri, Naoki; Borlongan, Cesar V.

    2016-01-01

    Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABAA receptor (GABAAR), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury. Pretreatment with oxytocin increased cell viability, decreased the cell damage against oxidative stress, and prevented the release of high mobility group box1 during OGD/R. However, introduction of oxytocin during OGD/R did not induce neuroprotection. Although oxytocin did not affect the glutathione-related cellular metabolism before OGD, oxytocin modulated the expression levels of GABAAR subunits, which function to remove excessive neuronal excitability via chloride ion influx. Oxytocin-pretreated cells significantly increased the chloride ion influx in response to GABA and THIP (δ-GABAAR specific agonist). This study provides evidence that oxytocin regulated GABAAR subunits in affording neuroprotection against OGD/R injury. PMID:27767042

  17. Phospholipase C-delta1 and oxytocin receptor signalling: evidence of its role as an effector.

    PubMed Central

    Park, E S; Won, J H; Han, K J; Suh, P G; Ryu, S H; Lee, H S; Yun, H Y; Kwon, N S; Baek, K J

    1998-01-01

    Although the oxytocin receptor modulates intracellular Ca2+ ion levels in myometrium, the identities of signal molecules have not been clearly clarified. Our previous studies on oxytocin receptor signalling demonstrated that 80 kDa Ghalpha is a signal mediator [Baek, Kwon, Lee, Kim, Muralidhar and Im (1996) Biochem. J. 315, 739-744]. To elucidate the effector in the oxytocin receptor signalling pathway, we evaluated the oxytocin-mediated activation of phospholipase C (PLC) by using solubilized membranes from human myometrium and a three-component preparation containing the oxytocin receptor-Ghalpha-PLC-delta1 complex. PLC-delta1 activity in the three-component preparation, as well as PLC activity in solubilized membranes, was increased by oxytocin in the presence of Ca2+ and activated Ghalpha (GTP-bound Ghalpha). Furthermore the stimulated PLC-delta1 activity resulting from activation of Ghalpha via the oxytocin receptor was significantly attenuated by the selective oxytocin antagonist desGly-NH2d(CH2)5[Tyr(Me)2,Thr4]ornithine vasotocin or GDP. Consistent with these observations, co-immunoprecipitation and co-immunoadsorption of PLC-delta1 in the three-component preparation by anti-Gh7alpha antibody resulted in the PLC-delta1 being tightly coupled to activated Ghalpha on stimulation of the oxytocin receptor. These results indicate that PLC-delta1 is the effector for Ghalpha-mediated oxytocin receptor signalling. PMID:9512491

  18. Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review

    PubMed Central

    Crockford, Catherine; Deschner, Tobias; Ziegler, Toni E.; Wittig, Roman M.

    2014-01-01

    The neuropeptide, oxytocin, receives increasing attention due to its role in stress regulation and promoting affiliative social behavior. Research across mammals points to a complex pattern whereby social context and individual differences moderate the central release of oxytocin as well as moderate the effects that exogenous administration of oxytocin has on social behavior. In addition, it is becoming evident that measuring endogenous peripheral oxytocin levels is an informative tool. This is particularly so when oxytocin can be measured from non-invasively collected samples, such as in urine. Although it is still debated as to whether peripheral measures of oxytocin relate to central measures of oxytocin, anatomical and functional evidence indicate a link between the two. We argue that non-invasive measures of peripheral oxytocin hold several research and potential therapeutic advantages. Principally, study subjects can be sampled repeatedly in different social contexts where social history between interaction partners can be taken into account. Several hormones can be measured simultaneously allowing examination of the influence of oxytocin interactions with other hormones on motivational states. Valence of relationships as well as changes in relationship quality over time can be measured through endocrine responses. Also, the approach of identifying natural social contexts that are associated with endogenous oxytocin release offers the potential of behavioral therapy as an addition or alternative to chemical therapy in the field of mental health. PMID:24672442

  19. The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures.

    PubMed

    van IJzendoorn, M H; Bakermans-Kranenburg, M J

    2016-08-01

    Despite the sometimes heated debate about the validity of human oxytocin studies, experimental oxytocin research with intranasal administration is a growing field with promising preliminary findings. The effects of intranasally administered oxytocin compared to placebo on brain neural activity have been supported in animal studies and in human studies of neural resting state. In several studies, oxytocin sniffs have been shown to lead to down-regulation of amygdala activation in response to infant attachment vocalisations. Meta-analytic evidence shows that oxytocin enhances the salience of (emotional) stimuli, lowers stress and arousal, and elevates empathic concern and tender care, in particular for offspring and in-group members. Less firm evidence points at the amnestic effects of oxytocin. We also note that the average effect sizes of oxytocin experiments are small to modest, and that most studies include a small number of subjects and thus are seriously underpowered, which implies a high risk for publication bias and nonreplicability. Nevertheless, we argue that the power of within-subjects experiments with oxytocin has been underestimated. Much more work is needed, however, to create a firm knowledge base of the neural and behavioural effects of oxytocin. Human oxytocin research is still taking place in the context of discovery, in which bold conjectures are being generated. In the context of justification, these conjectures should subsequently be subjected to stringent attempts at refutations before we jump to theoretical or clinical conclusions. For this context of justification, we propose a multisite multiple replications project on the social stimuli salience enhancing effect of oxytocin. Clinical application of oxytocin is premature. Meta-analytically, the use of oxytocin in clinical groups tends to show only effectiveness in changing symptomatology in individuals with autism spectrum disorders but, even then, it is not yet a validated therapy and its

  20. Oxytocin and vasopressin: distinct receptors in myometrium

    SciTech Connect

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

    1987-06-01

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

  1. Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes

    PubMed Central

    Kanat, Manuela; Heinrichs, Markus; Mader, Irina; van Elst, Ludger Tebartz; Domes, Gregor

    2015-01-01

    The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a double-blind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies. PMID:25881796

  2. Oxytocin reduces separation distress in piglets when given intranasally

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxytocin (OT) is one of the neurobiological foundations of sociality. It acts as a neuropeptide in numerous social processes, from ultra-social to anti-social behaviors. Evidence supports a role for OT in social support, possibly by attenuating separation distress. Nonetheless, research on OT is lac...

  3. Improving social perception in schizophrenia: the role of oxytocin.

    PubMed

    Fischer-Shofty, M; Brüne, M; Ebert, A; Shefet, D; Levkovitz, Y; Shamay-Tsoory, S G

    2013-05-01

    Previous research has shown that patients with schizophrenia are impaired in a wide range of social cognitive abilities, including emotion recognition, empathy for others, and mental perspective-taking. Recent studies suggest that a dysfunction of the oxytocinergic system contributes to the social impairment in schizophrenia. Accordingly, the present study sought to examine whether patients with schizophrenia would improve in a social perception task after taking a single dose of oxytocin, as compared to a placebo. Thirty-five patients diagnosed with schizophrenia were compared with 46 psychologically healthy matched controls on their recognition of kinship and intimacy, using the Interpersonal Perception Task. All participants received a single intranasal dose of 24 IU oxytocin or placebo, one week apart. Overall, the participants were more accurate in judging intimacy and kinship following the administration of oxytocin, as opposed to a placebo. However, when comparing patients with controls, only the recognition of kinship improved significantly in the patient group, whereas no such effect was observed in the control group or in the recognition of intimacy in either group. This is one of the first studies to demonstrate that social perception in schizophrenia can be improved by the administration of oxytocin and that patients show a greater treatment effect than controls. PMID:23433504

  4. The orgasmic history of oxytocin: Love, lust, and labor

    PubMed Central

    Magon, Navneet; Kalra, Sanjay

    2011-01-01

    Oxytocin has been best known for its roles in female reproduction. It is released in large amounts during labor, and after stimulation of the nipples. It is a facilitator for childbirth and breastfeeding. However, recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm, social recognition, bonding, and maternal behaviors. This small nine amino acid peptide is now believed to be involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterine contraction, milk ejection, maternal behavior, social bonding, stress and probably many more, which makes oxytocin and its receptor potential candidates as targets for drug therapy. From an innocuous agent as an aid in labor and delivery, oxytocin has come a long way in being touted as the latest party drug. The hormone of labor during the course of the last 100 years has had multiple orgasms to be the hormone of love. Many more shall be seen in the times to come! PMID:22029018

  5. The effects of intranasal oxytocin on contagious yawning.

    PubMed

    Gallup, Andrew C; Church, Allyson M

    2015-10-21

    Contagious yawning is thought to represent a basic form of empathy involved in state matching. Despite recent evidence in support of this connection, the neurochemical basis of contagious yawning remains largely unknown. Here, we investigate whether intranasal oxytocin, a hormone and neuropeptide involved in empathic processing, bonding and social affiliation, influences contagious yawning among human participants in a laboratory setting. Using a double blind procedure, 60 male college students received 30 IU of intranasal oxytocin or placebo and were then recorded during exposure to a contagious yawning video stimulus. Contrary to the empathic modeling hypothesis, oxytocin did not increase contagious yawning but rather appeared to modulate its expression in ways indicative of an enhanced awareness of the social stigma associated with this behavior. In particular, individuals in the oxytocin condition were more likely to conceal their yawns and less likely to display overt cues associated with the behavior. Follow-up research could explore how social context and affiliation with the target stimulus alter this response.

  6. Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes.

    PubMed

    Kanat, Manuela; Heinrichs, Markus; Mader, Irina; van Elst, Ludger Tebartz; Domes, Gregor

    2015-10-01

    The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a double-blind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies.

  7. Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes.

    PubMed

    Kanat, Manuela; Heinrichs, Markus; Mader, Irina; van Elst, Ludger Tebartz; Domes, Gregor

    2015-10-01

    The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a double-blind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies. PMID:25881796

  8. Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition.

    PubMed

    Macbeth, A H; Lee, H-J; Edds, J; Young, W S

    2009-07-01

    We studied three lines of oxytocin (Oxt) and oxytocin receptor (Oxtr) knockout (KO) male mice [Oxt(-/-), total Oxtr(-/-) and partial forebrain Oxtr (Oxtr(FB/FB))] with established deficits in social recognition to further refine our understanding of their deficits with regard to stimulus female's strain. We used a modified social discrimination paradigm in which subjects are singly housed only for the duration of the test. Additionally, stimulus females are singly housed throughout testing and are presented within corrals for rapid comparison of investigation by subject males. Wild-type (WT) males from all three lines discriminated between familiar and novel females of three different strains (C57BL/6, BALB/c and Swiss-Webster). No KO males discriminated between familiar and novel BALB/c or C57BL/6 females. Male Oxt(-/-) and Oxtr(-/-) mice, but not Oxtr(FB/FB) mice, discriminated between familiar and novel Swiss-Webster females. As this might indicate a global deficit in individual recognition for Oxtr(FB/FB) males, we examined their ability to discriminate between females from different strains and compared performance with Oxtr(-/-) males. WT and KO males from both lines were able to distinguish between familiar and novel females from different strains, indicating the social recognition deficit is not universal. Instead, we hypothesize that the Oxtr is involved in 'fine' intrastrain recognition, but is less important in 'broad' interstrain recognition. We also present the novel finding of decreased investigation across tests, which is likely an artifact of repeated testing and not because of stimulus female's strain or age of subject males.

  9. Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys.

    PubMed

    Smith, Aaron L; Freeman, Sara M; Barnhart, Todd E; Abbott, David H; Ahlers, Elizabeth O; Kukis, David L; Bales, Karen L; Goodman, Mark M; Young, Larry J

    2016-07-15

    The neuropeptide oxytocin is part of a neuroendocrine system that has physiological effects ranging from ensuring uterine myometrial contractions at parturition and post-partum mammary gland milk ejection to the modulation of neural control of social relationships. This initial study was performed to investigate the potential use of positron emission tomography (PET) for localizing oxytocin receptors in two New World primates. Three biomarkers for PET (1-3) that are known to have high affinity and selectivity for the human oxytocin receptor were investigated in the common marmoset (Callithrix jacchus) via PET imaging. Brain penetration, and uptake in the salivary gland area were both observed with biomarkers 2 and 3. No brain penetration was observed with 1, but uptake was observed more specifically in several peripheral endocrine glands compared to 2 or 3. Biomarker 2, which displayed the best brain penetration of the three biomarkers in the marmoset, was then investigated in the monogamous coppery titi monkey (Callicebus cupreus) in a brain scan and a limited full body scan. No significant brain penetration of 2 was observed in the titi monkey, but significant uptake was observed in various locations throughout the periphery. Metabolism of 2 was suspected to have been significant based upon HPLC analysis of blood draws, but parent compound was still present near the end of the scan. Follow-up investigations will focus on next generation biomarkers bearing improved binding characteristics and brain penetrability as well as investigating tissue in regions where biomarker uptake was observed.

  10. Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys.

    PubMed

    Smith, Aaron L; Freeman, Sara M; Barnhart, Todd E; Abbott, David H; Ahlers, Elizabeth O; Kukis, David L; Bales, Karen L; Goodman, Mark M; Young, Larry J

    2016-07-15

    The neuropeptide oxytocin is part of a neuroendocrine system that has physiological effects ranging from ensuring uterine myometrial contractions at parturition and post-partum mammary gland milk ejection to the modulation of neural control of social relationships. This initial study was performed to investigate the potential use of positron emission tomography (PET) for localizing oxytocin receptors in two New World primates. Three biomarkers for PET (1-3) that are known to have high affinity and selectivity for the human oxytocin receptor were investigated in the common marmoset (Callithrix jacchus) via PET imaging. Brain penetration, and uptake in the salivary gland area were both observed with biomarkers 2 and 3. No brain penetration was observed with 1, but uptake was observed more specifically in several peripheral endocrine glands compared to 2 or 3. Biomarker 2, which displayed the best brain penetration of the three biomarkers in the marmoset, was then investigated in the monogamous coppery titi monkey (Callicebus cupreus) in a brain scan and a limited full body scan. No significant brain penetration of 2 was observed in the titi monkey, but significant uptake was observed in various locations throughout the periphery. Metabolism of 2 was suspected to have been significant based upon HPLC analysis of blood draws, but parent compound was still present near the end of the scan. Follow-up investigations will focus on next generation biomarkers bearing improved binding characteristics and brain penetrability as well as investigating tissue in regions where biomarker uptake was observed. PMID:27209233

  11. Comparing Consider-Covariance Analysis with Sigma-Point Consider Filter and Linear-Theory Consider Filter Formulations

    NASA Technical Reports Server (NTRS)

    Lisano, Michael E.

    2007-01-01

    Recent literature in applied estimation theory reflects growing interest in the sigma-point (also called unscented ) formulation for optimal sequential state estimation, often describing performance comparisons with extended Kalman filters as applied to specific dynamical problems [c.f. 1, 2, 3]. Favorable attributes of sigma-point filters are described as including a lower expected error for nonlinear even non-differentiable dynamical systems, and a straightforward formulation not requiring derivation or implementation of any partial derivative Jacobian matrices. These attributes are particularly attractive, e.g. in terms of enabling simplified code architecture and streamlined testing, in the formulation of estimators for nonlinear spaceflight mechanics systems, such as filter software onboard deep-space robotic spacecraft. As presented in [4], the Sigma-Point Consider Filter (SPCF) algorithm extends the sigma-point filter algorithm to the problem of consider covariance analysis. Considering parameters in a dynamical system, while estimating its state, provides an upper bound on the estimated state covariance, which is viewed as a conservative approach to designing estimators for problems of general guidance, navigation and control. This is because, whether a parameter in the system model is observable or not, error in the knowledge of the value of a non-estimated parameter will increase the actual uncertainty of the estimated state of the system beyond the level formally indicated by the covariance of an estimator that neglects errors or uncertainty in that parameter. The equations for SPCF covariance evolution are obtained in a fashion similar to the derivation approach taken with standard (i.e. linearized or extended) consider parameterized Kalman filters (c.f. [5]). While in [4] the SPCF and linear-theory consider filter (LTCF) were applied to an illustrative linear dynamics/linear measurement problem, in the present work examines the SPCF as applied to

  12. Analysis of a High Velocity Oxygen-Fuel (HVOF) thermal spray torch. Part 1, Numerical formulation

    SciTech Connect

    Oberkampf, W.L.; Talpallikar, M.

    1994-01-01

    The fluid and particle dynamics of a High Velocity Oxygen-Fuel (HVOF) torch are analyzed using computational fluid dynamic (CFD) techniques. The thermal spray device analyzed is similar to a Metco Diamond Jet torch with powder injection. The spray nozzle is axisymmetric with powder injection on the centerline, premixed fuel and oxygen fed from an annulus, and air cooling injected along the interior surface of the aircap. Choked flow conditions occur at the exit of the aircap and a supersonic, under-expanded jet develops externally. The CFD simulation assumes three injection streams (solid metal particles with argon as a carrier gas, premixed oxygen/fuel, and air) inside the aircap and solves the combusting two-phase flow until the external spray stream decays to sonic conditions. The numerical formulation solves the mass, momentum, and energy transfer for both the gas and particle phase and strongly couples each phase. The combustion process is modeled using approximate equilibrium chemistry with dissociation of the gas with a total of nine species. Melting and re-solidification of the metal panicles is modeled as a lumped-mass system. Turbulent flow is modeled by a two equation k-{epsilon} turbulence model, including compressibility effects on turbulent dissipation. A time iterative, implicit, finite volume numerical method is used to solve the partial differential equations. A companion paper [10] presents the results of the numerical simulation and gives a detailed discussion of the gas and panicle dynamics.

  13. Nonlinear finite element formulation for the large displacement analysis in multibody system dynamics

    NASA Technical Reports Server (NTRS)

    Rismantab-Sany, J.; Chang, B.; Shabana, A. A.

    1989-01-01

    A total Lagrangian finite element formulation for the deformable bodies in multibody mechanical systems that undergo finite relative rotations is developed. The deformable bodies are discretized using finite element methods. The shape functions that are used to describe the displacement field are required to include the rigid body modes that describe only large translational displacements. This does not impose any limitations on the technique because most commonly used shape functions satisfy this requirement. The configuration of an element is defined using four sets of coordinate systems: Body, Element, Intermediate element, Global. The body coordinate system serves as a unique standard for the assembly of the elements forming the deformable body. The element coordinate system is rigidly attached to the element and therefore it translates and rotates with the element. The intermediate element coordinate system, whose axes are initially parallel to the element axes, has an origin which is rigidly attached to the origin of the body coordinate system and is used to conveniently describe the configuration of the element in undeformed state with respect to the body coordinate system.

  14. Prenatal stress puzzle, the oxytocin piece: Prenatal stress alters the behaviour and autonomic regulation in piglets, insights from oxytocin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developmental changes in response to prenatal stressors (PNS) may represent an adaptive strategy to enhance survival traits in the offspring. Yet, PNS could be maladaptive for captive animals, causing anxiety and abnormal social development. Oxytocin (OT) reduces anxiety, whereas OT deficiencies are...

  15. Formulation of consumables management models: Consumables analysis/crew simulator interface requirements

    NASA Technical Reports Server (NTRS)

    Zamora, M. A.

    1977-01-01

    Consumables analysis/crew training simulator interface requirements were defined. Two aspects were investigated: consumables analysis support techniques to crew training simulator for advanced spacecraft programs, and the applicability of the above techniques to the crew training simulator for the space shuttle program in particular.

  16. Disentangling the link between depressive symptoms and plasma oxytocin in men: The role of brooding rumination.

    PubMed

    Mohiyeddini, Changiz; Opacka-Juffry, Jolanta

    2015-09-01

    The links between plasma oxytocin and depression are controversial, ranging from negative to positive associations. The present study was conducted to reconcile those conflicting findings; amongst the features of depression, we considered rumination and hypothesised that rumination would function as moderator between depressive symptoms and oxytocin. Seventy five clinically normal adult male volunteers were assessed for depressive characteristics by means of the Ruminative Responses Scale and Beck's Depression Inventory-II; plasma oxytocin was measured by means of competitive enzyme immunoassay. The results demonstrate that high depressive symptoms were negatively associated with oxytocin concentrations at high rumination levels while such an association did not exist at low levels of rumination. The present findings suggest there are complex associations between oxytocin and brooding rumination, the latter being an important feature among depressive symptoms observed in clinically normal individuals. This complexity can underlie the current lack of consensus on the role of oxytocin in depression.

  17. Variational formulation and stability analysis of a three dimensional superelastic model for shape memory alloys

    NASA Astrophysics Data System (ADS)

    Alessi, Roberto; Pham, Kim

    2016-02-01

    This paper presents a variational framework for the three-dimensional macroscopic modelling of superelastic shape memory alloys in an isothermal setting. Phase transformation is accounted through a unique second order tensorial internal variable, acting as the transformation strain. Postulating the total strain energy density as the sum of a free energy and a dissipated energy, the model depends on two material scalar functions of the norm of the transformation strain and a material scalar constant. Appropriate calibration of these material functions allows to render a wide range of constitutive behaviours including stress-softening and stress-hardening. The quasi-static evolution problem of a domain is formulated in terms of two physical principles based on the total energy of the system: a stability criterion, which selects the local minima of the total energy, and an energy balance condition, which ensures the consistency of the evolution of the total energy with respect to the external loadings. The local phase transformation laws in terms of Kuhn-Tucker relations are deduced from the first-order stability condition and the energy balance condition. The response of the model is illustrated with a numerical traction-torsion test performed on a thin-walled cylinder. Evolutions of homogeneous states are given for proportional and non-proportional loadings. Influence of the stress-hardening/softening properties on the evolution of the transformation domain is emphasized. Finally, in view of an identification process, the issue of stability of homogeneous states in a multi-dimensional setting is answered based on the study of second-order derivative of the total energy. Explicit necessary and sufficient conditions of stability are provided.

  18. Stress-induced oxytocin release and oxytocin cell number and size in prepubertal and adult male and female rats.

    PubMed

    Minhas, Sumeet; Liu, Clarissa; Galdamez, Josselyn; So, Veronica M; Romeo, Russell D

    2016-08-01

    Studies indicate that adolescent exposure to stress is a potent environmental factor that contributes to psychological and physiological disorders, though the mechanisms that mediate these dysfunctions are not well understood. Periadolescent animals display greater stress-induced hypothalamic-pituitary-adrenal (HPA) axis responses than adults, which may contribute to these vulnerabilities. In addition to the HPA axis, the hypothalamo-neurohypophyseal tract (HNT) is also activated in response to stress. In adults, stress activates this system resulting in secretion of oxytocin from neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. However, it is currently unknown whether a similar or different response occurs in prepubertal animals. Given the influence of these hormones on a variety of emotional behaviors and physiological systems known to change as an animal transitions into adulthood, we investigated stress-induced HPA and HNT hormonal responses before and after stress, as well as the number and size of oxytocin-containing cells in the SON and PVN of prepubertal (30d) and adult (70d) male and female rats. Though we found the well-established protracted adrenocorticotropic hormone and corticosterone response in prepubertal males and females, only adult males and prepubertal females showed a significant stress-induced increase in plasma oxytocin levels. Moreover, though we found no pubertal changes in the number of oxytocin cells, we did find a pubertal-related increase in oxytocin somal size in both the SON and PVN of males and females. Taken together, these data indicate that neuroendocrine systems can show different patterns of stress reactivity before and after adolescent development and that these responses can be further modified by sex. Given the impact of these hormones on a variety of systems, it will be imperative to further explore these changes in hormonal stress reactivity and their role in adolescent health. PMID:26972154

  19. Validated RP-HPLC method for the simultaneous analysis of gemcitabine and LY-364947 in liposomal formulations.

    PubMed

    Bansal, Shyam S; Celia, Christian; Ferrati, Silvia; Zabre, Erika; Ferrari, Mauro; Palapattu, Ganesh; Grattoni, Alessandro

    2013-08-01

    Combined use of gemcitabine (Gem) and LY-364947 (LY), a TGF-β1 receptor inhibitor, has shown promise for the treatment of fibrotic pancreatic cancer, by reducing collagen production and improving tumor drug penetration. The preparation and optimization of novel Gem and LY formulations, including co-encapsulation in liposomes, require a validated method for the simultaneous quantification of both drugs, a method that had yet to be developed. Here we demonstrate an RP-HPLC protocol for the simultaneous detection of Gem and LY at 266 and 228 nm with retention times of 3.37 and 11.34 mins, respectively. The method, which uses a C18 column and a KH2PO4 (10 mM)-methanol mobile phase, was validated for linearity, precision, accuracy, limits of detection, and robustness. Co-loaded liposomes with both Gem and LY (Gem/LY liposomes) were developed to investigate the protocol applicability to pharmacokinetic analysis and formulation characterization. The method specificity was evaluated in presence of liposomal components in fetal bovine serum (FBS). Finally, the method was demonstrated by quantifying Gem/LY liposomal encapsulation efficiency and concentration liposomes-spiked FBS. PMID:23721184

  20. Development of Sensitive and Specific Analysis of Vildagliptin in Pharmaceutical Formulation by Gas Chromatography-Mass Spectrometry

    PubMed Central

    Uçaktürk, Ebru

    2015-01-01

    A sensitive and selective gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for the determination of vildagliptin (VIL) in pharmaceutical formulation. Prior to GC-MS analysis, VIL was efficiently derivatized with MSTFA/NH4I/β-mercaptoethanol at 60°C for 30 min. The obtained O-TMS derivative of VIL was detected by selected ion monitoring mode using the diagnostic ions m/z 223 and 252. Nandrolone was chosen as internal standard. The GC-MS method was fully validated by the following validation parameters: limit of detection (LOD) and quantitation (LOQ), linearity, precision, accuracy, specificity, stability, robustness, and ruggedness. LOD and LOQ were found to be 1.5 and 3.5 ng mL−1, respectively. The GC-MS method is linear in the range of 3.5–300 ng mL−1. The intra- and interday precision values were less than ≤3.62%. The intra- and interday accuracy values were found in the range of −0.26–2.06%. Finally, the GC-MS method was successfully applied to determine VIL in pharmaceutical formulation. PMID:26682085

  1. The role of nitric oxide on the oxytocin induce analgesia in mice

    PubMed Central

    Abbasnezhad, Abbasali; Khazdair, Mohammad Reza; Kianmehr, Majid

    2016-01-01

    Objective(s): Analgesic effects of oxytocin and it's the other physiological effects were well-known. The aim of present study was determination of nitric oxide role on analgesic effects of oxytocin in mice. Materials and Methods: 216 male Albino mice were divided randomly into two experimental groups, tail flick and formalin test. Each experimental group consists of three main groups including: saline, L-arginine (50 mg/kg) and L-NAME (10 mg/kg) intraperitoneal (IP) injection. 15 min after injection in each of the following groups, the animals in each groups divided to the three subgroups including: saline (n=12), oxytocin (1 mg/kg) (n=12) and oxytocin (1 mg/kg) + atosiban (1 mg/kg) (n=12) was injected IP and then after 30 min of use the formalin test and tail flick were to evaluate the response to pain. Results: Area under the curve (AUC) in the late phase of the formalin test, in sub-groups oxytocin + saline and L-NAME were significantly decreased compared with saline + saline group (P<0.05 to P< 0.001), and AUC in L-arginine + saline and atosiban + saline + oxytocin were significantly increased compared with oxytocin + saline group (P<0.05). Tail flick tests as well as a significant reduction in the AUC in oxytocin + L-arginine and atosiban + saline + oxytocin groups were compared with Oxytocin + Saline group (P<0.001). Conclusion: Oxytocin has analgesic effects in the acute and late phase of pain in the formalin test. Moreover, exogenous increasing of nitric oxide reduced the analgesic effect of oxytocin. PMID:27114792

  2. Endometrial oxytocin receptor and uterine prostaglandin secretion in mares during the oestrous cycle and early pregnancy.

    PubMed

    Starbuck, G R; Stout, T A; Lamming, G E; Allen, W R; Flint, A P

    1998-07-01

    Circulating concentrations of 13,14-dihydro-15-ketoprostaglandin F2 alpha (PGFM) were measured before and after administration of oxytocin and after endometrial biopsy, with or without uterine flushing performed per vaginam, on days 10, 14 and 18 after ovulation in nine pregnant and nine cyclic mares. Concentrations of oxytocin receptor were measured in endometrial biopsy samples. Neither pregnancy status nor time after ovulation affected basal PGFM concentrations. PGFM concentrations were increased after oxytocin administration on each of the days studied in cyclic mares; on day 14 the mean response was 4.5 times higher than the mean response on days 10 and 18. In contrast, during pregnancy, responses to oxytocin administration occurred only on days 10 and 18. Marked increases in PGFM concentrations in response to endometrial biopsy occurred only on day 14 in cyclic mares and on day 18 in pregnant mares. Mean concentrations of oxytocin receptor were between 200 and 300 fmol mg-1 protein on day 10 in both pregnant and cyclic mares; in cyclic mares oxytocin receptor concentrations were increased approximately threefold on day 14 compared with days 10 and 18, but no such increase was evident during pregnancy. Total amounts of PGFM secreted after oxytocin treatment correlated with endometrial oxytocin receptor concentrations in cyclic (P < 0.001) but not in pregnant (P > 0.5) mares, and the same was true for PGFM release induced by endometrial biopsy (cyclic: P = 0.0025; pregnant: P > 0.5). The data support the hypothesis that endometrial concentrations of oxytocin receptor determine uterine prostaglandin F2 alpha secretion in cyclic mares and that endometrial oxytocin receptor concentrations are reduced in early pregnancy by a product of the conceptus. The increase in response of the pregnant uterus to oxytocin treatment or biopsy-flushing between days 14 and 18 was not due to an increase in the concentration of oxytocin receptors but presumably reflected increased

  3. Plasma Oxytocin Immunoreactive Products and Response to Trust in Patients with Social Anxiety Disorder

    PubMed Central

    Hoge, EA; Lawson, EA; Metcalf, CA; Keshaviah, A; Zak, PJ; Pollack, MH; Simon, NM

    2013-01-01

    Background Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social “Trust Game,” a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. Methods Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. Results Mean oxytocin levels post-Trust Game (p=0.025), and overall (area under the curve, p=0.011) were lower in GSAD patients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the Game in either group. Conclusions We report low plasma oxytocin levels in patients with generalized social anxiety disorder during a pro-social laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD. PMID:22807189

  4. Oxytocin and Memory of Emotional Stimuli: Some Dance to Remember, Some Dance to Forget.

    PubMed

    Maroun, Mouna; Wagner, Shlomo

    2016-02-01

    An ever-growing body of evidence suggests that the hypothalamic neuropeptide oxytocin plays a central role in the regulation of mammalian social behavior and relationships. Yet, mammalian social interactions are extremely complex, involving both approach and avoidance behaviors toward specific individuals. While in the past oxytocin was conceived merely as a prosocial molecule that nonselectively facilitated affiliative emotions and behavior, it is now recognized that oxytocin plays a role in a wide range of social relationships, some of which involve negative emotions such as fear, aggression, and envy and lead to avoidance behavior. However, the way by which a single molecule such as oxytocin contributes to contrasting emotions and opposite behaviors is yet to be discovered. Here, we discuss the role of oxytocin in the modulation of emotional memories in rodents, focusing on two paradigms: social recognition and fear conditioning, representing approach and avoidance behaviors, respectively. We review recent pioneering studies that address the complex effects of oxytocin in a mechanistic approach, using genetic animal models and brain region-specific manipulations of oxytocin activity. These studies suggest that the multiple roles of oxytocin in social and fear behavior are due to its local effects in various brain areas, most notably distinct regions of the amygdala. Finally, we propose a model explaining some of the contradictory effects of oxytocin as products of the balance between two networks in the amygdala that are controlled by the medial prefrontal cortex. PMID:26300273

  5. Oxytocin: an emerging regulator of prolactin secretion in the female rat.

    PubMed

    Kennett, J E; McKee, D T

    2012-03-01

    In the female rat, a complex interplay of both stimulatory and inhibitory hypothalamic factors controls the secretion of prolactin. Prolactin regulates a large number of physiological processes from immunity to stress. Here, we have chosen to focus on the control of prolactin secretion in the female rat in response to suckling, mating and ovarian steroids. In all three of these states, dopamine, released from neurones in the mediobasal hypothalamus, is a potent inhibitory signal regulating prolactin secretion. Early research has determined that the relief of dopaminergic tone is not sufficent to account for the full surge of prolactin secretion observed in response to the suckling stimulus, launching a search for possible prolactin-releasing factors. This research has subsequently broadened to include searching for prolactin-releasing factors controlling prolactin secretion after mating or ovarian steroids. A great deal of literature has suggested that this prolactin-releasing factor may include oxytocin. Oxytocin receptors are present on lactotrophs. These oxytocin receptors respond to exogenous oxytocin and antagonism of endogenous oxytocin inhibits lactotroph activity. In addition, the pattern of oxytocin neuronal activity and oxytocin release correlate with the release of prolactin. Here, we suggest not only that oxytocin is stimulating prolactin secretion, but also that prolactin secretion is controlled by a complex network of positive (oxytocin) and negative (dopamine) feedback loops. We discuss the available literature and attempt to describe the circuitry we believe may be responsible for controlling prolactin secretion.

  6. Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids.

    PubMed

    Leuner, Benedetta; Caponiti, Julia M; Gould, Elizabeth

    2012-04-01

    Oxytocin has been linked to social behavior, including social recognition, pair bonding and parenting, but its potential role in promoting neuronal growth has not been investigated. We show here that oxytocin, but not vasopressin, stimulates both cell proliferation and adult neurogenesis in the hippocampus of rats. Oxytocin is also capable of stimulating adult neurogenesis in rats subjected to glucocorticoid administration or cold water swim stress. These findings suggest that oxytocin stimulates neuronal growth and may protect against the suppressive effects of stress hormones on hippocampal plasticity.

  7. Oxytocin: An emerging regulator of prolactin secretion in the female rat

    PubMed Central

    McKee, De’Nise T.

    2012-01-01

    In the female rat, a complex interplay of both stimulatory and inhibitory hypothalamic factors controls the secretion of prolactin. Prolactin regulates a large number of physiological processes from immunity to stress. In the following review, we have chosen to focus on the control of prolactin secretion in the female rat in response to suckling, mating and ovarian steroids. In all three of these states, dopamine, released from neurones in the mediobasal hypothalamus, is a potent inhibitory signal regulating prolactin secretion. Early research has determined that the relief of dopaminergic tone is not enough to account for the full surge of prolactin secretion observed in response to the suckling stimulus, launching a search for possible prolactin-releasing factors. This research has since broadened to include searching for prolactin-releasing factors controlling prolactin secretion following mating or ovarian steroids. A great deal of literature has suggested that this prolactin-releasing factor may include oxytocin. Oxytocin receptors are present on lactotrophs. These oxytocin receptors respond to exogenous oxytocin and antagonism of endogenous oxytocin inhibits lactotroph activity. In addition, the pattern of oxytocin neuronal activity and oxytocin release correlate with the release of prolactin. Here we suggest that not only is oxytocin stimulating prolactin secretion, but we also hypothesize that prolactin secretion is controlled by a complex network of positive (oxytocin) and negative (dopamine) feedback loops. In the present review, we will discuss this literature and attempt to describe the circuitry we believe may be responsible for controlling prolactin secretion. PMID:22129099

  8. A two-scale finite element formulation for the dynamic analysis of heterogeneous materials

    SciTech Connect

    Ionita, Axinte

    2008-01-01

    In the analysis of heterogeneous materials using a two-scale Finite Element Method (FEM) the usual assumption is that the Representative Volume Element (RVE) of the micro-scale is much smaller than the finite element discretization of the macro-scale. However there are situations in which the RVE becomes comparable with, or even bigger than the finite element. These situations are considered in this article from the perspective of a two-scale FEM dynamic analysis. Using the principle of virtual power, new equations for the fluctuating fields are developed in terms of velocities rather than displacements. To allow more flexibility in the analysis, a scaling deformation tensor is introduced together with a procedure for its determination. Numerical examples using the new approach are presented.

  9. New thermo-mechanical fluid flow modeling of multiscale deformations in the Levant basin: formulation, verification, and preliminary analysis

    NASA Astrophysics Data System (ADS)

    Belferman, Mariana; Katsman, Regina; Agnon, Amotz

    2015-04-01

    The Levant has been repeatedly devastated by numerous earthquakes since prehistorical time, as recorded in historical documents, archaeological ruins, and sedimentary archives. In order to understand the role of the dynamics of the water bodies in triggering the deformations in the Levant basin, a new theoretical thermo-mechanical model is constructed and extended by including a fluid flow component. The latter is modeled on a basis of two-way poroelastic coupling with momentum equation. This coupling is essential to capture the fluid flow evolution induced by dynamic water loading and to resolve porosity changes. All the components of the model, namely elasticity, creep, plasticity, fluid flow, etc., have been extensively verified and presented. Results of the initial sensitivity analysis addressing the relative importance of each process in earthquakes triggering are discussed. The rich archives of pre-instrumental destructive earthquakes will set constraints for future modeling under the present formulation.

  10. Enantiomeric separation of ketoconazole and terconazole antifungals by electrokinetic chromatography: Rapid quantitative analysis of ketoconazole in pharmaceutical formulations.

    PubMed

    Castro-Puyana, María; Crego, Antonio L; Marina, M Luisa

    2005-10-01

    EKC using a neutral CD as chiral selector was applied in this work to the development of a method enabling the enantiomeric separation of ketoconazole and terconazole antifungals. The influence of different experimental conditions such as temperature, CD concentration, pH, and nature and concentration of the buffer on the enantiomeric resolution of the compounds studied was investigated. The use of 10 mM heptakis-(2,3,6-tri-O-methyl)-beta-CD in a 100 mM phosphate buffer (pH 3.5) with a temperature of 15 degrees C allowed the separation of the enantiomers of ketoconazole and terconazole with high resolution (R(s) > 2.0). The rapid separation of ketoconazole enantiomers with an analysis time less than 3 min was carried out after fitting some experimental parameters. The developed method was applied to the determination of ketoconazole in different pharmaceutical formulations.

  11. Dilemmas in Formulating the Israeli High School Sociology Curriculum: Analysis of the 1988-1998 Curricula

    ERIC Educational Resources Information Center

    Naveh, Nissan

    2008-01-01

    The Israeli high school sociology curriculum underwent changes during the 1980s and 1990s, the main one of which was the replacing of the 1988 academic-oriented curriculum with the "new" (1998) pedagogical-didactic curriculum. An analysis of the two reveals issues regarding the content of the two curricula. The article covers nine issues framed as…

  12. Formulation and error analysis for a generalized image point correspondence algorithm

    NASA Technical Reports Server (NTRS)

    Shapiro, Linda (Editor); Rosenfeld, Azriel (Editor); Fotedar, Sunil; Defigueiredo, Rui J. P.; Krishen, Kumar

    1992-01-01

    A Generalized Image Point Correspondence (GIPC) algorithm, which enables the determination of 3-D motion parameters of an object in a configuration where both the object and the camera are moving, is discussed. A detailed error analysis of this algorithm has been carried out. Furthermore, the algorithm was tested on both simulated and video-acquired data, and its accuracy was determined.

  13. An analysis of Renewable Portfolio Standard policy formulation and its influence on state level energy prices

    NASA Astrophysics Data System (ADS)

    McCollester, Peter Colin

    understand the relationship between RPS and energy markets. This study utilizes state level panel data from 2000 to 2011 to examine this relationship. The model controls for several factors including the existence of state level RPS, the amount of electricity generation from renewable and non-renewable sources, fuel price mix, and other macroeconomic and demographic indicators. The study compares and contrasts several regressions to illuminate important relationships between RPS design and residential energy prices. The findings of this study have the potential to have far reaching implications for the future of RPS design, and RPS policy. This paper finds that RPS and more specifically the way a RPS is formulated is related to increased energy prices. Retail energy prices are particularly strongly related to variables having to do with compliance with a specific RPS, while Industrial energy prices are more strongly related to the magnitude of RPS goals. Both of these findings are important and they accentuate the fact that different energy markets are influenced by different drivers.

  14. Population Pharmacokinetic Analysis of Raltegravir Pediatric Formulations in HIV-infected Children 4 weeks to 18 years of age†

    PubMed Central

    Rizk, Matthew L.; Du, Lihong; Bennetto-Hood, Chantelle; Wenning, Larissa; Teppler, Hedy; Homony, Brenda; Graham, Bobbie; Fry, Carrie; Nachman, Sharon; Wiznia, Andrew; Worrell, Carol; Smith, Betsy; Acosta, Edward P.

    2015-01-01

    P1066 is an open-label study of raltegravir in HIV+ youth, ages 4 weeks-18 years. Here we summarize P1066 pharmacokinetic (PK) data and a population PK model for the pediatric chewable tablet and oral granules. Raltegravir PK parameters were calculated using non-compartmental analysis. A two-compartment model was developed using data from P1066 and an adult study of the pediatric formulations. Inter-individual variability was described by an exponential error model, and residual variability was captured by an additive/proportional error model. Twelve-hour concentrations (C12hr) were calculated from the model-derived elimination rate constant and 8-hour observed concentration. Simulated steady-state concentrations were analyzed by non-compartmental analysis. Target area-under-the-curve (AUC0-12hr) and C12hr were achieved in each cohort. For the pediatric formulations, geometric mean AUC0-12hr values were 18.0–22.6 μM*hr across cohorts, and C12hr values were 71–130 nM, with lower coefficients of variation vs the film-coated tablet. A two-compartment model with first-order absorption adequately described raltegravir plasma PK in pediatric and adult patients. Weight was a covariate on clearance and central volume, and incorporated using allometric scaling. Raltegravir chewable tablets and oral granules exhibited PK parameters consistent with those from prior adult studies and older children in P1066, as well as lower variability than the film-coated tablet. PMID:25753401

  15. Analysis and calculation of macrosegregation in a casting ingot. MPS solidification model. Volume 1: Formulation and analysis

    NASA Technical Reports Server (NTRS)

    Maples, A. L.; Poirier, D. R.

    1980-01-01

    The physical and numerical formulation of a model for the horizontal solidification of a binary alloy is described. It can be applied in an ingot. The major purpose of the model is to calculate macrosegregation in a casting ingot which results from flow of interdendritic liquid during solidification. The flow, driven by solidification contractions and by gravity acting on density gradients in the interdendritic liquid, was modeled as flow through a porous medium. The symbols used are defined. The physical formulation of the problem leading to a set of equations which can be used to obtain: (1) the pressure field; (2) the velocity field: (3) mass flow and (4) solute flow in the solid plus liquid zone during solidification is presented. With these established, the model calculates macrosegregation after solidification is complete. The numerical techniques used to obtain solution on a computational grid are presented. Results, evaluation of the results, and recommendations for future development of the model are given. The macrosegregation and flow field predictions for tin-lead, aluminum-copper, and tin-bismuth alloys are included as well as comparisons of some of the predictions with published predictions or with empirical data.

  16. Formulation, predictions, and sensitivity analysis of a pyrotechnically actuated pin puller model

    SciTech Connect

    Gonthier, K.A.; Powers, J.M.

    1994-07-01

    This article presents an analysis for pyrotechnic combustion and pin motion in the NASA Standard Initiator (NSI) actuated pin puller. The conservation principles and constitutive relations for a multiphase system are posed and reduced to a set of five ordinary differential equations which are solved to predict the system`s performance. The model tracks the interactions of the unreacted, incompressible solid pyrotechnic, incompressible condensed phase combustion products, and gas phase combustion products. Predicted pressure histories for the firing of an NSI into (1) the pin puller device, (2) a 10 cm(sup 3) closed vessel, and (3) an apparatus known as the Dynamic Test Device compare well with experimental results. A sensitivity analysis reveals large regions in parameter space where system performance is insensitive to particular parametric values; smaller regions of high sensitivity are also found. 15 refs.

  17. Nonequilibrium flow computations. I - An analysis of numerical formulations of conservation laws

    NASA Technical Reports Server (NTRS)

    Liu, Yen; Vinokur, Marcel

    1989-01-01

    Modern numerical techniques employing properties of flux Jacobian matrices are extended to general, nonequilibrium flows. Generalizations of the Beam-Warming scheme, Steger-Warming and van Leer Flux-vector splittings, and Roe's approximate Riemann solver are presented for 3-D, time-varying grids. The analysis is based on a thermodynamic model that includes the most general thermal and chemical nonequilibrium flow of an arbitrary gas. Various special cases are also discussed.

  18. Nonequilibrium flow computations. 1: An analysis of numerical formulations of conservation laws

    NASA Technical Reports Server (NTRS)

    Liu, Yen; Vinokur, Marcel

    1988-01-01

    Modern numerical techniques employing properties of flux Jacobian matrices are extended to general, nonequilibrium flows. Generalizations of the Beam-Warming scheme, Steger-Warming and van Leer Flux-vector splittings, and Roe's approximate Riemann solver are presented for 3-D, time-varying grids. The analysis is based on a thermodynamic model that includes the most general thermal and chemical nonequilibrium flow of an arbitrary gas. Various special cases are also discussed.

  19. Self-similar cosmological solutions with dark energy. I. Formulation and asymptotic analysis

    NASA Astrophysics Data System (ADS)

    Harada, Tomohiro; Maeda, Hideki; Carr, B. J.

    2008-01-01

    Based on the asymptotic analysis of ordinary differential equations, we classify all spherically symmetric self-similar solutions to the Einstein equations which are asymptotically Friedmann at large distances and contain a perfect fluid with equation of state p=(γ-1)μ with 0<γ<2/3. This corresponds to a “dark energy” fluid and the Friedmann solution is accelerated in this case due to antigravity. This extends the previous analysis of spherically symmetric self-similar solutions for fluids with positive pressure (γ>1). However, in the latter case there is an additional parameter associated with the weak discontinuity at the sonic point and the solutions are only asymptotically “quasi-Friedmann,” in the sense that they exhibit an angle deficit at large distances. In the 0<γ<2/3 case, there is no sonic point and there exists a one-parameter family of solutions which are genuinely asymptotically Friedmann at large distances. We find eight classes of asymptotic behavior: Friedmann or quasi-Friedmann or quasistatic or constant-velocity at large distances, quasi-Friedmann or positive-mass singular or negative-mass singular at small distances, and quasi-Kantowski-Sachs at intermediate distances. The self-similar asymptotically quasistatic and quasi-Kantowski-Sachs solutions are analytically extendible and of great cosmological interest. We also investigate their conformal diagrams. The results of the present analysis are utilized in an accompanying paper to obtain and physically interpret numerical solutions.

  20. Jones matrix formulation of a Porro prism laser resonator with waveplates: theoretical and experimental analysis

    NASA Astrophysics Data System (ADS)

    Agrawal, L.; Bhardwaj, A.; Pal, S.; Kumar, A.

    2007-11-01

    This article presents the results of a detailed theoretical and experimental analysis carried out on a folded Z-shaped polarization coupled, electro-optically Q-switched laser resonator with Porro prisms and waveplates. The advantages of adding waveplates in a Porro prism resonator have been explored for creating high loss condition prior to Q-switching and obtaining variable reflectivity with fixed orientation of Porro prism. Generalized expressions have been derived in terms of azimuth angles and phase shifts introduced by the polarizing elements. These expressions corroborate with known reported results under appropriate substitutions. A specific case of a crossed Porro prism diode-pumped Nd:YAG laser has been theoretically and experimentally investigated. In the feedback arm, a 0.57λ waveplate oriented at 135° completely compensates the phase shift of a fused silica Porro prism and provides better tolerances than a BK-7 prism/0.60λ waveplate combination to stop prelasing. The fused silica prism/0.57λ combination with waveplate at 112° acts like a 100% mirror and was utilized for optimization of free running performance. The effective reflectivity was determined for various orientations of the quarter waveplate in the gain arm to numerically estimate the Q-switched laser pulse parameters through rate equation analysis. Experimental results match well with the theoretical analysis.

  1. Stopping Oxytocin in Active Labor Rather Than Continuing it until Delivery: A Viable Option for the Induction of Labor

    PubMed Central

    Chopra, Seema; SenGupta, Sandip K.; Jain, Vanita; Kumar, Parveen

    2015-01-01

    Objective Induction of labor (IOL), using intravenous oxytocin, is the artificial initiation of labor before its spontaneous onset for the purpose of delivery of the fetoplacental unit. Although there are various studies looking at dosages of oxytocin, only a few have addressed the issue of discontinuation of oxytocin in the active stage of labor. Thus, our study was conducted to evaluate the need for continuation versus discontinuation of oxytocin during active labor. Methods This prospective, randomized controlled trial included 106 women who needed IOL. Oxytocin infusion was initiated at a rate of 3mIU/min and was incremental until 4–6cm cervical dilation. At this point the patients were randomly assigned into one of two groups. In group one, oxytocin was discontinued, and infusion was continued with 0.9% sodium chloride solution. In group two, oxytocin was continued at the same dose until delivery. Results The duration of oxytocin infusion was 5.5 hours in the oxytocin discontinuation group and 11.0 hours in oxytocin continuation group (p<0.001). The total dose of oxytocin was significantly higher in group two (6.1 units vs. 16.5 units; p=<0.001). The induction-delivery interval was significantly less in group one (9.1 and 11.2 hours in group one and group two, respectively; p=0.023). Conclusion Oxytocin discontinuation in the active stage of labor did not prolong the active stage. The total duration of labor and total oxytocin dose were significantly less in the oxytocin discontinuation group. Our results suggest that oxytocin discontinuation is an alternative and viable option particularly in resource poor and economically challenged settings. It not only reduces the need for intense monitoring and prolonged oxytocin use-associated dangers but reduces the total cost of labor management. PMID:26421111

  2. Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study

    PubMed Central

    2013-01-01

    Background Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known. Methods To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance. Results Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors. Conclusions Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302

  3. A Variational Formulation for the Finite Element Analysis of Sound Wave Propagation in a Spherical Shell

    NASA Technical Reports Server (NTRS)

    Lebiedzik, Catherine

    1995-01-01

    Development of design tools to furnish optimal acoustic environments for lightweight aircraft demands the ability to simulate the acoustic system on a workstation. In order to form an effective mathematical model of the phenomena at hand, we have begun by studying the propagation of acoustic waves inside closed spherical shells. Using a fully-coupled fluid-structure interaction model based upon variational principles, we have written a finite element analysis program and are in the process of examining several test cases. Future investigations are planned to increase model accuracy by incorporating non-linear and viscous effects.

  4. Stochastic modelling of landfill leachate and biogas production incorporating waste heterogeneity. Model formulation and uncertainty analysis.

    PubMed

    Zacharof, A I; Butler, A P

    2004-01-01

    A mathematical model simulating the hydrological and biochemical processes occurring in landfilled waste is presented and demonstrated. The model combines biochemical and hydrological models into an integrated representation of the landfill environment. Waste decomposition is modelled using traditional biochemical waste decomposition pathways combined with a simplified methodology for representing the rate of decomposition. Water flow through the waste is represented using a statistical velocity model capable of representing the effects of waste heterogeneity on leachate flow through the waste. Given the limitations in data capture from landfill sites, significant emphasis is placed on improving parameter identification and reducing parameter requirements. A sensitivity analysis is performed, highlighting the model's response to changes in input variables. A model test run is also presented, demonstrating the model capabilities. A parameter perturbation model sensitivity analysis was also performed. This has been able to show that although the model is sensitive to certain key parameters, its overall intuitive response provides a good basis for making reasonable predictions of the future state of the landfill system. Finally, due to the high uncertainty associated with landfill data, a tool for handling input data uncertainty is incorporated in the model's structure. It is concluded that the model can be used as a reasonable tool for modelling landfill processes and that further work should be undertaken to assess the model's performance. PMID:15120429

  5. A stabilized complementarity formulation for nonlinear analysis of 3D bimodular materials

    NASA Astrophysics Data System (ADS)

    Zhang, L.; Zhang, H. W.; Wu, J.; Yan, B.

    2016-06-01

    Bi-modulus materials with different mechanical responses in tension and compression are often found in civil, composite, and biological engineering. Numerical analysis of bimodular materials is strongly nonlinear and convergence is usually a problem for traditional iterative schemes. This paper aims to develop a stabilized computational method for nonlinear analysis of 3D bimodular materials. Based on the parametric variational principle, a unified constitutive equation of 3D bimodular materials is proposed, which allows the eight principal stress states to be indicated by three parametric variables introduced in the principal stress directions. The original problem is transformed into a standard linear complementarity problem (LCP) by the parametric virtual work principle and a quadratic programming algorithm is developed by solving the LCP with the classic Lemke's algorithm. Update of elasticity and stiffness matrices is avoided and, thus, the proposed algorithm shows an excellent convergence behavior compared with traditional iterative schemes. Numerical examples show that the proposed method is valid and can accurately analyze mechanical responses of 3D bimodular materials. Also, stability of the algorithm is greatly improved.

  6. Development of grout formulations for 106-AN waste: Mixture-experiment results and analysis. Volume 1, Narrative and recommendations

    SciTech Connect

    Spence, R.D.; McDaniel, E.W.; Anderson, C.M.; Lokken, R.O.; Piepel, G.F.

    1993-09-01

    Twenty potential ingredients were identified for use in developing a 106-AN grout formulation, and 18 were subsequently obtained and tested. Four ingredients-Type II-LA (moderate heat of hydration) Portland cement, Class F fly ash, attapulgite 150 drilling clay, and ground air-cooled blast-furnace slag (GABFS) were selected for developing the 106-AN grout formulations. A mixture experiment was designed and conducted around the following formulation: 2.5 lb of cement per gallon, 1.2 lb of fly ash per gallon, 0.8 lb of attapulgite per gallon, and 3.5 lb of GABFS per gallon. Reduced empirical models were generated from the results of the mixture experiment. These models were used to recommend several grout formulations for 106-AN. Westinghouse Hanford Company selected one of these formulations to be verified for use with 106-AN and a backup formulation in case problems arise with the first choice.

  7. Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain.

    PubMed

    Boksa, Patricia; Zhang, Ying; Nouel, Dominique

    2015-08-01

    Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth.

  8. Repeated treatment with oxytocin promotes hippocampal cell proliferation, dendritic maturation and affects socio-emotional behavior.

    PubMed

    Sánchez-Vidaña, Dalinda Isabel; Chan, Ngai-Man Jackie; Chan, Alan H L; Hui, Katy K Y; Lee, Sylvia; Chan, Hoi-Yi; Law, Yuen Shan; Sze, Mei Yi; Tsui, Wai-Ching Sarah; Fung, Timothy K H; Lau, Benson Wui-Man; Lai, Cynthia Y Y

    2016-10-01

    Rewarding social behaviors including positive social interactions and sexual behaviors are shown to regulate adult neurogenesis, but the underlying biological mechanisms remain elusive. Oxytocin, a neurohypophysial hormone secreted after exposure to social interaction or sexual behaviors, has a profound role in the formation of social bonding and regulation of emotional distress. While the acute effect of oxytocin was usually studied, relatively scarce evidence showed the behavioral consequence of repeated oxytocin treatment. The purpose of the current study was to investigate the effect of repeated oxytocin treatment on hippocampal cell proliferation, dendritic maturation of new born neurons and social/emotional behaviors. Adult male Sprague-Dawley rats received treatment with either vehicle or oxytocin (1mg/kg) daily for two weeks. Behavioral tests revealed that oxytocin increased social behaviors and reduced the anxiety- and depression-like behaviors. Cell proliferation, differentiation and the dendritic complexity of new born neurons in the hippocampus were promoted by oxytocin treatment. Depression- and anxiety-like behaviors were induced by repeated treatment of corticosterone (40mg/kg) for two weeks while oxytocin treatment reversed the behavioral disturbances. Suppression of cell proliferation caused by corticosterone was reverted by oxytocin treatment in which cell proliferation, cell differentiation, and dendritic complexity increased. The present findings reveal that oxytocin not only enhances cell proliferation, but also promotes the development of the new neurons which is associated with the induction of positive emotional and social behaviors. The results also suggest that oxytocin may be a potential therapeutic agent for treatment of emotional and social dysfunction. PMID:27418343

  9. The influence of a wind tunnel on helicopter rotational noise: Formulation of analysis

    NASA Technical Reports Server (NTRS)

    Mosher, M.

    1984-01-01

    An analytical model is discussed that can be used to examine the effects of wind tunnel walls on helicopter rotational noise. A complete physical model of an acoustic source in a wind tunnel is described and a simplified version is then developed. This simplified model retains the important physical processes involved, yet it is more amenable to analysis. The simplified physical model is then modeled as a mathematical problem. An inhomogeneous partial differential equation with mixed boundary conditions is set up and then transformed into an integral equation. Details of generating a suitable Green's function and integral equation are included and the equation is discussed and also given for a two-dimensional case.

  10. Liquid chromatographic analysis of a formulated ester from a gas-turbine engine test

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.; Morales, W.

    1983-01-01

    Size exclusion chromatography (SEC) utilizing mu-Bondagel and mu-Styragel columns with a tetrahydrofuran mobile phase was used to determine the chemical degradation of lubricant samples from a gas-turbine engine test. A MIL-L-27502 candidate, ester-based lubricant was run in a J57-29 engine at a bulk oil temperature of 216 C. In general, the analyses indicated a progressive loss of primary ester, additive depletion, and formation of higher molecular weight material. An oil sample taken at the conclusion of the test showed a reversal of this trend because of large additions of new oil. The high-molecular-weight product from the degraded ester absorbed strongly in the ultraviolet region at 254 nanometers. This would indicate the presence of chromophoric groups. An analysis of a similar ester lubricant from a separate high-temperature bearing test yielded qualitatively similar results.

  11. Thermomechanical analysis of an aircraft tire in cornering using coupled ale and lagrangian formulations

    NASA Astrophysics Data System (ADS)

    Kondé, Ange Kongo; Rosu, Iulian; Lebon, Frédéric; Brardo, Olivier; Devésa, Bernard

    2013-06-01

    The thermomechanical behavior of an aircraft tire is predicted, using experimental devices, a model based on finite element software and an appropriate method of expressing the heat generated by skid in terms of the local friction coefficient, depending on the temperature. In the thermomechanical model, a steady state mechanical analysis is combined with a transient thermal problem. This combined approach is based on three main computing steps: the deformation step, the dissipation step and the thermal step. The deformation step calculates the stress and the velocity fields, which are used as inputs in the dissipation step to calculate the heat generated due to friction. The internal dissipation is assumed to be negligible. Finally, the thermal step yields new thermal maps based on the heat flux computed in the dissipation step. The coupling is established by updating the friction coefficient in the first two steps.

  12. Highly selective electrode for potentiometric analysis of methadone in biological fluids and pharmaceutical formulations.

    PubMed

    Ardeshiri, Moslem; Jalali, Fahimeh

    2016-06-01

    In order to develop a fast and simple procedure for methadone analysis in biological fluids, a graphite paste electrode (GPE) was modified with the ion-pair of methadone-phosphotungstic acid, and multiwalled carbon nanotubes (MWCNTs). Optimized composition of the electrode with respect to graphite powder:paraffin oil:MWCNTs:ion pair, was 58:30:8:4 (w/w%). The electrode showed a near-Nernstian slope of 58.9 ± 0.3 mV/decade for methadone in a wide linear range of 1.0 × 10(-8)-4.6 × 10(-3)M, with a detection limit of 1.0 × 10(-8)M. The electrode response was independent of pH in the range of 5-11, with a fast response time (~4s) at 25 °C. The sensor showed high selectivity and was successfully applied to the determination of sub-micromolar concentrations of methadone in human blood serum and urine samples, with recoveries in the range of 95-99.8%. The average recovery of methadone from tablets (5 mg/tablet) by using the proposed method was 98%. The life time of the modified electrode was more than 5 months, due to the characteristic of GPE which can be cut off and fresh electrode surface be available. A titration procedure was performed for methadone analysis by using phosphotungstic acid, as titrating agent, which showed an accurate end point and 1:1 stoichiometry for the ion-pair formed (methadone:phosphotungstic acid). The simple and rapid procedure as well as excellent detection limit and selectivity are some of the advantages of the proposed sensor for methadone. PMID:27040192

  13. The neurochemistry and social flow of singing: bonding and oxytocin

    PubMed Central

    Keeler, Jason R.; Roth, Edward A.; Neuser, Brittany L.; Spitsbergen, John M.; Waters, Daniel J. M.; Vianney, John-Mary

    2015-01-01

    Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. Four participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasma oxytocin and adrenocorticotropic hormone (ACTH) were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. A validated assessment of flow state was administered after each singing condition to assess participants' absorption in the task. The feasibility of the research methods were assessed and initial neurochemical data was generated on group singing. Mean scores of the flow state scale indicated that participants experienced flow in both the pre-composed (M = 37.06) and improvised singing conditions (M = 34.25), with no significant difference between conditions. ACTH concentrations decreased in both conditions, significantly so in the pre-composed singing condition, which may have contributed to the social flow experience. Mean plasma oxytocin levels increased only in response to improvised singing, with no significant difference between improvised and pre-composed singing conditions observed. The results indicate that group singing reduces stress and arousal, as measured by ACTH, and induces social flow in participants. The effects of pre-composed and improvised group singing on oxytocin are less clear. Higher levels of plasma oxytocin in the improvised condition may perhaps be attributed to the social effects of improvising musically with others. Further research with a larger sample size is warranted. PMID:26441614

  14. Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy.

    PubMed

    Dadds, Mark R; Moul, Caroline; Cauchi, Avril; Dobson-Stone, Carol; Hawes, David J; Brennan, John; Ebstein, Richard E

    2014-02-01

    Child conduct problems (CPs) are a robust predictor of adult mental health; the concurrence of callous-unemotional (CU) traits confers specific risk for psychopathy. Psychopathy may be related to disturbances in the oxytocin (OXT) system. Evidence suggests that epigenetic changes in the OXT receptor gene (OXTR) are associated with lower circulating OXT and social-cognitive difficulties. We tested methylation levels of OXTR in 4- to 16-year-old males who met DSM criteria for a diagnosis of oppositional-defiant or conduct disorder and were stratified by CU traits and age. Measures were DNA methylation levels of six CpG sites in the promoter region of the OXTR gene (where a CpG site is a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its lenth, linked together by phosphate binding), and OXT blood levels. High CU traits were associated with greater methylation of the OXTR gene for two cytosine nucleotide and guanine nucleotide phosphate linked sites and lower circulating OXT in older males. Higher methylation correlated with lower OXT levels. We conclude that greater methylation of OXTR characterizes adolescent males with high levels of CU and CPs, and this methylation is associated with lower circulating OXT and functional impairment in interpersonal empathy. The results add genetic evidence that high CU traits specify a distinct subgroup within CP children, and they suggest models of psychopathy may be informed by further identification of these epigenetic processes and their functional significance. PMID:24059811

  15. Matrix formulation and singular-value decomposition algorithm for structured varimax rotation in multivariate singular spectrum analysis

    NASA Astrophysics Data System (ADS)

    Portes, Leonardo L.; Aguirre, Luis A.

    2016-05-01

    Groth and Ghil [Phys. Rev. E 84, 036206 (2011), 10.1103/PhysRevE.84.036206] developed a modified varimax rotation aimed at enhancing the ability of the multivariate singular spectrum analysis (M-SSA) to characterize phase synchronization in systems of coupled chaotic oscillators. Due to the special structure of the M-SSA eigenvectors, the modification proposed by Groth and Ghil imposes a constraint in the rotation of blocks of components associated with the different subsystems. Accordingly, here we call it a structured varimax rotation (SVR). The SVR was presented as successive pairwise rotations of the eigenvectors. The aim of this paper is threefold. First, we develop a closed matrix formulation for the entire family of structured orthomax rotation criteria, for which the SVR is a special case. Second, this matrix approach is used to enable the use of known singular value algorithms for fast computation, allowing a simultaneous rotation of the M-SSA eigenvectors (a Python code is provided in the Appendix). This could be critical in the characterization of phase synchronization phenomena in large real systems of coupled oscillators. Furthermore, the closed algebraic matrix formulation could be used in theoretical studies of the (modified) M-SSA approach. Third, we illustrate the use of the proposed singular value algorithm for the SVR in the context of the two benchmark examples of Groth and Ghil: the Rössler system in the chaotic (i) phase-coherent and (ii) funnel regimes. Comparison with the results obtained with Kaiser's original (unstructured) varimax rotation (UVR) reveals that both SVR and UVR give the same result for the phase-coherent scenario, but for the more complex behavior (ii) only the SVR improves on the M-SSA.

  16. Matrix formulation and singular-value decomposition algorithm for structured varimax rotation in multivariate singular spectrum analysis.

    PubMed

    Portes, Leonardo L; Aguirre, Luis A

    2016-05-01

    Groth and Ghil [Phys. Rev. E 84, 036206 (2011)PLEEE81539-375510.1103/PhysRevE.84.036206] developed a modified varimax rotation aimed at enhancing the ability of the multivariate singular spectrum analysis (M-SSA) to characterize phase synchronization in systems of coupled chaotic oscillators. Due to the special structure of the M-SSA eigenvectors, the modification proposed by Groth and Ghil imposes a constraint in the rotation of blocks of components associated with the different subsystems. Accordingly, here we call it a structured varimax rotation (SVR). The SVR was presented as successive pairwise rotations of the eigenvectors. The aim of this paper is threefold. First, we develop a closed matrix formulation for the entire family of structured orthomax rotation criteria, for which the SVR is a special case. Second, this matrix approach is used to enable the use of known singular value algorithms for fast computation, allowing a simultaneous rotation of the M-SSA eigenvectors (a Python code is provided in the Appendix). This could be critical in the characterization of phase synchronization phenomena in large real systems of coupled oscillators. Furthermore, the closed algebraic matrix formulation could be used in theoretical studies of the (modified) M-SSA approach. Third, we illustrate the use of the proposed singular value algorithm for the SVR in the context of the two benchmark examples of Groth and Ghil: the Rössler system in the chaotic (i) phase-coherent and (ii) funnel regimes. Comparison with the results obtained with Kaiser's original (unstructured) varimax rotation (UVR) reveals that both SVR and UVR give the same result for the phase-coherent scenario, but for the more complex behavior (ii) only the SVR improves on the M-SSA. PMID:27300889

  17. Matrix formulation and singular-value decomposition algorithm for structured varimax rotation in multivariate singular spectrum analysis.

    PubMed

    Portes, Leonardo L; Aguirre, Luis A

    2016-05-01

    Groth and Ghil [Phys. Rev. E 84, 036206 (2011)PLEEE81539-375510.1103/PhysRevE.84.036206] developed a modified varimax rotation aimed at enhancing the ability of the multivariate singular spectrum analysis (M-SSA) to characterize phase synchronization in systems of coupled chaotic oscillators. Due to the special structure of the M-SSA eigenvectors, the modification proposed by Groth and Ghil imposes a constraint in the rotation of blocks of components associated with the different subsystems. Accordingly, here we call it a structured varimax rotation (SVR). The SVR was presented as successive pairwise rotations of the eigenvectors. The aim of this paper is threefold. First, we develop a closed matrix formulation for the entire family of structured orthomax rotation criteria, for which the SVR is a special case. Second, this matrix approach is used to enable the use of known singular value algorithms for fast computation, allowing a simultaneous rotation of the M-SSA eigenvectors (a Python code is provided in the Appendix). This could be critical in the characterization of phase synchronization phenomena in large real systems of coupled oscillators. Furthermore, the closed algebraic matrix formulation could be used in theoretical studies of the (modified) M-SSA approach. Third, we illustrate the use of the proposed singular value algorithm for the SVR in the context of the two benchmark examples of Groth and Ghil: the Rössler system in the chaotic (i) phase-coherent and (ii) funnel regimes. Comparison with the results obtained with Kaiser's original (unstructured) varimax rotation (UVR) reveals that both SVR and UVR give the same result for the phase-coherent scenario, but for the more complex behavior (ii) only the SVR improves on the M-SSA.

  18. Intranasal administration of oxytocin increases compassion toward women

    PubMed Central

    Palgi, Sharon; Klein, Ehud

    2015-01-01

    It has been suggested that the degree of compassion—the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers’ views regarding the target’s vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in ‘tend-and-befriend’ behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants’ responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

  19. Maternal neglect: oxytocin, dopamine and the neurobiology of attachment.

    PubMed

    Strathearn, L

    2011-11-01

    Maternal neglect, including physical and emotional neglect, is a pervasive public health challenge with serious long-term effects on child health and development. I provide an overview of the neurobiological basis of maternal caregiving, aiming to better understand how to prevent and respond to maternal neglect. Drawing from both animal and human studies, key biological systems are identified that contribute to maternal caregiving behaviour, focusing on the oxytocinergic and dopaminergic systems. Mesocorticolimbic and nigrostriatal dopamine pathways contribute to the processing of infant-related sensory cues leading to a behavioural response. Oxytocin may activate the dopaminergic reward pathways in response to social cues. Human neuroimaging studies are summarised that demonstrate parallels between animal and human maternal caregiving responses in the brain. By comparing different patterns of human adult attachment, we gain a clearer understanding of how differences in maternal brain and endocrine responses may contribute to maternal neglect. For example, in insecure/dismissing attachment, which may be associated with emotional neglect, we see reduced activation of the mesocorticolimbic dopamine reward system in response to infant face cues, as well as decreased peripheral oxytocin response to mother-infant contact. We are currently testing whether the administration of intranasal oxytocin, as part of a randomised placebo controlled trial, may reverse some of these neurological differences, and potentially augment psychosocial and behavioural interventions for maternal neglect. PMID:21951160

  20. Oxytocin mediates copulation-induced hypoalgesia of male rats.

    PubMed

    Futagami, Hiroko; Sakuma, Yasuo; Kondo, Yasuhiko

    2016-04-01

    Copulatory behavior has been reported to raise the pain threshold in male rats. In this study, we examined the effect of copulatory behavior with or without ejaculation on pain threshold measured by electrical shock via an electrode attached to the tail. It was demonstrated that ejaculation is not necessary to raise the pain threshold in male rats. In addition, we examined whether oxytocin, a hypothalamic neuropeptide, was involved in copulation-induced hypoalgesia. Sexually experienced males were subjected to stereotaxic implantation of a guide cannula targeting the lateral ventricle. After the recovery period, half of the males were intracerebroventricularly treated with an oxytocin antagonist (OTA, 100ng d(CH2)51,Tyr(Me)2,Thr4, Orn8,Tyr-NH29]-vasotocin/1μL saline) and the remaining half were administered saline without anesthesia. Fifteen minutes later, half of each group were given sexual behavior with receptive females. We found no effect of OTA on sexual activity. Immediately after ejaculation, pain threshold was measured. While raised pain threshold was observed after sexual behavior in saline-treated males, no change in pain threshold was found in OTA-treated males even after copulation. The results suggest that central oxytocin mediates copulation-induced hypoalgesia in male rats. PMID:26960009

  1. Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility.

    PubMed

    Houlihan, Diarmaid D; Dennedy, Michael C; Morrison, John J

    2010-04-01

    The objective of this study was to investigate the effects of abnormal cannabidiol (abn-cbd) on oxytocin-induced myometrial contractility occurring during pregnancy. Isometric tension recordings were performed in isolated myometrial strips from biopsies obtained at elective cesarean section. The effects of cumulative doses of abn-cbd (10(-9)-10(-5) M) on oxytocin-induced myometrial contractions alone, and on those following pre-incubation with SR 144528, AM 251, methylene blue, and iberiotoxin were measured, and dose-response curves were constructed. The pD(2) (-log EC(50)) values and the maximal inhibitory (MMI) values that were achieved were compared for each tissue type. Abn-cbd exerted a potent relaxant effect on oxytocin-induced myometrial contractions in vitro. Pre-incubation with the guanylate cyclase inhibitor, methylene blue, and the BK(Ca) channel antagonist, iberiotoxin, significantly attenuated this effect (for pD(2), P<0.01; for MMI, P<0.01). Abn-cbd exerts a potent inhibitory effect on human uterine contractility. This effect is partially mediated through modulation of guanylate cyclase and activation of BK(Ca) channel activity. These findings have implications for physiologic regulation of myometrial quiescence.

  2. Intranasal administration of oxytocin increases compassion toward women.

    PubMed

    Palgi, Sharon; Klein, Ehud; Shamay-Tsoory, Simone G

    2015-03-01

    It has been suggested that the degree of compassion-the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers' views regarding the target's vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in 'tend-and-befriend' behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants' responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals.

  3. Intranasal administration of oxytocin increases compassion toward women.

    PubMed

    Palgi, Sharon; Klein, Ehud; Shamay-Tsoory, Simone G

    2015-03-01

    It has been suggested that the degree of compassion-the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers' views regarding the target's vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in 'tend-and-befriend' behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants' responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

  4. Maternal Neglect: Oxytocin, Dopamine and the Neurobiology of Attachment

    PubMed Central

    Strathearn, Lane

    2011-01-01

    Maternal neglect, including physical and emotional neglect, is a pervasive public health challenge with serious long-term effects on child health and development. The purpose of this paper is to provide an overview of the neurobiological basis of maternal caregiving, in order to better understand how to prevent and respond to maternal neglect. Drawing from both animal and human studies, key biological systems are identified which contribute to maternal caregiving behavior, focusing on the oxytocinergic and dopaminergic systems. Mesocorticolimbic and nigrostriatal dopamine pathways contribute to the processing of infant-related sensory cues leading to a behavioral response. Oxytocin may activate the dopaminergic reward pathways in response to social cues. Human neuroimaging studies are summarized which demonstrate parallels between animal and human maternal caregiving responses in the brain. By comparing different patterns of human adult attachment, we gain a clearer understanding of how differences in maternal brain and endocrine responses may contribute to maternal neglect. For example, in insecure/dismissing attachment, which may be associated with emotional neglect, we see reduced activation of the mesocorticolimbic dopamine reward system in response to infant face cues, as well as decreased peripheral oxytocin response to mother-infant contact. We are currently testing whether administration of intranasal oxytocin, as part of a randomized placebo controlled trial, may reverse some of these neurological differences, and potentially augment psychosocial and behavioral interventions for maternal neglect. PMID:21951160

  5. Intravaginally applied oxytocin improves post-menopausal vaginal atrophy

    PubMed Central

    Uvnäs-Moberg, Kerstin; Jonasson, Aino F

    2015-01-01

    Objective To explore the efficacy of local oxytocin for the treatment of post-menopausal vaginal atrophy. Design Double-blinded randomised controlled trial. Setting Healthy post-menopausal women in Stockholm, Sweden. Participants Sixty four post-menopausal women between February and June 2012 at the Karolinska University Hospital Huddinge/Sweden. Main outcome measures The efficacy of oxytocin for treatment of vaginal atrophy after seven weeks and cytological evaluation. Results The percentage of superficial cells in the vaginal smears and the maturation values were significantly increased after seven weeks of treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The vaginal pH decreased significantly after seven weeks of treatment with vagitocin 100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological evaluation, were significantly reduced after administration of vagitocin 100 IU (p = 0.03). The thickness of the endometrium did not differ between the treatment and placebo groups after seven weeks of treatment. The symptom experienced as the most bothersome was significantly reduced after seven weeks of treatment in the women receiving vagitocin 400 IU compared to women in the placebo group (p = 0.0089). Conclusions Treatment with intravaginally applied oxytocin could be an alternative to local estrogen treatment in women with post-menopausal vaginal atrophy. PMID:25995333

  6. Capillary electrophoresis-electrochemiluminescence detection method for the analysis of ibandronate in drug formulations and human urine.

    PubMed

    Huang, Yu-Shan; Chen, Shun-Niang; Whang, Chen-Wen

    2011-08-01

    A simple, rapid and sensitive CE method coupled with electrochemiluminescence (ECL) detection for direct analysis of ibandronate (IBAN) has been developed. Using a buffer solution of 20 mM sodium phosphate (pH 9.0) and a voltage of 13.5 kV, separation of IBAN in a 30-cm length capillary was achieved in 3 min. ECL detection was performed with an indium tin oxide working electrode bias at 1.6 V (versus a Pt wire reference) in a 200-mM sodium phosphate buffer (pH 8.0) containing 3.5 mM Ru(bpy)(3)(2+) (where bpy=2,2'-bipyridyl). Derivatization of IBAN prior to CE-ECL analysis was not needed. Linear correlation (r=0.9992, n=7) between ECL intensity and analyte concentration was obtained in the range of 0.25-50 μM IBAN. The LOD of IBAN in water was 0.08 μM. The developed method was applied to the analysis of IBAN in a drug formulation and human urine sample. SPE using magnetic Fe(3)O(4)@Al(2)O(3) nanoparticles as the extraction phase was employed to pretreat the urine sample before CE-ECL analysis. The linear range was 0.2-12.0 μM IBAN in human urine (r=0.9974, n=6). The LOD of IBAN in urine was 0.06 μM. Total analysis time including sample preparation was <1 h. PMID:21793001

  7. Pre-formulation studies on moisture absorption in microcrystalline cellulose using differential thermo-gravimetric analysis.

    PubMed

    Heng, Paul Wan Sia; Liew, Celine Valeria; Soh, Josephine Lay Peng

    2004-04-01

    A study on the differential thermo-gravimetric (DTG) measurements of microcrystalline cellulose (MCC) containing moisture indicated that particle size affected the amount of bound water and the flow indices. Thermal analysis of 6 commercial grades of MCC powders and MCC/water blends were performed using a thermo-gravimetric analyzer. These MCCs were differentiated by their particle size, bulk and tapped densities, crystallinity and micromeritic properties. From the DTG curves, it was observed that water loss from the MCC/water blends occurred in 3 phases which corresponded to the different states of water associated with the solid particles. Area under the third phase, or the falling rate phase, can be associated with the release of water that was physically shielded or bound to the solid. This water may be referred to as "structured" water. The large particle size grades of MCC-Avicel PH 102, PH 302 and Pharmacel 102 were found to possess smaller quantities of structured water. Water vapor sorption results revealed the monolayer capacities for the respective MCC grades. The amount of structured water appeared to correspond to the existence of bilayers on the surface of the small particle size MCC grades. Using the avalanche flow assessment method, flow properties of small particle size grades of MCC were found to be poorer as indicated by the significant correlation between their flow indices and size, in addition to the longer mean times to avalanche.

  8. Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets.

    PubMed

    Claycamp, H Gregg; Kona, Ravikanth; Fahmy, Raafat; Hoag, Stephen W

    2016-04-01

    Qualitative risk assessment methods are often used as the first step to determining design space boundaries; however, quantitative assessments of risk with respect to the design space, i.e., calculating the probability of failure for a given severity, are needed to fully characterize design space boundaries. Quantitative risk assessment methods in design and operational spaces are a significant aid to evaluating proposed design space boundaries. The goal of this paper is to demonstrate a relatively simple strategy for design space definition using a simplified Bayesian Monte Carlo simulation. This paper builds on a previous paper that used failure mode and effects analysis (FMEA) qualitative risk assessment and Plackett-Burman design of experiments to identity the critical quality attributes. The results show that the sequential use of qualitative and quantitative risk assessments can focus the design of experiments on a reduced set of critical material and process parameters that determine a robust design space under conditions of limited laboratory experimentation. This approach provides a strategy by which the degree of risk associated with each known parameter can be calculated and allocates resources in a manner that manages risk to an acceptable level.

  9. A hybrid wave-mode formulation for the vibro-acoustic analysis of 2D periodic structures

    NASA Astrophysics Data System (ADS)

    Droz, C.; Zhou, C.; Ichchou, M. N.; Lainé, J.-P.

    2016-02-01

    In the framework of vibrational analysis of 2D periodic waveguides, Floquet-Bloch theorem is widely applied for the determination of wave dispersion characteristics. In this context, the Wave Finite Element Method (WFEM) combines Periodic Structure Theory (PST) with standard FE packages, enabling wave dispersion analysis of waveguides involving structurally realistic unit-cells. For such applications, the computational efficiency of the WFEM depends on the choice of the formulation and can lead to numerical issues, worsen by extensive computational cost. This paper presents a coupled wave-mode approach for the determination of wave dispersion characteristics in structurally advanced periodic structures. It combines two scales of model order reduction. At the unit-cell's scale, Component Mode Synthesis (CMS) provides the displacement field associated with local resonances of the periodic structure, while the free wave propagation is considered using a spectral problem projection on a reduced set of shape functions associated with propagating waves, thus providing considerable reduction of the computational cost. An application is provided for a bi-directionally stiffened panel and the influence of reduction parameters is discussed, as well as the robustness of the numerical results.

  10. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    PubMed

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia.

  11. Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.

    PubMed

    Xu, Lei; Ma, Xiaole; Zhao, Weihua; Luo, Lizhu; Yao, Shuxia; Kendrick, Keith M

    2015-12-01

    There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder.

  12. Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.

    PubMed

    Xu, Lei; Ma, Xiaole; Zhao, Weihua; Luo, Lizhu; Yao, Shuxia; Kendrick, Keith M

    2015-12-01

    There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder. PMID:26372768

  13. Oxytocin Attenuates Neural Reactivity to Masked Threat Cues from the Eyes

    PubMed Central

    Kanat, Manuela; Heinrichs, Markus; Schwarzwald, Ralf; Domes, Gregor

    2015-01-01

    The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention to the eye vs the mouth region. Intranasal oxytocin administration reduced amygdala reactivity to masked emotions when attending to salient facial features, ie, the eyes of angry faces and the mouth of happy faces. In addition, oxytocin decreased neural responses within the fusiform gyrus and brain stem areas, as well as functional coupling between the amygdala and the fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on brain activity were not attributable to differences in behavioral performance, as oxytocin had no impact on mere emotion detection. Our results suggest that oxytocin attenuates neural correlates of early arousal by threat signals from the eye region. As reduced threat sensitivity may increase the likelihood of engaging in social interactions, our findings may have important implications for clinical states of social anxiety. PMID:25047745

  14. Oxytocin modulates cooperation within and competition between groups: an integrative review and research agenda.

    PubMed

    De Dreu, Carsten K W

    2012-03-01

    The author reviews evidence that hypothalamic release (or infusion) of the neuropeptide oxytocin modulates the regulation of cooperation and conflict among humans because of three reasons. First, oxytocin enables social categorization of others into in-group versus out-group. Second, oxytocin dampens amygdala activity and enables the development of trust. Third, and finally, oxytocin up-regulates neural circuitries (e.g., inferior frontal gyrus, ventromedial prefrontal cortex, caudate nucleus) involved in empathy and other-concern. Consistent with an evolutionary perspective on the functionality of cooperation, it is concluded that oxytocin-motivated cooperation is mostly parochial-it motivates (i) in-group favoritism, (ii) cooperation towards in-group but not out-group members, and (iii) defense-motivated non-cooperation towards threatening outsiders. Thus, in addition to its well-known role in reproduction and pair-bond formation, oxytocin's primary functions include in-group "tend-and-defend." This review concludes with avenues for new research on oxytocin's functions in within-group cooperation and between-group competition. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID:22227278

  15. 2,5-Diketopiperazines as potent and selective oxytocin antagonists 1: Identification, stereochemistry and initial SAR.

    PubMed

    Wyatt, Paul G; Allen, Michael J; Borthwick, Alan D; Davies, Dave E; Exall, Anne M; Hatley, Richard J D; Irving, Wendy R; Livermore, David G; Miller, Neil D; Nerozzi, Fabrizio; Sollis, Steve L; Szardenings, Anna Katrin

    2005-05-16

    This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds.

  16. Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

    2014-01-01

    The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

  17. Oxytocin eliminates the own-race bias in face recognition memory.

    PubMed

    Blandón-Gitlin, Iris; Pezdek, Kathy; Saldivar, Sesar; Steelman, Erin

    2014-09-11

    The neuropeptide Oxytocin influences a number of social behaviors, including processing of faces. We examined whether Oxytocin facilitates the processing of out-group faces and reduce the own-race bias (ORB). The ORB is a robust phenomenon characterized by poor recognition memory of other-race faces compared to the same-race faces. In Experiment 1, participants received intranasal solutions of Oxytocin or placebo prior to viewing White and Black faces. On a subsequent recognition test, whereas in the placebo condition the same-race faces were better recognized than other-race faces, in the Oxytocin condition Black and White faces were equally well recognized, effectively eliminating the ORB. In Experiment 2, Oxytocin was administered after the study phase. The ORB resulted, but Oxytocin did not significantly reduce the effect. This study is the first to show that Oxytocin can enhance face memory of out-group members and underscore the importance of social encoding mechanisms underlying the own-race bias. This article is part of a Special Issue entitled Oxytocin and Social Behav.

  18. Induction of oviposition by the administration of oxytocin in hawksbill turtles.

    PubMed

    Kawazu, Isao; Kino, Masakatsu; Maeda, Konomi; Yamaguchi, Yasuhiro; Sawamukai, Yutaka

    2014-12-01

    We set out to develop an oviposition induction technique for captive female hawksbill turtles Eretmochelys imbricata. The infertile eggs of nine females were induced to develop by the administration of follicle-stimulating hormone, after which we investigated the effects of administering oxytocin on oviposition. Seven of the turtles were held in a stationary horizontal position on a retention stand, and then oxytocin was administrated (0.6-0.8 units/kg of body weight; 5 mL). The seven turtles were retained for a mandatory 2 h period after oxytocin administration, and were then returned to the holding tanks. As the control, normal saline (5 mL) was administered to the other two turtles, followed by the administration of oxytocin after 24 h. The eggs in oviducts of all nine turtles were observed by ultrasonography at 24 h after oxytocin administration. The control experiment validated that stationary retention and normal saline administration had no effect on egg oviposition. Eight of the turtles began ovipositing eggs at 17-43 min after oxytocin administration, while one began ovipositing in the holding tank immediately after retention. All turtles finished ovipositing eggs within 24 h of oxytocin administration. This report is the first to demonstrate successful induced oviposition in sea turtles. We suggest that the muscles in the oviducts of hawksbill turtles may respond to relatively lower doses of oxytocin (inducing contractions) compared to land and freshwater turtles (4-40 units/kg) based on existing studies.

  19. Oxytocin enables novelty seeking and creative performance through upregulated approach: evidence and avenues for future research.

    PubMed

    De Dreu, Carsten K W; Baas, Matthijs; Boot, Nathalie C

    2015-01-01

    Oxytocin is an evolutionary ancient hypothalamic neuropeptide well known for its role in reproduction, social bonding, and group affiliation. Recent work has linked oxytocin in humans to creative cognition--the ability to produce insights, ideas, and problem solutions that are original and potentially useful. Here we review this literature, focusing on the relationship between (1) single-nucleotide polymorphisms in the oxytocin receptor (OXTR) gene; endogenous oxytocin from blood plasma, and intranasal administration of oxytocin (vs placebo), and (2) creativity-related traits (e.g., novelty seeking, extraversion, and openness to experience), and behaviors (e.g., exploration, divergent thinking, original ideation, and problem solving). Findings are interpreted in the context of the dual pathway to creativity model and except for OXTR: (1) reveal a weak to moderate but consistent association between oxytocin and creativity, which emerges because (2) oxytocin enables the cognitive flexibility pathway more than persistent information processing. Findings can be best understood in terms of oxytocin's putative effects on dopaminergic activity and concomitant approach tendency.

  20. Oxytocin in the male: an old hormone growing sexy with age.

    PubMed

    McGregor, G P; Lang, R E

    2001-01-01

    It has long been a mystery of oxytocin research that males have similar levels of the hormone in their blood as females, but there is no known function associated with this. This review brings together some diverse literature to point out a possible role of oxytocin in the context of stress and sexuality.

  1. Intrapartum Synthetic Oxytocin Reduce the Expression of Primitive Reflexes Associated with Breastfeeding

    PubMed Central

    Olza Fernández, Ibone; Malalana Martínez, Ana M.; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

    2015-01-01

    Abstract Aim: Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. Materials and Methods: A cohort prospective study was conducted at a tertiary hospital. Mother–infant dyads who received intrapartum oxytocin (n=53) were compared with mother–infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. Results: The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Conclusions: Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent. PMID:25785487

  2. Oxytocin enables novelty seeking and creative performance through upregulated approach: evidence and avenues for future research.

    PubMed

    De Dreu, Carsten K W; Baas, Matthijs; Boot, Nathalie C

    2015-01-01

    Oxytocin is an evolutionary ancient hypothalamic neuropeptide well known for its role in reproduction, social bonding, and group affiliation. Recent work has linked oxytocin in humans to creative cognition--the ability to produce insights, ideas, and problem solutions that are original and potentially useful. Here we review this literature, focusing on the relationship between (1) single-nucleotide polymorphisms in the oxytocin receptor (OXTR) gene; endogenous oxytocin from blood plasma, and intranasal administration of oxytocin (vs placebo), and (2) creativity-related traits (e.g., novelty seeking, extraversion, and openness to experience), and behaviors (e.g., exploration, divergent thinking, original ideation, and problem solving). Findings are interpreted in the context of the dual pathway to creativity model and except for OXTR: (1) reveal a weak to moderate but consistent association between oxytocin and creativity, which emerges because (2) oxytocin enables the cognitive flexibility pathway more than persistent information processing. Findings can be best understood in terms of oxytocin's putative effects on dopaminergic activity and concomitant approach tendency. PMID:26267407

  3. ¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations Part II: CP kinetics and relaxation analysis.

    PubMed

    Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika; Szeleszczuk, Łukasz; Wawer, Iwona

    2016-04-15

    Excipients used in the solid drug formulations differ in their NMR relaxation and (13)C cross-polarization (CP) kinetics parameters. Therefore, experimental parameters like contact time of cross-polarization and repetition time have a major impact on the registered solid state NMR spectra and in consequence on the results of the NMR analysis. In this work the CP kinetics and relaxation of the most common pharmaceutical excipients: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. The studied excipients differ significantly in their optimum repetition time (from 5 s to 1200 s) and T(1ρ)(I) parameters (from 2 ms to 73 ms). The practical use of those differences in the excipients composition analysis was demonstrated on the example of commercially available tablets containing indapamide as an API. The information presented in this article will help to choose the correct acquisition parameters and also will save the time and effort needed for their optimization in the NMR analysis of the solid drug formulations.

  4. ¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations Part II: CP kinetics and relaxation analysis.

    PubMed

    Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika; Szeleszczuk, Łukasz; Wawer, Iwona

    2016-04-15

    Excipients used in the solid drug formulations differ in their NMR relaxation and (13)C cross-polarization (CP) kinetics parameters. Therefore, experimental parameters like contact time of cross-polarization and repetition time have a major impact on the registered solid state NMR spectra and in consequence on the results of the NMR analysis. In this work the CP kinetics and relaxation of the most common pharmaceutical excipients: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. The studied excipients differ significantly in their optimum repetition time (from 5 s to 1200 s) and T(1ρ)(I) parameters (from 2 ms to 73 ms). The practical use of those differences in the excipients composition analysis was demonstrated on the example of commercially available tablets containing indapamide as an API. The information presented in this article will help to choose the correct acquisition parameters and also will save the time and effort needed for their optimization in the NMR analysis of the solid drug formulations. PMID:26836362

  5. Oxytocin Mediates Entrainment of Sensory Stimuli to Social Cues of Opposing Valence

    PubMed Central

    Choe, Han Kyoung; Reed, Michael Douglas; Benavidez, Nora; Montgomery, Daniel; Soares, Natalie; Yim, Yeong Shin; Choi, Gloria B.

    2015-01-01

    Meaningful social interactions modify behavioral responses to sensory stimuli. The neural mechanisms underlying the entrainment of neutral sensory stimuli to salient social cues to produce social learning remains unknown. We used odor-driven behavioral paradigms to ask if oxytocin, a neuropeptide implicated in various social behaviors, plays a crucial role in the formation of learned associations between odor and socially significant cues. Through genetic, optogenetic and pharmacological manipulations, we show that oxytocin receptor signaling is crucial for entrainment of odor to social cues, but is dispensable for entrainment to non-social cues. Furthermore, we demonstrate that oxytocin directly impacts the piriform, the olfactory sensory cortex, to mediate social learning. Lastly, we provide evidence that oxytocin plays a role in both appetitive and aversive social learning. These results suggest that oxytocin conveys saliency of social stimuli to sensory representations in the piriform cortex during odor-driven social learning. PMID:26139372

  6. The acute effects of intranasal oxytocin on automatic and effortful attentional shifting to emotional faces.

    PubMed

    Ellenbogen, Mark A; Linnen, Anne-Marie; Grumet, Robin; Cardoso, Christopher; Joober, Ridha

    2012-01-01

    Oxytocin is known to promote social affiliation. The mechanism by which this occurs is unknown, but it may involve changes in social information processing. In a placebo-controlled study, we examined the influence of intranasal oxytocin on effortful and automatic attentional shifting in 57 participants using a spatial cueing task with emotional and neutral faces. For effortful processing, oxytocin decreased the speed of shifting attention to sad faces presented for 750 ms and facilitated disengagement from right hemifield sad and angry faces presented for 200 ms. For automatic processing, symptoms of depression moderated the relationship between drug and disengagement. Oxytocin attenuated an attentional bias to masked angry faces on disengagement trials in persons with high depression scores. Oxytocin's influence on social behavior may occur, in part, by eliciting flexible attentional shifting in the early stages of information processing. PMID:22092248

  7. Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

    SciTech Connect

    Altszuler, N.; Puma, F.; Winkler, B.; Fontan, N.; Saudek, C.D.

    1986-05-01

    Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the (6-/sup 3/H)glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 ..mu..U/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.

  8. Implications of Oxytocin in Human Linguistic Cognition: From Genome to Phenome

    PubMed Central

    Theofanopoulou, Constantina

    2016-01-01

    The neurohormone oxytocin (OXT) has been found to mediate the regulation of complex socioemotional cognition in multiple ways both in humans and other animals. Recent studies have investigated the effects of OXT in different levels of analysis (from genetic to behavioral) chiefly targeting its impact on the social component and only indirectly indicating its implications in other components of our socio-interactive abilities. This article aims at shedding light onto how OXT might be modulating the multimodality that characterizes our higher-order linguistic abilities (vocal-auditory-attentional-memory-social systems). Based on evidence coming from genetic, EEG, fMRI, and behavioral studies, I attempt to establish the promises of this perspective with the goal of stressing the need for neuropeptide treatments to enter clinical practice. PMID:27378840

  9. Multiple sup 3 H-oxytocin binding sites in rat myometrial plasma membranes

    SciTech Connect

    Crankshaw, D.; Gaspar, V.; Pliska, V. )

    1990-01-01

    The affinity spectrum method has been used to analyse binding isotherms for {sup 3}H-oxytocin to rat myometrial plasma membranes. Three populations of binding sites with dissociation constants (Kd) of 0.6-1.5 x 10(-9), 0.4-1.0 x 10(-7) and 7 x 10(-6) mol/l were identified and their existence verified by cluster analysis based on similarities between Kd, binding capacity and Hill coefficient. When experimental values were compared to theoretical curves constructed using the estimated binding parameters, good fits were obtained. Binding parameters obtained by this method were not influenced by the presence of GTP gamma S (guanosine-5'-O-3-thiotriphosphate) in the incubation medium. The binding parameters agree reasonably well with those found in uterine cells, they support the existence of a medium affinity site and may allow for an explanation of some of the discrepancies between binding and response in this system.

  10. Implications of Oxytocin in Human Linguistic Cognition: From Genome to Phenome.

    PubMed

    Theofanopoulou, Constantina

    2016-01-01

    The neurohormone oxytocin (OXT) has been found to mediate the regulation of complex socioemotional cognition in multiple ways both in humans and other animals. Recent studies have investigated the effects of OXT in different levels of analysis (from genetic to behavioral) chiefly targeting its impact on the social component and only indirectly indicating its implications in other components of our socio-interactive abilities. This article aims at shedding light onto how OXT might be modulating the multimodality that characterizes our higher-order linguistic abilities (vocal-auditory-attentional-memory-social systems). Based on evidence coming from genetic, EEG, fMRI, and behavioral studies, I attempt to establish the promises of this perspective with the goal of stressing the need for neuropeptide treatments to enter clinical practice. PMID:27378840

  11. Plasma oxytocin concentrations during late pregnancy and parturition in the dog.

    PubMed

    Klarenbeek, M; Okkens, A C; Kooistra, H S; Mol, J A; M M Bevers; Taverne, M A M

    2007-11-01

    While oxytocin is widely used in the treatment of dystocia in dogs, there is little information about its secretion before and during normal unassisted whelping. We therefore measured plasma oxytocin concentrations during late pregnancy and the expulsive stage of parturition. Blood samples were collected from eight dogs at 3-min intervals during a 42-min period between the 2nd and 14th day before whelping and during parturition after the birth of 1-3 pups. The litters consisted of 5-15 pups and the progression of the expulsive stage was linear and nearly parallel in the eight bitches. The overall mean (+/-S.D.) plasma oxytocin concentration during late pregnancy was 3.6+/-2.1pg/ml. Mean values in individual dogs ranged from 1.2 to 7.4 pg/ml, but the intra-animal variation was rather small. During the expulsive stage the overall mean (+/-S.D.) plasma oxytocin concentration was 12.9+/-13.9 pg/ml, with mean values in individual dogs ranging from 3.5 to 46 pg/ml. The mean area under the oxytocin curve for parturient dogs was significantly higher (P<0.05) than for pregnant dogs. During the expulsive stage, the peak plasma oxytocin level in individual dogs ranged between 10 and 117 pg/ml. In six of the eight dogs a pup was born during blood collection and in five of these animals the plasma oxytocin concentration increased temporarily during periods of abdominal straining and expulsion. However, straining efforts and expulsion were not consistently associated with a rise in the circulating oxytocin level. It is concluded that in the dog plasma oxytocin levels are higher and more variable during the expulsive stage of parturition than during late pregnancy. Interrelationships between the secretion pattern of oxytocin, the level of uterine contractility, and the progress of fetal expulsion in dogs need further exploration.

  12. Parental oxytocin and early caregiving jointly shape children's oxytocin response and social reciprocity.

    PubMed

    Feldman, Ruth; Gordon, Ilanit; Influs, Moran; Gutbir, Tamar; Ebstein, Richard P

    2013-06-01

    Oxytocin (OT) has an important role in bond formation and social reciprocity, and animal studies indicate that OT functioning is transferred from parent to child through patterns of parental care. Perspectives on attachment suggest that the individual's various attachment bonds are underpinned by the oxytocinergic system. However, prospective human studies that demonstrate the cross-generation transfer of OT as mediated by early caregiving and its impact on children's multiple attachments are lacking. To address these concerns, the current study included 160 mothers and fathers and their firstborn child who participated in a 3-year longitudinal study. At the first and sixth postpartum months, parents' plasma OT was assayed, parent-infant interactions were videotaped and micro-coded, and allelic variations on the OXTR(rs2254298, rs1042778) and CD38rs3796863 genes were measured. At 3 years, parents' and child's salivary OT was assessed and children's social reciprocity observed during interactions with mother, father, and their first best friend. Parents' OT levels were individually stable across the 3-year period, correlated with low-risk OXTR and CD38 alleles, and predicted child OT. Child's social reciprocity with friend was associated with child OT levels, mother's OT-related genes and hormones, and mother-child reciprocity, but not with father's genes, hormones, or behavior. A cross-generation gene-by-environment effect emerged, with low child OT levels predicted by the interaction of maternal high-risk CD38 allele and diminished maternal care in infancy. These results demonstrate individual stability in peripheral OT across several years and describe a cross-generation transfer of OT through caregiving in humans within a prospective longitudinal design. Consistent with other mammals, biobehavioral experiences within the parent-infant bond shape children's affiliative biology and social behavior across multiple attachments. Our findings bear important

  13. Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders.

    PubMed

    Macdonald, K; Feifel, D

    2013-01-01

    Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over 30 year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline's flow of medications with unique mechanisms of action (i.e., glutamatergic agents, CRF antagonists) has slowed to a trickle. Might oxytocin (OT)-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify 10 key questions that we believe future OT research should address. From this overview, several conclusions are clear: (1) the OT system represents an extremely promising target for novel CNS drug development; (2) there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and (3) in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth OT-targeted treatments that can truly deliver on this system's therapeutic potential.

  14. Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders

    PubMed Central

    MacDonald, K.; Feifel, D.

    2013-01-01

    Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over 30 year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline's flow of medications with unique mechanisms of action (i.e., glutamatergic agents, CRF antagonists) has slowed to a trickle. Might oxytocin (OT)-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify 10 key questions that we believe future OT research should address. From this overview, several conclusions are clear: (1) the OT system represents an extremely promising target for novel CNS drug development; (2) there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and (3) in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth OT-targeted treatments that can truly deliver on this system's therapeutic potential. PMID:23508240

  15. Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

    PubMed

    Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

    2014-01-01

    The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

  16. Development of chiral methodologies by capillary electrophoresis with ultraviolet and mass spectrometry detection for duloxetine analysis in pharmaceutical formulations.

    PubMed

    Sánchez-López, Elena; Montealegre, Cristina; Marina, María Luisa; Crego, Antonio L

    2014-10-10

    Two chiral methodologies were developed by capillary electrophoresis (CE) with UV and mass spectrometry (MS) detection to ensure the quality control of the drug duloxetine, commercialized as a pure enantiomer. Both methods were optimized to achieve a high baseline enantioresolution (Rs>2) and an acceptable precision (RSD values <5% for instrumental repeatability and <10% for intermediate precision). In addition to allow the unequivocal identification of duloxetine enantiomers, the CE-MS method improved the sensitivity with respect to the use of CE-UV (LOD 200 ng/mL by CE-UV and 20 ng/mL by CE-MS) enabling to detect 0.02% of duloxetine enantiomeric impurity. This is the lowest LOD value ever reported for this drug, being this work the first one enabling to accomplish with the ICH guidelines requirements. The developed methods were validated and applied for the first time to the analysis of four pharmaceutical formulations. The content of R-duloxetine in all these samples was below the detection limit and the amount of S-duloxetine was in good agreement with the labeled content, obtaining results by the two methods that did not differ significantly (p-values >0.05).

  17. Predicting the aerosol performance of dry powder inhalation formulations by interparticulate interaction analysis using inverse gas chromatography.

    PubMed

    Tong, Henry H Y; Shekunov, Boris Y; York, Peter; Chow, Albert H L

    2006-01-01

    Previous studies have demonstrated the utility of inverse gas chromatography (IGC) in discriminating the differences in surface energy between salmeterol xinafoate (SX) powders prepared by conventional sequential batch crystallization and micronization and by supercritical fluid crystallization. In the present study, solubility parameters derived from IGC analysis at infinite dilution (zero coverage) were further utilized to evaluate the influence of solid-solid interactions on the in vitro aerosol performance of these SX samples, with or without the inclusion of a lactose carrier. To this end, the strength of cohesive SX-SX interactions and that of adhesive SX-lactose interactions were computed for the samples from the corresponding solubility parameters, and their fine particle fractions determined using a multi-stage liquid impinger. It was found that the aerosol performance of SX could be substantially improved by the addition of lactose carrier only if the adhesive SX-lactose interactions were stronger than the cohesive SX-SX interactions. The difference in strength between these two forms of interactions also displayed a significant correlation with the increase in fine particle fraction after the addition of lactose carrier. These results suggest that IGC-based interparticulate interaction measurements may serve as a useful means for predicting the aerosol performance of dry powder inhalation formulations.

  18. Algebraic connectivity analysis in molecular electronic structure theory II: total exponential formulation of second-quantised correlated methods

    NASA Astrophysics Data System (ADS)

    Lyakh, Dmitry I.; Bartlett, Rodney J.

    2014-01-01

    The fundamentality of the exponential representation of a second-quantised correlated wave function is emphasised with an accent on the physical sense of cluster amplitudes as cumulants of the correlated ansatz. Three main wave function formalisms, namely, the configuration-interaction theory, the coupled-cluster approach, and the many-body perturbation theory (as well as their extensions, e.g. the equation-of-motion coupled-cluster method, multireference schemes, etc.), are represented in an exponential form, leading to a formulation of the working equations in terms of cluster amplitudes. By expressing the corresponding many-body tensor equations in terms of cluster amplitudes, we could unambiguously check connectivity types and the asymptotic behaviour of all tensors/scalars involved (in the formal limit of an infinite number of correlated particles). In particular, the appearance of disconnected cluster amplitudes corresponds to unphysical correlations. Besides, we demonstrate that the equation-of-motion coupled-cluster approach, as well as certain excited-state configuration-interaction methods, can be recast in a fully connected (exponential) form, thus breaking the common belief that all truncated configuration-interaction methods violate connectivity. Our work is based on the recently developed algebraic framework which can be viewed as a complement to the classical diagrammatic analysis.

  19. Oxytocin-like immunoreactive nerves are associated with insulin-containing cells in pancreatic islets of anglerfish (Lophius americanus).

    PubMed

    McDonald, J K; Greiner, F; Wood, J G; Noe, B D

    1987-07-01

    Recent reports indicate that oxytocin exerts direct effects on the release of insulin and glucagon from the endocrine pancreas of the rat. The purpose of this study was to determine whether oxytocin-like immunoreactivity is present in the anglerfish islet, and if it is associated with subsets of hormone-producing cells. Antisera against oxytocin, insulin, glucagon, somatostatin, neuropeptide Y, and the 200-kd neurofilament polypeptide were applied to serial 5 micrometers sections of pancreatic islets. The antiserum to the 200-kd neurofilament polypeptide labeled nerve bundles and axons, some of which were also stained with the oxytocin antiserum. Oxytocin immunoreactivity was observed in large nerves that branched into varicose fibers. These fibers were consistently associated only with clusters of insulin-producing cells. Successive application of oxytocin and insulin antisera to the same section provided additional verification of this relationship. Oxytocin-labeled nerves were not associated with cells immunoreactive to glucagon, somatostatin, or neuropeptide Y (anglerfish peptide Yg). The results demonstrate that oxytocin or an oxytocin-like peptide is located in fibers that surround only insulin-producing cells in the anglerfish islet. Although the functional significance of this observation remains to be determined, the results imply that oxytocin, or an oxytocin-like peptide, may affect the synthesis or release of insulin from anglerfish islets. PMID:3304646

  20. Differential regulation of oxytocin receptor in various adipose tissue depots and skeletal muscle types in obese Zucker rats.

    PubMed

    Gajdosechova, L; Krskova, K; Olszanecki, R; Zorad, S

    2015-07-01

    Multifunctional peptide oxytocin currently undergoes intensive research due to its proposed anti-obesity properties. Until now, little is known about regulation of oxytocin receptor in metabolically active tissues in obesity. The aim of the present study was to measure expression of oxytocin receptor upon obese phenotype with respect to the variety among adipose tissue and skeletal muscles with distinct anatomical localisation. Total homogenates were prepared from epididymal, retroperitoneal and inguinal adipose tissues as well as quadriceps and soleus muscle from lean and obese Zucker rats. Oxytocin receptor protein was determined by immunoblot. Interestingly, elevated oxytocin receptor was observed in epididymal adipose tissue of obese rats in contrast to its downregulation in subcutaneous and no change in retroperitoneal fat. In lean animals, oxytocin receptor protein was expressed at similar levels in all adipose depots. This uniformity was not observed in the case of skeletal muscle in which fibre type composition seems to be determinant of oxytocin receptor expression. Quadriceps muscle with the predominance of glycolytic fibres exhibits higher oxytocin receptor expression than almost exclusively oxidative soleus muscle. Oxytocin receptor protein levels were decreased in both skeletal muscles analysed upon obese phenotype. The present work demonstrates that even under identical endocrine circumstances, oxytocin receptor is differentially regulated in adipose tissue of obese rats depending on fat depot localisation. These results also imply which tissues may be preferentially targeted by oxytocin treatment in metabolic disease.

  1. Association between Genetic Variation in the Oxytocin Receptor Gene and Emotional Withdrawal, but not between Oxytocin Pathway Genes and Diagnosis in Psychotic Disorders

    PubMed Central

    Haram, Marit; Tesli, Martin; Bettella, Francesco; Djurovic, Srdjan; Andreassen, Ole Andreas; Melle, Ingrid

    2015-01-01

    Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behavior. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, and CD38) and four areas of social behavior-related psychopathology as measured by Positive and Negative Syndrome Scale. For this purpose, we used both a polygenic risk score (PGRS) and single OXTR candidate single nucleotide polymorphism previously reported in the literature (rs53576, rs237902, and rs2254298). A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behavior. PMID:25667571

  2. Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

    PubMed Central

    Spitz, Aaron; Gittelman, Marc; Karsh, Lawrence I; Dragnic, Sanja; Soliman, Ahmed M; Lele, Aditya; Gruca, Damian; Norton, Michael

    2016-01-01

    Introduction Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels. Methods In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. Results Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks. Conclusion Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

  3. Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

    PubMed Central

    Spitz, Aaron; Gittelman, Marc; Karsh, Lawrence I; Dragnic, Sanja; Soliman, Ahmed M; Lele, Aditya; Gruca, Damian; Norton, Michael

    2016-01-01

    Introduction Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels. Methods In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. Results Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks. Conclusion Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted. PMID:27602344

  4. Congener-specific analysis of polychlorinated naphthalenes (PCNs) in the major Chinese technical PCB formulation from a stored Chinese electrical capacitor.

    PubMed

    Huang, Jun; Yu, Gang; Yamauchi, Makoto; Matsumura, Toru; Yamazaki, Norimasa; Weber, Roland

    2015-10-01

    Impurity of polychlorinated naphthalenes (PCNs) in commercial polychlorinated biphenyl (PCB) formulations has been recognized as a relevant source of PCNs in the environment. Congener-specific analysis of most main PCB formulations has been accomplished previously, excluding the Chinese product. The insulating oil in a stored Chinese electric capacitor containing the major Chinese technical formulation "PCB3" was sampled and tested by isotope dilution technology using high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). The detected concentration of PCNs in the Chinese PCB oil sample was 1,307.5 μg/g and therefore significantly higher than that reported in PCB formulations from other countries, as well as that in the transformer oil (ASKAREL Nr 1740) additionally tested in the present study for comparison. Based on the measurement, the total amount of PCNs in Chinese PCB3 oil is estimated to be 7.8 t, which would mean only 0.005 % of global production of PCNs of 150,000 t. The homolog profile is similar to those of PCN in Aroclor 1262 and Clophen A40, where the contributions from hexa-CNs and hepta-CNs are predominant and accounted for similar proportions. The Toxic Equivalent Quantity (TEQ) concentration of dioxin-like PCN congeners is 0.47 μg TEQ/g, with the dominant contributors of CN-73 and CN-66/67. This TEQ content from PCN is higher than that in most other PCB formulations with the exemption of the Russian Sovol formulation. The total TEQ in the historic 6,000 t of the Chinese PCB3 formulation is estimated to be 2.8 kg TEQ.

  5. Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques

    PubMed Central

    Parker, Karen J.; Hoffman, Christy L.; Hyde, Shellie A.; Cummings, Carl S.; Maestripieri, Dario

    2013-01-01

    There is growing interest in studying oxytocin biology in the context of social functioning in human and non-human primates. Studies of human subjects are typically restricted to peripheral oxytocin assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. A few studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of young infants. The main goal of the present study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on the island of Cayo Santiago, Puerto Rico. CSF oxytocin levels were examined in relation to individuals’ demographic and reproductive characteristics, as well as in relation to plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7–26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38–134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. In summary, these findings: 1) provide feasibility data for examining CSF oxytocin biology in free-ranging nonhuman primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Although our study did not report significant associations between CSF oxytocin levels and socially-relevant demographic variables, the relationships between CSF oxytocin levels and assessments of social functioning warrant future investigation. PMID:20528088

  6. Development of grout formulations for 106-AN waste: Mixture-experiment results and analysis. Volume 2, Data presentation

    SciTech Connect

    Spence, R.D.; McDaniel, E.W.; Anderson, C.M.; Lokken, R.O.; Piepel, G.F.

    1993-09-01

    Twenty potential ingredients were identified for use in developing a 106-AN grout formulation, and 18 were subsequently obtained and tested. Four ingredients: Type II-LA (moderate heat of hydration) Portland cement, Class F fly ash, attapulgite 150 drilling clay, and ground air-cooled blast-furnace slag (GABFS) -- were selected for developing the 106-AN grout formulations. A mixture experiment was designed and conducted around the following formulation: 2.5 lb of cement per gallon, 1.2 lb of fly ash per gallon, 0.8 lb of attapulgite per gallon, and 3.5 lb of GABFS per gallon. Reduced empirical models were generated from the results of the mixture experiment. These models were used to recommend several grout formulations for 106-AN. Westinghouse Hanford Company selected one of these formulations to be verified for use with 106-AN and a backup formulation in case problems arise with the first choice. This report presents the mixture-experimental results and leach data.

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

    SciTech Connect

    Marini, J.C.; Nelson, K.K.; Siracusa, L.D. ); Battey, J. )

    1993-01-01

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

  8. Oxytocin and socioemotional aging: Current knowledge and future trends

    PubMed Central

    Ebner, Natalie C.; Maura, Gabriela M.; MacDonald, Kai; Westberg, Lars; Fischer, Håkan

    2013-01-01

    The oxytocin (OT) system is involved in various aspects of social cognition and prosocial behavior. Specifically, OT has been examined in the context of social memory, emotion recognition, cooperation, trust, empathy, and bonding, and—though evidence is somewhat mixed-intranasal OT appears to benefit aspects of socioemotional functioning. However, most of the extant data on aging and OT is from animal research and human OT research has focused largely on young adults. As such, though we know that various socioemotional capacities change with age, we know little about whether age-related changes in the OT system may underlie age-related differences in socioemotional functioning. In this review, we take a genetic-neuro-behavioral approach and evaluate current evidence on age-related changes in the OT system as well as the putative effects of these alterations on age-related socioemotional functioning. Looking forward, we identify informational gaps and propose an Age-Related Genetic, Neurobiological, Sociobehavioral Model of Oxytocin (AGeNeS-OT model) which may structure and inform investigations into aging-related genetic, neural, and sociocognitive processes related to OT. As an exemplar of the use of the model, we report exploratory data suggesting differences in socioemotional processing associated with genetic variation in the oxytocin receptor gene (OXTR) in samples of young and older adults. Information gained from this arena has translational potential in depression, social stress, and anxiety-all of which have high relevance in aging—and may contribute to reducing social isolation and improving well-being of individuals across the lifespan. PMID:24009568

  9. The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task

    PubMed Central

    Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Riebold, Mathias; Laiba, Efrat; Bachner-Melman, Rachel; Maril, Anat; Bornstein, Gary; Knafo, Ariel; Ebstein, Richard P.

    2009-01-01

    Background Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a). In the current investigation, the gene encoding the related oxytocin receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. Methodology/Principal Findings Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2–5 locus haplotypes (p<0.05). A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher's exact test). Conclusions The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decision making converges with a large body of animal research showing that oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the oxytocin receptor gene, an important element of mammalian social circuitry, underlie such individual differences. PMID:19461999

  10. Oxytocin increases bias, but not accuracy, in face recognition line-ups.

    PubMed

    Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

    2015-07-01

    Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task-a standardized test of unfamiliar face recognition containing target-present and target-absent line-ups. Participants in the oxytocin condition outperformed those in the placebo condition on target-present trials, yet were more likely to make false-positive errors on target-absent trials. Signal detection analyses indicated that oxytocin induced a more liberal response bias, rather than increasing accuracy per se. These findings support a social salience account of the effects of oxytocin on face recognition and indicate that oxytocin may impede face recognition in certain scenarios. PMID:25433464

  11. Early Social Environment Affects the Endogenous Oxytocin System: A Review and Future Directions

    PubMed Central

    Alves, Emily; Fielder, Andrea; Ghabriel, Nerelle; Sawyer, Michael; Buisman-Pijlman, Femke T. A.

    2015-01-01

    Endogenous oxytocin plays an important role in a wide range of human functions including birth, milk ejection during lactation, and facilitation of social interaction. There is increasing evidence that both variations in the oxytocin receptor (OXTR) and concentrations of oxytocin are associated with differences in these functions. The causes for the differences that have been observed in tonic and stimulated oxytocin release remain unclear. Previous reviews have suggested that across the life course, these differences may be due to individual factors, e.g., genetic variation (of the OXTR), age or sex, or be the result of early environmental influences, such as social experiences, stress, or trauma partly by inducing epigenetic changes. This review has three aims. First, we briefly discuss the endogenous oxytocin system, including physiology, development, individual differences, and function. Second, current models describing the relationship between the early life environment and the development of the oxytocin system in humans and animals are discussed. Finally, we describe research designs that can be used to investigate the effects of the early environment on the oxytocin system, identifying specific areas of research that need further attention. PMID:25814979

  12. Oxytocin increases bias, but not accuracy, in face recognition line-ups.

    PubMed

    Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

    2015-07-01

    Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task-a standardized test of unfamiliar face recognition containing target-present and target-absent line-ups. Participants in the oxytocin condition outperformed those in the placebo condition on target-present trials, yet were more likely to make false-positive errors on target-absent trials. Signal detection analyses indicated that oxytocin induced a more liberal response bias, rather than increasing accuracy per se. These findings support a social salience account of the effects of oxytocin on face recognition and indicate that oxytocin may impede face recognition in certain scenarios.

  13. Biochemical and endocrine aspects of oxytocin production by the mammalian corpus luteum

    PubMed Central

    Stormshak, Fredrick

    2003-01-01

    A review of the current state of knowledge of oxytocin production by the preovulatory follicle and corpus luteum is presented. Corpora lutea of a number of mammalian species have been found to synthesize oxytocin. However, the synthesis and secretion of this nanopeptide by the corpus luteum of the ruminant has been most extensively studied because of the potential role of this peptide in facilitating luteal regression. While much information exists relative to various biochemical and endocrine factors that impact on oxytocin gene expression, this aspect about luteal synthesis of this peptide hormone remains enigmatic. Prostaglandin F-2α (PGF-2α) has been shown to be a primary endogenous hormone responsible for triggering luteal secretion of oxytocin. Details are provided regarding the PGF-2α-induced intracellular signal transduction pathway that ultimately results in exocytosis of luteal oxytocin. Evidence is also presented for potential autocrine/paracrine actions of oxytocin in regulating progesterone production by luteal and granulosa cells. Concluding remarks highlight aspects about luteal oxytocin production that require further research. PMID:14613532

  14. Oxytocin tempers calculated greed but not impulsive defense in predator–prey contests

    PubMed Central

    Scholte, H. Steven; van Winden, Frans A. A. M.; Ridderinkhof, K. Richard

    2015-01-01

    Human cooperation and competition is modulated by oxytocin, a hypothalamic neuropeptide that functions as both hormone and neurotransmitter. Oxytocin’s functions can be captured in two explanatory yet largely contradictory frameworks: the fear-dampening (FD) hypothesis that oxytocin has anxiolytic effects and reduces fear-motivated action; and the social approach/avoidance (SAA) hypothesis that oxytocin increases cooperative approach and facilitates protection against aversive stimuli and threat. We tested derivations from both frameworks in a novel predator–prey contest game. Healthy males given oxytocin or placebo invested as predator to win their prey’s endowment, or as prey to protect their endowment against predation. Neural activity was registered using 3T-MRI. In prey, (fear-motivated) investments were fast and conditioned on the amygdala. Inconsistent with FD, oxytocin did not modulate neural and behavioral responding in prey. In predators, (greed-motivated) investments were slower, and conditioned on the superior frontal gyrus (SFG). Consistent with SAA, oxytocin reduced predator investment, time to decide and activation in SFG. Thus, whereas oxytocin does not incapacitate the impulsive ability to protect and defend oneself, it lowers the greedy and more calculated appetite for coming out ahead. PMID:25140047

  15. Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

    PubMed

    Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

    2015-06-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

  16. Plasma oxytocin levels predict social cue recognition in individuals with schizophrenia.

    PubMed

    Strauss, Gregory P; Keller, William R; Koenig, James I; Gold, James M; Frost, Katherine H; Buchanan, Robert W

    2015-03-01

    Lower endogenous levels of the neuropeptide oxytocin may be an important biological predictor of social cognition impairments in schizophrenia (SZ). Prior studies have demonstrated that lower-level social cognitive processes (e.g., facial affect perception) are significantly associated with reduced plasma oxytocin levels in SZ; however, it is unclear whether higher-level social cognition, which requires inferential processes and knowledge not directly presented in the stimulus, is associated with endogenous oxytocin. The current study explored the association between endogenous oxytocin levels and lower- and higher-level social cognition in 40 individuals diagnosed with SZ and 22 demographically matched healthy controls (CN). All participants received the Social Cue Recognition Test (SCRT), which presents participants with videotaped interpersonal vignettes and subsequent true/false questions related to concrete or abstract aspects of social interactions in the vignettes. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ and CN did not differ on SCRT hits, but SZ had more false positives and lower sensitivity scores than CN. Higher plasma oxytocin levels were associated with better sensitivity scores for abstract items in CN and fewer false positives for concrete items in individuals with SZ. Findings indicate that endogenous oxytocin levels predict accurate encoding of lower-level socially relevant information in SZ. PMID:25673435

  17. Mathematical formulation and analysis of the nonlinear system reconstruction of the online image-guided adaptive control of hyperthermia

    PubMed Central

    Cheng, Kung-Shan; Dewhirst, Mark W.; Stauffer, Paul F.; Das, Shiva

    2010-01-01

    Purpose: A nonlinear system reconstruction can theoretically provide timely system reconstruction when designing a real-time image-guided adaptive control for multisource heating for hyperthermia. This clinical need motivates an analysis of the essential mathematical characteristics and constraints of such an approach. Methods: The implicit function theorem (IFT), the Karush–Kuhn–Tucker (KKT) necessary condition of optimality, and the Tikhonov–Phillips regularization (TPR) were used to analyze and determine the requirements of the optimal system reconstruction. Two mutually exclusive generic approaches were analyzed to reconstruct the physical system: The traditional full reconstruction and the recently suggested partial reconstruction. Rigorous mathematical analysis based on IFT, KKT, and TPR was provided for all four possible nonlinear reconstructions: (1) Nonlinear noiseless full reconstruction, (2) nonlinear noisy full reconstruction, (3) nonlinear noiseless partial reconstruction, and (4) nonlinear noisy partial reconstruction, when a class of nonlinear formulations of system reconstruction is employed. Results: Effective numerical algorithms for solving each of the aforementioned four nonlinear reconstructions were introduced and formal derivations and analyses were provided. The analyses revealed the necessity of adding regularization when partial reconstruction is used. Regularization provides the theoretical support for one to uniquely reconstruct the optimal system. It also helps alleviate the negative influences of unavoidable measurement noise. Both theoretical analysis and numerical examples showed the importance of having a good initial guess for accomplishing nonlinear system reconstruction. Conclusions: Regularization is mandatory for partial reconstruction to make it well posed. The Tikhonov–Phillips regularized Gauss–Newton algorithm has nice theoretical performance for partial reconstruction of systems with and without noise. The

  18. Exogenous oxytocin reduces signs of sickness behavior and modifies heart rate fluctuations of endotoxemic rats.

    PubMed

    Reyes-Lagos, José Javier; Hadamitzky, Martin; Peña-Castillo, Miguel Ángel; Echeverría, Juan Carlos; Bösche, Katharina; Lückemann, Laura; Schedlowski, Manfred; Pacheco-López, Gustavo

    2016-10-15

    Besides the well-known roles of oxytocin on birth, maternal bonding, and lactation, recent evidence shows that this hypothalamic hormone possesses cardioprotective, anti-inflammatory and parasympathetic neuromodulation properties. In this study, we explore the heart rate fluctuations (HRF) in an endotoxemic rodent model that was accompanied by the administration of exogenous oxytocin. The assessment of HRF has been widely used as an indirect measure of the cardiac autonomic function. In this context, adult male Dark Agouti rats were equipped with a telemetric transmitter to continuously and remotely measure the electrocardiogram, temperature, and locomotion. In a between-subjects experimental design, rats received the following peripheral treatment: saline solution as a vehicle (V); lipopolysaccharide (LPS); oxytocin (Ox); lipopolysaccharide + oxytocin (LPS+Ox). Linear and non-linear parameters of HRF were estimated starting 3h before to 24h after treatments. Our results showed that exogenous oxytocin does not modify by itself the HRF of oxytocin-treated rats in comparison to vehicle-treated rats. However, in animals undergoing endotoxemia it: a) provokes a less anticorrelated pattern in HRF, b) decreased mean heart rate, c) moderated the magnitude and duration of the LPS-induced hyperthermia, and d) increased locomotion, up to 6h after the LPS injection. The less anticorrelated pattern in the HRF and decreased mean heart rate may reflect a cardiac pacemaker coupling with cholinergic influences mediated by oxytocin during LPS-induced endotoxemia. Finally, the anti-lethargic and long-term temperature moderating effects of the administration of oxytocin during endotoxemia could be a consequence of the systemic anti-inflammatory properties of oxytocin.

  19. Involvement of central cholinergic mechanisms in the effects of oxytocin and an oxytocin receptor antagonist on retention performance in mice.

    PubMed

    Boccia, M M; Baratti, C M

    2000-11-01

    Oxytocin (OT, 0.10 microg/kg, sc) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. In contrast, the immediate post-training administration of the putative oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2), Thr(4), Thy-NH(9)(2)] OVT (AOT, 0.30 microg/kg, sc) significantly enhanced retention performance. Neither OT nor AOT affected response latencies in mice not given footshock on the training trial, and neither the impairing effects of OT nor the enhancing effects of AOT were seen when the training-treatment interval was 180 min, suggesting that both treatments influenced memory storage. The effects of OT (0.10 microg/kg, sc) on retention were prevented by AOT (0.03 microg/kg, sc) given immediately after training, but 10 min prior to OT treatment. The central acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, i.p.), but not its quaternary analogue neostigmine (150 microg/kg, i.p.), reversed the impairment of retention performance induced by OT, whereas low subeffective doses of the centrally active muscarinic cholinergic antagonist atropine (0.5 mg/kg, i.p.) or the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg, i.p.), but not methylatropine (0.5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.) prevented the enhancement of retention performance caused by AOT. We suggest that oxytocin negatively modulates the activity of central cholinergic mechanisms during the posttraining period that follows an aversively motivated learning experience, leading to an impairment of retention performance of the inhibitory avoidance response. PMID:11031128

  20. Effects of oxytocin and an oxytocin receptor antagonist on retention of a nose-poke habituation response in mice.

    PubMed

    Boccia, M M; Baratti, C M

    1999-01-01

    The present study describes the use of nose-poke habituation as a memory task in mice and demonstrates that it is sensitive to oxytocin (OT) and an oxytocin receptor antagonist (AOT) administered after the learning trial. Habituation of nose-poke behavior of mice was defined as a reduction in number of nose-pokes compared to baseline, and was measured in a hole-board apparatus to which male Swiss mice were exposed on two consecutive days for 5 min, respectively. Immediate post-training subcutaneous administration of OT (2.00 micrograms/kg) impaired retention performance, whereas AOT (0.20 microgram/kg) enhanced it. Neither the impairing effects of OT (2.00 micrograms/kg) nor the enhancing effects of AOT (0.20 microgram/kg) were seen when the training treatment interval was 180 min, suggesting that both treatments influenced the storage of recently acquired information. The effects of OT (2.00 micrograms/kg) on retention were prevented by AOT (0.02 microgram/kg) administered immediately after training but 10 min prior OT treatment. This dose of antagonist did not affect retention by itself which suggest that impairing effects of OT on retention are probably due to an interaction of the neuropeptide with specific receptors. The actions of OT and AOT on retention were not due to enduring proactive effects of the compounds on performance during the retention test, since when given to untrained mice did not modify their spontaneous activities in the hole-board when recorded 24 h later. We suggest that nose-poke habituation learning can be a suitable method to investigate the mnestic effects of drugs, and that oxytocin negatively modulates memory storage of this form of learning elicited by stimuli repeatedly presented without reinforcement. PMID:10797854

  1. Effects of oxytocin and an oxytocin receptor antagonist on retention of a nose-poke habituation response in mice.

    PubMed

    Boccia, M M; Baratti, C M

    1999-01-01

    The present study describes the use of nose-poke habituation as a memory task in mice and demonstrates that it is sensitive to oxytocin (OT) and an oxytocin receptor antagonist (AOT) administered after the learning trial. Habituation of nose-poke behavior of mice was defined as a reduction in number of nose-pokes compared to baseline, and was measured in a hole-board apparatus to which male Swiss mice were exposed on two consecutive days for 5 min, respectively. Immediate post-training subcutaneous administration of OT (2.00 micrograms/kg) impaired retention performance, whereas AOT (0.20 microgram/kg) enhanced it. Neither the impairing effects of OT (2.00 micrograms/kg) nor the enhancing effects of AOT (0.20 microgram/kg) were seen when the training treatment interval was 180 min, suggesting that both treatments influenced the storage of recently acquired information. The effects of OT (2.00 micrograms/kg) on retention were prevented by AOT (0.02 microgram/kg) administered immediately after training but 10 min prior OT treatment. This dose of antagonist did not affect retention by itself which suggest that impairing effects of OT on retention are probably due to an interaction of the neuropeptide with specific receptors. The actions of OT and AOT on retention were not due to enduring proactive effects of the compounds on performance during the retention test, since when given to untrained mice did not modify their spontaneous activities in the hole-board when recorded 24 h later. We suggest that nose-poke habituation learning can be a suitable method to investigate the mnestic effects of drugs, and that oxytocin negatively modulates memory storage of this form of learning elicited by stimuli repeatedly presented without reinforcement.

  2. Involvement of central cholinergic mechanisms in the effects of oxytocin and an oxytocin receptor antagonist on retention performance in mice.

    PubMed

    Boccia, M M; Baratti, C M

    2000-11-01

    Oxytocin (OT, 0.10 microg/kg, sc) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. In contrast, the immediate post-training administration of the putative oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2), Thr(4), Thy-NH(9)(2)] OVT (AOT, 0.30 microg/kg, sc) significantly enhanced retention performance. Neither OT nor AOT affected response latencies in mice not given footshock on the training trial, and neither the impairing effects of OT nor the enhancing effects of AOT were seen when the training-treatment interval was 180 min, suggesting that both treatments influenced memory storage. The effects of OT (0.10 microg/kg, sc) on retention were prevented by AOT (0.03 microg/kg, sc) given immediately after training, but 10 min prior to OT treatment. The central acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, i.p.), but not its quaternary analogue neostigmine (150 microg/kg, i.p.), reversed the impairment of retention performance induced by OT, whereas low subeffective doses of the centrally active muscarinic cholinergic antagonist atropine (0.5 mg/kg, i.p.) or the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg, i.p.), but not methylatropine (0.5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.) prevented the enhancement of retention performance caused by AOT. We suggest that oxytocin negatively modulates the activity of central cholinergic mechanisms during the posttraining period that follows an aversively motivated learning experience, leading to an impairment of retention performance of the inhibitory avoidance response.

  3. Effects of Oxytocin Administration on the Response of Piglets to Weaning

    PubMed Central

    Rault, Jean-Loup; Dunshea, Frank R.; Pluske, John R.

    2015-01-01

    Simple Summary Weaning is a stressful milestone for domestic animals. It is often performed at an early age and as an abrupt change in comparison to the transitional period seen in feral or wild animals. Oxytocin, a hormone associated with attachment, could improve the response of piglets to weaning. Piglets were either given oxytocin intranasally, subcutaneously, or handled as controls. Oxytocin had no effect on the physiological response to weaning. However, oxytocin increased the frequency of mild aggressive social behaviors between OT-administered and control pigs. Hence, the use of a single administration of oxytocin prior to weaning in pigs is not recommended. Abstract Weaning is often an abrupt and stressful process. We studied the effects of administering oxytocin, subcutaneously or intranasally, on the ability of pigs to cope with weaning. On a commercial farm 144, 30 day-old pigs from 24 litters were used. On the day of weaning, one male and one female in each litter were administered one of three treatments: intranasal oxytocin (24 International Unit), subcutaneous oxytocin (10 International Unit per kg of body weight), or handled as a control. The pigs were placed in one of eight weaner pens, split by sex and with an equal representation of treatments. Data included body weight and growth, physiology (neutrophil:lymphocyte ratio, plasma cortisol, C-reactive protein and Tumor Necrosis Factor-α concentrations), and behavior (feeding, drinking, social behavior). Both oxytocin treatments tended to result in higher levels of mild aggression within groups (p = 0.08), specifically between oxytocin-administered and control pigs (subcutaneous to control p = 0.03; intranasal to control p = 0.10). Subcutaneously-administered pigs tended to frequent the feeder more often than intranasally-administered pigs (p < 0.10), with the latter having slightly lower body weight 38 days post-weaning (p = 0.03). However, acute oxytocin administration did not result in any

  4. Saltcrete formulation

    SciTech Connect

    Semones, G.B.; Connell, J.M.; Jorgensen, S.C.

    1994-09-28

    The information gathered since the first report shows that the currently generated waste and most of the waste in inventory has low concentrations of hazardous chemicals and is certifiable for disposable. This is based on preliminary analyses. Sampling and analysis for the purpose of gathering the legally defensible data required for certification and permanent disposal is in progress. The main technical issue is the expansion of the waste form. Some of the cemented waste expands and damages the containers. According to a petrology study, the expansion is caused by the formation of darapskite, a nitrate-sulfate salt. Darapskite occurs when there is high porosity causing microfractures and waste form expansion.

  5. Mission planning, mission analysis and software formulation. Level C requirements for the shuttle mission control center orbital guidance software

    NASA Technical Reports Server (NTRS)

    Langston, L. J.

    1976-01-01

    The formulation of Level C requirements for guidance software was reported. Requirements for a PEG supervisor which controls all input/output interfaces with other processors and determines which PEG mode is to be utilized were studied in detail. A description of the two guidance modes for which Level C requirements have been formulated was presented. Functions required for proper execution of the guidance software were defined. The requirements for a navigation function that is used in the prediction logic of PEG mode 4 were discussed. It is concluded that this function is extracted from the current navigation FSSR.

  6. Oxytocin Receptor Genetic Variation Promotes Human Trust Behavior

    PubMed Central

    Krueger, Frank; Parasuraman, Raja; Iyengar, Vijeth; Thornburg, Matthew; Weel, Jaap; Lin, Mingkuan; Clarke, Ellen; McCabe, Kevin; Lipsky, Robert H.

    2012-01-01

    Given that human trust behavior is heritable and intranasal administration of oxytocin enhances trust, the oxytocin receptor (OXTR) gene is an excellent candidate to investigate genetic contributions to individual variations in trust behavior. Although a single-nucleotide polymorphism involving an adenine (A)/guanine (G) transition (rs53576) has been associated with socio-emotional phenotypes, its link to trust behavior is unclear. We combined genotyping of healthy male students (n = 108) with the administration of a trust game experiment. Our results show that a common occurring genetic variation (rs53576) in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors. Individuals homozygous for the G allele (GG) showed higher trust behavior than individuals with A allele carriers (AA/AG). Although the molecular functionality of this polymorphism is still unknown, future research should clarify how the OXTR gene interacts with other genes and the environment in promoting socio-emotional behaviors. PMID:22347177

  7. Oxytocin and the Development of Parenting in Humans

    PubMed Central

    Gordon, Ilanit; Zagoory-Sharon, Orna; Leckman, James F.; Feldman, Ruth

    2014-01-01

    Background The nonapeptide oxytocin (OT) has been repeatedly implicated in processes of parent-infant bonding in animal models; yet, its role in the development of human parenting has received less attention and no research has addressed the involvement of OT in the transition to fatherhood. Methods Using a prospective longitudinal design, 160 cohabitating mothers and fathers and their firstborn infant were visited at home during the first postpartum weeks and again at 6 months postpartum. Mothers’ and fathers’ plasma OT was analyzed at each time point with enzyme-linked immunosorbent assay methodology. Interactions between each parent and the infant were observed in the postpartum and microcoded for parenting behavior. Results Overall, parental OT increased across the study period and there were no differences between maternal and paternal OT at each time point. Oxytocin showed high intraindividual stability across the first 6 months of parenting and the OT levels of husband and wife were interrelated at both assessments. Maternal OT was related to the amount of affectionate parenting behaviors, including “motherese” vocalizations, the expression of positive affect, and affectionate touch, whereas paternal OT correlated with the degree of stimulatory parenting behaviors, including proprioceptive contact, tactile stimulation, and object presentation. Conclusions Results are the first to describe plasma OT levels in new fathers and mothers across the transition to parenthood in relation to maternal and paternal typical parenting behaviors. These data may provide a normative basis for the study of parenting under conditions of high risk. PMID:20359699

  8. Application of the Galerkin/least-squares formulation to the analysis of hypersonic flows. II - Flow past a double ellipse

    NASA Technical Reports Server (NTRS)

    Chalot, F.; Hughes, T. J. R.; Johan, Z.; Shakib, F.

    1991-01-01

    A finite element method for the compressible Navier-Stokes equations is introduced. The discretization is based on entropy variables. The methodology is developed within the framework of a Galerkin/least-squares formulation to which a discontinuity-capturing operator is added. Results for four test cases selected among those of the Workshop on Hypersonic Flows for Reentry Problems are presented.

  9. Formulation of sage essential oil (Salvia officinalis, L.) monoterpenes into chitosan hydrogels and permeation study with GC-MS analysis.

    PubMed

    Kodadová, Alexandra; Vitková, Zuzana; Herdová, Petra; Ťažký, Anton; Oremusová, Jarmila; Grančai, Daniel; Mikuš, Peter

    2015-01-01

    This study deals with the formulation of natural drugs into hydrogels. For the first time, compounds from the sage essential oil were formulated into chitosan hydrogels. A sample preparation procedure for hydrophobic volatile analytes present in a hydrophilic water matrix along with an analytical method based on the gas chromatography coupled with the mass spectrometry (GC-MS) was developed and applied for the evaluation of the identity and quantity of essential oil components in the hydrogels and saline samples. The experimental results revealed that the chitosan hydrogels are suitable for the formulation of sage essential oil. The monoterpene release can be effectively controlled by both chitosan and caffeine concentration in the hydrogels. Permeation experiment, based on a hydrogel with the optimized composition [3.5% (w/w) sage essential oil, 2.0% (w/w) caffeine, 2.5% (w/w) chitosan and 0.1% (w/w) Tween-80] in donor compartment, saline solution in acceptor compartment, and semi-permeable cellophane membrane, demonstrated the useful permeation selectivity. Here, (according to lipophilicity) an enhanced permeation of the bicyclic monoterpenes with antiflogistic and antiseptic properties (eucalyptol, camphor and borneol) and, at the same time, suppressed permeation of toxic thujone (not exceeding its permitted applicable concentration) was observed. These properties highlight the pharmaceutical importance of the developed chitosan hydrogel formulating sage essential oil in the dermal applications.

  10. A new finite element formulation for computational fluid dynamics. IX - Fourier analysis of space-time Galerkin/least-squares algorithms

    NASA Technical Reports Server (NTRS)

    Shakib, Farzin; Hughes, Thomas J. R.

    1991-01-01

    A Fourier stability and accuracy analysis of the space-time Galerkin/least-squares method as applied to a time-dependent advective-diffusive model problem is presented. Two time discretizations are studied: a constant-in-time approximation and a linear-in-time approximation. Corresponding space-time predictor multi-corrector algorithms are also derived and studied. The behavior of the space-time algorithms is compared to algorithms based on semidiscrete formulations.

  11. 5alpha-Reduced androgens block estradiol-BSA-stimulated release of oxytocin.

    PubMed

    Caldwell, Jack D; Song, Yan; Englöf, Ila; Höfle, Simone; Key, Mary; Morris, Mariana

    2003-06-27

    In this study we test the postulate that estradiol conjugated to bovine serum albumin (E-BSA) acts via receptors for the steroid-binding protein sex hormone binding globulin (SHBG) by attempting to block E-BSA-stimulated release of oxytocin with two antagonists of SHBG receptor actions: the 5alpha-reduced androgens dihydrotestosterone (DHT) and 3alpha-diol. Simultaneous superfusion with either DHT or 3alpha-diol significantly blocked E-BSA-stimulated release of oxytocin. We also found that a wide range of free 17beta-estradiol was unable to stimulate oxytocin release, suggesting that E-BSA stimulates receptors other than those for free estradiol to release oxytocin, perhaps SHBG receptors.

  12. Oxytocin and Postpartum Depression: Delivering on What’s Known and What’s Not

    PubMed Central

    Kim, Sohye; Soeken, Timothy A.; Cromer, Sara J.; Martinez, Sheila R.; Hardy, Leah R.; Strathearn, Lane

    2013-01-01

    The role of oxytocin in the treatment of postpartum depression has been a topic of growing interest. This subject carries important implications, given that postpartum depression can have detrimental effects on both the mother and her infant, with lifelong consequences for infant socioemotional and cognitive development. In recent years, oxytocin has received attention for its potential role in many neuropsychiatric conditions beyond its well-described functions in childbirth and lactation. In the present review, we present available data on the clinical characteristics and neuroendocrine foundations of postpartum depression. We outline current treatment modalities and their limitations, and proceed to evaluate the potential role of oxytocin in the treatment of postpartum depression. The aim of the present review is twofold: a) to bring together evidence from animal and human research concerning the role of oxytocin in postpartum depression, and b) to highlight areas that deserve further research in order to bring a fuller understanding of oxytocin’s therapeutic potential. PMID:24239932

  13. The role of oxytocin in mothers' theory of mind and interactive behavior during the perinatal period.

    PubMed

    MacKinnon, Anna L; Gold, Ian; Feeley, Nancy; Hayton, Barbara; Carter, C Sue; Zelkowitz, Phyllis

    2014-10-01

    The present longitudinal study examined the relations between plasma oxytocin, theory of mind, and maternal interactive behavior during the perinatal period. A community sample of women was assessed at 12-14 weeks gestation, 32-34 weeks gestation, and 7-9 weeks postpartum. Oxytocin during late pregnancy was significantly positively correlated with a measure of theory of mind, and predicted theory of mind ability after controlling for parity, maternal education, prenatal psychosocial risk, and general anxiety, measured during the first trimester. Theory of mind was associated with less remote and less depressive maternal interactive behavior. Oxytocin, across all time points, was not directly related to maternal interactive behavior. However, there was a significant indirect effect of oxytocin during late pregnancy on depressive maternal behavior via theory of mind ability. These preliminary findings suggest that changes in the oxytocinergic system during the perinatal period may contribute to the awareness of social cues, which in turn plays a role in maternal interactive behavior.

  14. In situ hybridization of oxytocin messenger RNA: macroscopic distribution and quantitation in rat hypothalamic cell groups

    SciTech Connect

    Burbach, J.P.; Voorhuis, T.A.; van Tol, H.H.; Ivell, R.

    1987-05-29

    Oxytocin mRNA was detected in the rat hypothalamus by in situ hybridization to a single stranded /sup 35/S-labelled DNA probe and the distribution of oxytocin mRNA-containing cell groups was studied at the macroscopic level. Specificity of hybridization was confirmed by comparison to vasopressin mRNA hybridization in parallel tissue sections. Cell groups containing oxytocin mRNA were confined to a set of hypothalamic cell groups, i.c. the supraoptic, paraventricular, anterior commissural nuclei, nucleus circularis and scattered hypothalamic islets. These cell groups displayed similar densities of autoradiographic signals indicating that the oxytocin gene is expressed at approximately the same average level at these various sites.

  15. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans

    PubMed Central

    Feng, Chunliang; Lori, Adriana; Waldman, Irwin D.; Binder, Elisabeth B.; Haroon, Ebrahim; Rilling, James K.

    2015-01-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner’s Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. PMID:26178189

  16. Oxytocin does not improve performance of patients with schizophrenia and healthy volunteers in a facial emotion matching task.

    PubMed

    Horta de Macedo, Ligia R; Zuardi, Antonio Waldo; Machado-de-Sousa, João Paulo; Chagas, Marcos Hortes N; Hallak, Jaime E C

    2014-12-15

    The neuropeptide oxytocin improves the performance in facial emotion recognition tests in healthy volunteers and in individuals with schizophrenia. Different paradigms are used in emotion recognition tasks, engaging different neurobiological bases. To date, the effects of oxytocin in facial emotion matching tasks have not been studied. The objective of this study was to evaluate the effects of intranasal oxytocin in a facial emotion matching task in patients with schizophrenia and healthy volunteers. Twenty patients and 20 healthy volunteers received 48 IU intranasal oxytocin and placebo in a double-blind, randomized, placebo-controlled, within subjects design. Fifty minutes after treatment, subjects completed a facial emotion matching task and three control tests. Oxytocin failed to improve facial affect processing, in contrast with previous results. Possible explanations are the fact that we used a facial emotion matching paradigm instead of emotion labeling tasks and a higher dose of oxytocin than the one used in most similar studies.

  17. [Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing].

    PubMed

    Uvnas-Moberg, Kerstin; Petersson, Maria

    2005-01-01

    The neuroendocrine and physiological systems related to pain and stress have long been subjected to study. More recently, the corresponding systems promoting anti-stress and restoration have also come into focus. It is not only important to investigate the mechanisms underlying disease but also to examine the physiological and psychological mechanisms which protect and heal the body and soul. The nonapeptide oxytocin, originally known to stimulate labour and milk ejection, appears to play an important role in this regard. Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels. It increases pain thresholds, exerts an anxiolytic-like effect and stimulates various types of positive social interaction. In addition, it promotes growth and healing. Repeated exposure to oxytocin causes long-lasting effects by influencing the activity of other transmitter systems, a pattern which makes oxytocin potentially clinically relevant. Oxytocin can be released by various types of non-noxious sensory stimulation, for example by touch and warmth. Ingestion of food triggers oxytocin release by activation of vagal afferents. Most likely, oxytocin can also be released by stimulation of other senses such as olfaction, as well as by certain types of sound and light. In addition, purely psychological mechanisms may trigger the release of oxytocin. This means that positive interaction involving touch and psychological support may be health-promoting. The social interaction of daily life, as well as a positive environment, continuously activate this system. In addition, various types of psychotherapy involving transfer of support, warmth and empathy are likely to induce similar effects, which thus contribute to the positive effects of these kinds of therapies. PMID:15834840

  18. Oxytocin reversed MK-801-induced social interaction and aggression deficits in zebrafish.

    PubMed

    Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Siebel, Anna Maria; Bonan, Carla Denise

    2016-09-15

    Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia.

  19. Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms.

    PubMed

    Jobst, Andrea; Krause, Daniela; Maiwald, Carina; Härtl, Kristin; Myint, Aye-Mu; Kästner, Ralph; Obermeier, Michael; Padberg, Frank; Brücklmeier, Benedikt; Weidinger, Elif; Kieper, Susann; Schwarz, Markus; Zill, Peter; Müller, Norbert

    2016-08-01

    During the postpartum period, women are at higher risk of developing a mental disorder such as postpartum depression (PPD), a disorder that associates with mother-infant bonding and child development. Oxytocin is considered to play a key role in mother-infant bonding and social interactions and altered oxytocin plasma concentrations were found to be associated with PPD. In the present study, we evaluated oxytocin plasma levels and depressive symptoms during pregnancy and the postpartum period in healthy women. We evaluated 100 women twice during pregnancy (weeks 35 and 38) and three times in the postpartum period (within 2 days and 7 weeks and 6 months after delivery) by measuring oxytocin plasma levels with enzyme-linked immunosorbent assay (ELISA) and assessing depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Oxytocin plasma levels significantly increased from the 35th week of gestation to 6 months postpartum in all women. However, levels decreased from the 38th week of gestation to 2 days after delivery in participants with postpartum depressive symptoms, whereas they continuously increased in the group without postpartum depressive symptoms; the difference between the course of oxytocin levels in the two groups was significant (Δt2-t3: t = 2.14; p = 0.036*). Previous depressive episodes and breastfeeding problems predicted postpartum depressive symptoms. Our results indicate that alterations in the oxytocin system during pregnancy might be specific for women who develop postpartum depressive symptoms. Future studies should investigate whether oxytocin plasma levels might have predictive value in women at high risk for PPD. PMID:27320943

  20. Maternal Oxytocin Is Linked to Close Mother-Infant Proximity in Grey Seals (Halichoerus grypus).

    PubMed

    Robinson, Kelly J; Twiss, Sean D; Hazon, Neil; Pomeroy, Patrick P

    2015-01-01

    Maternal behaviour is a crucial component of reproduction in all mammals; however the quality of care that mothers give to infants can vary greatly. It is vital to document variation in maternal behaviour caused by the physiological processes controlling its expression. This underlying physiology should be conserved throughout reproductive events and should be replicated across all individuals of a species; therefore, any correlates to maternal care quality may be present across many individuals or contexts. Oxytocin modulates the initiation and expression of maternal behaviour in mammals; therefore we tested whether maternal plasma oxytocin concentrations correlated to key maternal behaviours in wild grey seals (Halichoerus grypus). Plasma oxytocin concentrations in non-breeding individuals (4.3 ± 0.5 pg/ml) were significantly lower than those in mothers with dependent pups in both early (8.2 ± 0.8 pg/ml) and late (6.9 ± 0.7 pg/ml) lactation. Maternal plasma oxytocin concentrations were not correlated to the amount of nursing prior to sampling, or a mother's nursing intensity throughout the dependent period. Mothers with high plasma oxytocin concentrations stayed closer to their pups, reducing the likelihood of mother-pup separation during lactation which is credited with causing starvation, the largest cause of pup mortality in grey seals. This is the first study to link endogenous oxytocin concentrations in wild mammalian mothers with any type of maternal behaviour. Oxytocin's structure and function is widely conserved across mammalian mothers, including humans. Defining the impact the oxytocin system has on maternal behaviour highlights relationships that may occur across many individuals or species, and such behaviours heavily influence infant development and an individual's lifetime reproductive success.

  1. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    PubMed

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. PMID:26150070

  2. [Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing].

    PubMed

    Uvnas-Moberg, Kerstin; Petersson, Maria

    2005-01-01

    The neuroendocrine and physiological systems related to pain and stress have long been subjected to study. More recently, the corresponding systems promoting anti-stress and restoration have also come into focus. It is not only important to investigate the mechanisms underlying disease but also to examine the physiological and psychological mechanisms which protect and heal the body and soul. The nonapeptide oxytocin, originally known to stimulate labour and milk ejection, appears to play an important role in this regard. Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels. It increases pain thresholds, exerts an anxiolytic-like effect and stimulates various types of positive social interaction. In addition, it promotes growth and healing. Repeated exposure to oxytocin causes long-lasting effects by influencing the activity of other transmitter systems, a pattern which makes oxytocin potentially clinically relevant. Oxytocin can be released by various types of non-noxious sensory stimulation, for example by touch and warmth. Ingestion of food triggers oxytocin release by activation of vagal afferents. Most likely, oxytocin can also be released by stimulation of other senses such as olfaction, as well as by certain types of sound and light. In addition, purely psychological mechanisms may trigger the release of oxytocin. This means that positive interaction involving touch and psychological support may be health-promoting. The social interaction of daily life, as well as a positive environment, continuously activate this system. In addition, various types of psychotherapy involving transfer of support, warmth and empathy are likely to induce similar effects, which thus contribute to the positive effects of these kinds of therapies.

  3. On-Line Electrochemical Reduction of Disulfide Bonds: Improved FTICR-CID and -ETD Coverage of Oxytocin and Hepcidin

    NASA Astrophysics Data System (ADS)

    Nicolardi, Simone; Giera, Martin; Kooijman, Pieter; Kraj, Agnieszka; Chervet, Jean-Pierre; Deelder, André M.; van der Burgt, Yuri E. M.

    2013-12-01

    Particularly in the field of middle- and top-down peptide and protein analysis, disulfide bridges can severely hinder fragmentation and thus impede sequence analysis (coverage). Here we present an on-line/electrochemistry/ESI-FTICR-MS approach, which was applied to the analysis of the primary structure of oxytocin, containing one disulfide bridge, and of hepcidin, containing four disulfide bridges. The presented workflow provided up to 80 % (on-line) conversion of disulfide bonds in both peptides. With minimal sample preparation, such reduction resulted in a higher number of peptide backbone cleavages upon CID or ETD fragmentation, and thus yielded improved sequence coverage. The cycle times, including electrode recovery, were rapid and, therefore, might very well be coupled with liquid chromatography for protein or peptide separation, which has great potential for high-throughput analysis.

  4. Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation.

    PubMed

    Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

    2014-01-01

    Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to "low intensity" stimulation of the skin will be highlighted. PMID:25628581

  5. Transient receptor potential melastatin-2 and temperature participate in the process of CD38-regulated oxytocin secretion.

    PubMed

    Liu, Hong-Xiang; Ma, Shuang; Nan, Yong; Yang, Wan-Hua

    2016-08-17

    In recent studies, oxytocin showed potential for the treatment of mental diseases. CD38 is essential for oxytocin release, and hence plays a critical role in social behavior. CD38 catalyzes β-NAD into cyclic ADP ribose (cADPR), which could elevate the intracellular Ca by Ca-permeable channels for oxytocin secretion. The temperature-sensitive cation channel, transient receptor potential melastatin-2 (TRPM2), is a cation-nonselective cation and has been shown to affect oxytocin indirectly. The aim of the present study was to verify the participation of temperature and TRPM2 in CD38-regulated oxytocin release. The crude membranes were prepared to isolate the nerve terminals from the posterior pituitary. At 34°C, 37°C, and 39°C, agonists (β-NAD, ADPR, cADPR) and antagonists (8-Br-cADPR, 2-APB) were used to stimulate the nerve terminals. Oxytocin releases were investigated by enzyme-linked immunosorbent assay. In addition, the expression of TRPM2 and CD38 in the hypothalamus and pituitary was detected by western blotting and quantitative PCR. CD38 agonists (β-NAD, cADPR) and antagonist (8-Br-cADPR) could increase or reduce the oxytocin release, respectively. TRPM2 agonist (ADPR) and antagonist (2-APB) alone could also regulate oxytocin release. Furthermore, temperature could increase agonist stimulation and attenuate the antagonist inhibition on oxytocin release. In addition, CD38 and TRPM2 were expressed in the hypothalamus and pituitary at both the mRNA and the protein level. TRPM2 in pituitary nerve terminals plays a role in oxytocin release. Temperature- enhanced oxytocin release by CD38 and TRPM2. TRPM2 might be involved in the process of CD38-regulated oxytocin release.

  6. Inhibition of oxytocin-induced but not angiotensin-induced rat uterine contractions following exposure to sodium sulfide

    SciTech Connect

    Hayden, L.J.; Franklin, K.J.; Roth, S.H.; Moore, G.J. )

    1989-01-01

    Low concentrations of sodium sulfide reversibly attenuate the contractile response of the isolate rat uterus to oxytocin without affecting angiotensin II responsiveness. These findings suggest that functionally important disulfide bonds in the rat uterine oxytocin receptor, but not the angiotensin receptor, are sensitive to hydrosulfide ion. Reduction of oxytocin receptors by hydrosulfide ion may be a mechanism by which low level of H{sub 2}S delay parturition in rats.

  7. Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation.

    PubMed

    Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

    2014-01-01

    Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to "low intensity" stimulation of the skin will be highlighted.

  8. Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation

    PubMed Central

    Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

    2015-01-01

    Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to “low intensity” stimulation of the skin will be highlighted. PMID:25628581

  9. Finite-element formulation for the analysis of interfaces, nonlinear and large displacement problems in geotechnical engineering

    NASA Astrophysics Data System (ADS)

    Zeevaert, A. E.

    1980-03-01

    A mathematical formulation to model the behavior under load of a reinforced soil system, where a fabric is placed over a soft soil and covered with stone for use as a temporary haul road is discussed. This approach is used to improve the behavior of temporary roadways, particularly where very soft soils are encountered. The stress distribution and the load-deformation characteristics of the soil-fabric system for varying geometries and material properties are defined. Included in the mathematical formulation are such features as: nonlinear behavior of the soil and fabric materials, friction parameters of the interface, tension characteristics of the fabric materials, large displacements in finite deformation, "no tension" conditions of the cohesionless materials, and yielding of plastic materials. The mathematical model is a more complete approximation of the actual fabric-soil system than is presently available.

  10. Oxytocin-stimulated responses in a pregnant human immortalized myometrial cell line.

    PubMed

    Monga, M; Ku, C Y; Dodge, K; Sanborn, B M

    1996-08-01

    Smooth muscle cells isolated from the myometrium of a pregnant woman at term were infected with a replication-defective adenovirus vector expressing the E6/E7 proteins of human papilloma virus 16. A clonal line, PHM1-41, was selected by resistance to Geneticin and examined for maintenance of smooth muscle phenotype and response to oxytocin. The immortalized cell line retained morphological characteristics of proliferating smooth muscle cells in culture for up to 22 passages and has been used for over 2 years. The cells expressed smooth muscle-specific alpha-actin and retained estrogen receptors. Oxytocin receptors were present, as measured by whole cell binding assay using the oxytocin antagonist 125I-d(CH2)5[Tyr-(Me)2,Thr4,-Orn8,Tyr9-NH2] as ligand and oxytocin as competitor. The data were best described by a one-site binding model, with a Kd of 0.36 nM and a binding site concentration of 37 fmol/microgram DNA. PHM1-41 cells responded to oxytocin with an increase in intracellular free calcium (EC50 15 nM) and an increase in phosphatidylinositol turnover. Oxytocin-stimulated phosphatidylinositol turnover was inhibited by preincubation with the cAMP analog CPT-cAMP. This immortalized myometrial cell line should prove useful for studies relating to human myometrial function. PMID:8828850

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

    SciTech Connect

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P. )

    1990-04-01

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

  12. Effects of MDMA and Intranasal oxytocin on social and emotional processing.

    PubMed

    Kirkpatrick, Matthew G; Lee, Royce; Wardle, Margaret C; Jacob, Suma; de Wit, Harriet

    2014-06-01

    MDMA (± 3,4-methylenedioxymethamphetamine, 'ecstasy') is used recreationally, reportedly because it increases feelings of empathy, sociability, and interpersonal closeness. One line of evidence suggests that MDMA produces these effects by releasing oxytocin, a peptide involved in social bonding. In the current study, we investigated the acute effects of MDMA and oxytocin on social and emotional processing in healthy human volunteers. MDMA users (N = 65) participated in a 4-session, within-between-subjects study in which they received oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under double-blind conditions. The primary outcomes included measures of emotion recognition and sociability (desire to be with others). Cardiovascular and subjective effects were also assessed. As expected, MDMA dose-dependently increased heart rate and blood pressure and feelings of euphoria (eg, 'High' and 'Like Drug'). On measures of social function, MDMA impaired recognition of angry and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire to be with others, compared with placebo. Oxytocin produced small but significant increases in feelings of sociability and enhanced recognition of sad facial expressions. Additionally, responses to oxytocin were related to responses to MDMA with subjects on two subjective measures of sociability. Thus, MDMA increased euphoria and feelings of sociability, perhaps by reducing sensitivity to subtle signs of negative emotions in others. The present findings provide only limited support for the idea that oxytocin produces the prosocial effects of MDMA.

  13. Fear or greed? Oxytocin regulates inter-individual conflict by enhancing fear in men.

    PubMed

    Zheng, Huimin; Kendrick, Keith M; Yu, Rongjun

    2016-09-01

    People may choose non-cooperation in social dilemmas either out of fear (if others choose to defect) or out of greed (when others choose to cooperate). Previous studies have shown that exogenous oxytocin motivates a "tend and defend" pattern in inter-group conflict in which oxytocin stimulates in-group cooperation and out-group defense. Using a double-blind placebo-controlled design combined with a modified Prisoner's dilemma game (PDG), we examined the effect of oxytocin on social motivations in inter-individual conflict in men. Results showed that compared with the placebo group, oxytocin-exposed participants were less cooperative in general. Specifically, oxytocin amplified the effect of fear on defection but did not influence the effect of greed. Another non-social control study confirmed participants' decisions were sensitive to social factors. Our findings suggest that even when social group conflict is removed, oxytocin promotes distrust of strangers in "me and you" inter-individual conflict by elevating social fear in men.

  14. Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and its Neural Correlates

    PubMed Central

    Westberg, Lars; Henningsson, Susanne; Zettergren, Anna; Svärd, Joakim; Hovey, Daniel; Lin, Tian; Ebner, Natalie C.; Fischer, Håkan

    2016-01-01

    The ability to recognize faces is crucial for daily social interactions. Recent studies suggest that intranasal oxytocin administration improves social recognition in humans. Oxytocin signaling in the amygdala plays an essential role for social recognition in mice, and oxytocin administration has been shown to influence amygdala activity in humans. It is therefore possible that the effects of oxytocin on human social recognition depend on mechanisms that take place in the amygdala—a central region for memory processing also in humans. Variation in the gene encoding the oxytocin receptor (OXTR) has been associated with several aspects of social behavior. The present study examined the potential associations between nine OXTR polymorphisms, distributed across the gene, and the ability to recognize faces, as well as face-elicited amygdala activity measured by functional magnetic resonance imaging (fMRI) during incidental encoding of faces. The OXTR 3′ polymorphism rs7632287, previously related to social bonding behavior and autism risk, was associated with participants’ ability to recognize faces. Carriers of the GA genotype, associated with enhanced memory, displayed higher amygdala activity during face encoding compared to carriers of the GG genotype. In line with work in rodents, these findings suggest that, in humans, naturally occurring endogenous modulation of OXTR function affects social recognition through an amygdala-dependent mechanism. These findings contribute to the understanding of how oxytocin regulates human social behaviors. PMID:27713694

  15. "The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings"

    PubMed Central

    Cochran, David; Fallon, Daniel; Hill, Michael; Frazier, Jean A.

    2014-01-01

    Oxytocin is a peptide hormone integral in parturition, milk let-down, and maternal behaviors that has been demonstrated in animal studies to be important in the formation of pair bonds and in social behaviors. This hormone is increasingly recognized as an important regulator of human social behaviors, including social decision making, evaluating and responding to social stimuli, mediating social interactions, and forming social memories. In addition, oxytocin is intricately involved in a broad array of neuropsychiatric functions, and may be a common factor important in multiple psychiatric disorders such as autism, schizophrenia, mood and anxiety disorders. This review article examines the extant literature on the evidence for oxytocin dysfunction in a variety of psychiatric disorders and highlights the need for further research to understand the complex role of the oxytocin system in psychiatric disease to pave the way for developing new therapeutic modalities. Articles were selected that involved human participants with various psychiatric disorders, either comparing oxytocin biology to healthy controls or examining the effects of exogenous oxytocin administration. PMID:24651556

  16. Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia.

    PubMed

    Strauss, Gregory P; Keller, William R; Koenig, James I; Sullivan, Sara K; Gold, James M; Buchanan, Robert W

    2015-03-01

    Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group×sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy.

  17. Modulation of interpersonal trust in borderline personality disorder by intranasal oxytocin and childhood trauma.

    PubMed

    Ebert, Andreas; Kolb, Meike; Heller, Jörg; Edel, Marc-Andreas; Roser, Patrik; Brüne, Martin

    2013-01-01

    Borderline personality disorder (BPD) is characterized by interpersonal difficulties, whereby patients are negatively biased concerning the evaluation of others' trustworthiness. Here, we examined the effect of oxytocin on interpersonal behavior of BPD patients in a trust game, emphasizing the assessment of facial attractiveness of the patients' counterparts in the game, and patients' history of childhood trauma. Thirteen BPD patients and thirteen healthy controls played a trust game after receiving oxytocin or placebo in a randomized, double-blind crossover design. Childhood trauma was evaluated using the Childhood Trauma Questionnaire (CTQ). Patients transferred less money in the oxytocin condition compared to placebo. While healthy controls transferred more money units (MUs) to attractive counterparts than to unattractive ones only after the administration of oxytocin, BPD patients showed this pattern in both conditions. Emotional neglect during childhood negatively correlated with the amount of MUs transferred by patients under oxytocin, but not placebo. Oxytocin had a trust-lowering effect in BPD, which was correlated with patients' history of childhood trauma. Patients' evaluation of interpersonal trust seems to depend more on attractiveness features of their counterparts than in controls, a finding that may have important implications for further research on the usefulness of "prosocial" peptides as an adjunct to psychotherapeutic interventions. PMID:23802121

  18. Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only.

    PubMed

    Pagani, J H; Williams Avram, S K; Cui, Z; Song, J; Mezey, É; Senerth, J M; Baumann, M H; Young, W S

    2015-02-01

    Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care.

  19. Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only

    PubMed Central

    Pagani, Jerome H.; Williams Avram, Sarah K.; Cui, Zhenzhong; Song, June; Mezey, Éva; Senerth, Julia M.; Baumann, Michael H.; Young, W. Scott

    2015-01-01

    Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically-mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to eight of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care. PMID:25677455

  20. A Stability Analysis of Cylindrical Panels Using a Finite Element Formulation. Ph.D. Thesis - Va. Polytechnic Inst. and State Univ.

    NASA Technical Reports Server (NTRS)

    Snyder, R. E.

    1971-01-01

    A cylindrical finite element suitable for the linear stability analysis of cylindrical shells is developed. Energy principles and variational methods lead to a problem formulation which lends itself to physical interpretations of the governing matrices of the finite element. By properly grouping the terms which result from taking the second variation of the potential energy of the element, it is possible to identify three distinct types of matrices. The first matrix is the conventional stiffness matrix; the second is an initial stress stiffness matrix; and the third is an initial displacement stiffness matrix. With the assumption of linearity, the buckling problem is stated in terms of the classical linear real eigenvalue equation. This problem formulation was programmed on the CDC 6600 series computer. The computer program is used to analyze the buckling of a variety of structures. Columns, arches, flat plates and curved panels with and without cutouts are considered.

  1. Oxytocin during Development: Possible Organizational Effects on Behavior

    PubMed Central

    Miller, Travis V.; Caldwell, Heather K.

    2015-01-01

    Oxytocin (Oxt) is a neurohormone known for its physiological roles associated with lactation and parturition in mammals. Oxt can also profoundly influence mammalian social behaviors such as affiliative, parental, and aggressive behaviors. While the acute effects of Oxt signaling on adult behavior have been heavily researched in many species, including humans, the developmental effects of Oxt on the brain and behavior are just beginning to be explored. There is evidence that Oxt in early postnatal and peripubertal development, and perhaps during prenatal life, affects adult behavior by altering neural structure and function. However, the specific mechanisms by which this occurs remain unknown. Thus, this review will detail what is known about how developmental Oxt impacts behavior as well as explore the specific neurochemicals and neural substrates that are important to these behaviors. PMID:26042087

  2. Oxytocin, Vasopressin, and the Motivational Forces that Drive Social Behaviors.

    PubMed

    Caldwell, Heather K; Albers, H Elliott

    2016-01-01

    The motivation to engage in social behaviors is influenced by past experience and internal state, but also depends on the behavior of other animals. Across species, the oxytocin (Oxt) and vasopressin (Avp) systems have consistently been linked to the modulation of motivated social behaviors. However, how they interact with other systems, such as the mesolimbic dopamine system, remains understudied. Further, while the neurobiological mechanisms that regulate prosocial/cooperative behaviors have been extensively examined, far less is understood about competitive behaviors, particularly in females. In this chapter, we highlight the specific contributions of Oxt and Avp to several cooperative and competitive behaviors and discuss their relevance to the concept of social motivation across species, including humans. Further, we discuss the implications for neuropsychiatric diseases and suggest future areas of investigation. PMID:26472550

  3. Oxytocin in the socioemotional brain: implications for psychiatric disorders

    PubMed Central

    Kirsch, Peter

    2015-01-01

    The neuropeptide oxytocin (OXT), highly conserved during evolution, is an important modulator of social and emotional processes across many species. During the last decade, a large body of literature has revealed its effects on different aspects of social behavior, including social stress and anxiety, social memory, affiliation and bonding, emotion recognition, mentalizing, empathy, and interpersonal trust. In addition, as impairments in these social domains can be observed in a number of neuropsychiatric disorders, such as autism, social anxiety disorder, depression, schizophrenia, and borderline personality disorder, the role of OXT in mental disorders and their treatment has been intensively studied. The present paper gives a short overview of these lines of research and shows how OXT has become a promising target for novel treatment approaches for mental disorders characterized by social impairments. PMID:26869847

  4. Oxytocin in the socioemotional brain: implications for psychiatric disorders.

    PubMed

    Kirsch, Peter

    2015-12-01

    The neuropeptide oxytocin (OXT), highly conserved during evolution, is an important modulator of social and emotional processes across many species. During the last decade, a large body of literature has revealed its effects on different aspects of social behavior, including social stress and anxiety, social memory, affiliation and bonding, emotion recognition, mentalizing, empathy, and interpersonal trust. In addition, as impairments in these social domains can be observed in a number of neuropsychiatric disorders, such as autism, social anxiety disorder, depression, schizophrenia, and borderline personality disorder, the role of OXT in mental disorders and their treatment has been intensively studied. The present paper gives a short overview of these lines of research and shows how OXT has become a promising target for novel treatment approaches for mental disorders characterized by social impairments.

  5. Life in groups: the roles of oxytocin in mammalian sociality

    PubMed Central

    Anacker, Allison M. J.; Beery, Annaliese K.

    2013-01-01

    In recent decades, scientific understanding of the many roles of oxytocin (OT) in social behavior has advanced tremendously. The focus of this research has been on maternal attachments and reproductive pair-bonds, and much less is known about the substrates of sociality outside of reproductive contexts. It is now apparent that OT influences many aspects of social behavior including recognition, trust, empathy, and other components of the behavioral repertoire of social species. This review provides a comparative perspective on the contributions of OT to life in mammalian social groups. We provide background on the functions of OT in maternal attachments and the early social environment, and give an overview of the role of OT circuitry in support of different mating systems. We then introduce peer relationships in group-living rodents as a means for studying the importance of OT in non-reproductive affiliative behaviors. We review species differences in oxytocin receptor (OTR) distributions in solitary and group-living species of South American tuco-tucos and in African mole-rats, as well as singing mice. We discuss variation in OTR levels with seasonal changes in social behavior in female meadow voles, and the effects of OT manipulations on peer huddling behavior. Finally, we discuss avenues of promise for future investigation, and relate current findings to research in humans and non-human primates. There is growing evidence that OT is involved in social selectivity, including increases in aggression toward social outgroups and decreased huddling with unfamiliar individuals, which may support existing social structures or relationships at the expense of others. OT’s effects reach beyond maternal attachment and pair bonds to play a role in affiliative behavior underlying “friendships”, organization of broad social structures, and maintenance of established social relationships with individuals or groups. PMID:24376404

  6. The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour

    PubMed Central

    Baracz, Sarah Jane; Everett, Nicholas Adams; Cornish, Jennifer Louise

    2015-01-01

    The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol) or co-administration of oxytocin (3.6 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (3 nmol) into the STh (200 nl/side) was examined on METH-primed reinstatement (1 mg/kg; i.p.). We found that local administration of the highest oxytocin dose (3.6 pmol) into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse. PMID:26284529

  7. Evaluation of Microflow Digital Imaging Particle Analysis for Sub-Visible Particles Formulated with an Opaque Vaccine Adjuvant

    PubMed Central

    Frahm, Grant E.; Pochopsky, Alex W. T.; Clarke, Tessa M.; Johnston, Michael J. W.

    2016-01-01

    Microflow digital imaging (MDI) has become a widely accepted method for assessing sub-visible particles in pharmaceutical formulations however, to date; no data have been presented on the utility of this methodology when formulations include opaque vaccine adjuvants. This study evaluates the ability of MDI to assess sub-visible particles under these conditions. A Fluid Imaging Technologies Inc. FlowCAM® instrument was used to assess a number of sub-visible particle types in solution with increasing concentrations of AddaVax™, a nanoscale squalene-based adjuvant. With the objective (10X) used and the limitations of the sensor resolution, the instrument was incapable of distinguishing between sub-visible particles and AddaVax™ droplets at particle sizes less than 5 μm. The instrument was capable of imaging all particle types assessed (polystyrene beads, borosilicate glass, cellulose, polyethylene protein aggregate mimics, and lysozyme protein aggregates) at sizes greater than 5 μm in concentrations of AddaVax™ up to 50% (vol:vol). Reduced edge gradients and a decrease in measured particle sizes were noted as adjuvant concentrations increased. No significant changes in particle counts were observed for polystyrene particle standards and lysozyme protein aggregates, however significant reductions in particle counts were observed for borosilicate (80% of original) and cellulose (92% of original) particles. This reduction in particle counts may be due to the opaque adjuvant masking translucent particles present in borosilicate and cellulose samples. Although the results suggest that the utility of MDI for assessing sub-visible particles in high concentrations of adjuvant may be highly dependent on particle morphology, we believe that further investigation of this methodology to assess sub-visible particles in challenging formulations is warranted. PMID:26925777

  8. Evaluation of Microflow Digital Imaging Particle Analysis for Sub-Visible Particles Formulated with an Opaque Vaccine Adjuvant.

    PubMed

    Frahm, Grant E; Pochopsky, Alex W T; Clarke, Tessa M; Johnston, Michael J W

    2016-01-01

    Microflow digital imaging (MDI) has become a widely accepted method for assessing sub-visible particles in pharmaceutical formulations however, to date; no data have been presented on the utility of this methodology when formulations include opaque vaccine adjuvants. This study evaluates the ability of MDI to assess sub-visible particles under these conditions. A Fluid Imaging Technologies Inc. FlowCAM® instrument was used to assess a number of sub-visible particle types in solution with increasing concentrations of AddaVax™, a nanoscale squalene-based adjuvant. With the objective (10X) used and the limitations of the sensor resolution, the instrument was incapable of distinguishing between sub-visible particles and AddaVax™ droplets at particle sizes less than 5 μm. The instrument was capable of imaging all particle types assessed (polystyrene beads, borosilicate glass, cellulose, polyethylene protein aggregate mimics, and lysozyme protein aggregates) at sizes greater than 5 μm in concentrations of AddaVax™ up to 50% (vol:vol). Reduced edge gradients and a decrease in measured particle sizes were noted as adjuvant concentrations increased. No significant changes in particle counts were observed for polystyrene particle standards and lysozyme protein aggregates, however significant reductions in particle counts were observed for borosilicate (80% of original) and cellulose (92% of original) particles. This reduction in particle counts may be due to the opaque adjuvant masking translucent particles present in borosilicate and cellulose samples. Although the results suggest that the utility of MDI for assessing sub-visible particles in high concentrations of adjuvant may be highly dependent on particle morphology, we believe that further investigation of this methodology to assess sub-visible particles in challenging formulations is warranted.

  9. A stochastic regulator for integrated communication and control systems. I - Formulation of control law. II - Numerical analysis and simulation

    NASA Technical Reports Server (NTRS)

    Liou, Luen-Woei; Ray, Asok

    1991-01-01

    A state feedback control law for integrated communication and control systems (ICCS) is formulated by using the dynamic programming and optimality principle on a finite-time horizon. The control law is derived on the basis of a stochastic model of the plant which is augmented in state space to allow for the effects of randomly varying delays in the feedback loop. A numerical procedure for synthesizing the control parameters is then presented, and the performance of the control law is evaluated by simulating the flight dynamics model of an advanced aircraft. Finally, recommendations for future work are made.

  10. High-performance liquid chromatographic analysis of neomycin in petrolatum-based ointments and in veterinary formulations.

    PubMed

    Binns, R B; Tsuji, K

    1984-01-01

    A high-performance liquid chromatographic (HPLC) method has been developed for the assay of neomycin in petrolatum-based ophthalmic and topical ointments and in veterinary formulations. Neomycin assay interferences from drugs, such as bacitracin and polymyxin B and inactive components, e.g. wax, were eliminated by a methanol wash and/or a partitioning method. The extracted neomycin was derivatized with 2,4-dinitrofluorobenzene followed by normal-phase HPLC with detection at 254 nm. The average recovery of neomycin from spiked samples was approximately 100% with a relative standard deviation of less than 1%.

  11. Development of a novel nanoparticle formulation of thymoquinone with a cold wet-milling system and its pharmacokinetic analysis.

    PubMed

    Nihei, Takuya; Suzuki, Hiroki; Aoki, Asako; Yuminoki, Kayo; Hashimoto, Naofumi; Sato, Hideyuki; Seto, Yoshiki; Onoue, Satomi

    2016-09-10

    The present study aimed to develop a nanoparticle (NP) formulation of thymoquinone (TQ), a potent anti-oxidant chemical, with use of a cold wet-milling (CWM) system to improve its dissolution behavior and pharmacokinetic properties. The NP formulation of TQ (TQ/CWM) was prepared by CWM system, and its physicochemical properties were characterized in terms of particle size distribution, morphology, crystallinity, and dissolution. The photochemical properties of TQ were also examined upon UV/VIS absorption, reactive oxygen species (ROS) generation, and photostability. Pharmacokinetic studies were carried out in rats. Application of the CWM system to TQ led to successful development of nano-sized TQ. The mean diameter of TQ in TQ/CWM was calculated to be 143nm, and TQ particles in TQ/CWM were found to be amorphous. There was a marked improvement in dissolution rate compared with TQ. TQ showed significant generation of singlet oxygen and superoxide upon exposure to simulated sunlight, suggesting its high photoreactivity, and solid samples such as TQ and TQ/CWM exhibited higher photostability than TQ solution. In comparison with TQ, enhanced TQ exposure was observed with a ca. 6-fold increase of oral bioavailability, and the Tmax was shown to be a quarter. From these findings, the NP approach employing the CWM system might be a promising dosage option for improving the nutraceutical values of TQ. PMID:27451272

  12. Development of a novel nanoparticle formulation of thymoquinone with a cold wet-milling system and its pharmacokinetic analysis.

    PubMed

    Nihei, Takuya; Suzuki, Hiroki; Aoki, Asako; Yuminoki, Kayo; Hashimoto, Naofumi; Sato, Hideyuki; Seto, Yoshiki; Onoue, Satomi

    2016-09-10

    The present study aimed to develop a nanoparticle (NP) formulation of thymoquinone (TQ), a potent anti-oxidant chemical, with use of a cold wet-milling (CWM) system to improve its dissolution behavior and pharmacokinetic properties. The NP formulation of TQ (TQ/CWM) was prepared by CWM system, and its physicochemical properties were characterized in terms of particle size distribution, morphology, crystallinity, and dissolution. The photochemical properties of TQ were also examined upon UV/VIS absorption, reactive oxygen species (ROS) generation, and photostability. Pharmacokinetic studies were carried out in rats. Application of the CWM system to TQ led to successful development of nano-sized TQ. The mean diameter of TQ in TQ/CWM was calculated to be 143nm, and TQ particles in TQ/CWM were found to be amorphous. There was a marked improvement in dissolution rate compared with TQ. TQ showed significant generation of singlet oxygen and superoxide upon exposure to simulated sunlight, suggesting its high photoreactivity, and solid samples such as TQ and TQ/CWM exhibited higher photostability than TQ solution. In comparison with TQ, enhanced TQ exposure was observed with a ca. 6-fold increase of oral bioavailability, and the Tmax was shown to be a quarter. From these findings, the NP approach employing the CWM system might be a promising dosage option for improving the nutraceutical values of TQ.

  13. Analysis of annatto (Bixa orellana) food coloring formulations. 2. Determination of aromatic hydrocarbon thermal degradation products by gas chromatography.

    PubMed

    Scotter, M J; Wilson, L A; Appleton, G P; Castle, L

    2000-02-01

    Twenty samples of commercial annatto formulations have been analyzed for m-xylene and toluene using ambient alkaline hydrolysis, followed by solvent extraction and capillary gas chromatography. Fifteen of the samples contained <5 mg/kg toluene, four samples contained between 5 and 10 mg/kg toluene, and one sample contained 12 mg/kg toluene. The amounts found of m-xylene were 200 mg/kg (one sample), 160 mg/kg (one sample), between 30 and 88 mg/kg (four samples), between 7 and 25 mg/kg (seven samples), and <5 mg/kg (seven samples). Bixin-in-oil formulations contained the highest m-xylene concentrations and also gave the largest increase in headspace m-xylene concentration when heated in closed systems. The results are evidence for the thermal degradation of annatto during source extraction and processing, resulting in contamination by internal generation of both bixin and norbixin types with aromatic hydrocarbons. Two samples of norbixin of known production history (i. e., thermal versus nonthermal processes) were analyzed specifically to identify possible differences in their degradation component profiles. They were found to differ significantly in m-xylene content, which is consistent with their respective production histories. PMID:10691661

  14. Oxytocin-Motivated Ally Selection is Moderated by Fetal Testosterone Exposure and Empathic Concern

    PubMed Central

    Kret, Mariska E.; De Dreu, Carsten K. W.

    2012-01-01

    In humans, the hypothalamic neuropeptide oxytocin shifts the individual’s focus on self-interest toward group-serving cognitions and decision-making. Here we examine this general tendency in the context of group formation, where individuals included into their group (or not) 18 targets morphed as having low or high-threat potential (with high-threat targets being beneficial to group-interests but potentially hurting the recruiter’s self-interest). Ninety healthy males self-administered oxytocin or placebo in a randomized double-blind, placebo-controlled study design, had their hands scanned to derive fetal testosterone vs. estradiol exposure from their 2D:4D ratio, and self-reported on their chronic empathic concern. Multilevel regression models revealed that when given oxytocin rather than placebo, individuals with low fetal testosterone priming included low-threat targets more and high-threat targets (somewhat) less. Individuals with high fetal testosterone (i.e., low estradiol) exposure, however, included high-threat targets more, and low-threat targets less when given oxytocin rather than placebo. Second, when given oxytocin rather than placebo, individuals with low empathic concern included low-threat targets more and high-threat targets less. Individuals with high empathic concern, however, included high-threat targets more, and low-threat targets less when given oxytocin rather than placebo. We conclude that oxytocin shifts the individual’s focus from self to group-serving cognition and decision-making, and that these tendencies are stronger for males with high rather than low fetal testosterone vs. estradiol exposure, and high rather than low empathic concern. Implications and avenues for future research are discussed. PMID:23386807

  15. Maternal Oxytocin Is Linked to Close Mother-Infant Proximity in Grey Seals (Halichoerus grypus)

    PubMed Central

    Robinson, Kelly J.; Twiss, Sean D.; Hazon, Neil; Pomeroy, Patrick P.

    2015-01-01

    Maternal behaviour is a crucial component of reproduction in all mammals; however the quality of care that mothers give to infants can vary greatly. It is vital to document variation in maternal behaviour caused by the physiological processes controlling its expression. This underlying physiology should be conserved throughout reproductive events and should be replicated across all individuals of a species; therefore, any correlates to maternal care quality may be present across many individuals or contexts. Oxytocin modulates the initiation and expression of maternal behaviour in mammals; therefore we tested whether maternal plasma oxytocin concentrations correlated to key maternal behaviours in wild grey seals (Halichoerus grypus). Plasma oxytocin concentrations in non-breeding individuals (4.3 ±0.5 pg/ml) were significantly lower than those in mothers with dependent pups in both early (8.2 ±0.8 pg/ml) and late (6.9 ±0.7 pg/ml) lactation. Maternal plasma oxytocin concentrations were not correlated to the amount of nursing prior to sampling, or a mother’s nursing intensity throughout the dependant period. Mothers with high plasma oxytocin concentrations stayed closer to their pups, reducing the likelihood of mother-pup separation during lactation which is credited with causing starvation, the largest cause of pup mortality in grey seals. This is the first study to link endogenous oxytocin concentrations in wild mammalian mothers with any type of maternal behaviour. Oxytocin’s structure and function is widely conserved across mammalian mothers, including humans. Defining the impact the oxytocin system has on maternal behaviour highlights relationships that may occur across many individuals or species, and such behaviours heavily influence infant development and an individual’s lifetime reproductive success. PMID:26698856

  16. Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the biogenic amine level of the adult rat brain: could oxytocin-induced labor cause pervasive developmental diseases?

    PubMed

    Hashemi, F; Tekes, Kornélia; Laufer, R; Szegi, P; Tóthfalusi, L; Csaba, G

    2013-10-01

    Perinatal single-hormone treatment causes hormonal imprinting with lifelong consequences in receptor-binding capacity, hormone production as well as in social and sexual behavior. In the present experiments, newborn rats were treated with a single dose of oxytocin, and the levels of biogenic amines and their metabolites were studied in 8 different brain regions and in the sera when the male and female animals were 4 months old. Both dopaminergic and serotonergic neurotransmission was found to be significantly influenced. The levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole acetic acid metabolites decreased in the hypothalamus and striatum. Dopamine, serotonin, norepinephrine, and 5-hydroxytryptophol levels were hardly altered, and there was no difference in the epinephrine levels. The results show that dopamine and serotonin metabolism of hypothalamus and striatum are deeply and lifelong influenced by a single neonatal oxytocin treatment Oxytocin imprinting resulted in decreased dopamine turnover in the hypothalamus and decreased serotonin turnover in the hypothalamus, medulla oblongata, and striatum of females. As the disturbance of brain dopamine and serotonin system has an important role in the development of pervasive developmental diseases (eg, autism) and neuropsychiatric disorders (eg, schizophrenia), the growing number of oxytocin-induced labor as a causal factor, cannot be omitted. PMID:23548412

  17. Carbon deposition model for oxygen-hydrocarbon combustion. Task 6: Data analysis and formulation of an empirical model

    NASA Technical Reports Server (NTRS)

    Makel, Darby B.; Rosenberg, Sanders D.

    1990-01-01

    The formation and deposition of carbon (soot) was studied in the Carbon Deposition Model for Oxygen-Hydrocarbon Combustion Program. An empirical, 1-D model for predicting soot formation and deposition in LO2/hydrocarbon gas generators/preburners was derived. The experimental data required to anchor the model were identified and a test program to obtain the data was defined. In support of the model development, cold flow mixing experiments using a high injection density injector were performed. The purpose of this investigation was to advance the state-of-the-art in LO2/hydrocarbon gas generator design by developing a reliable engineering model of gas generator operation. The model was formulated to account for the influences of fluid dynamics, chemical kinetics, and gas generator hardware design on soot formation and deposition.

  18. Validation of a LC method for the analysis of oxaliplatin in a pharmaceutical formulation using an experimental design.

    PubMed

    Ficarra, R; Calabrò, M L; Cutroneo, P; Tommasini, S; Melardi, S; Semreen, M; Furlanetto, S; Ficarra, P; Altavilla, G

    2002-08-01

    A rapid and sensitive RP-HPLC method with UV detection for routine control of oxaliplatin in a pharmaceutical formulation (Eloxatin) was developed. Quantitation was accomplished with the internal standard method. The procedure was validated by linearity (correlation coefficient=0.999948), accuracy, robustness and intermediate precision. Experimental design was used during validation to calculate method robustness and intermediate precision. For robustness test three factors were considered: percentage v/v of acetonitrile, flow rate and temperature; an increase in the flow rate results in a decrease of the drug found concentration, while the percentage of organic modifier and temperature have no important effect on the response. For intermediate precision measure the considered variables were: analyst, equipment and days. The RSD value (2.27%, n=24) indicated a good precision of the analytical method.

  19. A randomized trial comparing vaginal misoprostol versus Foley catheter with concurrent oxytocin for labor induction in nulliparous women.

    PubMed

    Culver, James; Strauss, Robert A; Brody, Seth; Dorman, Karen; Timlin, Sally; McMahon, Michael J

    2004-04-01

    The objective of this study was to compare the efficacy and safety of intracervical Foley catheter with concurrent use of oxytocin versus vaginal misoprostol for labor induction in nulliparous women. Nulliparous women with Bishop score <6 who presented for labor induction were randomized to either 25 microg vaginal misoprostol every 4 hours followed by oxytocin, if indicated, or intracervical Foley catheter with simultaneous use of oxytocin. Among the 162 patients enrolled, 79 (49%) received misoprostol and 83 (51%) received Foley/oxytocin. We were unable to demonstrate a statistically significant difference between the misoprostol group and Foley/oxytocin group in the incidence of cesarean delivery (35% versus 29%; p = 0.37). The induction-to-delivery time was significantly shorter in the Foley/oxytocin group (18 versus 24 hours; p < 0.01). No differences in intrapartum complications, neonatal outcomes, or maternal morbidity were found. When compared with vaginal misoprostol, intracervical Foley catheter combined with oxytocin has a similar efficacy and safety profile for labor induction in nulliparous women. Foley/oxytocin results in a shorter induction-to-vaginal delivery time compared with misoprostol.

  20. Peripheral oxytocin treatment affects the rat adreno-medullary catecholamine content modulating expression of vesicular monoamine transporter 2.

    PubMed

    Jovanovic, P; Spasojevic, N; Stefanovic, B; Bozovic, N; Jasnic, N; Djordjevic, J; Dronjak, S

    2014-01-01

    The neuropeptide oxytocin has been shown to influence on neuroendocrine function. The aim of the present study was to investigate the effect of peripheral oxytocin treatment on the synthesis, uptake and content of adreno-medullary catecholamine. For this purpose oxytocin (3.6μg/100g body weight, s.c) was administrated to male rats once a day over 14 days. In order to assess the effect of peripheral oxytocin treatment on adreno-medullary catecholamine we measured epinephrine and norepinephrine content and gene expression of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. Our results show a significant increase of epinephrine (1.7-fold, p<0.05) and norepinephrine (1.5-fold, p<0.05) content in oxytocin treated animals compared to saline treated ones. Oxytocin treatment had no effect either on mRNA or protein level of TH and NET. Under oxytocin treatment the increase in VMAT2 mRNA level was not statistically significant, but it caused a significant increase in protein level of VMAT2 (3.7-fold, p<0.001). These findings indicate that oxytocin treatment increases catecholamine content in the rat adrenal medulla modulating VMAT2 expression. PMID:24239562

  1. Oxytocin effects on mind-reading are moderated by experiences of maternal love withdrawal: an fMRI study.

    PubMed

    Riem, Madelon M E; Bakermans-Kranenburg, Marian J; Voorthuis, Alexandra; van IJzendoorn, Marinus H

    2014-06-01

    The neuropeptide oxytocin has been shown to stimulate a range of social behaviors. However, recent studies indicate that the effects of intranasal oxytocin are more nuanced than previously thought and that contextual factors and individual characteristics moderate the beneficiary oxytocin effects. In this randomized-controlled trial we examine the influence of intranasally administered oxytocin on neural activity during mind-reading with fMRI, taking into account harsh caregiving experiences as a potential moderator. Participants were 50 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and had reported how often their mother used love withdrawal as a disciplinary strategy. Participants performed an adapted version of the Reading the Mind in the Eyes Test (RMET), a task which requires individuals to infer mental states by looking at photographs of the eye region of faces. We found that oxytocin enhanced neural activation in the superior temporal gyrus (STG) and insula during the RMET. Moreover, oxytocin increased RMET performance outside the scanner. However, the oxytocin induced changes in STG activation and RMET performance were only brought about in potentially less socially proficient individuals who had low RMET performance, that is, participants reporting higher levels of maternal love withdrawal.

  2. A rise in the intracellular Ca2+ concentration of isolated rat supraoptic cells in response to oxytocin.

    PubMed Central

    Lambert, R C; Dayanithi, G; Moos, F C; Richard, P

    1994-01-01

    1. Intracellular Ca2+ concentration ([Ca2+]i) was monitored in single cells isolated from adult rat supraoptic (SO) nuclei. The great majority of cells (85%) were neurones and most were immunoreactive to oxytocin or to vasopressin (AVP). 2. The resting [Ca2+]i of the majority (80%) of the neurones remained stable while 20% of the neurones displayed spontaneous [Ca2+]i oscillations which disappeared in low-Ca2+ (100 nM) EGTA buffer. 3. Addition of 100 nM oxytocin increased the [Ca2+]i in both stable and oscillating cells. Two types of responses were observed: (i) a sustained response with [Ca2+]i being maintained at an elevated level and (ii) a brief response with [Ca2+]i quickly returning to a near-resting level. Responses were reproducible, dose dependent and blocked with a specific oxytocin antagonist. 4. Removal of extracellular Ca2+ did not block the oxytocin response. In EGTA buffer, application of thapsigargin (200 nM) onto oxytocin-sensitive cells induced an increase in [Ca2+]i and inhibited the oxytocin response. These effects were not induced by other intracellular Ca2+ mobilizers such as tBuBHQ (see Methods) or caffeine. 5. In conclusion, half of the SO cells respond to oxytocin with a rise in [Ca2+]i. The effect is mediated by oxytocin receptors and results from release of Ca2+ from thapsigargin-sensitive stores. Images Figure 1 PMID:7525943

  3. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome.

    PubMed

    Domes, Gregor; Kumbier, Ekkehardt; Heinrichs, Markus; Herpertz, Sabine C

    2014-02-01

    The neuropeptide oxytocin has recently been shown to enhance eye gaze and emotion recognition in healthy men. Here, we report a randomized double-blind, placebo-controlled trial that examined the neural and behavioral effects of a single dose of intranasal oxytocin on emotion recognition in individuals with Asperger syndrome (AS), a clinical condition characterized by impaired eye gaze and facial emotion recognition. Using functional magnetic resonance imaging, we examined whether oxytocin would enhance emotion recognition from facial sections of the eye vs the mouth region and modulate regional activity in brain areas associated with face perception in both adults with AS, and a neurotypical control group. Intranasal administration of the neuropeptide oxytocin improved performance in a facial emotion recognition task in individuals with AS. This was linked to increased left amygdala reactivity in response to facial stimuli and increased activity in the neural network involved in social cognition. Our data suggest that the amygdala, together with functionally associated cortical areas mediate the positive effect of oxytocin on social cognitive functioning in AS.

  4. Clinicians' guide to the use of oxytocin for labor induction and augmentation.

    PubMed

    Simpson, Kathleen Rice

    2011-01-01

    Oxytocin is commonly used in obstetrics for labor induction and augmentation. Careful assessment of the individual clinical situation based on indications and contraindications is essential to enhancing safe and effective use. Counseling the woman and her partner regarding potential risks and benefits before use is necessary to promote informed consent. At least 39 weeks of gestation is required for elective labor induction. Recent research has shown that deferring elective induction until cervical readiness has been achieved without the use of pharmacologic agents can be beneficial in reducing the risk of cesarean birth associated with elective induction. A conservative physiologic oxytocin protocol for labor induction and augmentation is recommended to minimize the risk of side effects. Although treatment of excessive uterine activity related to oxytocin has not been studied prospectively, several interventions such as maternal repositioning, an intravenous fluid bolus, and discontinuation of the oxytocin infusion are beneficial in returning uterine activity to normal, based on retrospective review of oxytocin-induced tachysystole. Perinatal quality measures from the National Quality Forum and the Joint Commission can be useful in monitoring care related to induction of labor. These include elective births before 39 weeks of pregnancy and cesarean births for low-risk, first-birth mothers.

  5. Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects.

    PubMed

    Lucht, Michael J; Barnow, Sven; Sonnenfeld, Christine; Rosenberger, Albert; Grabe, Hans Joergen; Schroeder, Winnie; Völzke, Henry; Freyberger, Harald J; Herrmann, Falko H; Kroemer, Heyo; Rosskopf, Dieter

    2009-08-01

    Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ. PMID:19376182

  6. [The role of oxytocin and vasopressin in central nervous system activity and mental disorders].

    PubMed

    Wójciak, Paweł; Remlinger-Molenda, Agnieszka; Rybakowski, Janusz

    2012-01-01

    Oxytocin and vasopressin, "peptides of love and fear", except for their classic role in control of labor and breastfeeding and blood pressure regulation, are also implicated in various processes like sexual behaviours, social recognition and stress response. These hormones seems to be essential for appropriate and beneficial social interactions, play a very important role in maternal care and closeness, promote general trust and cooperation and prolong social memory. They also play a very important role in modulating fear and anxiety response, especially by regulating the hypothalamic-pituitary-adrenal axis and amygdala activity by its projections to the brain stem and hypothalamic structures. Both hormones, particularly oxytocin, appears to be activating sexual behaviour or is responsible for increased sexual arousal. Evidence from clinical trials suggests their potential role in pathogenesis of schizophrenia, depression, autism and addiction together with possible therapeutic use in the above conditions. In schizophrenia, patients with higher peripheral oxytocin levels showed less severe positive, general and social symptoms and better prosocial behaviours. Literature suggests that exogenous oxytocin may be effective as an adjunctive therapy for that illness. Some data suggest that naturally occurring autoantibodies reacting with oxytocin and vasopressin are involved in depression, eating disorders and conduct disorder genesis. PMID:23479945

  7. Urinary oxytocin and social bonding in related and unrelated wild chimpanzees

    PubMed Central

    Crockford, C.; Wittig, R. M.; Langergraber, K.; Ziegler, T. E.; Zuberbühler, K.; Deschner, T.

    2013-01-01

    Animals that maintain cooperative relationships show gains in longevity and offspring survival. However, little is known about the cognitive or hormonal mechanisms involved in cooperation. Indeed, there is little support for a main hypothesis that non-human animals have the cognitive capacities required for bookkeeping of cooperative exchanges. We tested an alternative hypothesis that cooperative relationships are facilitated by an endocrinological mechanism involving oxytocin, a hormone required for bonding in parental and sexual relationships across mammals. We measured urinary oxytocin after single bouts of grooming in wild chimpanzees. Oxytocin levels were higher after grooming with bond partners compared with non-bond partners or after no grooming, regardless of genetic relatedness or sexual interest. We ruled out other possible confounds, such as grooming duration, grooming direction or sampling regime issues, indicating that changes in oxytocin levels were mediated by social bond strength. Oxytocin, which is thought to act directly on neural reward and social memory systems, is likely to play a key role in keeping track of social interactions with multiple individuals over time. The evolutionary linkage of an ancestral hormonal system with complex social cognition may be the primary mechanism through which long-term cooperative relationships develop between both kin and non-kin in mammals. PMID:23345575

  8. Oxytocin motivates non-cooperation in intergroup conflict to protect vulnerable in-group members.

    PubMed

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

    2012-01-01

    Intergroup conflict is often driven by an individual's motivation to protect oneself and fellow group members against the threat of out-group aggression, including the tendency to pre-empt out-group threat through a competitive approach. Here we link such defense-motivated competition to oxytocin, a hypothalamic neuropeptide involved in reproduction and social bonding. An intergroup conflict game was developed to disentangle whether oxytocin motivates competitive approach to protect (i) immediate self-interest, (ii) vulnerable in-group members, or (iii) both. Males self-administered oxytocin or placebo (double-blind placebo-controlled) and made decisions with financial consequences to themselves, their fellow in-group members, and a competing out-group. Game payoffs were manipulated between-subjects so that non-cooperation by the out-group had high vs. low impact on personal payoff (personal vulnerability), and high vs. low impact on payoff to fellow in-group members (in-group vulnerability). When personal vulnerability was high, non-cooperation was unaffected by treatment and in-group vulnerability. When personal vulnerability was low, however, in-group vulnerability motivated non-cooperation but only when males received oxytocin. Oxytocin fuels a defense-motivated competitive approach to protect vulnerable group members, even when personal fate is not at stake.

  9. Oxytocin induces positive expectations about ambivalent stimuli (cognitive bias) in dogs.

    PubMed

    Kis, Anna; Hernádi, Anna; Kanizsár, Orsolya; Gácsi, Márta; Topál, József

    2015-03-01

    Expectancy bias towards positive outcomes is a potential key to subjective well-being, and has been widely investigated in different species. Here we test whether oxytocin, suggested to play a role in human optimism and emotional processing, influences how dogs judge ambivalent situations (in a cognitive bias paradigm). Subjects first learned in a location discrimination task that a bowl either contained food (at the 'positive' location) or was empty (at the 'negative' location). Then, after receiving oxytocin or placebo nasal spray, they were presented with the bowl located halfway between the positive and negative positions in communicative or non-communicative contexts (N=4×16). A Positive Expectancy Score was calculated for each subject using the latency to approach this ambivalent location. Compared to placebo groups, subjects that received oxytocin pretreatment showed a positive expectation bias in both contexts, and this effect was more pronounced in the communicative context. Our study provides the first evidence for the impact of oxytocin on dogs' judgement bias and also shows that the social-communicative nature of the task situation modulates the effect of oxytocin. PMID:25530486

  10. Oxytocin enhances implicit social conformity to both in-group and out-group opinions.

    PubMed

    Huang, Yi; Kendrick, Keith M; Zheng, Huimin; Yu, Rongjun

    2015-10-01

    People often alter their own preferences when facing conflicting opinions expressed by others. This is known as the social conformity effect and tends to be stronger in response to opinions expressed by in-group relative to out-group members. The hypothalamic neuropeptide oxytocin promotes in-group favoritism, elicits parochial altruism, and stimulates in-group conformity under explicit social pressure. In a double-blind, placebo-controlled design experiment using a facial attractiveness judgment task, we therefore investigated whether social conformity to either in-group or out-group opinions is influenced by intranasal oxytocin treatment when social pressure is implicit. After oxytocin or placebo treatment, male participants were asked to rate the attractiveness of unfamiliar Chinese female faces, and then they were informed of ratings given by peers from an in-group (Chinese) and out-group (Japanese) simultaneously. They were subsequently asked unexpectedly to re-rate the same faces. Results showed that oxytocin increased conformity to both in- and out-group opinions. Thus oxytocin promotes conformity to opinions of both in- and out-group members when social pressure is implicit, suggesting that it facilitates 'tend and befriend' behaviors by increasing the general level of social conformity.

  11. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    SciTech Connect

    Michelini, S.; Urbanek, M.; Goldman, D.

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

  12. Oxytocin's impact on social face processing is stronger in homosexual than heterosexual men.

    PubMed

    Thienel, Matthias; Heinrichs, Markus; Fischer, Stefan; Ott, Volker; Born, Jan; Hallschmid, Manfred

    2014-01-01

    Oxytocin is an evolutionarily highly preserved neuropeptide that contributes to the regulation of social interactions including the processing of facial stimuli. We hypothesized that its improving effect on social approach behavior depends on perceived sexual features and, consequently, on sexual orientation. In 19 homosexual and 18 heterosexual healthy young men, we investigated the acute effect of intranasal oxytocin (24IU) and placebo, respectively, on the processing of social stimuli as assessed by ratings of trustworthiness, attractiveness and approachability for male and female faces. Faces were each presented with a neutral, a happy, and an angry expression, respectively. In heterosexual subjects, the effect of oxytocin administration was restricted to a decrease in ratings of trustworthiness for angry female faces (p<0.02). In contrast, in homosexual men oxytocin administration robustly increased ratings of attractiveness and approachability for male faces regardless of the facial expression (all p ≤ 0.05), as well as ratings of approachability for happy female faces (p<0.01). Results indicate that homosexual in comparison to heterosexual men display higher sensitivity to oxytocin's enhancing impact on social approach tendencies, suggesting that differences in sexual orientation imply differential oxytocinergic signaling.

  13. Obstetric and fetal outcomes in dystocic and eutocic sows to an injection of exogenous oxytocin during farrowing

    PubMed Central

    González-Lozano, Miguel; Mota-Rojas, Daniel; Velázquez-Armenta, E. Yadira; Nava-Ocampo, Alejandro A.; Hernández-González, Rafael; Becerril-Herrera, Marcelino; Trujillo-Ortega, María E.; Alonso-Spilsbury, María

    2009-01-01

    Sixty hybrid Yorkshire-Landrace penned sows, 30 with eutocic farrowing and 30 experiencing a dystocic parturition, were studied to evaluate the obstetric and neonatal outcomes to low doses of oxytocin administered at advanced stages of parturition. Animals in each group were randomly subdivided into 2 subgroups: 15 eutocic and 15 dystocic sows received oxytocin 0.083 IU/kg (equivalent to 1 IU/12 kg body weight), administered intramuscularly after the delivery of the 5th piglet; the other 15 eutocic and 15 dystocic sows received saline solution intramuscularly at the same time. Oxytocin decreased the number of intrapartum deaths by approximately 50% (P = 0.002). No piglet was born dead from the saline- and oxytocin-treated eutocic sows. The highest viability score was observed among piglets born to eutocic sows treated with oxytocin. In summary, this dose schedule would help to decrease the number of stillbirths in both eutocic and dystocic farrowing sows. PMID:20190977

  14. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

    PubMed

    Febo, Marcelo; Ferris, Craig F

    2014-09-11

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

  15. Vasopressin, but not oxytocin, increases empathic concern among individuals who received higher levels of paternal warmth: a randomized controlled trial

    PubMed Central

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

    2014-01-01

    Background Empathy improves our ability to communicate in social interactions and motivates prosocial behavior. The neuropeptides arginine vasopressin and oxytocin play key roles in socioemotional processes such as pair bonding and parental care, which suggests that they may be involved in empathic processing. Methods We investigated how vasopressin and oxytocin affect empathic responding in a randomized, double-blind, placebo controlled, between-subjects study design. We also examined the moderating role of parental warmth, as reported in the early family environment, on empathic responding following vasopressin, oxytocin, or placebo administration. Results Among participants who reported higher levels of paternal warmth (but not maternal warmth), vasopressin (vs. placebo and oxytocin) increased ratings of empathic concern after viewing distressing and uplifting videos. No main or interaction effects were found for individuals who received oxytocin. Conclusions Vasopressin has a role in enhancing empathy among individuals who received higher levels of paternal warmth. Trial registration NCT01680718 PMID:25462898

  16. Effects of Couple Interactions and Relationship Quality on Plasma Oxytocin and Cardiovascular Reactivity: Empirical Findings and Methodological Considerations

    PubMed Central

    Smith, Timothy W.; Uchino, Bert N.; MacKenzie, Justin; Hicks, Angela; Campo, Rebecca A.; Reblin, Maija; Grewen, Karen; Amico, Janet A.; Light, Kathleen C.

    2016-01-01

    Cardiovascular reactivity is a potential mechanism underlying associations of close relationship quality with cardiovascular disease. Two models describe oxytocin as another mechanism. The “calm and connect” model posits an association between positive relationship experiences and oxytocin levels and responses, whereas the “tend and befriend” model emphasizes the effects of negative relationship experiences in evoking oxytocin release. In this study of 180 younger couples, relationship quality had a small, marginally significant inverse association with plasma oxytocin levels, and neither positive nor negative couple interactions evoked change in plasma oxytocin. Negative couple interactions evoked significant cardiovascular reactivity, especially among women. Hence, in the largest study of these issues to date, there was little support for key tenets of the “calm and connect” model, and only very modest support for the ”tend and befriend” model. However, findings were consistent with the view that CVR contributes to the effects of relationship difficulties on health. PMID:22543270

  17. Comparison of prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin for induction of labour.

    PubMed

    Lo, L; Ho, M W; Leung, P

    1994-05-01

    Prostaglandins have been increasingly used in obstetrical practice for cervical ripening and induction of labour. We set out to investigate the effectiveness of prostaglandin E2 (PGE2) vaginal pessaries in inducing labour in the Chinese population in Hong Kong. In the period August, 1991 to August, 1992, we recruited 206 pregnant Chinese women who required induction of labour for various obstetrical indications into the trial. The study group had induction of labour by PGE2 vaginal pessaries and the control group underwent amniotomy plus oxytocin infusion. These patients were alternately assigned either method of induction. They were further divided into primiparous and multiparous (parity 1 and 2 only) groups. Only 101 primiparas and 99 multiparas were available in the final analysis of the trial. Various aspects of labour, delivery, maternal and fetal outcome were compared. For primiparas, the traditional combined induction was the preferred method. For multiparas, both induction methods were quite satisfactory and there was a trend toward lesser blood loss and pethidine requirement in the PGE2 users.

  18. Population pharmacodynamic modeling of various extended-release formulations of methylphenidate in children with attention deficit hyperactivity disorder via meta-analysis.

    PubMed

    Kimko, Holly; Gibiansky, Ekaterina; Gibiansky, Leonid; Starr, H Lynn; Berwaerts, Joris; Massarella, Joseph; Wiegand, Frank

    2012-04-01

    Placebo and pharmacodynamic (PD) models were developed which link temporal measures of efficacy in children with attention deficit hyperactivity disorder (ADHD) and methylphenidate (MPH) plasma concentrations from adults. These models can be used to predict daily pediatric clinical measure profiles following administration of different MPH formulations in children without conducting pediatric pharmacokinetic (PK) or PD studies by using more easily obtained adult PK data. Mean PK data from various extended-release MPH formulations studied in adults and mean PD data from nine pediatric efficacy studies were obtained from the literature. The individual time-course of the clinical measures from three pediatric trials were also analyzed after being combined with the meta-analysis data. The clinical measure profiles following placebo administration were described by indirect response models with time-varying elimination rates. MPH pharmacodynamic effect was described by E(max) models, which included time-dependent tolerance. Internal and external evaluations using a visual predictive check technique confirmed the prediction capability of the models. This modeling exercise demonstrated that time courses of MPH concentrations in adults with different drug release patterns can be used to predict time courses of clinical efficacy parameters in pediatrics by employing the models developed by meta-analysis.

  19. Could oxytocin administration during labor contribute to autism and related behavioral disorders?--A look at the literature.

    PubMed

    Wahl, Roy U Rojas

    2004-01-01

    This literature review summarizes recent potential evidence, most of which is at the molecular/mechanistic level, in support of Hollander's hypothesis that excess oxytocin (OT), possibly through OT administration at birth, could contribute to the development of autistic spectrum disorders and related syndromes by proposed down regulation of the OT receptor (OTR). In this review, recent molecular evidence for OTR internalization by excess OT is related to OT's reported effects on animal social behavior, favoring social bondage, notably in sheep, voles, rats and especially mice. Adding indications for OT's capability of crossing the maternal placenta and OT's possibility of crossing an underdeveloped or stressed infantile blood brain barrier at birth, a causal connection between OT excess and behavioral disorders such as autism can be supported from a molecular perspective. Possible strategies such as a thorough statistical analysis of numerous birth records as well as molecular studies such as radiotracing using labeled OT are proposed to test this hypothesis. PMID:15288368

  20. High-Throughput Analysis of Lidocaine in Pharmaceutical Formulation by Capillary Zone Electrophoresis Using Multiple Injections in a Single Run

    PubMed Central

    Valese, Andressa C.; Spudeit, Daniel A.; Dolzan, Maressa D.; Bretanha, Lizandra C.; Micke, Gustavo A.

    2016-01-01

    This paper reports the development of a subminute separation method by capillary zone electrophoresis in an uncoated capillary using multiple injection procedure for the determination of lidocaine in samples of pharmaceutical formulations. The separation was performed in less than a minute leading to doing four injections in a single run. The cathodic electroosmotic flow contributed to reducing the analyses time. The background electrolyte was composed of 20 mmol L−1 2-amino-2-(hydroxymethyl)-1,3-propanediol and 40 mmol L−1 2-(N-morpholino)ethanesulfonic acid at pH 6.1. The internal standard used was benzylamine. Separations were performed in a fused uncoated silica capillary (32 cm total length, 23.5 cm effective length, and 50 μm internal diameter) with direct UV detection at 200 nm. Samples and standards were injected hydrodynamically using 40 mbar/3 s interspersed with spacer electrolyte using 40 mbar/7 s. The electrophoretic system was operated under constant voltage of 30 kV with positive polarity on the injection side. The evaluation of some analytical parameters of the method showed good linearity (r2 > 0.999), a limit of detection 0.92 mg L−1, intermediate precision better than 3.2% (peak area), and recovery in the range of 92–102%. PMID:27069712

  1. Linking anthropological analysis and epidemiological evidence: formulating a narrative of HIV transmission in Acholiland of northern Uganda.

    PubMed

    Westerhaus, M

    2007-08-01

    For twenty years, a region of northern Uganda known as Acholiland has been heavily affected by war, leading to the formation of internally displaced people's camps, rape, transactional sex and child abductions. While it is clear that the war has had onerous consequences for the health of the Acholi people, the specific impact of the war on HIV transmission remains unclear, as the epidemiological evidence presents an ambiguous picture of HIV prevalence patterns. Other than a few non-governmental organization reports, very little qualitative data exists about the impact of HIV on the Acholi population. Attempting to formulate a clearer narrative of HIV transmission in Acholiland, this paper jointly analyses the historical and political context of the Acholi people and the war, the epidemiologic evidence of HIV prevalence patterns, and the ethnographic perspectives of Acholi healthcare workers and patients living with HIV/AIDS. Juxtaposing these sources of information allows for the emergence of a rich understanding of HIV in Acholiland. It is argued that three specific forms of violence--physical, symbolic and structural--create vulnerability to HIV infection in Acholiland, although to variable degrees dependent on location. The ethnographic evidence presented regarding HIV's impact on Acholiland suggests that an incorporation of historical, political, cultural and social factors must form the backbone of efforts both to understand HIV transmission and design strategies for curbing the epidemic in war settings.

  2. Restructuring BOD : COD ratio of dairy milk industrial wastewaters in BOD analysis by formulating a specific microbial seed.

    PubMed

    Dhall, Purnima; Siddiqi,