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Sample records for oxytocin formulations analysis

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

    PubMed

    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. Complete NMR analysis of oxytocin in phosphate buffer.

    PubMed

    Ohno, Akiko; Kawasaki, Nana; Fukuhara, Kiyoshi; Okuda, Haruhiro; Yamaguchi, Teruhide

    2010-02-01

    Complete NMR analysis of oxytocin (OXT) in phosphate buffer was elucidated by one-dimensional (1D)- and two-dimensional (2D)-NMR techniques, which involve the assignment of peptide amide NH protons and carbamoyl NH(2) protons. The (1)H-(15)N correlation of seven amide NH protons and three carbamoyl NH(2) protons were also shown by HSQC NMR of OXT without (15)N enrichment.

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

    PubMed

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

    2015-12-01

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

  4. Liquid chromatographic analysis of oxytocin and its related substances.

    PubMed

    Ashenafi, Dunge; Van Hemelrijck, Elise; Chopra, Shruti; Hoogmartens, Jos; Adams, Erwin

    2010-01-05

    A selective gradient liquid chromatographic (LC) method for the determination of oxytocin (OT) and its related substances in bulk drugs has been developed. The method uses a reversed-phase C18 column (25 cm x 4.0 mm i.d.), 5 microm kept at 40 degrees C. The mobile phases consist of acetonitrile, dihydrogen phosphate solution pH 4.4 and water. The flow rate is 1.0 ml/min. UV detection is performed at 220 nm. A system suitability test (SST) was developed to govern the quality of the separation. The separation towards OT components was investigated on different C18 columns. The developed method was further validated with respect to robustness, precision, sensitivity and linearity. A central composite design was applied to examine the robustness of the method. The method shows good precision, sensitivity, linearity and robustness. Two commercial OT samples were examined using this method. Furthermore, the method proved to be successful when applied to analyze a marketed OT formulation for injection.

  5. Oxytocin Injection

    MedlinePlus

    Oxytocin injection is used to begin or improve contractions during labor. Oxytocin also is used to reduce bleeding after childbirth. ... other medications or procedures to end a pregnancy. Oxytocin is in a class of medications called oxytocic ...

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

    PubMed

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

    2014-10-01

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

  7. 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.

  8. 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

  9. 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.

  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. 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

  12. 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.

  13. Oxytocin and Autism Spectrum Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Ooi, Yoon Phaik; Weng, Shih-Jen; Kossowsky, Joe; Gerger, Heike; Sung, Min

    2017-01-01

    Aim: Oxytocin presents an exciting potential to target the core symptoms of autism spectrum disorder (ASD) pharmacologically in an easily administered, cost-effective form with possibly minimal adverse effects. But, there are still major gaps in this area of research. This paper reviewed randomized controlled trials (RCTs) examining the effects of oxytocin administration on social cognition and restricted, repetitive behaviors in individuals with an ASD. Method: Electronic literature searches were conducted from PsycINFO, PubMed, Web of Knowledge, and EMBASE for RCTs published through June 2015. Results: 12 RCTs were included in this review. 7 out of the 11 studies that examined social cognition reported improvements. Additionally, one out of the 4 studies on restricted, repetitive behaviors, reported improvements following oxytocin administration. However, results from our meta-analyses suggest that oxytocin has no significant effect on these 2 domains. Conclusion: Previous evidence revealed mixed findings about the effects of oxytocin on ASD. Given the limited number of RCTs, our summary of findings on the effectiveness of oxytocin on ASD should still be considered tentative.

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

    PubMed Central

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

    2015-01-01

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

  15. Nonlinear finite element analysis: An alternative formulation

    NASA Technical Reports Server (NTRS)

    Merazzi, S.; Stehlin, P.

    1980-01-01

    A geometrical nonlinear analysis based on an alternative definition of strain is presented. Expressions for strain are obtained by computing the change in length of the base vectors in the curvilinear element coordinate system. The isoparametric element formulation is assumed in the global Cartesian coordinate system. The approach is based on the minimization of the strain energy, and the resulting nonlinear equations are solved by the modified Newton method. Integration of the first and second variation of the strain energy is performed numerically in the case of two and three dimensional elements. Application is made to a simple long cantilever beam.

  16. Effect of Intranasal Oxytocin Administration on Psychiatric Symptoms: A Meta-Analysis of Placebo-Controlled Studies

    PubMed Central

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

    2015-01-01

    Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1,828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges’ g = 0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. PMID:26094200

  17. 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

  18. Oxytocin stimulates migration and invasion in human endothelial cells

    PubMed Central

    Cattaneo, M G; Chini, B; Vicentini, L M

    2007-01-01

    Background and purpose: It has recently been reported that oxytocin is produced by some tumour cell types, and that oxytocin receptors, belonging to the G-protein-coupled receptor (GPCR) family, are expressed in a variety of cell types. Among these, human umbilical vein endothelial cells (HUVECs) respond to oxytocin with an increased proliferation, suggesting a possible role for the hormone in the regulation of angiogenesis. Experimental approach: We employed chemotaxis and chemoinvasion assays to characterize the effect of oxytocin on HUVEC motility, and immunoblot analysis to study its molecular mechanisms of action. Key results: We showed that oxytocin stimulates migration and invasion in HUVECs via oxytocin receptor activation. Searching for the molecular mechanism(s) responsible for oxytocin's pro-migratory effect, we identified the Gq coupling of oxytocin receptors and phospholipase C (PLC) as the main effectors of oxytocin's action in HUVECs. We also found that oxytocin stimulates the phosphorylation of endothelial nitric oxide synthase (eNOS) via the phosphatidylinositol-3-kinase (PI-3-K)/AKT pathway, and that the activation of PI-3-K and formation of nitric oxide (NO) are required for the pro-migratory effect of oxytocin. Conclusions and implications: The ability of oxytocin to stimulate HUVEC motility and invasion suggests that the hormone can participate in physiopathological processes where activation of endothelial cells plays an important role, for example, in angiogenesis. Interestingly, both the AKT and eNOS phosphorylation induced by oxytocin receptor activation depended on PLC activity, thus suggesting the existence of a still undefined mechanism connecting PLC to the PI-3-K/AKT pathway, upon oxytocin stimulation. PMID:18059319

  19. Desensitization of oxytocin receptors in human myometrium.

    PubMed

    Phaneuf, S; Asbóth, G; Carrasco, M P; Liñares, B R; Kimura, T; Harris, A; Bernal, A L

    1998-01-01

    In the present study, we investigated the possible mechanisms by which oxytocin might regulate oxytocin receptor (OTR) density. Exposure of cultured myometrial cells to oxytocin for a prolonged period caused desensitization: the steady-state level of oxytocin binding was 210 x 10(3) binding sites/cell, but this was time-dependently reduced to 20.1 x 10(3) sites/cell by exposing the cells to oxytocin for up to 20 h. In contrast, Western blotting data showed that the total amount of OTR protein was not affected by oxytocin treatment for up to 24 h. Flow cytometry experiments demonstrated that OTRs were not internalized during this treatment. However, RNase protection assays and Northern analysis showed that in cultured myometrial cells OTR mRNA was reduced by oxytocin treatment to reach a new low steady-state concentration. Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour. Samples obtained after 12 h of labour contained approximately 50 times less OTR mRNA than samples obtained from patients in labour for less than 12 h. We speculate that this decrease in OTR mRNA represents in-vivo OTR desensitization.

  20. 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

  1. 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.

  2. [Transitory hyperbilirubinemia and oxytocin infusion].

    PubMed

    Quoss, I

    1978-01-01

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

  3. 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.

  4. 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.

  5. Low CSF oxytocin reflects high intent in suicide attempters.

    PubMed

    Jokinen, Jussi; Chatzittofis, Andreas; Hellström, Christer; Nordström, Peter; Uvnäs-Moberg, Kerstin; Asberg, Marie

    2012-04-01

    Data from animal studies suggest that oxytocin is an important modulating neuropeptide in regulation of social interaction. One human study has reported a negative correlation between CSF oxytocin levels, life history of aggression and suicidal behaviour. We hypothesized that CSF oxytocin levels would be related to suicidal behaviour, suicide intent, lifetime interpersonal violence and suicide risk. 28 medication free suicide attempters and 19 healthy volunteers participated in this cross sectional and longitudinal study. CSF and plasma morning basal levels of oxytocin were assessed with specific radio-immunoassays. The Beck Suicide Intent Scale (SIS), the Freeman scale and the Karolinska Interpersonal Violence Scale (KIVS) were used to assess suicide intent and lifetime violent behaviour. All patients were followed up for cause of death. The mean follow-up was 21 years. Suicide attempters had lower CSF oxytocin levels compared to healthy volunteers p=0.077. In suicide attempters CSF oxytocin showed a significant negative correlation with the planning subscale of SIS. CSF oxytocin showed a significant negative correlation with suicide intent, the planning subscale of SIS and Freeman interruption probability in male suicide attempters. Correlations between plasma oxytocin levels and the planning subscale of SIS and Freeman interruption probability were significant in male suicide attempters. Lifetime violent behaviour showed a trend to negative correlation with CSF oxytocin. In the regression analysis suicide intent remained a significant predictor of CSF oxytocin corrected for age and gender whereas lifetime violent behaviour showed a trend to be a predictor of CSF oxytocin. Oxytocin levels did not differ significantly in suicide victims compared to survivors. CSF oxytocin may be an important modulator of suicide intent and interpersonal violence in suicide attempters.

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

    PubMed

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

    2016-08-01

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

  7. Oxytocin and oxytocin receptors in cancer cells and proliferation.

    PubMed

    Cassoni, P; Sapino, A; Marrocco, T; Chini, B; Bussolati, G

    2004-04-01

    The hypothalamic nonapeptide oxytocin plays a crucial role in many reproductive and behavioural functions. However, in recent years, an additional new role for oxytocin has been identified in neoplastic pathology. In tumours, oxytocin acts as a growth regulator, through the activation of a specific G-coupled transmembrane receptor, the oxytocin receptor. In vitro, oxytocin inhibits proliferation of neoplastic cells of either epithelial (mammary and endometrial), nervous or bone origin, all expressing oxytocin receptor. Furthermore, an oxytocin growth-inhibiting effect was also tested and confirmed in vivo in mouse and rat mammary carcinomas. In neoplastic cells derived from two additional oxytocin target tissues, trophoblast and endothelium, oxytocin was found to promote cell proliferation, an effect opposite to that previously described in all other neoplastic oxytocin-responsive cells. The signal transduction pathways coupled to the biological effects of oxytocin are different in oxytocin growth-inhibited or growth-stimulated cells, and may depend on the membrane localization of the oxytocin receptor itself. The inhibitory effect of oxytocin is apparently mediated by activation of the cAMP-protein kinase A pathway, a nonconventional oxytocin signalling pathway, whereas the mitogenic effect is coupled to the increase of intracellular [Ca(2+)] and tyrosine phosphorylation, 'classical' oxytocin transducers. Moreover, the oxytocin receptor localization in lipid rafts enriched in caveolin-1 turns the inhibition of cell growth into a proliferative response, eliciting different epidermal growth factor receptor/mitogen-activated protein kinase activation patterns. This unexpected role of oxytocin (and oxytocin analogues) in regulating cell proliferation, as well as the widespread expression of oxytocin receptors in neoplastic tissues of different origin, opens up new perspectives on the biological role of the oxytocin-oxytocin receptor system in cancer.

  8. 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.

  9. 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.

  10. Efficacy of oxytocin antagonist infusion in improving in vitro fertilization outcomes on the day of embryo transfer: A meta-analysis

    PubMed Central

    Kim, Seul Ki; Han, E-Jung; Kim, Sun Mie; Jee, Byung Chul; Suh, Chang Suk; Kim, Seok Hyun

    2016-01-01

    Objective Uterine contraction induced by the embryo transfer (ET) process has an adverse effect on embryo implantation. The aim of this study was to determine the effect of oxytocin antagonist supplementation on the day of ET on in vitro fertilization outcomes via a meta-analysis. Methods We performed a meta-analysis of randomized controlled trials (RCTs). Four online databases (Embase, Medline, PubMed, and Cochrane Library) were searched through May 2015 for RCTs that investigated oxytocin antagonist supplementation on the day of ET. Studies were selected according to predefined inclusion criteria and meta-analyzed using RevMan 5.3. Only RCTs were included in this study. The main outcome measures were the clinical pregnancy rate, the implantation rate, and the miscarriage rate. Results A total of 123 studies were reviewed and assessed for eligibility. Three RCTs, which included 1,020 patients, met the selection criteria. The implantation rate was significantly better in patients who underwent oxytocin antagonist infusion (19.8%) than in the control group (11.3%) (n=681; odds ratio [OR], 1.92; 95% confidence interval [CI], 1.25–2.96). No significant difference was found between the two groups in the clinical pregnancy rate (n=1,020; OR, 1.57; 95% CI, 0.92–2.67) or the miscarriage rate (n=456; OR, 0.76; 95% CI, 0.44–1.33). Conclusion The results of this meta-analysis of the currently available literature suggest that the administration of an oxytocin antagonist on the day of ET improves the implantation rate but not the clinical pregnancy rate or miscarriage rate. Additional, large-scale, prospective, randomized studies are necessary to confirm these findings. PMID:28090463

  11. 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,

  12. 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

  13. Oxytocin and emotion processing.

    PubMed

    Di Simplicio, Martina; Harmer, Catherine J

    2016-11-01

    Since the observation that oxytocin has key effects on social decision making, research on this exciting neuropeptide has doubled in volume: hundreds of studies have pursued the promise of a specific oxytocin action on high-level cognition and social function with wide potential translational implications (from autism to social anxiety to dementia). Here we review the evidence on whether the complex behavioural effects observed in humans after exogenous oxytocin administration build on changes in basic emotional information processing, in particular emotional facial expressions recognition, and attention and memory for emotionally-valenced stimuli.We observe that recent studies confirm a facilitatory effect of oxytocin to more accurate emotion processing, irrespective of emotion type. However, it remains unclear whether this action precedes, is independent of or even secondary to the neuropeptide promoting a greater salience of social stimuli. Overall, this growing research area has shown that oxytocin produces behavioural and neurofunctional outcomes that are highly dependent on the experimental context and on individual differences (gender, personality, life experiences). This poses an exciting challenge for future experimental medicine designs to address and unpack complex interactions between individual and context characteristic, which is needed for the development of more precise clinical applications.

  14. Male anorgasmia treated with oxytocin.

    PubMed

    Ishak, Waguih William; Berman, Daniel S; Peters, Anne

    2008-04-01

    Introduction. This is a case report on male anorgasmia that was successfully treated with oxytocin. Oxytocin is increased during arousal and peaks during orgasm. More recently, a study on humans published in Nature has shown its value in social bonding, increasing trust, and enhancing the sense of well-being. Aim. To test the effectiveness of administering oxytocin in a case of treatment-resistant anorgasmia. Methods. The patient underwent a biopsychosocial evaluation by a psychiatrist trained in sexual medicine and sex therapy for male orgasmic disorder, acquired type. Medical conditions, effect of substances, and psychological issues were ruled out. The patient was properly consented to using oxytocin as an off-label trial. Oxytocin was administered using a nasal spray intracoitally because of its ultra-short half-life. Results. Oxytocin was effective in restoring ejaculation. Conclusions. A case of treatment-resistant male anorgasmia was successfully treated with intracoital administration of intranasal oxytocin.

  15. Oxytocin receptor signalling.

    PubMed

    Devost, Dominic; Wrzal, Paulina; Zingg, Hans H

    2008-01-01

    The great diversity of the expression sites and proposed function of the oxytocin (OXT) receptor (OXTR) is paralleled by a diversity of its signalling pathways, many of which have still remained unexplored. We have used different approaches to discover novel pathways. By means of a phosphoproteomics approach, we have detected several distinct OXT-induced changes in tyrosine as well as threonine phosphorylation states of intracellular protein in myometrial cells. The most prominent change involved dephosphorylation of a 95-kDa phosphothreonine moiety. By N-terminal amino acid microsequence analysis, this moiety was shown to correspond to eukaryotic translation factor eEF2. This protein is a key regulator of protein synthesis and mediates, upon dephosphorylation, the translocation step of peptide chain elongation. These findings define a novel mechanism by which OXT assumes a so far unrecognized trophic function. We next elucidated the intracellular pathway(s) involved. We found that this effect is not mediated by any of the known pathways known to induce eEF2 dephosphorylation (mTOR, ERK1/2 or p38) but by protein kinase C. Consistent with this idea, we also found that direct stimulation of protein kinase C with a phorbol ester induced eEF2 dephosphorylation in myometrial cells. Using phosphoERK antibodies, we discovered by Western blotting that OXT induced phosphorylation of a higher molecular weight ERK-related protein. We were able to show that this band corresponded to "big MAP kinase1" or ERK5. ERK5 is part of a distinct MAPK cascade and promotes expression of the myosin light chain gene and plays an obligatory role in muscle cell development and differentiation. The role of ERK5 in myometrium has remained unexplored, but it is likely to represent an important novel pathway mediating OXT's effects on smooth muscle function. Further elucidation of these novel signalling pathways will have significant relevance for the development of novel pathway-specific OXTR

  16. 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.

  17. Real height analysis of ionograms - a generalized formulation

    SciTech Connect

    Titheridge, J.E.

    1988-10-01

    A new procedure is described for the calculation of real height profiles from ionospheric h(f) records. The equations are formulated in a way which can reproduce all current methods of analysis and provide many powerful extensions. For general use, a sixth-order overlapping polynomial analysis is recommended, with real height sections determined by a least squares fit to real and virtual height data. Coefficients can also be obtained for single polynomials fitted separately to each ionospheric layer. All methods include Chapman layer peaks and a model valley between layers. High-order, least squares calculations give greater accuracy and stability than any current procedures, and are particularly suitable for the analysis of high-density data from digital ionosondes. 33 references.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Tiotropium formulations and safety: a network meta-analysis

    PubMed Central

    Cazzola, Mario; Calzetta, Luigino; Rogliani, Paola; Matera, Maria Gabriella

    2016-01-01

    Tiotropium is now delivered via two different inhaler devices: the original Handihaler 18 μg once daily, which uses a powder formulation; and the newer Respimat Soft Mist Inhaler (SMI) 5 μg once daily. It has been questioned whether the two devices can be assumed to have the same safety profile, although the TIOSPIR trial showed that tiotropium when administered via Respimat SMI 5 μg is not less safe than Handihaler 18 μg. Therefore, we have carried out a safety evaluation of tiotropium Handihaler 18 µg versus tiotropium Respimat SMI 5 µg and 2.5 µg, via systematic review and network meta-analysis of the currently available clinical evidence. The results of our meta-analysis with an extremely large number of patients analysed demonstrate that the safety profile of tiotropium HandiHaler is generally superior to that of tiotropium Respimat SMI, although no statistical difference was detected between these two devices. However, the SUCRA analysis favoured tiotropium Respimat SMI with regards to serious adverse events (AEs). We do not believe that using Respimat SMI rather that HandiHaler exposes patients to higher risks of real AEs. Rather, we believe that there may be a different cardiovascular (CV) response to muscarinic receptors blockage in individual patients. Therefore, it will be essential to make all possible efforts to proactively identify patients at increased risk of CV AEs when treated with tiotropium or another antimuscarinic drug. PMID:28203364

  3. Partial differential equation transform - Variational formulation and Fourier analysis.

    PubMed

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

    2011-12-01

    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

  4. 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

  5. Oxytocin signalling in human myometrium.

    PubMed

    Phaneuf, S; Europe-Finner, G N; Carrasco, M P; Hamilton, C H; López Bernal, A

    1995-01-01

    A physiological role for oxytocin in stimulating uterine contractions during labour is well accepted, but has not yet been well defined. Oxytocin activates phospholipase C to produce inositol 1,4,5-trisphosphate, which releases Ca2+ from intracellular stores. There is considerable evidence that G-proteins are involved in this signalling pathway. The objectives of the present study were to determine the mechanisms of action of oxytocin in human myometrium. We have measured the effect of oxytocin on the formation of inositol phosphates (InsPs) in cultured human myometrial cells labelled with [3H] inositol and on changes in intracellular free Ca2+ concentration ([Ca2+i]) in single cells using a dynamic calcium imaging system. Pertussis toxin was used to obtain information on the G-proteins involved. Oxytocin induced InsPs formation and [Ca2+i] mobilisation in a concentration-dependent manner in human myometrial cells. Our data suggest that two distinct types of G-proteins are involved in the oxytocin response: one most probably a member of the Gq family (pertussis toxin-resistant) and another of the Gi family (pertussis toxin-sensitive). Using Western blotting, we have found that the pertussis toxin-resistant G-proteins alpha(q), alpha(11) and alpha(2), and pertussis toxin-sensitive alpha(i1), alpha(i2), and alpha(i3) are expressed in these cells. We have also detected the phospholipase C isoforms beta(1), beta(2) and beta(3) which are regulated by G-proteins, and phospholipase C isoforms gamma(1) and gamma(2), regulated by receptor tyrosine kinase pathways. However, oxytocin does not stimulate tyrosine phosphorylation in myometrial cells. Extracellular Ca2+ does not play a direct role in the activation of phospholipase C by oxytocin. Protein kinase C causes a strong inhibitory feedback on the oxytocin pathway: protein kinase C activators abolish the response to oxytocin while inhibitors potentiate it. Oxytocin responsiveness is upregulated by incubating the cells in

  6. The Impact of a Single Administration of Intranasal Oxytocin on the Recognition of Basic Emotions in Humans: A Meta-Analysis

    PubMed Central

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

    2013-01-01

    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. PMID:23575742

  7. 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.

  8. 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.

  9. Constitutive formulation and analysis of heel pad tissues mechanics.

    PubMed

    Natali, A N; Fontanella, C G; Carniel, E L

    2010-06-01

    This paper presents a visco-hyperelastic constitutive model developed to describe the biomechanical response of heel pad tissues. The model takes into account the typical features of the mechanical response such as large displacement, strain phenomena, and non-linear elasticity together with time-dependent effects. The constitutive model was formulated, starting from the analysis of the complex structural and micro-structural configuration of the tissues, to evaluate the relationship between tissue histology and mechanical properties. To define the constitutive model, experimental data from mechanical tests were analyzed. To obtain information about the mechanical response of the tissue so that the constitutive parameters could be established, data from both in vitro and in vivo tests were investigated. Specifically, the first evaluation of the constitutive parameters was performed by a coupled deterministic and stochastic optimization method, accounting for data from in vitro tests. The comparison of constitutive model results and experimental data confirmed the model's capability to describe the compression behaviour of the heel pad tissues, regarding both constant strain rate and stress relaxation tests. Based on the data from additional experimental tests, some of the constitutive parameters were modified in order to interpret the in vivo mechanical response of the heel pad tissues. This approach made it possible to interpret the actual mechanical function of the tissues.

  10. 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

  11. 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.

  12. Lack of association between human plasma oxytocin and interpersonal trust in a Prisoner's Dilemma paradigm.

    PubMed

    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.

  13. Numerical bifurcation analysis of conformal formulations of the Einstein constraints

    NASA Astrophysics Data System (ADS)

    Holst, M.; Kungurtsev, V.

    2011-12-01

    The Einstein constraint equations have been the subject of study for more than 50 years. The introduction of the conformal method in the 1970s as a parametrization of initial data for the Einstein equations led to increased interest in the development of a complete solution theory for the constraints, with the theory for constant mean curvature (CMC) spatial slices and closed manifolds completely developed by 1995. The first general non-CMC existence result was establish by Holst et al. in 2008, with extensions to rough data by Holst et al. in 2009, and to vacuum spacetimes by Maxwell in 2009. The non-CMC theory remains mostly open; moreover, recent work of Maxwell on specific symmetry models sheds light on fundamental nonuniqueness problems with the conformal method as a parametrization in non-CMC settings. In parallel with these mathematical developments, computational physicists have uncovered surprising behavior in numerical solutions to the extended conformal thin sandwich formulation of the Einstein constraints. In particular, numerical evidence suggests the existence of multiple solutions with a quadratic fold, and a recent analysis of a simplified model supports this conclusion. In this article, we examine this apparent bifurcation phenomena in a methodical way, using modern techniques in bifurcation theory and in numerical homotopy methods. We first review the evidence for the presence of bifurcation in the Hamiltonian constraint in the time-symmetric case. We give a brief introduction to the mathematical framework for analyzing bifurcation phenomena, and then develop the main ideas behind the construction of numerical homotopy, or path-following, methods in the analysis of bifurcation phenomena. We then apply the continuation software package AUTO to this problem, and verify the presence of the fold with homotopy-based numerical methods. We discuss these results and their physical significance, which lead to some interesting remaining questions to

  14. Intranasal Oxytocin: Myths and Delusions.

    PubMed

    Leng, Gareth; Ludwig, Mike

    2016-02-01

    Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best.

  15. Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: A detailed behavioral analysis with knockout female mice.

    PubMed

    Choleris, E; Ogawa, S; Kavaliers, M; Gustafsson, J-A; Korach, K S; Muglia, L J; Pfaff, D W

    2006-10-01

    Social recognition, processing, and retaining information about conspecific individuals is crucial for the development of normal social relationships. The neuropeptide oxytocin (OT) is necessary for social recognition in male and female mice, with its effects being modulated by estrogens in females. In previous studies, mice whose genes for the estrogen receptor-alpha (alpha-ERKO) and estrogen receptor-beta (beta-ERKO) as well as OTKO were knocked out failed to habituate to a repeatedly presented conspecific and to dishabituate when the familiar mouse is replaced by a novel animal (Choleris et al. 2003, Proc Natl Acad Sci USA 100, 6192-6197). However, a binary social discrimination assay, where animals are given a simultaneous choice between a familiar and a previously unknown individual, offers a more direct test of social recognition. Here, we used alpha-ERKO, beta-ERKO, and OTKO female mice in the binary social discrimination paradigm. Differently from their wild-type controls, when given a choice, the KO mice showed either reduced (beta-ERKO) or completely impaired (OTKO and alpha-ERKO) social discrimination. Detailed behavioral analyses indicate that all of the KO mice have reduced anxiety-related stretched approaches to the social stimulus with no overall impairment in horizontal and vertical activity, non-social investigation, and various other behaviors such as, self-grooming, digging, and inactivity. Therefore, the OT, ER-alpha, and ER-beta genes are necessary, to different degrees, for social discrimination and, thus, for the modulation of social behavior (e.g. aggression, affiliation).

  16. Oxytocin discontinuation after the active phase of labor is established.

    PubMed

    Vlachos, Dimitrios-Efthymios G; Pergialiotis, Vasilios; Papantoniou, Nikolaos; Trompoukis, Stamoulis; Vlachos, Georgios D

    2015-08-01

    Despite the widespread usage of oxytocin, there is still no consensus on its mode of administration. The scope of the present meta-analysis was to assess the effect of oxytocin discontinuation after the active phase of labor is established on maternal fetal and neonatal outcomes. We searched Medline, Scopus, Popline, ClinicalTrials.gov and Google Scholar databases. Eight studies were finally retrieved, which involved 1232 parturient. We observed significantly decreased rates of cesarean sections among parturient that discontinued oxytocin (OR 0.51, 95% CI 0.35, 0.74) as well as decreased rates of uterine hyperstimulation (OR 0.33, 95% CI 0.19, 0.58). Similarly, cases of non-reassuring fetal heart rates were fewer among women that did not receive oxytocin after the establishment of the active phase of labor (OR 0.63, 95% CI 0.41, 0.97). Keeping in mind the aforementioned maternal and neonatal adverse effects that seem to result from infusion of oxytocin until delivery, future practice should aim towards its discontinuation after the establishment of the active phase of labor, as it does not seem to influence the total duration of labor. Future studies should aim towards specific populations of parturient in order to clarify whether different approaches are needed.

  17. Water intoxication associated with oxytocin infusion

    PubMed Central

    Ahmad, Audrey J.; Clark, Elizabeth H.; Jacobs, Howard S.

    1975-01-01

    During a mid-trimester abortion with high dose oxytocin infusion and intravenous fluids, a patient developed an acute dilutational hyponatraemia and coma. The relationship of water intoxication and synthetic oxytocin infusion is discussed and the literature reviewed. PMID:1197156

  18. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food... Oxytocin injection. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b... Cows 0.5 to 1.0 10 to 20. Sows 0.25 to 1.0 5 to 20. (2) Indications for use. Oxytocin may be used as...

  19. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food... Oxytocin injection. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b... Cows 0.5 to 1.0 10 to 20. Sows 0.25 to 1.0 5 to 20. (2) Indications for use. Oxytocin may be used as...

  20. 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...

  1. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food... Oxytocin injection. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b... Cows 0.5 to 1.0 10 to 20. Sows 0.25 to 1.0 5 to 20. (2) Indications for use. Oxytocin may be used as...

  2. 21 CFR 522.1680 - Oxytocin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytocin. 522.1680 Section 522.1680 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b) Sponsors. See Nos. ,...

  3. 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.

  4. 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-...

  5. 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.

  6. Newborn Analgesia Mediated by Oxytocin during Delivery.

    PubMed

    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.

  7. Vasopressin/oxytocin and aggression.

    PubMed

    Ferris, Craig F

    2005-01-01

    Vasopressin/oxytocin and related peptides comprise a phylogenetically old superfamily of chemical signals in both vertebrates and invertebrates. Each peptide isoform has its own distinct receptor subtype and specific cellular action. The conservation and dispersion of vasopressin/oxytocin signalling systems across the animal kingdom attests to their functional significance in evolution. Indeed, they are involved in the physiology of fluid balance, carbohydrate metabolism, thermoregulation, immunity and reproduction. In addition, these peptides evolved a role in social behaviours related to aggression and affiliation. The focus of this chapter is the role of vasopressin/oxytocin as chemical signals in the brain altering aggressive responding in a context- and species-dependent manner. There is compelling evidence from several mammalian species including humans that vasopressin enhances aggression. The activity of the vasopressin appears linked to the serotonin system providing a mechanism for enhancing and suppressing aggressive behaviour.

  8. 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...

  9. 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

  10. 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.

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

    PubMed Central

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

    2015-01-01

    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

  12. 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.

  13. Canonical correlation analysis for multilabel classification: a least-squares formulation, extensions, and analysis.

    PubMed

    Sun, Liang; Ji, Shuiwang; Ye, Jieping

    2011-01-01

    Canonical Correlation Analysis (CCA) is a well-known technique for finding the correlations between two sets of multidimensional variables. It projects both sets of variables onto a lower-dimensional space in which they are maximally correlated. CCA is commonly applied for supervised dimensionality reduction in which the two sets of variables are derived from the data and the class labels, respectively. It is well-known that CCA can be formulated as a least-squares problem in the binary class case. However, the extension to the more general setting remains unclear. In this paper, we show that under a mild condition which tends to hold for high-dimensional data, CCA in the multilabel case can be formulated as a least-squares problem. Based on this equivalence relationship, efficient algorithms for solving least-squares problems can be applied to scale CCA to very large data sets. In addition, we propose several CCA extensions, including the sparse CCA formulation based on the 1-norm regularization. We further extend the least-squares formulation to partial least squares. In addition, we show that the CCA projection for one set of variables is independent of the regularization on the other set of multidimensional variables, providing new insights on the effect of regularization on CCA. We have conducted experiments using benchmark data sets. Experiments on multilabel data sets confirm the established equivalence relationships. Results also demonstrate the effectiveness and efficiency of the proposed CCA extensions.

  14. 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.

  15. 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

  16. 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.

  17. Integral Equation Formulation for the Analysis of Open-Ended Rectangular Waveguide Arrays on Cylindrical Surfaces

    NASA Astrophysics Data System (ADS)

    Gerini, G.; Visser, H. J.

    In this paper we present an efficient theoretical formulation for a full-wave analysis of phased arrays conformal to cylindrical structures. The theory is based on an integral equation formulation and the Unit Cell Approach. Thanks to its generality and efficiency, this method represents a good starting point for the development of accurate CAD tools for the analysis of integrated cylindrical structures including radome, coaxial excitations and tuning elements in waveguide.

  18. 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

  19. New variational bounds on convective transport. I. Formulation and analysis

    NASA Astrophysics Data System (ADS)

    Tobasco, Ian; Souza, Andre N.; Doering, Charles R.

    2016-11-01

    We study the maximal rate of scalar transport between parallel walls separated by distance h, by an incompressible fluid with scalar diffusion coefficient κ. Given velocity vector field u with intensity measured by the Péclet number Pe =h2 < | ∇ u |2 >1/2 / κ (where < . > is space-time average) the challenge is to determine the largest enhancement of wall-to-wall scalar flux over purely diffusive transport, i.e., the Nusselt number Nu . Variational formulations of the problem are presented and it is determined that Nu <= cPe 2 / 3 , where c is an absolute constant, as Pe -> ∞ . Moreover, this scaling for optimal transport-possibly modulo logarithmic corrections-is asymptotically sharp: admissible steady flows with Nu >=c' Pe 2 / 3 /[ log Pe ] 2 are constructed. The structure of (nearly) maximally transporting flow fields is discussed. Supported in part by National Science Foundation Graduate Research Fellowship DGE-0813964, awards OISE-0967140, PHY-1205219, DMS-1311833, and DMS-1515161, and the John Simon Guggenheim Memorial Foundation.

  20. 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.

  1. Concept Formulation, Part III: Analysis of Mentality. Cognitive Science Research No. 12.

    ERIC Educational Resources Information Center

    Bierschenk, Bernhard; Bierschenk, Inger

    This third of three articles on the ways in which people formulate their observations presents an analysis of the perspective or attitude dominating the discourse of an interview. The analysis is conducted according to a paradigm that views the speaker as the controller of discourse perspective. The relationships found in the analysis are…

  2. Role of oxytocin in energy metabolism.

    PubMed

    Chaves, Valéria Ernestânia; Tilelli, Cristiane Queixa; Brito, Nilton Almeida; Brito, Márcia Nascimento

    2013-07-01

    The basic mechanisms that lead obesity are not fully understood; however, several peptides undoubtedly play a role in regulating body weight. Obesity, a highly complex metabolic disorder, involves central mechanisms that control food intake and energy expenditure. Previous studies have shown that central or peripheral oxytocin administration induces anorexia. Recently, in an apparent discrepancy, rodents that were deficient in oxytocin or the oxytocin receptor were shown to develop late-onset obesity without changing their total food intake, which indicates the physiological importance of oxytocin to body metabolism. Oxytocin is synthesized not only within magnocellular and parvocellular neurons but also in several organs, including the ovary, uterus, placenta, testis, thymus, kidney, heart, blood vessels, and skin. The presence of oxytocin receptors in neurons, the myometrium and myoepithelial cells is well recognized; however, this receptor has also been identified in other tissues, including the pancreas and adipose tissue. The oxytocin receptor is a typical class I G protein-coupled receptor that is primarily linked to phospholipase C-β via Gq proteins but can also be coupled to other G proteins, leading to different functional effects. In this review, we summarize the present knowledge of the effects of oxytocin on controlling energy metabolism, focusing primarily on the role of oxytocin on appetite regulation, thermoregulation, and metabolic homeostasis.

  3. 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.

  4. Boundary formulations for sensitivity analysis without matrix derivatives

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  5. Biologically active macromolecular forms of oxytocin. [8-Lysine]oxytocin as a suitable ligand.

    PubMed Central

    Snell, C R; Smyth, D G

    1977-01-01

    [8-Lysine]oxytocin was synthesized on a solid support and possessed an oxytocic activity of 100 +/- 6 units mumol on the isolated rat uterus. The epsilon-carbamoyl, epsilon-3-carboxypropionyl and epsilon-3-carboxybutryl derivatives were prepared and had uterotonic activities of 400, 55 and 50 units/mumol respectively. [8-Lysine]oxytocin was coupled unambiguously through the epsilon-amino group to the carboxyl groups of carboxymethylated dextrans or epsilon-3-carboxypropionly-gelatin. The macromolecular oxytocins were water-soluble and retained signigicant oxytocic activity. [8-Lysine]oxytocin should prove a useful ligand for affinity chromatography of oxytocin-binding proteins. PMID:889573

  6. 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.

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

    PubMed Central

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

    2016-01-01

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

  8. Dopamine-oxytocin interactions in penile erection.

    PubMed

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

    2009-12-03

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

  9. 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.

  10. High speed cylindrical rolling element bearing analysis 'CYBEAN' - Analytic formulation

    NASA Technical Reports Server (NTRS)

    Kleckner, R. J.; Pirvics, J.; Castelli, V.

    1979-01-01

    This paper documents the analytic foundation and software architecture for the computerized mathematical simulation of high speed cylindrical rolling element bearing behavior. The software, CYBEAN (CYlindrical BEaring ANalysis), considers a flexible, variable geometry outer ring, EHD films, roller centrifugal and quasidynamic loads, roller tilt and skew, mounting fits, cage and flange interactions. The representation includes both steady state and time transient simulation of thermal interactions internal to and coupled with the surroundings of the bearing. A sample problem illustrating program use is presented.

  11. Thermal-structural finite element analysis using linear flux formulation

    NASA Technical Reports Server (NTRS)

    Pandey, Ajay K.; Dechaumphai, Pramote; Wieting, Allan R.

    1990-01-01

    A linear flux approach is developed for a finite element thermal-structural analysis of steady state thermal and structural problems. The element fluxes are assumed to vary linearly in the same form as the element unknown variables, and the finite element matrices are evaluated in closed form. Since numerical integration is avoided, significant computational time saving is achieved. Solution accuracy and computational speed improvements are demonstrated by solving several two and three dimensional thermal-structural examples.

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

    PubMed

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

    2015-02-01

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

  13. Oxytocin enhances social persuasion during hypnosis.

    PubMed

    Bryant, Richard A; Hung, Lynette

    2013-01-01

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

  14. Oxytocin plasma concentrations after single intranasal oxytocin administration - a study in healthy men.

    PubMed

    Gossen, A; Hahn, A; Westphal, L; Prinz, S; Schultz, R T; Gründer, G; Spreckelmeyer, K N

    2012-10-01

    The neuropeptide oxytocin has become a subject of great interest in studies investigating human social cognition. Single intranasal administration of the hormone has been reported to have positive behavioral effects, such as increasing trust or facilitating social approach, 45-80 min after administration. However, little is still known about the long-term pharmacokinetics of oxytocin nasal spray application in humans. This study addressed the question how long oxytocin plasma levels remain elevated following nasal spray administration. Another goal was to examine the influence of oxytocin administration on endogenous steroid hormones since such alterations might modulate social behavior via an indirect way. Eight healthy Caucasian men were challenged with a single intranasal application of 26 international units of oxytocin. Changes in oxytocin blood plasma levels, as well as steroid hormone levels of progesterone, testosterone and estradiol were assessed at 5 consecutive time points over a period of 3.5 h (-5, +30, +90, +150, +210 min relative to oxytocin administration). Results gave evidence for a substantial rise of oxytocin plasma levels 30 min after intranasal administration, observed in 7 of 8 participants. Group mean oxytocin plasma level was found to have returned to baseline already 90 min post administration, though in some individuals the plasma levels was still elevated relative to sampling at post 150 min. Steroid hormone analyses yielded a slight augmentation of endogenous testosterone levels 210 min after oxytocin administration. Our data confirms previous findings that oxytocin administered as a nasal spray enters the blood circulation, elevating oxytocin plasma levels for a limited time. Our findings suggest that this time window differs between individuals, but that, for the used dose, it does not extend beyond 150 min post administration. The data further provides preliminary evidence that intranasal oxytocin has an enhancing effect on

  15. 17β-estradiol upregulates oxytocin and the oxytocin receptor in C2C12 myotubes

    PubMed Central

    Berio, Enrica; Starvaggi Cucuzza, Laura; Biolatti, Bartolomeo; Cannizzo, Francesca Tiziana

    2017-01-01

    Background The endocrinology of skeletal muscle is highly complex and many issues about hormone action in skeletal muscle are still unresolved. Aim of the work is to improve our knowledge on the relationship between skeletal muscle and 17β-estradiol. Methods The skeletal muscle cell line C2C12 was treated with 17β-estradiol, the oxytocin peptide and a combination of the two hormones. The mRNA levels of myogenic regulatory factors, myosin heavy chain, oxytocin, oxytocin receptor and adipogenic factors were analysed in C2C12 myotubes. Results It was demonstrated that C2C12 myoblasts and myotubes express oxytocin and its receptor, in particular the receptor levels physiologically increase in differentiated myotubes. Myotubes treated with 17β-estradiol overexpressed oxytocin and oxytocin receptor genes by approximately 3- and 29-fold, respectively. A decrease in the expression of fatty acid binding protein 4 (0.62-fold), a fat metabolism-associated gene, was observed in oxytocin-treated myotubes. On the contrary, fatty acid binding protein 4 was upregulated (2.66-fold) after the administration of the combination of 17β-estradiol and oxytocin. 17β-estradiol regulates oxytocin and its receptor in skeletal muscle cells and they act in a synergic way on fatty acid metabolism. Discussion Oxytocin and its receptor are physiologically regulated along differentiation. 17β-estradiol regulates oxytocin and its receptor in skeletal muscle cells. 17β-estradiol and oxytocin act in a synergic way on fatty acid metabolism. A better understanding of the regulation of skeletal muscle homeostasis by estrogens and oxytocin peptide could contribute to increase our knowledge of muscle and its metabolism. PMID:28382233

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

    PubMed

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

    2013-05-01

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

  17. 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

  18. 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

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

    NASA Technical Reports Server (NTRS)

    Gabriele, A.; Loewy, R.

    1981-01-01

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

  20. 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.

  1. 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.

  2. Oxytocin for frontotemporal dementia: a systematic review

    PubMed Central

    Tampi, Rajesh R.; Maksimowski, Michael; Ahmed, Mohsina; Tampi, Deena J.

    2016-01-01

    Background: The aim of this systematic review is to identify published randomized controlled trials (RCTs) that evaluated the use of oxytocin in individuals with frontotemporal dementia (FTD). Methods: A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs in any language that evaluated the use of oxytocin in individuals with FTD. Bibliographic databases of published articles were also searched for additional studies. Results: A total of two RCTs that evaluated the use of oxytocin in individuals with FTD were identified. In one study, the use of oxytocin in individuals with FTD produced a reduction in identification of negative facial expressions (anger and fear) which can be hypothesized to improve trust and increase cooperation in these individuals. Both studies noted oxytocin was well tolerated and showed short term benefits on behavioral symptoms in individuals with FTD. Conclusions: Oxytocin appears to improve social aspects of cognition and behavioral symptoms in individuals with FTD and is well tolerated. However, positive data from larger and longer duration RCTs are needed before the routine use of oxytocin in individuals with FTD can be recommended. PMID:28101324

  3. Von Neumann stability analysis of the u- p reproducing kernel formulation for saturated porous media

    NASA Astrophysics Data System (ADS)

    Chi, Sheng-Wei; Siriaksorn, Thanakorn; Lin, Shih-Po

    2017-02-01

    This paper introduces the von Neumann method to investigate the temporal stability of the displacement-pressure (u{-}p) reproducing kernel formulation for saturated porous media. Both dynamic and quasi-static formulations are considered and the critical time steps are derived. The effect of lumped and consistent matrices on temporal stability is analyzed under explicit temporal discretization. It is shown that lumped matrices have better temporal stability than consistent matrices. The study also shows that nodal support size greatly affects the critical time step size of the formulations. For consistent matrices, larger support size results in smaller critical time step size; however, opposite relation occurs if lumped scheme is used. The numerical study shows that stabilization parameter of the stabilized nodal integration methods reduces the critical time step size. Transient analyses are performed to verify the results from von Neumann analysis.

  4. Latent structure analysis in pharmaceutical formulations using Kohonen's self-organizing map and a Bayesian network.

    PubMed

    Kikuchi, Shingo; Onuki, Yoshinori; Yasuda, Akihito; Hayashi, Yoshihiro; Takayama, Kozo

    2011-03-01

    A latent structure analysis of pharmaceutical formulations was performed using Kohonen's self-organizing map (SOM) and a Bayesian network. A hydrophilic matrix tablet containing diltiazem hydrochloride (DTZ), a highly water-soluble model drug, was used as a model formulation. Nonlinear relationship correlations among formulation factors (oppositely charged dextran derivatives and hydroxypropyl methylcellulose), latent variables (turbidity and viscosity of the polymer mixtures and binding affinity of DTZ to polymers), and release properties [50% dissolution times (t50s) and similarity factor] were clearly visualized by self organizing feature maps. The quantities of dextran derivatives forming polyion complexes were strongly related to the binding affinity of DTZ to polymers and t50s. The latent variables were classified into five characteristic clusters with similar properties by SOM clustering. The probabilistic graphical model of the latent structure was successfully constructed using a Bayesian network. The causal relationships among the factors were quantitatively estimated by inferring conditional probability distributions. Moreover, these causal relationships estimated by the Bayesian network coincided well with estimations by SOM clustering, and the probabilistic graphical model was reflected in the characteristics of SOM clusters. These techniques provide a better understanding of the latent structure between formulation factors and responses in DTZ hydrophilic matrix tablet formulations.

  5. 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.

  6. 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.

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

    PubMed

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

    2006-11-01

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

  8. 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

  9. 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.

  10. Elastoplastic buckling analysis of cylindrical shells using a semi-analytical formulation

    NASA Astrophysics Data System (ADS)

    Deerenberg, E.

    1994-10-01

    In this thesis, a semi-analytical formulation for the buckling analysis of circular cylindrical shells is described that takes into account the combined effects of initial geometric imperfections, elastoplastic material behavior and boundary conditions. The model is based on small strains-moderate rotations shell theory. The governing equations are formulated as a coupled set of first-order ordinary differential and algebraic equations. The basic variables in these equations are the variables that can be prescribed at the shell edges. The model described in this thesis is valid for cylinders with a multi-layer wall construction that may be loaded by axial compression, external pressure and/or torsion. The governing differential/algebraic equations are solved using Newton-type iteration methods. Separate equations are formulated for the bifurcation analysis of axisymmetric prebuckling states and an efficient solution method for the eigenvalue problem is described. The correctness of the formulation is checked by analyzing a number of elastic and elastoplastic buckling problems of perfect and imperfect shells.

  11. 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.

  12. 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.

  13. 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.

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

    PubMed Central

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

    2016-01-01

    The electrochemical detection of oxytocin using boron-doped diamond (BDD) electrodes was studied. Cyclic voltammetry of oxytocin in a phosphate buffer solution exhibits an oxidation peak at +0.7 V (vs. Ag/AgCl), which is attributable to oxidation of the phenolic group in the tyrosyl moiety. Furthermore, the linearity of the current peaks obtained in flow injection analysis (FIA) using BDD microelectrodes over the oxytocin concentration range from 0.1 to 10.0 μM with a detection limit of 50 nM (S/N = 3) was high (R2 = 0.995). Although the voltammograms of oxytocin and vasopressin observed with an as-deposited BDD electrode, as well as with a cathodically-reduced BDD electrode, were similar, a clear distinction was observed with anodically-oxidized BDD electrodes due to the attractive interaction between vasopressin and the oxidized BDD surface. By means of this distinction, selective measurements using chronoamperometry combined with flow injection analysis at an optimized potential were demonstrated, indicating the possibility of making selective in situ or in vivo measurements of oxytocin. PMID:27599852

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

    PubMed

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

    2014-01-01

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

  16. Physiology of invertebrate oxytocin and vasopressin neuropeptides

    PubMed Central

    Gruber, Christian W

    2014-01-01

    New findings • What is the topic of this review? This article describes the discovery and function of invertebrate oxytocin and vasopressin neuropeptides. • What advances does it highlight? The novel discovery of oxytocin-like peptides in arthropods is described. An up-to date overview is gven of the functional role (physiology and behaviour) of oxytocin and vasopressin signalling. The application of natural peptides for drug development is discussed. Neuropeptides and regulatory peptide hormones control many developmental, physiological and behavioural processes in animals, including humans. The nonapeptides oxytocin and arginine vasopressin are produced and released by the pituitary gland and have actions on many organs and tissues. Receptive cells possess particular receptors to which the peptides bind as ligands, leading to activation of G-protein-coupled receptors, hence cellular responses. In humans and other mammalian species, oxytocin and vasopressin mediate a range of peripheral and central physiological functions that are important for osmoregulation, reproduction, complex social behaviours, memory and learning. The origin of the oxytocin/vasopressin signalling system is thought to date back more than 600 million years. All vertebrate oxytocin- and vasopressin-like peptides have presumably evolved from the ancestral nonapeptide vasotocin by gene duplication and today are present in vertebrates, including mammals, birds, reptiles, amphibians and fish. Oxytocin- and vasopressin-like peptides have been identified in several invertebrate species, including molluscs, annelids, nematodes and arthropods. Members of this peptide family share high sequence similarity, and it is possible that they are functionally related across the entire animal kingdom. However, it is evident that not all animals express oxytocin/vasopressin neuropeptides and that there is little information available about the biology and physiology of this signalling system of invertebrates

  17. Physiology of invertebrate oxytocin and vasopressin neuropeptides.

    PubMed

    Gruber, Christian W

    2014-01-01

    Neuropeptides and regulatory peptide hormones control many developmental, physiological and behavioural processes in animals, including humans. The nonapeptides oxytocin and arginine vasopressin are produced and released by the pituitary gland and have actions on many organs and tissues. Receptive cells possess particular receptors to which the peptides bind as ligands, leading to activation of G-protein-coupled receptors, hence cellular responses. In humans and other mammalian species, oxytocin and vasopressin mediate a range of peripheral and central physiological functions that are important for osmoregulation, reproduction, complex social behaviours, memory and learning. The origin of the oxytocin/vasopressin signalling system is thought to date back more than 600 million years. All vertebrate oxytocin- and vasopressin-like peptides have presumably evolved from the ancestral nonapeptide vasotocin by gene duplication and today are present in vertebrates, including mammals, birds, reptiles, amphibians and fish. Oxytocin- and vasopressin-like peptides have been identified in several invertebrate species, including molluscs, annelids, nematodes and arthropods. Members of this peptide family share high sequence similarity, and it is possible that they are functionally related across the entire animal kingdom. However, it is evident that not all animals express oxytocin/vasopressin neuropeptides and that there is little information available about the biology and physiology of this signalling system of invertebrates and, in particular, of insects, which represent more than half of all known living organisms. This report describes the discovery of novel oxytocin- and vasopressin-like peptides in arthropods and summarizes the status quo of the functional relevance of this neuropeptide signalling system in invertebrates, which will have beneficial implications for the design of selective and potent ligands to human oxytocin and vasopressin receptors.

  18. Estrogen increases renal oxytocin receptor gene expression.

    PubMed

    Ostrowski, N L; Young, W S; Lolait, S J

    1995-04-01

    Estrogens have been implicated in the sodium and fluid imbalances associated with the menstrual cycle and late pregnancy. An estrogen-dependent role for renal oxytocin receptors in fluid homeostasis is suggested by the present findings which demonstrate that estradiol benzoate treatment increases the expression of the oxytocin receptor messenger ribonucleic acid and 125I-OTA binding to oxytocin receptors in the renal cortex and medullary collecting ducts of ovariectomized female rats. Moreover, estradiol induced high levels of oxytocin receptor expression in outer stripe proximal tubules of ovariectomized female and adrenalectomized male rats. Proximal tubule induction was inhibited in a dose-dependent manner by the antiestrogen tamoxifen, but cortical expression of oxytocin receptors in macula densa cells was unaffected by tamoxifen. These data demonstrate cell-specific regulation of oxytocin receptor expression in macula densa and proximal tubule cells, and suggest a important role for these receptors in mediating estrogen-induced alterations in renal fluid dynamics by possibly affecting glomerular filtration and water and solute reabsorption during high estrogen states.

  19. Factorial analysis of the binding properties of acetylated ginger starch in metronidazole tablet formulations

    PubMed Central

    Bamiro, Oluyemisi Adebowale; Duro-Emanuel, Abioye Josephina

    2017-01-01

    Introduction: The delivery of drug is often affected by formulation processes and the excipients used in the formulation. Materials and Methods: A 23 factorial analysis was used in this study to evaluate the effect of acetylated ginger starch (AGS) (Zingiber officinale) as a binder in metronidazole tablets, in comparison to corn starch (CS) BP. The individual and interacting effects of variables (binder type X1, binder concentration X2, and compression pressure X3) used on tablet properties such as friability, crushing strength, crushing strength friability ratio (CSFR), disintegration and crushing strength friability/disintegration time ratio (CSFR/DT) were determined. The effect of these binders on the granule properties using Hausner's ratio, Carr's index (CI), angle of repose, and densities as response parameters was also determined. Results: Granules prepared with AGS had high densities and small granule sizes when compared with those containing CS. Granules containing CS have better flow properties. X1 (binder type) has a significant effect on the crushing strength of the tablet. It also had the highest effects on CSFR and CSFR/DT. The combination of XIX3 had the highest effect on crushing strength and DT. Conclusion: This study shows that, in formulations, care must be taken in choosing the excipients and the process parameters required for the formulation since these can affect the delivery of the drug individually or in combination. AGS could be useful as a binder when a tablet with low crushing strength and fast disintegration is desired.

  20. Analysis of aromatic polyamine mixtures for formulation of LARC-160 resin

    NASA Technical Reports Server (NTRS)

    Young, P. R.; Sykes, G. F.

    1980-01-01

    An investigation was conducted to identify a potential substitute for the aromatic polyamine mixture, Jeffamine AP-22, currently used to formulate LARC-160 polyimide precursor resin. Jeffamine AP-22 was characterized by high pressure liquid chromatography and mass spectrometry. Eleven different aromatic amines in the mixture were isolated and identified. Subsequent liquid chromatographic analysis of nine additional commercially available aromatic polyamine mixtures identified three candidates that are similar in composition to AP-22.

  1. 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.

  2. Effect of oxytocin on expression of cytosolic phospholipase A2 mRNA and protein in ovine endometrial tissue in vivo.

    PubMed

    Burns, P D; Graf, G A; Hayes, S H; Silvia, W J

    2000-11-01

    The induction of endometrial prostaglandin (PG) F2alpha synthesis by oxytocin is dependent upon activation of phospholipase (PL) A2 and mobilization of arachidonic acid. The objective of this study was to determine if oxytocin stimulates PGF2alpha synthesis by inducing synthesis of cytosolic PLA2 (cPLA2). In Experiment 1, 15 ovariectomized ewes were given progesterone and estradiol to simulate an estrous cycle. Ewes were then given an injection of oxytocin on Day 14 of the simulated estrous cycle. Jugular blood samples were collected and assayed for 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Uteri were collected at 0, 7.5, 25, 90, or 240 min postinjection (n = 3 ewes/time point). Total RNA was isolated from caruncular endometrium and subjected to dot-blot analysis. Oxytocin induced a rapid and transient increase in serum PGFM (P < 0.01). However, endometrial concentrations of cPLA2 mRNA did not change following oxytocin administration (P > 0.10). In Experiment 2, 11 ovary-intact ewes were given oxytocin (n = 5) or saline (n = 6) on Day 15 after estrus. Jugular blood samples were collected and assayed for serum concentrations of PGFM. Uteri were collected at 15 min postinjection. Homogenates were prepared from caruncular endometrium and subjected to Western blot analysis. Concentrations of PGFM were higher in oxytocin treated ewes compared to saline treated ewes at 15 min postinjection (P < 0.01). Endometrial concentrations of cPLA2 protein were greater in the cytosolic than in the microsomal fraction (P < 0.01). Oxytocin did not affect the amount of cPLA2 protein in either fraction (P > 0.10). In conclusion, oxytocin did not effect expression of either cPLA2 mRNA or protein in ovine endometrium. Oxytocin may stimulate PGF2alpha synthesis by activating cPLA2 protein that is already present in an inactive form.

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

    PubMed

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

    2015-01-01

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

  4. Oxytocin Enables Maternal Behavior by Balancing Cortical Inhibition

    PubMed Central

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

    2015-01-01

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

  5. [Oxytocin model of formation of psychotic symptoms and its implications for research on oxytocinergic pathway in schizophrenia].

    PubMed

    Holka-Pokorska, Justyna; Jarema, Marek

    2014-01-01

    There are more and more data to support the dysregulation of the oxytocinergic pathway in schizophrenia. The development of the above branch of knowledge began to evolve alongside the mainstream of studies concerning gene polymorphisms for dopaminergic, glutamatergic and serotoninergic systems. Both experimental studies and clinical trials have demonstrated an antipsychotic effect of oxytocin. Starting with the pioneering neuroendocrinobehavioral experiment which demonstrated that oxytocin nasal spray increases the level of trust in healthy volunteers dozens of experiments were carried out confirming the modulatory role of oxytocin for the recognition of emotion, social memory, pro-social behaviours, collaborative behaviours and behaviours that require generosity and altruism. According to,oxytocin model' of development of psychotic symptoms--oxytocinergic system dysregulation may affect the incorrect attribution of meaning of emotional information from the environment. This can be manifested in the form of social cognition dysfunction and leads to abnormal social behaviour as withdrawal from social contact, isolation and formulation of paranoid delusions. From the clinical psychiatry point of view it became crucially need for research on selective oxytocin receptor agonists, as they may be used in the treatment of diseases which manifest in social withdrawal, lack of trust and the absence of affiliation behaviour as in schizophrenia.

  6. 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.

  7. Development of an HPLC method for the analysis of Apomine in a topical cream formulation.

    PubMed

    Kuehl, Philip J; Angersbach, B Steven; Stratton, Steven P; Myrdal, Paul B

    2006-03-03

    A stability indicating, reversed-phase high performance liquid chromatographic method was developed for the quantification of Apomine, tetraisopropyl 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-ethyl-1, 1-bisphosphonate, in a topical cream formulation. Analysis of Apomine in the cream formulation was performed through a dilution of the cream base with tetrahydrofuran. This allowed the current method to bypass extraction and/or centrifugation for direct injection and analysis. Separation was achieved using an Alltima C18 5 microm, 150 mm x 2.1 mm column and employed a gradient procedure, beginning with acetonitrile-water (65:35, v/v), at 0.6 mL/min for 9 min, followed by a rinse with isopropyl alcohol for 9 min. The complete gradient method has been optimized to separate Apomine from the nonpolar cream components, wash and equilibrate the column in a 30-min assay. This report demonstrates that this method is effective for quantification of Apomine in a cream formulation.

  8. 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.

  9. 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

  10. Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial

    PubMed Central

    Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

    2015-01-01

    The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using 1H-magnetic resonance spectroscopy (1H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and 1H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC. PMID:25070538

  11. Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.

    PubMed

    Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

    2015-04-01

    The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.

  12. 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

  13. 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

  14. 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.

  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. 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

  17. 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.

  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. 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.

  20. Oxytocin nasal spray in fibromyalgic patients.

    PubMed

    Mameli, S; Pisanu, G M; Sardo, S; Marchi, A; Pili, A; Carboni, M; Minerba, L; Trincas, G; Carta, M G; Melis, M R; Agabio, R

    2014-08-01

    Fibromyalgia is a pain disorder associated with frequent comorbid mood, anxiety, and sleep disorders. Despite the frequent use of a complex, poly-drug pharmacotherapy, treatment for fibromyalgia is of limited efficacy. Oxytocin has been reported to reduce the severity of pain, anxiety, and depression, and improve the quality of sleep, suggesting that it may be useful to treat fibromyalgia. To evaluate this hypothesis, 14 women affected by fibromyalgia and comorbid disorders, assuming a complex pharmacotherapy, were enrolled in a double-blind, crossover, randomized trial to receive oxytocin and placebo nasal spray daily for 3 weeks for each treatment. Order of treatment (placebo-oxytocin or oxytocin-placebo) was randomly assigned. Patients were visited once a week. At each visit, the following instruments were administered: an adverse drug reaction record card, Visual Analog Scale of Pain Intensity, Spielberger State Anxiety Inventory, Zung Self-rating Depression Scale, and SF-12. Women self-registered painkiller assumption, pain severity, and quality of sleep in a diary. Unlikely, oxytocin nasal spray (80 IU a day) did not induce positive therapeutic effects but resulted to be safe, devoid of toxicity, and easy to handle.

  1. Oxytocin as a moderator of hypnotizability.

    PubMed

    Bryant, Richard A; Hung, Lynette; Guastella, Adam J; Mitchell, Philip B

    2012-01-01

    Since hypnosis was popularly recognized in the nineteenth century, the phenomenon of hypnotizability has remained poorly understood. The capacity to increase hypnotizability has important implications because it may increase the number of people who can benefit from hypnotic interventions for psychological and medical conditions. Current theories emphasize that rapport between hypnotist and subject is pivotal to motivate the respondent to engage in strategies that allows them to suspend reality and respond to suggestions. The neuropeptide oxytocin is implicated in social bonding, and enhances a range of social behaviors in animals and humans. This study tested the proposal that oxytocin administration, which enhances social bonding in humans, may enhance hypnotic responding by administering intranasal spray of oxytocin or placebo prior to hypnosis in 40 low hypnotizable male subjects. When low hypnotizable individuals were administered oxytocin via nasal spray, their level of hypnotic responding increased significantly compared to hypnotic responding levels prior to oxytocin administration. This is the first demonstration of a neurochemical basis for hypnotic responding, and points to a potential neural mechanism to explain hypnotizability.

  2. Oxytocin, Motivation and the Role of Dopamine

    PubMed Central

    Love, Tiffany M.

    2013-01-01

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

  3. Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants

    PubMed Central

    Fewtrell, M S; Loh, K L; Blake, A; Ridout, D A; Hawdon, J

    2006-01-01

    Background Human milk has considerable short and long term benefits for preterm infants, but mothers may experience difficulties in expressing breast milk for infants too immature or sick to breast feed. Oxytocin has been used to assist breast feeding and milk expression, but few data are available to support this intervention in the neonatal unit setting. Aim To test the hypothesis that oxytocin nasal spray increases early milk output in mothers expressing milk for preterm infants. Methods A randomised, double blind trial of oxytocin nasal spray (100 µl per dose) versus placebo was conducted in mothers delivering infants <35 weeks gestation. Sprays were used before expression of milk using an electric pump up to day 5. Main outcome Total weight of milk expressed while using spray (study powered to detect >1SD difference between groups). Secondary outcomes Pattern of milk production; number of pumping sessions; weight/fat content of milk expressed during a fixed 20 minute period on day 5 (“physiological study”); mother's opinion of expressing and spray assessed by questionnaire. Results Fifty one mothers were randomised (27 oxytocin, 24 placebo). Total milk production did not differ between groups. Repeated measures analysis of variance suggested significantly (p  =  0.001) different patterns of milk production, with initial faster production in the oxytocin group then convergence between groups. Parity did not influence the response to the intervention. No significant differences were seen in milk weight or fat content in the physiological study nor in mothers' opinions of milk expression and treatment. Conclusions Despite marginal differences in the pattern of early milk production, the use of oxytocin nasal spray did not significantly improve outcome. Most mothers believed they were receiving the active spray, suggesting a significant placebo effect (supported by limited data from historical controls) and benefits from the extra breast feeding

  4. 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

  5. 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.

  6. Quantitative determination of sibutramine in adulterated herbal slimming formulations by TLC-image analysis method.

    PubMed

    Phattanawasin, Panadda; Sotanaphun, Uthai; Sukwattanasinit, Tasamaporn; Akkarawaranthorn, Jariya; Kitchaiya, Sarunyaporn

    2012-06-10

    A simple thin layer chromatographic (TLC)-image analysis method was developed for rapid determination and quantitation of sibutramine hydrochloride (SH) adulterated in herbal slimming products. Chromatographic separation of SH was achieved on a silica gel 60 F(254) TLC plate, using toluene-n-hexane-diethylamine (9:1:0.3, v/v/v) as the mobile phase and Dragendorff reagent as spot detection. Image analysis of the scanned TLC plate was performed to quantify the amount of SH. The polynomial regression data for the calibration plots showed good linear relationship in the concentration range of 1-6 μg/spot. The limits of detection and quantitation were 190 and 634 ng/spot, respectively. The method gave satisfactory specificity, precision, accuracy, robustness and was applied for determination of SH in herbal formulations. The contents of SH in adulterated samples determined by the TLC-image analysis and TLC-densitometry were also compared.

  7. Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques.

    PubMed

    Modi, Meera E; Connor-Stroud, Fawn; Landgraf, Rainer; Young, Larry J; Parr, Lisa A

    2014-07-01

    Intranasal (IN) administration is a widely used method for examining the effect of oxytocin (OT) on social behavior and cognition in healthy subjects and psychiatric populations. IN-OT in humans enhances trust, emotional perception, and empathetic behavior and is under investigation as a potential pharmacotherapy to enhance social functioning in a variety of neuropsychiatric disorders, including autism spectrum disorders (ASD). Nonhuman primates (NHP) are an important model for understanding the effect of OT on social cognition, its neural mechanisms, and the development of IN-OT as a pharmacotherapy for treating social deficits in humans. However, NHP and even some human populations, such as very young infants and children, cannot easily follow the detailed self-administration protocol used in the majority of human IN-OT studies. Therefore, we evaluated the efficacy of several OT-administration routes for elevating central OT concentrations in rhesus macaques. First, we examined the effect of IN and intravenous (IV) routes of OT administration on concentrations of OT and vasopressin (AVP) in plasma and lumbar CSF. Second, we examined these same measures in monkeys after an aerosolized (AE) OT delivery route. All three administration routes significantly increased plasma OT concentrations, but only the AE-OT route significantly increased concentrations of CSF OT. No route affected concentrations of AVP in plasma or CSF. This study confirms that the AE route is the most effective method for increasing central OT concentrations in monkeys, and may also be an effective route, alternative to IN, for administering OT to some human populations.

  8. 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

  9. 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.

  10. Optimized and validated flow-injection spectrophotometric analysis of topiramate, piracetam and levetiracetam in pharmaceutical formulations.

    PubMed

    Hadad, Ghada M; Abdel-Salam, Randa A; Emara, Samy

    2011-12-01

    Application of a sensitive and rapid flow injection analysis (FIA) method for determination of topiramate, piracetam, and levetiracetam in pharmaceutical formulations has been investigated. The method is based on the reaction with ortho-phtalaldehyde and 2-mercaptoethanol in a basic buffer and measurement of absorbance at 295 nm under flow conditions. Variables affecting the determination such as sample injection volume, pH, ionic strength, reagent concentrations, flow rate of reagent and other FIA parameters were optimized to produce the most sensitive and reproducible results using a quarter-fraction factorial design, for five factors at two levels. Also, the method has been optimized and fully validated in terms of linearity and range, limit of detection and quantitation, precision, selectivity and accuracy. The method was successfully applied to the analysis of pharmaceutical preparations.

  11. 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.

  12. Quantitative Analysis for Monitoring Formulation of Lubricating Oil Using Terahertz Time-Domain Transmission Spectroscopy

    NASA Astrophysics Data System (ADS)

    Tian, Lu; Zhao, Kun; Zhou, Qing-Li; Shi, Yu-Lei; Zhang, Cun-Lin

    2012-04-01

    The quantitative analysis of zinc isopropyl-isooctyl-dithiophosphate (T204) mixed with lube base oil from Korea with viscosity index 70 (T204-Korea70) is presented by using terahertz time-domain spectroscopy (THz-TDS). Compared with the middle-infrared spectra of zinc n-butyl-isooctyl-dithiophosphate (T202) and T204, THz spectra of T202 and T204 show the weak broad absorption bands. Then, the absorption coefficients of the T204-Korea70 system follow Beer's law at the concentration from 0.124 to 4.024%. The experimental absorption spectra of T204-Korea70 agree with the calculated ones based on the standard absorption coefficients of T204 and Korea70. The quantitative analysis enables a strategy to monitor the formulation of lubricating oil in real time.

  13. Role of oxytocin/oxytocin receptor system in regulation of cell growth and neoplastic processes.

    PubMed

    Strunecká, A; Hynie, S; Klenerová, V

    2009-01-01

    Novel sites of oxytocin receptor expression have recently been detected in central nervous system, cardiomyocytes, endothelial cells, various carcinoma cells, etc. These and other discoveries have greatly expanded the classical biological roles of oxytocin, which are stimulation of uterine smooth muscle contraction at parturition and milk ejection during lactation. It is becoming clear that the great diversity of oxytocin actions in the brain and peripheral organs is paralleled by activation of a diversity of signalling pathways. On the other hand, until now only one single oxytocin receptor type has been detected. This receptor belongs to G protein-coupled receptors and in dependence on cell conditions it binds to different G proteins; this phenomenon is called receptor-G protein promiscuity. Thus, in the same cells oxytocin can activate multiple responses at the same time. Recently, the oxytocinergic system has also been implicated in the growth modulation of various neoplastic cells, where it may inhibit or stimulate cell proliferation in dependence on cell type and activated metabolic pathways. The discovery of novel oxytocin receptor-linked signalling cascades brings interesting knowledge opening new avenues for research in oncology and molecular pharmacology with perspectives of finding new therapeutic agents.

  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. A semi-analytical formulation for the elastoplastic analysis of imperfect cylindrical shells

    NASA Astrophysics Data System (ADS)

    Deerenberg, E.

    1991-12-01

    A semi-analytical formulation for the elastoplastic analysis of initially imperfect cylindrical shells under axial compression and lateral pressure was developed. The formulation is based on a small strain, moderate rotation shell theory and small strain incremental constitutive theory. The basic shell equations and the partially inverted constitutive relations in total form are reduced to a set of coupled nonlinear algebraic/ordinary differential equations by means of a Fourier decomposition of the state variables, imperfections and loads in circumferential direction of the shell, and application of Galerkin's method. The governing nonlinear equations are solved with an incremental iterative technique. The method of quasilinearization is used to generate the governing equations of the iterative procedure which consistently takes into account both geometrical and material nonlinearities. Plasticity effects are described using a layered approach. The classical flow theory based on the von Mises yield surface, associative flow rule, and the isotropic hardening law is used to describe the evolution of the plastic strains in the integration points. In every iteration a set of linear ordinary differential equations is solved numerically with a shooting method and a return mapping algorithm is used to integrate the constitutive equations locally. A number of elastic and elastoplastic buckling problems are solved for which results are known from literature. It is shown that the quadratic rate of convergence, characteristic for a Newton type iteration procedure, is retained even for large load steps. A comparison between the present results and the results from literature shows a good agreement.

  17. HPTLC densitometric method for analysis of thymoquinone in Nigella sativa extracts and marketed formulations

    PubMed Central

    Alam, Prawez; Yusufoglu, Hasan; Alam, Aftab

    2013-01-01

    Objective To develop a sensitive and accurate high-performance thin layer chromatography method and to determine the quantity of thymoquinone in in two different N. sativa extracts and marketed formulations. Methods Thymoquinone was seperated on aluminum-backed silica gel 60 F254 plates with n-hexane-ethyl acetate 8:2 (%, v/v) as mobile phase. Results A compact band was obtained for thymoquinone at Rf value of 0.48±0.04. The calibration plot was linear in the range of 50–700 ng/spot of thymoquinone and the correlation coefficient of 0.998 9 was indicative of good linear dependence of peak area on concentration. Limit of detection (8.67 ng/spot), limit of quantification (17.43 ng/spot) accuracy (less than 2) and recovery (ranging from 98.39–99.17) were found satisfactory. Conclusions The developed high-performance thin layer chromatography densitometric method was found cheap, selective, precise and accurate and can be used for routine analysis of N. sativa extracts and marketed formulations.

  18. Longwave radiative exchange analysis of cloudy atmospheres with a net exchange formulation

    NASA Astrophysics Data System (ADS)

    Eymet, V.; Blanco, S.; Dufresne, J.-L.; Fournier, R.

    2003-04-01

    The Next Exchange Formulation (NEF) is an alternative to the usual radiative transfer equation. It was proposed in 1967 by Green for atmospheric sciences and by Hottel for engineering sciences. Until now, the NEF has been used only in a very few cases for atmospheric studies. Recently we have developed a longwave radiative code based on this formulation for a GCM of the Mars planet. Here, we will present results for the Earth atmosphere, obtained with a Monte Carlo Method based on the NEF. In this method, the fluxes are no more considered. The basic variables are the net exchange rates (NER) between each pair of atmospheric layer {i,j}, i.e. the radiative power emitted by i and absorbed by j minus the radiative power emitted by j and absorbed by i. The graphical representation of the NER matrix highlight the radiative exchanges which dominate the radiative budget of the atmosphere and allows one to have a very good insight of the radiative exchanges. Results will be shown for clear sky atmosphere, cloudy atmosphere and atmosphere with dust aerosols. The role of scattering in the longwave radiative exchanges will also be analyzed. The calculation of sensitivity parameter being automatically implemented in the Monte Carlo Method, a complementary sensitivity analysis will be presented that examines how radiative exchanges depend on concentrations profiles of main absorbing and scattering species.

  19. The oxytocin-bone axis.

    PubMed

    Colaianni, G; Tamma, R; Di Benedetto, A; Yuen, T; Sun, L; Zaidi, M; Zallone, A

    2014-02-01

    We recently demonstrated a direct action of oxytocin (OT) on skeletal homeostasis, mainly mediated through stimulation of osteoblasts (OBs) formation and through the reciprocal modulation of osteoclast (OCs) formation and function. Thus, mice lacking the hormone or its receptor develop a low turnover osteoporosis that worsens with age in both sexes. The skeletons of OT (Ot) and OT receptor (Oxtr) null mice display a pronounced decrease in vertebral and femoral trabecular volume. At the cellular level, OBs from Ot KO and Oxtr KO mice exhibit lower mineralization activity and, at the mRNA level, all master genes for osteoblast differentiation are down-regulated. Moreover, OT has dual effects on OCs: it increases osteoclast formation both directly, by activating nuclear factor kB (NFkB) and mitogen-activated protein kinase (MAPK) signalling and, indirectly, through the up-regulation of receptor activator nuclear factor-kappaB ligand synthesis by OBs. On the other hand, it inhibits bone resorption by triggering cytosolic Ca(2+) release and nitric oxide synthesis in mature OCs. OT is locally produced by osteoblasts acting as paracrine-autocrine regulators of bone formation modulated by oestrogens. The oestrogen signal involved in this feedforward circuit is nongenomic because it requires an intact MAPK kinase signal transduction pathway, instead of the classical nuclear translocation of oestrogen receptor. The ability of oestrogen to increase bone mass in vivo is to some extent OXTR-dependent. Thus, Oxtr KO mice injected 17β-oestradiol did not show any effects on bone formation parameters, whereas the same treatment increases trabecular and cortical bone in wild-type mice. An intact OT autocrine-paracrine circuit appears to be essential for optimal skeletal remodelling.

  20. 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.

  1. 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

  2. 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.

  3. Genetic Regulation of Maternal Oxytocin Response and Its Influences on Maternal Behavior

    PubMed Central

    Eapen, Valsamma; Kohlhoff, Jane; Mendoza Diaz, Antonio; Barnett, Bryanne; Silove, Derrick; Dadds, Mark R.

    2016-01-01

    We interrogated the genetic modulation of maternal oxytocin response and its association with maternal behavior using genetic risk scores within the oxytocin receptor (OXTR) gene. We identified a novel SNP, rs968389, to be significantly associated with maternal oxytocin response after a challenging mother-infant interaction task (Still Face Paradigm) and maternal separation anxiety from the infant. Performing a multiallelic analysis across OXTR by calculating a cumulative genetic risk score revealed a significant gene-by-environment (G × E) interaction, with OXTR genetic risk score interacting with adult separation anxiety to modulate levels of maternal sensitivity. Mothers with higher OXTR genetic risk score and adult separation anxiety showed significantly reduced levels of maternal sensitivity during free play with the infant. The same G × E interaction was also observed for the extended OXTR cumulative genetic risk score that included rs968389. Moreover, the extended cumulative OXTR genetic risk score itself was found to be significantly associated with maternal separation anxiety as it specifically relates to the infant. Our results suggest a complex montage of individual and synergistic genetic mediators of maternal behavior. These findings add to specific knowledge about genetic regulation of maternal oxytocin response in relation to maternal adjustment and infant bonding through the first few months of life. PMID:27872764

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  6. Oxytocin mediated behavior in invertebrates: An evolutionary perspective.

    PubMed

    Lockard, Meghan A; Ebert, Margaret S; Bargmann, Cornelia I

    2017-02-01

    The molecular and functional conservation of oxytocin-related neuropeptides in behavior is striking. In animals separated by at least 600 million years of evolution, from roundworms to humans, oxytocin homologs play critical roles in the modulation of reproductive behavior and other biological functions. Here, we review the roles of oxytocin in invertebrate behavior from an evolutionary perspective. We begin by tracing the evolution of oxytocin through the invertebrate animal lineages, and then describe common themes in invertebrate behaviors that are mediated by oxytocin-related peptides, including reproductive behavior, learning and memory, food arousal, and predator/prey relationships. Finally, we discuss interesting future directions that have recently become experimentally tractable. Studying oxytocin in invertebrates offers precise insights into the activity of neuropeptides on well-defined neural circuits; the principles that emerge may also be represented in the more complex vertebrate brain. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 128-142, 2017.

  7. 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

  8. 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.

  9. Oxytocin excites nucleus accumbens shell neurons in vivo.

    PubMed

    Moaddab, Mahsa; Hyland, Brian I; Brown, Colin H

    2015-09-01

    Oxytocin modulates reward-related behaviors. The nucleus accumbens shell (NAcSh) is a major relay in the brain reward pathway and expresses oxytocin receptors, but the effects of oxytocin on the activity of NAcSh neurons in vivo are unknown. Hence, we used in vivo extracellular recording to show that intracerebroventricular (ICV) oxytocin administration (0.2μg) robustly increased medial NAcSh neuron mean firing rate; this increase was almost exclusively evident in slow-firing neurons and was not associated with any change in firing pattern. To determine whether oxytocin excitation of medial NAcSh neurons is modulated by drugs that impact the brain reward pathway, we next tested the effects of ICV oxytocin following repeated morphine treatment. In morphine-treated rats, ICV oxytocin did not affect the mean firing rate of medial NAcSh neurons. Taken together, these results show that oxytocin excites medial NAcSh neurons but does not do so after repeated morphine. This could be an important factor in oxytocin modulation of reward-related behaviors, such as drug addiction.

  10. Oxytocin enhances onset of lactation among mothers delivering prematurely.

    PubMed Central

    Ruis, H; Rolland, R; Doesburg, W; Broeders, G; Corbey, R

    1981-01-01

    In a double-blind group sequential trial the efficiency of an oxytocin nasal spray in enhancing lactation was studied during the first five days after delivery in women who had given birth prematurely. The cumulative volume of breast milk obtained between the second and fifth days after delivery was 3.5 times greater in primiparas given oxytocin than in primiparas given placebo. There was no significant difference in the composition of the milk between the untreated women and those given oxytocin. The results of this study show that oxytocin nasal spray is an effective and safe means of enhancing lactation in women using a breast pump. PMID:6788318

  11. 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

  12. 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

  13. 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.

  14. Constitutive formulation and numerical analysis of the biomechanical behaviour of forefoot plantar soft tissue.

    PubMed

    Fontanella, Chiara Giulia; Favaretto, Elena; Carniel, Emanuele Luigi; Natali, Arturo Nicola

    2014-09-01

    The aim of this work is to provide a numerical approach for the investigation of the mechanical behaviour of the forefoot soft tissues. The development of reliable numerical models of biological structures requires the definition of constitutive formulations that actually interpret the mechanical response of the constituent biological tissues and their structural arrangement. A specific visco-hyperelastic constitutive model is provided to account for the typical features of soft plantar tissue mechanics, as geometric and material non-linearity, almost-incompressible behaviour and time-dependent phenomena. Constitutive parameters are evaluated by the analysis of experimental data from compression and stress relaxation tests on tissue samples. A three-dimensional finite element model of the forefoot region is developed starting from the analysis of biomedical images, leading to the evaluation of overall structural response. The reliability of model and analyses is assessed by the comparison of experimental and numerical results pertaining to indentation tests. The numerical model developed allows to evaluate the mechanical response of plantar soft tissue in terms of stress and strain distribution.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Evidence of Dysregulated Peripheral Oxytocin Release Among Depressed Women

    PubMed Central

    Cyranowski, Jill M.; Hofkens, Tara L.; Frank, Ellen; Seltman, Howard; Cai, Hou-Ming; Amico, Janet A.

    2012-01-01

    Objective Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female reproductive function. Animal research indicates that central oxytocin facilitates adaptive social attachments and modulates stress and anxiety responses. Major depression is prevalent among postpubertal females, and is associated with perturbations in social attachments, dysregulation of the hypothalamic-pituitary-adrenal stress axis, and elevated levels of anxiety. Thus, depressed women may be at risk to display oxytocin dysregulation. The current study was developed to compare patterns of peripheral oxytocin release exhibited by depressed and nondepressed women. Methods Currently depressed (N = 17) and never-depressed (N = 17) women participated in a laboratory protocol designed to stimulate, measure, and compare peripheral oxytocin release in response to two tasks: an affiliation-focused Guided Imagery task and a Speech Stress task. Intermittent blood samples were drawn over the course of two, 1-hour sessions including 20-minute baseline, 10-minute task, and 30-minute recovery periods. Results The 10-minute laboratory tasks did not induce identifiable, acute changes in peripheral oxytocin. However, as compared with nondepressed controls, depressed women displayed greater variability in pulsatile oxytocin release over the course of both 1-hour sessions, and greater oxytocin concentrations during the 1-hour affiliation-focused imagery session. Oxytocin concentrations obtained during the imagery session were also associated with greater symptoms of depression, anxiety, and interpersonal dysfunction. Conclusions Depressed women are more likely than controls to display a dysregulated pattern of peripheral oxytocin release. Further research is warranted to elucidate the clinical significance of peripheral oxytocin release in both depressed and nondepressed women. PMID:19005082

  1. 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

  2. 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.

  3. 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.

  4. Myometrial oxytocin receptor expression and intracellular pathways.

    PubMed

    Yulia, A; Johnson, M R

    2014-06-01

    Oxytocin (OT) signalling plays a fundamental role in the mechanisms of parturition. OT is one of the most frequently used drugs in obstetrics, promoting uterine contractions for labor induction and augmentation and to prevent postpartum hemorrhage (PPH). Expression of the oxytocin receptor (OTR) in the human myometrium is tightly regulated during pregnancy and its levels have been shown to peak upon labour onset and to fall sharply in advanced labour and the postpartum period, when the uterus become refractive to OT. However, uterine sensitivity to OT varies between pregnant women, probably reflecting differences in their myometrial OTR expression. Control of OTR expression is mediated by a combination of steroid hormone stimulation, stretch, and inflammation. This review summarises current knowledge regarding the complex regulation of myometrial OTR expression and its associated intracellular signaling pathways.

  5. 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.

  6. In Vivo Analysis of the Potency of Silicone Oil Microdroplets as Immunological Adjuvants in Protein Formulations

    PubMed Central

    Chisholm, Carly Fleagle; Nguyen, Bao Han; Soucie, Kaitlin R.; Torres, Raul M.; Carpenter, John F.; Randolph, Theodore W.

    2015-01-01

    Subvisible particles in a therapeutic protein product may act as adjuvants to promote unwanted immune responses against the protein. Silicone oil is used as a lubricant in prefilled syringes, and microdroplets of silicone oil are often detected in protein formulations expelled from prefilled syringes. In order to test the adjuvant potency of silicone oil microdroplets, antibody responses in mice to subcutaneous injections of formulations of ovalbumin (OVA) that contained silicone oil microdroplets were measured. These responses were compared against responses to oil-free OVA formulations and to OVA formulations that contained microparticulate aluminum hydroxide (“alum”), the common vaccine adjuvant. When administered with high concentrations of silicone oil microdroplets, OVA formulations elicited strong anti-OVA IgG1 and IgG2a antibody responses. These responses were equivalent to those observed when alum microparticles were added to OVA formulations, suggesting that silicone oil can act as a potent adjuvant. However, when OVA formulations were prepared with lower levels of silicone oil that had been obtained directly from commercial siliconized syringes, the anti-OVA antibody response was not enhanced significantly compared to responses against OVA alone. PMID:26190624

  7. Developmental Perspectives on Oxytocin and Vasopressin

    PubMed Central

    Hammock, Elizabeth A D

    2015-01-01

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

  8. 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.

  9. Frequency analysis of a heterogeneous perforated panel using a super-element formulation

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Fallah, A. S.; Louca, L. A.

    2009-10-01

    Heterogeneous perforated panels represent a wide class of structural elements with holes where perforations and matrix are of dissimilar materials e.g. metallic member of a perforated hybrid joint with resin-fillings. There is a variety of objectives for introducing holes e.g. weight saving or mechanical interlock. Where there is a regular pattern to the arrangement of holes the perforated element can be assimilated to a lattice. In the present study, numerical analysis has been conducted on investigating the shock frequency filtering phenomenon encountered in two-dimensional (2D) lattice structures. A super-element of the primitive cell (unit cell) of the lattice has been formulated and applied in conjunction with the Floquet-Bloch's principle to study the shock response characteristics. Plane wave propagation is investigated by constructing the first Brillouin zone of the primitive cell in associated Fourier space ( k-space). The frequency characteristics are presented in the band structure diagram. The study emphasizes the existence of frequency pass and stop bands and the extent of this phenomenon. The frequency filtering effects of the heterogeneous perforated 2D lattice has shown its potential value to improve the structural performance of perforated hybrid joints subjected to dynamic loads.

  10. Analysis of ingredient functionality and formulation optimization of an instant peanut beverage mix.

    PubMed

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

    2010-01-01

    Powder for an instant shake-style beverage was created using partially defatted peanut flour (12% fat), granulated sugar, and nonfat dry milk (NFDM). The 3 main components, along with constant amounts of stabilizing gums and anti-caking silica, were mixed together and finely milled in a Super Wing Mill to further reduce the particle sizes. Drinks from each formula variation were prepared and analyzed for viscosity (digital viscometer), color (colorimeter), and separation rate. Each beverage was also analyzed by consumers to determine acceptability of flavor, mouth-feel, and color. Physical test results show that viscosity increased with increasing proportion of peanut flour in the formula, and viscosity decreased with increasing levels of sugar and NFDM. For each formula, the samples at refrigerated temperature (4 degrees C) were less viscous than those at ambient temperatures (23 to 25 degrees C). Color values show that the beverage powder color was mostly influenced by peanut flour percentage, becoming darker with increasing levels of peanut flour. Prepared beverage color was influenced by both NFDM and peanut flour percentage; lightness increased with increasing NFDM percentage and decreased with increasing peanut flour percentage. Separation rates were most affected by the proportion of NFDM in the formula; higher levels decreased the rate of separation. Refrigeration slowed the rate of separation in all samples. Response surface analysis of consumer test data showed that the most acceptable formulation for the peanut beverage included approximately equal amounts of peanut flour, sugar, and NFDM.

  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. 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...

  13. 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.

  14. 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

  15. Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional expressions.

    PubMed

    Leknes, Siri; Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

    2013-10-01

    Sensing others' emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and 'hidden' emotional expressions and related the results to individual differences in sensitivity to others' subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or 'sharpened' evaluative processing of others' positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin's prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin's effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation.

  16. Oxytocin: the neuropeptide of love reveals some of its secrets.

    PubMed

    Neumann, Inga D

    2007-04-01

    The neuropeptide oxytocin is synthesized in the brain and released from neurohypophyseal terminals into the blood and within defined brain regions that regulate emotional, cognitive, and social behaviors. A recent study of CD38-/- mice (Jin et al., 2007) has demonstrated an essential role for the transmembrane receptor CD38 in secretion of oxytocin into the blood.

  17. Sex differences in methamphetamine seeking in rats: impact of oxytocin.

    PubMed

    Cox, Brittney M; Young, Amy B; See, Ronald E; Reichel, Carmela M

    2013-10-01

    Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1mg/kg, IP) 30min before a meth priming injection (1mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The

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

    NASA Technical Reports Server (NTRS)

    Jaggers, R. F.

    1976-01-01

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

  19. 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

  20. Oxytocin increases the likeability of physically formidable men.

    PubMed

    Chen, Frances S; Mayer, Jennifer; Mussweiler, Thomas; Heinrichs, Markus

    2015-06-01

    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.

  1. 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

  2. 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.

  3. Oxytocin stimulates colonic motor activity in healthy women.

    PubMed

    Ohlsson, B; Ringström, G; Abrahamsson, H; Simrén, M; Björnsson, E S

    2004-04-01

    The effects of oxytocin in the gastrointestinal tract are unclear. The aim of this study was to examine the effect of infusion of oxytocin on colonic motility and sensitivity in healthy women. Fourteen healthy women were investigated twice. A 6-channel perfusion catheter, with three recording points (2 cm apart) proximally and three recording points distally to a barostat balloon, was inserted to the splenic flexure. An intestinal feeding tube was placed in the mid-duodenum. A 90-min duodenal lipid infusion of 3 kcal min(-1) was administered. Thirty minutes after the start of the lipid infusion, the subject randomly received either 20 or 40 mU min(-1) of oxytocin, or isotonic saline as intravenous infusions for 90 min. Meanwhile, the colonic motility was recorded. During the last 30 min of oxytocin and saline infusion, the visceral sensitivity to balloon distensions was examined. During lipid infusion the number of antegrade contractions per hour was 0.7 +/- 0.3 after saline and 3.9 +/- 1.4 after oxytocin (P = 0.03), indicating more pronounced lumen-occlusive contractile activity after oxytocin administration. Some of these consisted of high-amplitude (> 103 mmHg in amplitude) antegrade contractions. Lipid infusion evoked a decrease of the balloon volume, reflecting increased colonic tone, but there was no difference between saline and oxytocin. Sensory thresholds did not differ significantly between saline and oxytocin. Infusion of oxytocin stimulates antegrade peristaltic contractions in stimulated colon in healthy women. The effects of oxytocin on colonic motor activity deserve to be further explored, especially in patients with colonic peristaltic dysfunction.

  4. 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

  5. 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

  6. 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.

  7. Micro-flow imaging: flow microscopy applied to sub-visible particulate analysis in protein formulations.

    PubMed

    Sharma, Deepak K; King, Dave; Oma, Peter; Merchant, Clark

    2010-09-01

    The need to monitor, measure, and control sub-visible proteinaceous particulates in biopharmaceutical formulations has been emphasized in recent publications and commentaries. Some of these particulates can be highly transparent, fragile, and unstable. In addition, for much of the size range of concern, no practical measurement method with adequate sensitivity and repeatability has been available. A complication in measuring protein particulates in many formulations is the simultaneous presence of other particle types such as silicone micro-droplets, air bubbles, and extrinsic contaminants. The need has therefore been identified for new analytical methods which can accurately measure and characterize sub-visible particulates in formulations. Micro-flow imaging has been shown to provide high sensitivity in detecting and imaging transparent protein particles and a unique capability to independently analyze such populations even when other particle types are present.

  8. 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

    2011-10-09

    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.

  9. Oxytocin improves synchronisation in leader-follower interaction

    PubMed Central

    Gebauer, L.; Witek, M. A. G.; Hansen, N. C.; Thomas, J.; Konvalinka, I.; Vuust, P.

    2016-01-01

    The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member – i.e. one was following another who was leading/self-pacing – dyads given oxytocin were more synchronised than dyads given placebo. However, there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive partner’s behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition. PMID:27929100

  10. 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

  11. Oxytocin improves synchronisation in leader-follower interaction.

    PubMed

    Gebauer, L; Witek, M A G; Hansen, N C; Thomas, J; Konvalinka, I; Vuust, P

    2016-12-08

    The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member - i.e. one was following another who was leading/self-pacing - dyads given oxytocin were more synchronised than dyads given placebo. However, there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive partner's behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition.

  12. HMX: Analysis of Dosing Formulations Used in Acute, Sub-Acute and Sub-Chronic Toxicity Studies.

    DTIC Science & Technology

    1985-07-31

    14.72 - 1 50 78 1 79 1 1 I I 72 15.30 1 I 50 781 I I I 3 1 1 1 1 5 0 1 1 1 I i 15.07 -5 1 112 1 ,? 3 1 4,3 74 15.251 " 1 1 50 1 114 1 113 0 I I I 75...NUMBER 2. GOVT ACCESSION NO 3 . RECIPIENT’S CATALOG NUMBER 4. TITLE (end Subtitle) S. TYPE OF REPORT & PERIOD COVERED HMX: Analysis of dosing formulations...HMX: Analysis of Dosing Formulations Used in Acute, Sub-acute and Sub-chronic Toxicity Studies Final Report by: M.S. Henderson 3 , July,, 1985 Supported

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

    PubMed Central

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

    2014-01-01

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

  14. Maternal Oxytocin Response Predicts Mother-to-Infant Gaze

    PubMed Central

    Kim, Sohye; Fonagy, Peter; Koos, Orsolya; Dorsett, Kimberly; Strathearn, Lane

    2014-01-01

    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 mother makes social contact and engages with her infant. Furthermore, prior oxytocin studies have assessed maternal engagement primarily during episodes free of infant distress, while maternal engagement during infant distress is considered to be uniquely relevant to the formation of secure mother-infant attachment. Two patterns of maternal gaze, maternal gaze toward and gaze shifts away from the infant, were micro-coded while 50 mothers interacted with their 7-month-old infants during a modified still-face procedure. Maternal oxytocin response was defined as a change in the mother’s plasma oxytocin level following interaction with her infant as compared to baseline. The mother’s oxytocin response was positively associated with the duration of time her gaze was directed toward her infant, while negatively associated with the frequency with which her gaze shifted away from her infant. Importantly, mothers who showed low/average oxytocin response demonstrated a significant decrease in their gaze toward their infants during periods of infant distress, while such change was not observed in mothers with high oxytocin response. The findings underscore the involvement of oxytocin in regulating the mother’s responsive engagement with her infant, particularly in times when the infant’s need for access to the mother is greatest. PMID:24184574

  15. The two fold role of oxytocin in social developmental disorders: A cause and a remedy?

    PubMed

    Lefevre, Arthur; Sirigu, Angela

    2016-04-01

    Oxytocin is widely used by obstetricians to induce or facilitate labor. The long lasting consequences of oxytocin administration remain however unknown. Here, we discuss recent evidence suggesting a link between oxytocin labor induction and developmental social impairments such as autism spectrum disorders (ASD). Because these associations are methodologically questionable, we provide a review of animal studies investigating the long term effects of neonatal injection of oxytocin to shed light on the biological mechanisms that mediate the contribution of early oxytocin supplementation on the development of social impairments. In contrast to this potential negative impact on development, oxytocin has been shown to ameliorate social skills of ASD patients. However, results of chronic oxytocin administration from animal experiments are contradictory. We also review recent studies looking at chronic oxytocin effects in animal and in humans. Obstetric and psychiatric uses of exogenous oxytocin both impact on oxytocinergic neurotransmission but the effects may be sharply dissimilar.

  16. 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…

  17. Oxytocin modulates selection of allies in intergroup conflict.

    PubMed

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

    2012-03-22

    In intergroup competition and conflict, humans benefit from coalitions with strong partners who help them to protect their in-group and prevail over competing out-groups. Here, we link oxytocin, a neuropeptide produced in the hypothalamus, to ally selection in intergroup competition. In a double-blind placebo-controlled experiment, males self-administered oxytocin or placebo, and made selection decisions about six high-threat and six low-threat targets as potential allies in intergroup competition. Males given oxytocin rather than placebo viewed high-threat targets as more useful allies and more frequently selected them into their team than low-threat targets.

  18. Conformation of Lysine Vasopressin: A Comparison with Oxytocin

    PubMed Central

    Walter, Roderich; Glickson, J. D.; Schwartz, I. L.; Havran, R. T.; Meienhofer, Johannes; Urry, D. W.

    1972-01-01

    Starting with assignments of proton nuclear magnetic resonance previously made for oxytocin in deuterated dimethylsulfoxide at 220 MHz, we have assigned resonances for the mammalian antidiuretic hormone, lysine vasopressin. The results demonstrate that spectral assignments of neurohypophyseal hormones and their congeners can, within certain limits, be derived from each other. Comparison of the spectra of lysine vasopressin and oxytocin suggests that the gross backbone conformations of their 20-membered ring components are for the most part similar in deuterated dimethylsulfoxide, whereas the C-terminal acyclic amino-acid sequence of lysine vasopressin is more flexible than that of oxytocin. PMID:4505670

  19. Oxytocin--ensuring appropriate use and balancing efficacy with safety.

    PubMed

    Farina, Z; Fawcus, S

    2015-04-01

    Maternal deaths due to haemorrhage continue to increase in South Africa (SA). It appears that oxytocin and other uterotonics are not being used optimally, even though they are an essential part of managing maternal haemorrhage. Oxytocin should be administered to every mother delivering in SA. Awareness is required of the side-effects that can occur and the appropriate measures to avoid harm from these. Second-line uterotonics should also be available and utilised in conjunction with mechanical and surgical means to arrest haemorrhage in women who continue to bleed after the appropriate administration of oxytocin.

  20. A prospective randomized trial comparing Foley catheter, oxytocin, and combination Foley catheter-oxytocin for labour induction with unfavourable cervix.

    PubMed

    El Khouly, Nabih I

    2016-12-06

    The purpose of this study was to evaluate the effectiveness and safety of transcervical Foley catheter with and without oxytocin versus oxytocin alone for labour induction with unfavourable cervix. This trial enrolled 108 women with singleton pregnancies presented for labour induction with unfavourable cervix. Patients were randomly assigned to receive Foley catheter alone (I), Foley catheter plus oxytocin (II) or oxytocin alone (III). Outcomes were analysed in terms of success of induction, induction delivery interval, route of delivery, dose and duration of oxytocin, and complications. Successful normal vaginal delivery was more common in group I (p = .02) compared to group III. Induction delivery time was statistically shorter in group II and group III (p < .001). Patients in group I required significantly less oxytocin dose and duration (p < .001). This led to our conclusion that induction of labour with Foley catheter without oxytocin increases success rate of normal vaginal delivery; however, it has a longer induction delivery interval with similar complications.

  1. On exact and approximated formulations for scaling-mode shapes in operational modal analysis by mass and stiffness change

    NASA Astrophysics Data System (ADS)

    López-Aenlle, M.; Brincker, R.; Pelayo, F.; Canteli, A. F.

    2012-01-01

    When operational modal analysis (OMA) is used to estimate modal parameters, mode shapes cannot be mass normalized. In the past few years, some equations have been proposed to scale mode shapes using the mass-change method, which consists of repeating modal testing after changing the mass at different points of the structure where the mode shapes are known. In this paper, the structural-dynamic-modification theory is used to derive a set of equations, from which all the existing formulations can be derived. It is shown that the known equations can be divided into two types, the exact and the approximated equations, where the former type does in fact fulfill the equations derived from the theory of structural modification, whereas the remaining equations do not, mainly because the change of the mode shapes of the modified structure is not properly taken into account. By simulations, the paper illustrates the large difference in accuracy between the approximate and the exact formulations. The paper provides two new exact formulations for the scaling factors, one for the non-modified structure and - for the first time in the literature - one for the modified structure. The simulations indicate the influence of errors from the measured natural frequencies and mode shapes on the estimation of the scaling factors using the two exact formulations from the literature and the new exact formulation proposed in this paper. In addition, the paper illustrates statistics of the errors on mode-shape scaling. All simulations were carried out using a plate with closely spaced modes.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

    Stults, Ian C.

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

  4. A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis.

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. 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.

  7. Comparative pharmacokinetic and cytotoxic analysis of three different formulations of mitoxantrone in mice.

    PubMed Central

    Rentsch, K. M.; Horber, D. H.; Schwendener, R. A.; Wunderli-Allenspach, H.; Hänseler, E.

    1997-01-01

    Two liposomal formulations of mitoxantrone (MTO) were compared with the aqueous solution (free MTO) in terms of their pharmacokinetic behaviour in ICR mice and cytotoxic activity in a nude mouse xenograft model. The three different formulations of MTO [free MTO, phosphatidic acid (PA)-MTO liposomes, pH-MTO liposomes] were administered intravenously (three mice per formulation and time point) at a dose of 4.7 micromol kg(-1) for free MTO, 6.1 micromol kg(-1) for PA-MTO and 4.5 micromol kg(-1) for pH-MTO. The concentrations of MTO were determined using high-performance liquid chromatography (HPLC) in blood, liver, heart, spleen and kidneys of the mice. Additionally, the toxicity and anti-tumour activity of MTO was evaluated in a xenograft model using a human LXFL 529/6 large-cell lung carcinoma. The dose administered was 90% of the maximum tolerated dose (MTD) of the corresponding formulation (8.1 micromol kg(-1) for free MTO, 12.1 micromol kg(-1) for PA-MTO and pH-MTO). The pharmacokinetic behaviour of PA-MTO in blood was faster than that of free MTO, but the cytotoxic effect was improved. In contrast, pH-MTO showed a tenfold increased area under the curve (AUC) in blood compared with free MTO, without improvement of the cytotoxic effect. This discrepancy between the pharmacokinetic and cytotoxic results could be explained by the fact that MTO in pH-MTO liposomes remains mainly in the vascular space, whereas MTO in PA-MTO liposomes is rapidly distributed into deep compartments, even more so than free MTO. PMID:9083333

  8. Algorithm for Surface of Translation Attached Radiators (A-STAR). Volume 1: Formulation of the analysis

    NASA Astrophysics Data System (ADS)

    Medgyesimitschang, L. N.; Putnam, J. M.

    1982-05-01

    A general analytical formulation, based on the method of moments (MM) is described for solving electromagnetic problems associated with off-surface (wire) and aperture radiators on finite-length cylinders of arbitrary cross section, denoted in this report as bodies of translation (BOT). This class of bodies can be used to model structures with noncircular cross sections such as wings, fins and aircraft fuselages.

  9. 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.

  10. Direct analysis of pharmaceutical tablet formulations using Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging.

    PubMed

    Earnshaw, Caroline J; Carolan, Vikki A; Richards, Don S; Clench, Malcolm R

    2010-06-15

    Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging (MALDI MSI) has been used to directly analyse a range of tablets in order to assess the homogeneity of the active drug compound throughout the excipients contained within the tablets studied. The information gained from the imaging experiments can be used to improve and gain a greater understanding of the manufacturing process; such knowledge will enable improvements in finished product quality to make safer and more efficacious tablet formulations. Commercially available and prescription tablet formulations have been analysed, including aspirin, paracetamol, sildenafil citrate (Viagra(R)) and a batch of tablets in development (tablet X: placebo; 1 mg; 3 mg and 6 mg). MALDI MSI provides semi-quantitative information that is related to ion abundance, therefore Principal Component Analysis (PCA), a multivariate analysis technique, has been used to differentiate between tablets containing different amounts of active drug ingredient. Aspects of sample preparation have also been investigated with regard to tablet shape and texture. The results obtained indicate that MALDI MSI can be used effectively to analyse the spatial distribution of the active pharmaceutical component (API) in pharmaceutical tablet formulations.

  11. Dual modulation of inward rectifier potassium currents in olfactory neuronal cells by promiscuous G protein coupling of the oxytocin receptor.

    PubMed

    Gravati, Marta; Busnelli, Marta; Bulgheroni, Elisabetta; Reversi, Alessandra; Spaiardi, Paolo; Parenti, Marco; Toselli, Mauro; Chini, Bice

    2010-09-01

    Oxytocin receptor is a seven transmembrane receptor widely expressed in the CNS that triggers G(i) or G(q) protein-mediated signaling cascades leading to the regulation of a variety of neuroendocrine and cognitive functions. We decided to investigate whether and how the promiscuous receptor/G protein coupling affects neuronal excitability. As an experimental model, we used the immortalized gonadotropin-releasing hormone-positive GN11 cell line displaying the features of immature, migrating olfactory neurons. Using RT-PCR analysis, we detected the presence of oxytocin receptors whose stimulation by oxytocin led to the accumulation of inositol phosphates and to the inhibition of cell proliferation, and the expression of several inward rectifier (IR) K+ channel subtypes. Moreover, electrophysiological and pharmacological inspections using whole-cell patch-clamp recordings evidenced that in GN11 cells, IR channel subtypes are responsive to oxytocin. In particular, we found that: (i) peptide activation of receptor either inhibited or stimulated IR conductances, and (ii) IR current inhibition was mediated by a pertussis toxin-resistant G protein presumably of the G(q/11) subtype, and by phospholipase C, whereas IR current activation was achieved via receptor coupling to a pertussis toxin-sensitive G(i/o) protein. The findings suggest that neuronal excitability might be tuned by a single peptide receptor that mediates opposing effects on distinct K+ channels through the promiscuous coupling to different G proteins.

  12. Oxytocin and the biopsychology of performance in team sports.

    PubMed

    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.

  13. 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.

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

    PubMed

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

    2016-06-01

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

  15. Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration.

    PubMed

    van Ijzendoorn, Marinus H; Bhandari, Ritu; van der Veen, Rixt; Grewen, Karen M; Bakermans-Kranenburg, Marian J

    2012-01-01

    We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 a.m.) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7 h in total. Oxytocin levels did not differ among conditions before use of the nasal spray. Salivary oxytocin levels in the placebo group showed high stability across the day. After oxytocin administration oxytocin levels markedly increased, they peaked around 1 h after administration, and were still significantly elevated 7 h after administration. The amount of oxytocin (16 or 24 IU) did not make a difference for oxytocin levels. The increase of oxytocin levels for at least 7 h shows how effective intranasal administration of oxytocin is. Our findings may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting. More research into the long-term neurological and behavioral effects of sniffs of oxytocin is urgently needed.

  16. Variation in oxytocin is related to variation in affiliative behavior in monogamous, pairbonded tamarins.

    PubMed

    Snowdon, Charles T; Pieper, Bridget A; Boe, Carla Y; Cronin, Katherine A; Kurian, Aimee V; Ziegler, Toni E

    2010-09-01

    Oxytocin plays an important role in monogamous pairbonded female voles, but not in polygamous voles. Here we examined a socially monogamous cooperatively breeding primate where both sexes share in parental care and territory defense for within species variation in behavior and female and male oxytocin levels in 14 pairs of cotton-top tamarins (Saguinus oedipus). In order to obtain a stable chronic assessment of hormones and behavior, we observed behavior and collected urinary hormonal samples across the tamarins' 3-week ovulatory cycle. We found similar levels of urinary oxytocin in both sexes. However, basal urinary oxytocin levels varied 10-fold across pairs and pair-mates displayed similar oxytocin levels. Affiliative behavior (contact, grooming, sex) also varied greatly across the sample and explained more than half the variance in pair oxytocin levels. The variables accounting for variation in oxytocin levels differed by sex. Mutual contact and grooming explained most of the variance in female oxytocin levels, whereas sexual behavior explained most of the variance in male oxytocin levels. The initiation of contact by males and solicitation of sex by females were related to increased levels of oxytocin in both. This study demonstrates within-species variation in oxytocin that is directly related to levels of affiliative and sexual behavior. However, different behavioral mechanisms influence oxytocin levels in males and females and a strong pair relationship (as indexed by high levels of oxytocin) may require the activation of appropriate mechanisms for both sexes.

  17. Gender differences in oxytocin-associated disruption of decision bias during emotion perception.

    PubMed

    Lynn, Spencer K; Hoge, Elizabeth A; Fischer, Laura E; Barrett, Lisa Feldman; Simon, Naomi M

    2014-09-30

    Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin׳s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin׳s effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocin׳s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence women׳s performance. These results suggest that oxytocin may impair men׳s ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction.

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

    NASA Technical Reports Server (NTRS)

    1972-01-01

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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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…

  4. 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).

  5. 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.

  6. 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.

  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 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

  8. Compulsory administration of oxytocin does not result in genuine moral enhancement.

    PubMed

    Rakić, Vojin

    2017-02-28

    The question will be raised whether oxytocin can serve as an effective moral enhancer. Different types of moral enhancement will be addressed, one of them being compulsory moral enhancement. It will be argued that oxytocin cannot serve as an effective moral enhancer if its use is being made compulsory. Hence, compulsory administration of oxytocin does not result in genuine moral enhancement. In order to demonstrate this, a stipulation of the main potentially beneficial outcomes of using oxytocin as a moral enhancer will be offered, as well as a discussion of objections to the notion that oxytocin can be an effective moral enhancer. It will be concluded that mandatory administration of oxytocin is ineffective because of a combination of two reasons: (1) mandatory administration of oxytocin renders moral reflection practically superfluous; (2) without moral reflection the beneficial outcomes of the use of oxytocin do not outweigh its drawbacks to the degree that we could speak of effective moral enhancement.

  9. 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.

  10. 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.

  11. 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

  12. Oxytocin and behavior: Lessons from knockout mice.

    PubMed

    Caldwell, Heather K; Aulino, Elizabeth A; Freeman, Angela R; Miller, Travis V; Witchey, Shannah K

    2017-02-01

    It is well established that the nonapeptide oxytocin (Oxt) is important for the neural modulation of behaviors in many mammalian species. Since its discovery in 1906 and synthesis in the early 1950s, elegant pharmacological work has helped identify specific neural substrates on which Oxt exerts its effects. More recently, mice with targeted genetic disruptions of the Oxt system-i.e., both the peptide and its receptor (the Oxtr)-have further defined Oxt's actions and laid some important scientific groundwork for studies in other species. In this article, we highlight the scientific contributions that various mouse knockouts of the Oxt system have made to our understanding of Oxt's modulation of behavior. We specifically focus on how the use of these mice has shed light on our understanding of social recognition memory, maternal behavior, aggression, and several nonsocial behaviors. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 190-201, 2017.

  13. 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.

  14. Analysis and bioequivalency study on two tablet formulations of co-trimoxazole.

    PubMed

    Sheikh Salem, M; Alkaysi, H N; Gharaibeh, A M; Amari, F F; Sallam, E; Shubair, M S

    1993-04-01

    This paper describes an analytical procedure for simultaneous quantification of trimethoprim (TMP) and sulphamethoxazole (SMZ) in serum. Serum samples were rendered alkaline with glycine-sodium hydroxide buffer (pH 9.1) and extracted with ethyl acetate. The reconstituted sample was analysed using reversed-phase C-18 column high-performance chromatography. The mobile phase consisted of 75% triethyl ammonium acetate buffer, 20% methanol and 5% acetonitrile. The analytes were monitored at 289 nm and tetroxoprim was used as an internal standard. The maximum values for intra-day coefficients of variation (CV) for TMP-and SMZ were 5.7 and 2.1%, respectively. Interday CV values were 6.4 and 2.2%, respectively. The method was used to compare the bioavailability of two tablet formulations in terms of their pharmacokinetic parameters following oral administration of the tablets to 18 volunteers.

  15. 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.

  16. Taking the Focus Away from the Self: Low Individualism Mediates the Effect of Oxytocin on Creativity

    ERIC Educational Resources Information Center

    Pfundmair, Michaela; Frey, Dieter; Hodgson, Timothy L.

    2017-01-01

    Recently, it has been shown that the hormone oxytocin can enable creative cognition. The aim of this investigation was to examine the psychological mechanism via which oxytocin influences creativity. Two opposing explanatory approaches suggested by previous research were investigated: It was predicted that the effect of oxytocin on creativity…

  17. 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

  18. 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.

  19. Endocannabinoid signaling mediates oxytocin-driven social reward.

    PubMed

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

    2015-11-10

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

  20. Inhibition of oxytocin receptor function by direct binding of progesterone.

    PubMed

    Grazzini, E; Guillon, G; Mouillac, B; Zingg, H H

    1998-04-02

    The steroid hormone progesterone (P4) is essential for establishing and maintaining pregnancy in mammals. One of its functions includes maintenance of uterine quiescence by decreasing uterine sensitivity to the uterotonic peptide hormone oxytocin. Although it is generally held that steroid hormones such as P4 act at a genomic level by binding to nuclear receptors and modulating the expression of specific target genes, we show here that the effect of P4 on uterine sensitivity to oxytocin involves direct, non-genomic action of P4 on the uterine oxytocin receptor (OTR), a member of the G-protein-coupled receptor family. P4 inhibits oxytocin binding to OTR-containing membranes in vitro, binds with high affinity to recombinant rat OTR expressed in CHO cells, and suppresses oxytocin-induced inositol phosphate production and calcium mobilization. These effects are highly steroid- and receptor-specific, because binding and signalling functions of the closely related human OTR are not affected by P4 itself but by the P4 metabolite 5beta-dihydroprogesterone. Our findings provide the first evidence for a direct interaction between a steroid hormone and a G-protein-coupled receptor and define a new level of crosstalk between the peptide- and steroid-hormone signalling pathways.

  1. 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.

  2. Generous to whom? The influence of oxytocin on social discounting.

    PubMed

    Pornpattananangkul, Narun; Zhang, Junfeng; Chen, Qiaoyu; Kok, Bing Cai; Yu, Rongjun

    2017-02-20

    Oxytocin is thought to play an essential role in pro-social behaviors, such as generosity and altruism, in humans. Yet, most research in humans that demonstrated the pro-social effect of oxytocin had participants interact with partners who were total strangers to them. In real life, however, people often interact with others varying in social relatedness with them (a concept known as social distance), ranging from their parents to total strangers. Here we employed the social-discounting framework to investigate whether the effect of oxytocin on prosociality depends on the social distance between the participants and their interaction partners. In a double-blind, placebo-controlled experiment (n=172 participants), we measured the amount of money participants were willing to forgo to another person as a function of social distance. We found that oxytocin administration selectively enhanced amount of money forgone toward total strangers, as opposed to someone closer to participants, suggesting that social distance constrained the pro-social effect of oxytocin.

  3. Emotion recognition and oxytocin in patients with schizophrenia

    PubMed Central

    Averbeck, B. B.; Bobin, T.; Evans, S.; Shergill, S. S.

    2012-01-01

    Background Studies have suggested that patients with schizophrenia are impaired at recognizing emotions. Recently, it has been shown that the neuropeptide oxytocin can have beneficial effects on social behaviors. Method To examine emotion recognition deficits in patients and see whether oxytocin could improve these deficits, we carried out two experiments. In the first experiment we recruited 30 patients with schizophrenia and 29 age- and IQ-matched control subjects, and gave them an emotion recognition task. Following this, we carried out a second experiment in which we recruited 21 patients with schizophrenia for a double-blind, placebo-controlled cross-over study of the effects of oxytocin on the same emotion recognition task. Results In the first experiment we found that patients with schizophrenia had a deficit relative to controls in recognizing emotions. In the second experiment we found that administration of oxytocin improved the ability of patients to recognize emotions. The improvement was consistent and occurred for most emotions, and was present whether patients were identifying morphed or non-morphed faces. Conclusions These data add to a growing literature showing beneficial effects of oxytocin on social–behavioral tasks, as well as clinical symptoms. PMID:21835090

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

    PubMed

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

    2011-12-01

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

  5. 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.

  6. Quality analysis of salmon calcitonin in a polymeric bioadhesive pharmaceutical formulation: sample preparation optimization by DOE.

    PubMed

    D'Hondt, Matthias; Van Dorpe, Sylvia; Mehuys, Els; Deforce, Dieter; DeSpiegeleer, Bart

    2010-12-01

    A sensitive and selective HPLC method for the assay and degradation of salmon calcitonin, a 32-amino acid peptide drug, formulated at low concentrations (400 ppm m/m) in a bioadhesive nasal powder containing polymers, was developed and validated. The sample preparation step was optimized using Plackett-Burman and Onion experimental designs. The response functions evaluated were calcitonin recovery and analytical stability. The best results were obtained by treating the sample with 0.45% (v/v) trifluoroacetic acid at 60 degrees C for 40 min. These extraction conditions did not yield any observable degradation, while a maximum recovery for salmon calcitonin of 99.6% was obtained. The HPLC-UV/MS methods used a reversed-phase C(18) Vydac Everest column, with a gradient system based on aqueous acid and acetonitrile. UV detection, using trifluoroacetic acid in the mobile phase, was used for the assay of calcitonin and related degradants. Electrospray ionization (ESI) ion trap mass spectrometry, using formic acid in the mobile phase, was implemented for the confirmatory identification of degradation products. Validation results showed that the methodology was fit for the intended use, with accuracy of 97.4+/-4.3% for the assay and detection limits for degradants ranging between 0.5 and 2.4%. Pilot stability tests of the bioadhesive powder under different storage conditions showed a temperature-dependent decrease in salmon calcitonin assay value, with no equivalent increase in degradation products, explained by the chemical interaction between salmon calcitonin and the carbomer polymer.

  7. Dehydration anorexia is attenuated in oxytocin-deficient mice.

    PubMed

    Rinaman, Linda; Vollmer, Regis R; Karam, Joseph; Phillips, Donnesha; Li, Xia; Amico, Janet A

    2005-06-01

    Evidence in rats suggests that central oxytocin (OT) signaling pathways contribute to suppression of food intake during dehydration (i.e., dehydration anorexia). The present study examined water deprivation-induced dehydration anorexia in wild-type and OT -/- mice. Mice were deprived of food alone (fasted, euhydrated) or were deprived of both food and water (fasted, dehydrated) for 18 h overnight. Fasted wild-type mice consumed significantly less chow during a 60-min refeeding period when dehydrated compared with their intake when euhydrated. Conversely, fasting-induced food intake was slightly but not significantly suppressed by dehydration in OT -/- mice, evidence for attenuated dehydration anorexia. In a separate experiment, mice were deprived of water (but not food) overnight for 18 h; then they were anesthetized and perfused with fixative for immunocytochemical analysis of central Fos expression. Fos was elevated similarly in osmo- and volume-sensitive regions of the basal forebrain and hypothalamus in wild-type and OT -/- mice after water deprivation. OT-positive neurons expressed Fos in dehydrated wild-type mice, and vasopressin-positive neurons were activated to a similar extent in wild-type and OT -/- mice. Conversely, significantly fewer neurons within the hindbrain dorsal vagal complex were activated in OT -/- mice after water deprivation compared with activation in wild-type mice. These findings support the view that OT-containing projections from the hypothalamus to the hindbrain are necessary for the full expression of compensatory behavioral and physiological responses to dehydration.

  8. [Modifications of contingent negative variation (CNV) induced by oxytocin infusion].

    PubMed

    Timsit-Berthier, M; Mantanus, H; Geenen, V; Adam, F; Legros, J J

    1988-12-01

    The central effects of an intravenous infusion of oxytocin (OT), 3,680 mIU in 45 min, were investigated in 20 male volunteers in a double-blind study combining an electrophysiological and a psychometrical approach. The electrophysiological approach consisted in the simultaneous recording of the CNV (Fz-A1 and Cz-A1) and the spontaneous EEG (bipolar P3-P4) recording on which was carried out an FFT analysis. On the other hand, various psychometric tests allowed to assess memory (Rey's tests), attention (K-T test) processes and mood changes (visual analogue scales). Within the hour following the infusion, OT induced a significant decrease of CNV amplitude and an increase of the post-imperative positive component at Cz-A1. A similar effect was still observed one week later, but was more marked at Fz-A1. Neither mood nor attention tests evidenced any significant effect of OT. Only one item of the memory test PRM (item 4) revealed a significant impairment after OT infusion. There were no subjective effects reported. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man. This action, which may be characterized as an acceleration of CNV "habituation" is the opposite of the one described with vasopressin.

  9. 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.

  10. Effect of oxytocin pretreatment on cannabis outcomes in a brief motivational intervention.

    PubMed

    Sherman, Brian J; Baker, Nathaniel L; McRae-Clark, Aimee L

    2017-03-01

    Motivational enhancement therapy (MET) is efficacious in reducing cannabis use, yet benefits are generally short-lived. Oxytocin is a hypothalamic neuropeptide that promotes prosocial behaviors and plays a role in drug-related neuroadaptations; as such, oxytocin may enhance the effect of MET on cannabis outcomes. Cannabis dependent adults were randomized to receive MET plus oxytocin (n =8) or placebo (n =8). Participants receiving oxytocin showed reductions in amount of cannabis used daily and number of sessions per day. Participants receiving placebo did not evidence significant reductions. Powered clinical trials of oxytocin-enhanced MET for cannabis use disorder are warranted.

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

    PubMed

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

    2013-01-01

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

  12. 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

  13. 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.

  14. Oxytocin: its role in benign prostatic hyperplasia via the ERK pathway.

    PubMed

    Xu, Huan; Fu, Shi; Chen, Yanbo; Chen, Qi; Gu, Meng; Liu, Chong; Qiao, Zhiguang; Zhou, Juan; Wang, Zhong

    2017-04-01

    The aim of the present study was to evaluate oxytocin and benign prostatic hyperplasia (BPH), and study the cell signalling mechanism. Investigation was performed in patients about the correlation between oxytocin level and BPH. Mice were injected with oxytocin or oxytocin antagonist for 2 weeks and the prostate morphology was studied after their sacrifice. Furthermore, in vitro experiments were performed to evaluate the oxytocin effect through the MEK/ERK/RSK pathway. Oxytocin was significantly elevated in the serum and prostate tissue of patients with BPH, and a positive correlation with prostate volume indicated. In the animal experiments, prostate enlargement was observed in the oxytocin-treated group, whereas oxytocin antagonist reduced prostate hyperplasia. The in vitro study confirmed this result and also revealed activation of the MEK/ERK/RSK pathway. Oxytocin is highly expressed in the serum and prostate tissue of patients with BPH. In addition, oxytocin aggravates BPH and the oxytocin-induced proliferative effect on prostatic cells is mediated through the MEK/ERK/RSK pathway, at least partly. Thus, the hypothalamic regulation may be involved in development of BPH, which may open a new door to more medications for BPH in the future.

  15. PLASMA OXYTOCIN CONCENTRATION AND DEPRESSIVE SYMPTOMS: A REVIEW OF CURRENT EVIDENCE AND DIRECTIONS FOR FUTURE RESEARCH.

    PubMed

    Massey, Suena H; Backes, Katherine A; Schuette, Stephanie A

    2016-04-01

    There is substantial recent interest in the role of oxytocin in social and affiliative behaviors-animal models of depression have suggested a link between oxytocin and mood. We reviewed literature to date for evidence of a potential relationship between peripheral oxytocin concentration and depressive symptoms in humans. Pubmed(®) and PsychINFO(®) were searched for biomedical and social sciences literature from 1960 to May 19, 2015 for empirical articles in English involving human subjects focused on the relationship between peripheral oxytocin concentration and depressive symptoms, excluding articles on the oxytocin receptor gene, or involving exogenous (i.e. intranasal) administration of oxytocin. Eight studies meeting criteria were identified and formally reviewed. Studies of pregnant women suggested an inverse relationship between oxytocin level and depressive symptom severity. Findings in nonpregnant women were broadly consistent with the role of oxytocin release in response to stress supported by animal studies. The relationship between oxytocin and depression in men appeared to be in the opposite direction, possibly reflecting the influence of gonadal hormones on oxytocinergic functioning found in other mammalian species. Overall, small sample sizes, heterogeneity in study designs, and other methodological limitations may account for inconsistent findings. Future research utilizing reliable oxytocin measurement protocols including measurements across time, larger sample sizes, and sample homogeneity with respect to multiple possible confounders (age, gender, race and ethnicity, ovarian status among women, and psychosocial context) are needed to elucidate the role of oxytocin in the pathogenesis of depression, and could guide the design of novel pharmacologic agents.

  16. Oxytocin reduces background anxiety in a fear-potentiated startle paradigm: peripheral vs central administration.

    PubMed

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

    2011-11-01

    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.

  17. 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.

  18. Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date.

    PubMed

    Lee, Mary R; Rohn, Matthew C H; Tanda, Gianluigi; Leggio, Lorenzo

    2016-02-01

    The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning, and memory processes. As such, there is increasing interest in oxytocin as a potential treatment for addictions. The endogenous oxytocin system is itself altered by short- or long-term exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin administration on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis, and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction.

  19. Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons.

    PubMed

    Ripamonti, Silvia; Ambrozkiewicz, Mateusz C; Guzzi, Francesca; Gravati, Marta; Biella, Gerardo; Bormuth, Ingo; Hammer, Matthieu; Tuffy, Liam P; Sigler, Albrecht; Kawabe, Hiroshi; Nishimori, Katsuhiko; Toselli, Mauro; Brose, Nils; Parenti, Marco; Rhee, JeongSeop

    2017-02-23

    Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons. Conversely, genetic elimination of oxytocin receptors increases the expression of protein components of excitatory synapses and excitatory synaptic transmission in vitro. In vivo, oxytocin-receptor-deficient hippocampal pyramidal neurons develop more complex dendrites, which leads to increased spine number and reduced γ-oscillations. These results indicate that oxytocin controls the development of hippocampal excitatory neurons and contributes to the maintenance of a physiological excitation/inhibition balance, whose disruption can cause neurobehavioral disturbances.

  20. Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date

    PubMed Central

    Lee, Mary R.; Rohn, Matthew C.H.; Tanda, Gianluigi; Leggio, Lorenzo

    2016-01-01

    The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning and memory processes. As such there is increasing interest in oxytocin as a potential treatment for addictions. The oxytocin system is itself altered by acute or chronic exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction. PMID:26932552

  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. Oxytocin increases the influence of public service advertisements.

    PubMed

    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.

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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.

  9. Analysis of Lard in Lipstick Formulation Using FTIR Spectroscopy and Multivariate Calibration: A Comparison of Three Extraction Methods.

    PubMed

    Waskitho, Dri; Lukitaningsih, Endang; Sudjadi; Rohman, Abdul

    2016-01-01

    Analysis of lard extracted from lipstick formulation containing castor oil has been performed using FTIR spectroscopic method combined with multivariate calibration. Three different extraction methods were compared, namely saponification method followed by liquid/liquid extraction with hexane/dichlorometane/ethanol/water, saponification method followed by liquid/liquid extraction with dichloromethane/ethanol/water, and Bligh & Dyer method using chloroform/methanol/water as extracting solvent. Qualitative and quantitative analysis of lard were performed using principle component (PCA) and partial least square (PLS) analysis, respectively. The results showed that, in all samples prepared by the three extraction methods, PCA was capable of identifying lard at wavelength region of 1200-800 cm(-1) with the best result was obtained by Bligh & Dyer method. Furthermore, PLS analysis at the same wavelength region used for qualification showed that Bligh and Dyer was the most suitable extraction method with the highest determination coefficient (R(2)) and the lowest root mean square error of calibration (RMSEC) as well as root mean square error of prediction (RMSEP) values.

  10. 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

  11. 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

  12. Oxytocin promotes social bonding in dogs

    PubMed Central

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

    2014-01-01

    Recent evidence suggests that enduring social bonds have fitness benefits. However, very little is known about the neural circuitry and neurochemistry underlying the formation and maintenance of stable social bonds outside reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the hypothalamus in mammals, regulates many complex forms of social behavior and cognition in both human and nonhuman animals. Animal research, however, has concentrated on monogamous mammals, and it remains unknown whether OT also modulates social bonds in nonreproductive contexts. In this study we provide behavioral evidence that exogenous OT promotes positive social behaviors in the domestic dog toward not only conspecifics but also human partners. Specifically, when sprayed with OT, dogs showed higher social orientation and affiliation toward their owners and higher affiliation and approach behaviors toward dog partners than when sprayed with placebo. Additionally, the exchange of socio-positive behaviors with dog partners triggered the release of endogenous OT, highlighting the involvement of OT in the development of social relationships in the domestic dog. These data provide new insight into the mechanisms that facilitate the maintenance of close social bonds beyond immediate reproductive interest or genetic ties and complement a growing body of evidence that identifies OT as one of the neurochemical foundations of sociality in mammalian species. PMID:24927552

  13. Learning about oxytocin: pharmacologic and behavioral issues.

    PubMed

    Chini, Bice; Leonzino, Marianna; Braida, Daniela; Sala, Mariaelvina

    2014-09-01

    Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT) plays a role in neuropsychiatric disorders characterized by social dysfunction, the influence of OT on the nonsocial aspects of learning and memory have been less investigated. To foster research in this area, we review the effects of OT on learning and memory in animal models and humans. In healthy animal models, OT improves memory consolidation and extinction, but only if given at a low dose immediately after the acquisition phase. On the contrary, OT effects in healthy humans have been inconsistent; although, in this case, OT was always given before the acquisition phase and no dose-response curves have ever been drawn up. Interestingly, a specific impairment in the reversal of learning has been found in mice devoid of OT receptors and OT has been demonstrated to enhance fear extinction in rodents. All together, these data suggest that OT plays a role in elementary forms of behavioral flexibility and adaptive responses and support its therapeutic potential in neuropsychiatric disorders characterized by cognitive inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease, Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has been shown to improve cognitive flexibility in OT receptor-deficient mice, and scattered findings indicate that intranasal OT has positive effects on the memory of patients with schizophrenia or posttraumatic stress disorders. Further studies of the therapeutic potential of OT as an enhancer of learning and memory are warranted.

  14. The neuropeptide oxytocin modulates consumer brand relationships.

    PubMed

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

    2015-10-09

    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.

  15. 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

  16. Organizational effects of oxytocin on serotonin innervation.

    PubMed

    Eaton, Jennifer L; Roache, Laura; Nguyen, Khanhbao N; Cushing, Bruce S; Troyer, Emma; Papademetriou, Eros; Raghanti, Mary Ann

    2012-01-01

    Oxytocin (OT) has an organizational effect within the central nervous system and can have long-lasting effects on the expression of social behavior. OT has recently been implicated in modulating the release of serotonin through activation of receptors in the raphe nuclei. Here we test the hypothesis that OT can have an organizational effect on the serotonergic system. Male prairie voles received an intraperitoneal injection on postnatal day 1 with 3.0 or .3 µg OT, an OT antagonist, or a saline control. Brains were collected on day 21 and immunostained for serotonin. Serotonin axons were quantified in the anterior hypothalamus, cortical amygdala, medial amygdala, paraventricular nucleus of the hypothalamus, and ventromedial hypothalamus. Males treated with 3.0 µg OT displayed significantly higher serotonin axon length densities in the anterior hypothalamus, cortical amygdala, and the ventromedial hypothalamus than control males. These results support the hypothesis that OT has an organizational effect on the serotonin system during the neonatal period, and that these effects are site-specific.

  17. 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

  18. 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.

  19. Requirements Formulation and Dynamic Jitter Analysis for Fourier-Kelvin Stellar Interferometer

    NASA Technical Reports Server (NTRS)

    Liu, Kuo-Chia; Hyde, Tristram; Blaurock, Carl; Bolognese, Jeff; Howard, Joseph; Danchi, William

    2004-01-01

    The Fourier-Kelvin Stellar Interferometer (FKSI) has been proposed to detect and characterize extra solar giant planets. The baseline configuration for FKSI is a two- aperture, structurally connected nulling interferometer, capable of providing null depth less than lo4 in the infrared. The objective of this paper is to summarize the process for setting the top level requirements and the jitter analysis performed on FKSI to date. The first part of the paper discusses the derivation of dynamic stability requirements, necessary for meeting the FKSI nulling demands. An integrated model including structures, optics, and control systems has been developed to support dynamic jitter analysis and requirements verification. The second part of the paper describes how the integrated model is used to investigate the effects of reaction wheel disturbances on pointing and optical path difference stabilities.

  20. CFD analysis of the aerosolization of carrier-based dry powder inhaler formulations

    NASA Astrophysics Data System (ADS)

    Zhou, Qi (Tony); Tong, Zhenbo; Tang, Patricia; Yang, Runyu; Chan, Hak-Kim

    2013-06-01

    This study applied computational fluid dynamics (CFD) analysis to investigate the role of device design on the aerosolization of a carrier-based dry powder inhaler (DPI). The inhaler device was modified by reducing the inlet size, decreasing the mouthpiece length and increasing the mesh grid voidage. The flow patterns in the inhaler device were examined. It was observed that there was no significant influence on the aerosol performance with the reduced mouthpiece. When the inlet size was reduced to one third of the original one, the fine particle fraction (FPF), defined as mount of inhalable fine particles below 5μm in the aerosol, was improved significantly from 17.7% to 24.3%. The CFD analysis indicated that the increase in FPF was due to increasing air velocity for the smaller inlet. No significant difference was shown in FPF when the grid voidage was increased, but more drugs deposited in the mouthpiece and throat.

  1. 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.

  2. 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.

  3. 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.

  4. Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors.

    PubMed

    Pobbe, Roger L H; Pearson, Brandon L; Defensor, Erwin B; Bolivar, Valerie J; Young, W Scott; Lee, Heon-Jin; Blanchard, D Caroline; Blanchard, Robert J

    2012-03-01

    A wealth of studies has implicated oxytocin (Oxt) and its receptors (Oxtr) in the mediation of social behaviors and social memory in rodents. It has been suggested that failures in this system contribute to deficits in social interaction that characterize autism spectrum disorders (ASD). In the current analyses, we investigated the expression of autism-related behaviors in mice that lack the ability to synthesize the oxytocin receptor itself, Oxtr knockout (KO) mice, as compared to their wild-type (WT) littermates. In the visible burrow system, Oxtr KO mice showed robust reductions in frontal approach, huddling, allo-grooming, and flight, with more time spent alone, and in self-grooming, as compared to WT. These results were corroborated in the three-chambered test: unlike WT, Oxtr KO mice failed to spend more time in the side of the test box containing an unfamiliar CD-1 mouse. In the social proximity test, Oxtr KO mice showed clear reductions in nose to nose and anogenital sniff behaviors oriented to an unfamiliar C57BL/6J (B6) mouse. In addition, our study revealed no differences between Oxtr WT and KO genotypes in the occurrence of motor and cognitive stereotyped behaviors. A significant genotype effect was found in the scent marking analysis, with Oxtr KO mice showing a decreased number of scent marks, as compared to WT. Overall, the present data indicate that the profile for Oxtr KO mice, including consistent social deficits, and reduced levels of communication, models multiple components of the ASD phenotype. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  5. 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.

  6. 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.

  7. HPLC/UV analysis of chlorfenapyr residues in cabbage and soil to study the dynamics of different formulations.

    PubMed

    Cao, Yongsong; Chen, Jiuxin; Wang, Yuelong; Liang, Ji; Chen, Lihua; Lu, Yitong

    2005-11-01

    The chlorfenapyr analysis method of residue, its degradation and final residue in soil and cabbage were studied. Residues of chlorfenapyr were extracted from soil and cabbage with acetone/water, purified by liquid/liquid partition and chromatographic column, concentrated to a small volume, and then determined by HPLC equipped with UV detector. The mean accuracy of analytical method were 93.3% and 90.6% in soil and cabbage, respectively; the precision (repeatability) in cabbage ranging from 1.7% to 11.8%, in soil ranging from 2.8% to 11.2%; the precision (reproducibility) in cabbage ranged from 2.2% to 12.1%, in soil it ranged from 2.4% to 11.5%. The minimum detectable amount of chlorfenapyr was 0.65 ng, the minimum detectable concentration was 0.0162 mg kg-1. The degradation of chlorfenapyr formulations in soil and cabbage was determined. The results showed that chlorfenapyr nanoformulation and suspension concentration degradation in soil coincided with C=0.2538 e-0.1612t, C=0.537 e-0.1754t, respectively; the half-lives were about 4.3 d and 3.9 d, respectively. Two kinds of chlorfenapyr formulation degradation in cabbage coincided with C=4.0431 e-0.3103t, C=6.9611 e-0.2686t respectively; the half-lives were about 2.2 d and 2.6, d, respectively. When chlorfenapyr formulations were applied according to the double recommended dose, the final residues in cabbage were much lower than the USA EPA's maximum residue limit of 1 mg kg-1 in vegetables. The degradation rate of chlorfenapyr nanoformulation was faster than that of suspension concentration, and the former residue was also less in soil. Therefore, a harvest interval should be more than 5 d, and a dosage of 900 mL/hm2 was suggested for chlorfenapyr suspension concentration, which could be considered as safe to human beings and animals. Chlorfenapyr nanoformulation was safer than suspension concentration, its harvest interval and dosage can attain a high level.

  8. Analysis and formulation of a class of complex dynamic optimization problems

    NASA Astrophysics Data System (ADS)

    Kameswaran, Shivakumar

    The Direct Transcription approach, also known as the direct simultaneous approach, is a widely used solution strategy for the solution of dynamic optimization problems involving differential-algebraic equations (DAEs). Direct transcription refers to the procedure of approximating the infinite dimensional problem by a finite dimensional one, which is then solved using a nonlinear programming (NLP) solver tailored to large-scale problems. Systems governed by partial differential equations (PDEs) can also be handled by spatially discretizing the PDEs to convert them to a system of DAEs. The objective of this thesis is firstly to ensure that direct transcription using Radau collocation is provably correct, and secondly to widen the applicability of the direct simultaneous approach to a larger class of dynamic optimization and optimal control problems (OCPs). This thesis aims at addressing these issues using rigorous theoretical tools and/or characteristic examples, and at the same time use the results for solving large-scale industrial applications to realize the benefits. The first part of this work deals with the analysis of convergence rates for direct transcription of unconstrained and final-time equality constrained optimal control problems. The problems are discretized using collocation at Radau points. Convergence is analyzed from an NLP/matrix-algebra perspective, which enables the prediction of the conditioning of the direct transcription NLP as the mesh size becomes finer. Several convergence results are presented along with tests on numerous example problems. These convergence results lead to an adjoint estimation procedure given the Lagrange multipliers for the large-scale NLP. The work also reveals the role of process control concepts such as controllability on the convergence analysis, and provides a very important link between control and optimization inside the framework of dynamic optimization. As an effort to extend the applicability of the direct

  9. 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.

  10. 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.

  11. 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.

  12. Mining constraint relationships and redundancies with association analysis for optimization problem formulation

    NASA Astrophysics Data System (ADS)

    Cutbill, Adam; Wang, G. Gary

    2016-01-01

    Constraints are necessary in optimization problems to steer optimization algorithms away from solutions which are not feasible or practical. However, redundant constraints are often added, which needlessly complicate the problem's description. This article introduces a probabilistic method to identify redundant inequality constraints for black-box optimization problems. The method uses Jaccard similarity to find item groups where the occurrence of a single item implies the occurrence of all other items in the group. The remaining groups are then mined with association analysis. Furthermore, unnecessary constraints are classified as redundant owing to co-occurrence, implication or covering. These classifications are presented as rules (in readable text), to indicate the relationships among constraints. The algorithm is applied to mathematical problems and to the engineering design of a pressure vessel. It was found that the rules are informative and correct, based on the available samples. Limitations of the proposed methods are also discussed.

  13. 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.

  14. Orexin action on oxytocin neurons in the paraventricular nucleus of the hypothalamus.

    PubMed

    Maejima, Yuko; Takahashi, Shinichi; Takasu, Katsuya; Takenoshita, Seiichi; Ueta, Yoichi; Shimomura, Kenju

    2017-04-12

    Oxytocin neurons in the paraventricular nucleus (PVN) of the hypothalamus play an important role in food intake regulation. It has been shown that the secretion of oxytocin from the hypothalamus shows a diurnal circadian rhythmic pattern and disturbance of this pattern leads to the development of obesity. However, whether oxytocin secretion from the PVN has a diurnal pattern remains unknown. Here, we show that oxytocin secretion from the PVN does have a diurnal pattern and that the terminals of orexin neurons, the neuropeptide responsible for regulating the sleep-wake rhythm, are synapsed with PVN oxytocin neurons. Using transgenic rats selectively expressing monomeric red fluorescent protein 1 in oxytocin neurons, we found that orexin-A inhibits the activities of PVN oxytocin neurons by inhibiting glutamatergic excitatory synaptic input. These data suggest that orexin is a possible candidate to regulate the circadian rhythm of PVN oxytocin neurons. The circadian rhythmic secretion of oxytocin is considered to play an important role in maintaining homeostasis, including body weight regulation. Our present data indicate a possible contribution of orexin toward the development of circadian rhythm in PVN oxytocin neurons.

  15. 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

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

    PubMed

    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

    1998-04-01

    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.

  17. 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.

  18. 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.

  19. Separation and analysis of trace degradants in a pharmaceutical formulation using on-line capillary isotachophoresis-NMR.

    PubMed

    Eldridge, Stacie L; Almeida, Valentino K; Korir, Albert K; Larive, Cynthia K

    2007-11-15

    NMR spectroscopy is widely used in the pharmaceutical industry for the structure elucidation of pharmaceutical impurities, especially when coupled to a separation method, such as HPLC. However, NMR has relatively poor sensitivity compared with other techniques such as mass spectrometry, limiting its applicability in impurity analyses. This limitation is addressed here through the on-line coupling of microcoil NMR with capillary isotachophoresis (cITP), a separation method that can concentrate dilute components by 2-3 orders of magnitude. With this approach, 1H NMR spectra can be acquired for microgram (nanomole) quantities of trace impurities in a complex sample matrix. cITP-NMR was used in this work to isolate and detect 4-aminophenol (PAP) in an acetaminophen sample spiked at the 0.1% level, with no interference from the parent compound. Analysis of an acetaminophen thermal degradation sample revealed resonances of several degradation products in addition to PAP, confirming the effectiveness of on-line cITP-NMR for trace analyses of pharmaceutical formulations. Subsequent LC-MS/MS analysis provided complementary information for the structure elucidation of the unknown degradation products, which were dimers formed during the degradation process.

  20. Enantiomeric analysis of overlapped chromatographic profiles in the presence of interferences. Determination of ibuprofen in a pharmaceutical formulation containing homatropine.

    PubMed

    Padró, J M; Osorio-Grisales, J; Arancibia, J A; Olivieri, A C; Castells, C B

    2016-10-07

    In this work, we studied the combination of chemometric methods with chromatographic separations as a strategy applied to the analysis of enantiomers when complete enantioseparation is difficult or requires long analysis times and, in addition, the target signals have interference from the matrix. We present the determination of ibuprofen enantiomers in pharmaceutical formulations containing homatropine as interference by chiral HPLC-DAD detection in combination with partial least-squares algorithms. The method has been applied to samples containing enantiomeric ratios from 95:5 to 99.5:0.5 and coelution of interferents. The results were validated using univariate calibration and without homatropine. Relative error of the method was less than 4.0%, for both enantiomers. Limits of detection (LOD) and quantification (LOQ) for (S)-(+)-ibuprofen were 4.96×10(-10) and 1.50×10(-9)mol, respectively. LOD and LOQ for the R-(-)-ibuprofen were LOD=1.60×10(-11)mol and LOQ=4.85×10(-11)mol, respectively. Finally, the chemometric method was applied to the determination of enantiomeric purity of commercial pharmaceuticals. The ultimate goal of this research was the development of rapid, reliable, and robust methods for assessing enantiomeric purity by conventional diode array detector assisted by chemometric tools.

  1. Finite-difference analysis of plasmon-induced forces of metal nano-clusters by the Lorentz force formulation.

    PubMed

    Fujii, Masafumi

    2010-12-20

    We analyze light-induced forces on metal nano-spheres by using the three-dimensional finite-difference time-domain method with the Lorentz force formulation. Convergent analysis of the force on metal nano-particle clusters has been achieved by integrating the Lorentz and the Coulomb forces over the volume of the metal particles. Comparison to the Mie theory of radiation pressure on metal spheres under a plane wave illumination has verified rigorously the accuracy of the numerical method. We also analyze separate two metal spheres in close proximity and the results of the induced forces are compared to those in previous publications. The present method allows analysis of forces on various irregular structures; we apply the method to touching metal spheres, forming a simple cluster with a slight deformation at the contact point, to analyze the forces induced by the plasmonic resonance of the clusters. We show that the fundamental resonance modes, which newly appear in an infrared range when spheres are touching, exhibit strong binding forces within the clusters. Based on the numerical analyses we identify the resonance modes and evaluate quantitatively the infrared-induced forces on metal nano-sphere clusters.

  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. The regulation of oxytocin receptor gene expression during adipogenesis.

    PubMed

    Yi, K J; So, K H; Hata, Y; Suzuki, Y; Kato, D; Watanabe, K; Aso, H; Kasahara, Y; Nishimori, K; Chen, C; Katoh, K; Roh, S G

    2015-05-01

    Although it has been reported that oxytocin stimulates lipolysis in adipocytes, changes in the expression of oxytocin receptor (OTR) mRNA in adipogenesis are still unknown. The present study aimed to investigate the expression of OTR mRNA during adipocyte differentiation and fat accumulation in adipocytes. OTR mRNA was highly expressed in adipocytes prepared from mouse adipose tissues compared to stromal-vascular cells. OTR mRNA expression was increased during the adipocyte differentiation of 3T3-L1 cells. OTR expression levels were higher in subcutaneous and epididymal adipose tissues of 14-week-old male mice compared to 7-week-old male mice. Levels of OTR mRNA expression were higher in adipose tissues at four different sites of mice fed a high-fat diet than in those of mice fed a normal diet. The OTR expression level was also increased by refeeding for 4 h after fasting for 16 h. Oxytocin significantly induced lipolysis in 3T3-L1 adipocytes. In conclusion, a new regulatory mechanism is demonstrated for oxytocin to control the differentiation and fat accumulation in adipocytes via activation of OTR as a part of the hypothalamic-pituitary-adipose axis.

  4. 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.

  5. Electrophysiological Actions of Oxytocin on the Rabbit Myometrium

    PubMed Central

    Kleinhaus, A. L.; Kao, C. Y.

    1969-01-01

    The electrical activities of myometrial cells of the pregnant rabbit uterus have been studied by means of sucrose-gap and intracellular micro-electrode recording techniques. The resting potential of the myometrial cell was about -50 mv, and it is unaffected by the duration of pregnancy or placental attachment. Action potentials of the myometrium, although dependent on external Na+, were not always of the regenerative type; preparations from nonparturient uteri often produce mainly small spikes. The mean spike amplitude was 35 mv, rising at a mean maximum rate of 3 v/sec. Oxytocin, in concentrations less than 500 µU/ml, increased the mean spike amplitude to 48 mv and the mean maximum rate of rise to 7 v/sec, without affecting the resting potential. The relation between membrane potential and dV/dt of the spike was steepened by oxytocin, suggesting that oxytocin increased the number of normally sparse sodium gates in the myometrial membrane. By this action, oxytocin is believed to increase the probability of successful regenerative spikes and thereby initiate electrical activity in quiescent preparations, increase the frequency of burst discharges, the number of spikes in each burst, and the amplitude of spikes in individual cells. PMID:5783010

  6. 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.

  7. Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted?

    PubMed

    McCullough, Michael E; Churchland, Patricia Smith; Mendez, Armando J

    2013-09-01

    Research on the neurobiological and behavioral effects of oxytocin (OT), as well as on its possible therapeutic applications, has intensified in the past decade. Accurate determination of peripheral OT levels is essential to reach meaningful conclusions and to motivate, support and inform clinical interventions. Different, but concordant, methods for measuring plasma OT have been developed over the past four decades, but since 2004 several commercially available methods have been favored in research with humans. Evaluation of these methods reveals that they lack reliability when used on unextracted samples of human fluids, and that they tag molecules in addition to OT, yielding estimates that are wildly discrepant with an extensive body of earlier findings that were obtained using methods that are well validated, but more laborious. An accurate, specific, and readily available method for measuring OT that can be adopted as the standard in the field is urgently needed for advances in our understanding of OT's roles in cognition and behavior.

  8. 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.

  9. Sunscreen product formulation.

    PubMed

    Tanner, Paul R

    2006-01-01

    On the surface, sunscreen products are pretty simple. They consist of a delivery vehicle containing one or more sunscreen active ingredients. When applied to the skin, these sunscreen actives intercept solar ultraviolet (UV) rays before they can damage the underlying skin. However, while conceptually simple, a detailed analysis reveals that sunscreen formulations are quite complex, requiring careful selection of sunscreen active and vehicle components to control multiple performance and in-use parameters.Thus, to enable a better understanding and appreciation of sunscreen products, the typical steps in formulating a sunscreen product are described. Throughout this process, the key is to apply scientific principles together with a bit of formulation art to holistically create the best sunscreen product that meets the design targets--a sunscreen product that people will use regularly and properly.

  10. Role of oxytocin signaling in the regulation of body weight.

    PubMed

    Blevins, James E; Ho, Jacqueline M

    2013-12-01

    Obesity and its associated metabolic disorders are growing health concerns in the US and worldwide. In the US alone, more than two-thirds of the adult population is classified as either overweight or obese [1], highlighting the need to develop new, effective treatments for these conditions. Whereas the hormone oxytocin is well known for its peripheral effects on uterine contraction during parturition and milk ejection during lactation, release of oxytocin from somatodendrites and axonal terminals within the central nervous system (CNS) is implicated in both the formation of prosocial behaviors and in the control of energy balance. Recent findings demonstrate that chronic administration of oxytocin reduces food intake and body weight in diet-induced obese (DIO) and genetically obese rodents with impaired or defective leptin signaling. Importantly, chronic systemic administration of oxytocin out to 6 weeks recapitulates the effects of central administration on body weight loss in DIO rodents at doses that do not result in the development of tolerance. Furthermore, these effects are coupled with induction of Fos (a marker of neuronal activation) in hindbrain areas (e.g. dorsal vagal complex (DVC)) linked to the control of meal size and forebrain areas (e.g. hypothalamus, amygdala) linked to the regulation of food intake and body weight. This review assesses the potential central and peripheral targets by which oxytocin may inhibit body weight gain, its regulation by anorexigenic and orexigenic signals, and its potential use as a therapy that can circumvent leptin resistance and reverse the behavioral and metabolic abnormalities associated with DIO and genetically obese models.

  11. 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...

  12. 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.

  13. Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration.

    PubMed

    Elabd, Christian; Cousin, Wendy; Upadhyayula, Pavan; Chen, Robert Y; Chooljian, Marc S; Li, Ju; Kung, Sunny; Jiang, Kevin P; Conboy, Irina M

    2014-06-10

    The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation; however, systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin--a hormone best known for its role in lactation, parturition and social behaviours--is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signalling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation through activation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle but instead leads to premature sarcopenia. Considering that oxytocin is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle ageing.

  14. Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion.

    PubMed

    De Dreu, Carsten K W

    2012-07-01

    An experiment examined whether and how the relationship between individual differences in social attachment and cooperation is modulated by brain oxytocin, a neuropeptide implicated both in parent-child bonding, and in social approach. Healthy males completed a validated attachment style measure, received intranasal oxytocin or placebo, and privately chose between cooperation and non-cooperation in an incentivized social dilemma with an anonymous stranger. Attachment anxiety--the tendency to fear rejection by others--had few effects and was not modulated by oxytocin. However, oxytocin interacted with attachment avoidance--the tendency to fear dependency and closeness in interpersonal relations. Especially among participants high rather than low in attachment avoidance, oxytocin reduced betrayal aversion, and increased trust and cooperation compared to placebo. Effects of attachment avoidance and oxytocin on cooperation were mediated by betrayal aversion, and not by affiliation tendencies.

  15. Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices.

    PubMed

    Zheng, Jing-Jing; Li, Shu-Jing; Zhang, Xiao-Di; Miao, Wan-Ying; Zhang, Dinghong; Yao, Haishan; Yu, Xiang

    2014-03-01

    Sensory experience is critical to development and plasticity of neural circuits. Here we report a new form of plasticity in neonatal mice, where early sensory experience cross-modally regulates development of all sensory cortices via oxytocin signaling. Unimodal sensory deprivation from birth through whisker deprivation or dark rearing reduced excitatory synaptic transmission in the correspondent sensory cortex and cross-modally in other sensory cortices. Sensory experience regulated synthesis and secretion of the neuropeptide oxytocin as well as its level in the cortex. Both in vivo oxytocin injection and increased sensory experience elevated excitatory synaptic transmission in multiple sensory cortices and significantly rescued the effects of sensory deprivation. Together, these results identify a new function for oxytocin in promoting cross-modal, experience-dependent cortical development. This link between sensory experience and oxytocin is particularly relevant to autism, where hypersensitivity or hyposensitivity to sensory inputs is prevalent and oxytocin is a hotly debated potential therapy.

  16. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.

    PubMed

    Dumont, G J H; Sweep, F C G J; van der Steen, R; Hermsen, R; Donders, A R T; Touw, D J; van Gerven, J M A; Buitelaar, J K; Verkes, R J

    2009-01-01

    MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

  17. Salivary oxytocin mediates the association between emotional maltreatment and responses to emotional infant faces.

    PubMed

    Bhandari, Ritu; Bakermans-Kranenburg, Marian J; van der Veen, Rixt; Parsons, Christine E; Young, Katherine S; Grewen, Karen M; Stein, Alan; Kringelbach, Morten L; van IJzendoorn, Marinus H

    2014-05-28

    Childhood emotional maltreatment has been associated with a higher risk for maltreating one's own offspring. In the current study, we explored a possible role of oxytocin in mediating the association between childhood emotional maltreatment and participants' interpretation of infant facial expressions. Oxytocin levels were measured in 102 female participants using saliva samples. They rated the mood of thirteen infants with happy, sad and neutral facial expressions. Emotional maltreatment indirectly influenced responses to happy infant faces by modulating oxytocin levels: higher self-reported emotional maltreatment was related to higher levels of salivary oxytocin which were in turn related to a more positive evaluation of happy infant expressions, but not to the evaluation of sad infant expressions. Oxytocin receptor polymorphism rs53576 did not moderate the relation between maltreatment experiences and salivary oxytocin levels. Early emotional maltreatment might indirectly affect emotional information processing by altering the oxytonergic system.

  18. Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration

    PubMed Central

    Upadhyayula, Pavan; Chen, Robert Y.; Chooljian, Marc S.; Li, Ju; Kung, Sunny; Jiang, Kevin P.; Conboy, Irina M.

    2014-01-01

    The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation, but systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin- a hormone best known for its role in lactation, parturition, and social behaviors - is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signaling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation throughactivation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle, but instead leads to premature sarcopenia. Considering that oxytocin is an FDA approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle aging. PMID:24915299

  19. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

    PubMed Central

    Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

    2010-01-01

    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients’ gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism. PMID:20160081

  20. CD38 and its role in oxytocin secretion and social behavior.

    PubMed

    Higashida, Haruhiro; Yokoyama, Shigeru; Kikuchi, Mitsuru; Munesue, Toshio

    2012-03-01

    Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release, an essential component of social cognition. Herein we describe data detailing the molecular mechanism of CD38-dependent OXT secretion in CD38 knockout mice. We also review studies that used OXT, OXT receptor (OXTR), or CD38 knockout mice. Additionally, we compare the behavioral impairments that occur in these knockout mice in relation to the OXT system and CD38. This review also examines autism spectrum disorder (ASD), which is characterized by social and communication impairments, in relation to defects in the OXT system. Two single nucleotide polymorphisms (SNPs) in the human CD38 gene are possible risk factors for ASD via inhibition of OXT function. Further analysis of CD38 in relation to the OXT system may provide a better understanding of the neuroendocrinological roles of OXT and CD38 in the hypothalamus and of the pathophysiology of ASD. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  1. Comparison of two aerosol-based detectors for the analysis of gabapentin in pharmaceutical formulations by hydrophilic interaction chromatography.

    PubMed

    Jia, Shaodong; Park, Jeong Hill; Lee, Jeongmi; Kwon, Sung Won

    2011-10-15

    Comparison of hydrophilic interaction chromatography (HILIC) columns coupled with an evaporative light scattering detector (ELSD) or charged aerosol detector (CAD) was done for the detection of gabapentin in pharmaceutical formulations. The chromatographic separations were achieved on four HILIC columns: ZIC HILIC, ZIC pHILIC, Luna HILIC, and Atlantis HILIC. Experimental factors such as mobile phase composition, acetonitrile content, and mobile phase pH were evaluated. Validation of method was done in terms of linearity, sensitivity, accuracy, and precision. The performance of ELSD detection method is comparable to that of CAD. The intra-day and inter-day variations were below 1.7% and 3.2% for CAD and 2.8%, and 3.4% for ELSD, respectively. In addition, detection sensitivities of ELSD, CAD, and UV detectors were also compared for HILIC and reversed phase (RP) modes and the highest sensitivities were obtained in the HILIC mode when connected with CAD and ELSD. The developed HILIC aerosol based detection methods were successfully applied to the analysis of gabapentin in commercial tablets and capsules.

  2. Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.

    PubMed

    Carson, Dean S; Hunt, Glenn E; Guastella, Adam J; Barber, Lachlan; Cornish, Jennifer L; Arnold, Jonathon C; Boucher, Aurelie A; McGregor, Iain S

    2010-10-01

    Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.

  3. Antinociceptive role of oxytocin in the nucleus raphe magnus of rats, an involvement of mu-opioid receptor.

    PubMed

    Wang, Jing-Wen; Lundeberg, Thomas; Yu, Long-Chuan

    2003-10-15

    Recent studies showed that oxytocin plays an important role in nociceptive modulation in the central nervous system. The present study was undertaken to investigate the role of oxytocin in antinociception in the nucleus raphe magnus (NRM) of rats and the possible interaction between oxytocin and the opioid systems. Intra-NRM injection of oxytocin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulation in rats. The antinociceptive effect of oxytocin was significantly attenuated by subsequent intra-NRM injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. Intra-NRM injection of naloxone dose-dependently antagonized the increased HWLs induced by preceding intra-NRM injection of oxytocin, indicating an involvement of opioid receptors in oxytocin-induced antinociception in the NRM of rats. Furthermore, the antinociceptive effect of oxytocin was dose-dependently attenuated by subsequent intra-NRM injection of the mu-opioid antagonist beta-funaltrexamine (beta-FNA), but not by the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) or the delta-opioid antagonist naltrindole. The results demonstrated that oxytocin plays an antinociceptive role in the NRM of rats through activating the oxytocin receptor. Moreover, mu-opioid receptors, not kappa and delta receptors, are involved in the oxytocin-induced antinociception in the NRM of rats.

  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. 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

  6. The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality.

    PubMed

    De Wilde, Tim R W; Ten Velden, Femke S; De Dreu, Carsten K W

    2017-01-11

    Groups can make better decisions than individuals when members cooperatively exchange and integrate their uniquely held information and insights. However, under conformity pressures group members are biased towards exchanging commonly known information, and away from exchanging unique information, thus undermining group decision-making quality. At the neurobiological level, conformity associates with the neuropeptide oxytocin. A double-blind placebo controlled study found no evidence for oxytocin induced conformity. Compared to placebo groups, three-person groups whose members received intranasal oxytocin, focused more on unique information (i) and repeated this information more often (ii). These findings reveal oxytocin as a neurobiological driver of group decision-making processes.

  7. The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders

    PubMed Central

    Okamoto, Yuko; Ishitobi, Makoto; Wada, Yuji; Kosaka, Hirotaka

    2016-01-01

    Administration of oxytocin has been proposed as a treatment for the core symptoms of autism spectrum disorder (ASD), including social-communicative deficit. Previous clinical trials have investigated the efficacy and safety of oxytocin intranasal single-dose and long-term administration for individuals with ASD. All studies suggest that single-dose and long-term administration are well tolerated, and no severe adverse events have been reported. However, the efficacy of long-term oxytocin administration is controversial. Some studies have reported significant improvement of the core symptoms of ASD by long-term oxytocin administration, while other studies showed no such improvement. To elucidate the factors influencing the efficacy of oxytocin administration, it is necessary to examine the effects of administration schedules (e.g., dosage amount, frequency per day) and participant characteristics (e.g., age, sex, intellectual ability). In addition to doubts about the efficacy of particular methods of administration, questions remain about the mechanism of action of intranasal oxytocin on the central nervous system. Examination of changes in the neural underpinnings of social behavior and simultaneous oxytocin levels in blood or cerebrospinal fluid could prove important in elucidating the pharmacokinetics of intranasal oxytocin administration, which could be essential for establishing optimal oxytocin treatments for individuals with ASD. PMID:27071789

  8. Strongly bonded family members in common marmosets show synchronized fluctuations in oxytocin.

    PubMed

    Finkenwirth, Christa; van Schaik, Carel; Ziegler, Toni E; Burkart, Judith M

    2015-11-01

    Oxytocin is a key regulator of social bonding and is positively linked to affiliation and prosocial behavior in several mammal species. In chimpanzees, this link is dyad-specific as affiliative interactions only elicit high oxytocin release if they involve strongly bonded individuals. These studies involved isolated dyads and sampling events. Little is known about the role of oxytocin in affiliation and social bonding, and about potential long-term patterns of bonding-related and dyad-specific oxytocin effects within highly affiliative and cooperative social groups. Our aim was to investigate whether bonding-related oxytocin signatures linked to dyadic affiliation are present in family groups of cooperatively breeding marmoset monkeys (Callithrix jacchus) that show high levels of cohesion and cooperation. In 30 dyads from four family groups and one pair, we measured urinary baseline oxytocin over six weeks and analyzed the link to bond strength (mean dyadic affiliation). Strongly bonded dyads showed synchronized longitudinal fluctuations of oxytocin, indicating that dyad-specific oxytocin effects can also be traced in the group context and in an interdependent species. We discuss these results in light of the potential function of differentiated relationships between marmoset dyads other than the breeding pair, and the role of oxytocin as a mediator for social bonding.

  9. Evidence for an interaction between CB1 cannabinoid and oxytocin receptors in food and water intake.

    PubMed

    Verty, A N A; McFarlane, J R; McGregor, I S; Mallet, P E

    2004-09-01

    Oxytocin and CB(1) cannabinoid receptors independently modulate food intake. Although an interaction between oxytocin and cannabinoid systems has been demonstrated with respect to the cannabinoid withdrawal syndrome, the interaction between these systems in modulating food intake has not yet been examined. The present study had three primary purposes: (1) to determine whether oxytocin and a CB(1) receptor antagonist block food and fluid intake in a supra-additive manner, (2) to determine the relative position of the CB(1) receptors in the chain of control of food intake in relation to the oxytocin system, and (3) to determine whether the increase in fluid intake induced by an oxytocin antagonist is mediated via cannabinoid receptors. Rats were habituated to the test environment and injection procedure, and then received intracerebroventricular (ICV) injections of various combinations of the oxytocin receptor antagonist tocinoic acid, the cannabionid receptor agonist delta(9)-tetrahydrocannabinol (THC), oxytocin, or the cannabinoid receptor antagonist SR 141716. Food and water intake and locomotor activity were then measured for 120 min. When administrated alone, SR 141716 and oxytocin dose-dependently attenuated baseline food intake, while oxytocin but not SR 141716 reduced water intake. Sub-anorectic doses of SR 141716 and oxytocin attenuated baseline feeding beyond what would be expected by the sum of the individual drug effects without affecting baseline water intake. THC stimulated feeding but not water intake. THC-induced feeding was not blocked by oxytocin, however, the oxytocin did attenuate water intake during such feeding. SR 141716 dose-dependently reduced tocinoic-acid-stimulated food intake and partially attenuated water intake. Locomotor activity was not significantly affected by any drug treatments, suggesting that effects on feeding were not due to a non-specific reduction in motivated behaviour. These findings reveal an interaction between

  10. The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders.

    PubMed

    Okamoto, Yuko; Ishitobi, Makoto; Wada, Yuji; Kosaka, Hirotaka

    2016-01-01

    Administration of oxytocin has been proposed as a treatment for the core symptoms of autism spectrum disorder (ASD), including social-communicative deficit. Previous clinical trials have investigated the efficacy and safety of oxytocin intranasal single-dose and long-term administration for individuals with ASD. All studies suggest that singledose and long-term administration are well tolerated, and no severe adverse events have been reported. However, the efficacy of long-term oxytocin administration is controversial. Some studies have reported significant improvement of the core symptoms of ASD by long-term oxytocin administration, while other studies showed no such improvement. To elucidate the factors influencing the efficacy of oxytocin administration, it is necessary to examine the effects of administration schedules (e.g., dosage amount, frequency per day) and participant characteristics (e.g., age, sex, intellectual ability). In addition to doubts about the efficacy of particular methods of administration, questions remain about the mechanism of action of intranasal oxytocin on the central nervous system. Examination of changes in the neural underpinnings of social behavior and simultaneous oxytocin levels in blood or cerebrospinal fluid could prove important in elucidating the pharmacokinetics of intranasal oxytocin administration, which could be essential for establishing optimal oxytocin treatments for individuals with ASD.

  11. Influence of oxytocin on human memory processes: validation by a control study.

    PubMed

    Kennett, D J; Devlin, M C; Ferrier, B M

    1982-07-19

    An earlier report (1) of an adverse effect of high doses of oxytocin on human memory included results of studies on women receiving oxytocin as part of the treatment to induce 2nd trimester therapeutic abortion. These women served as their own controls. We have now been able to study a group of women who have been treated in all ways like the original group, with the exception that they did not receive oxytocin. The results from this external control corroborate the finding that oxytocin affected memory.

  12. 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.

  13. [Oxytocin: the hormone of love, trust and social bond. Clinical use in autism and social phobia].

    PubMed

    Martin-Du Pan, R C

    2012-03-21

    Oxytocin, an octapeptide synthesized in the hypothalamus, stimulates milk election and uterine contractions. In the brain this hormone acts as a neuropeptide. It could inhibit through the GABAergic system the activity of limbic amygdala, which is involved in the response to fear. Oxytocin could also induce the protective behaviour of the mother towards its offspring through the dopaminergic system. In mankind, oxytocin plays a role in trust, empathy, generosity, stress and sexuality. Clinical studies are testing potential benefits of oxytocin administration in autism, depression and social phobia. Results are still preliminary.

  14. The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality

    PubMed Central

    De Wilde, Tim R. W.; Ten Velden, Femke S.; De Dreu, Carsten K. W.

    2017-01-01

    Groups can make better decisions than individuals when members cooperatively exchange and integrate their uniquely held information and insights. However, under conformity pressures group members are biased towards exchanging commonly known information, and away from exchanging unique information, thus undermining group decision-making quality. At the neurobiological level, conformity associates with the neuropeptide oxytocin. A double-blind placebo controlled study found no evidence for oxytocin induced conformity. Compared to placebo groups, three-person groups whose members received intranasal oxytocin, focused more on unique information (i) and repeated this information more often (ii). These findings reveal oxytocin as a neurobiological driver of group decision-making processes. PMID:28074896

  15. Verification and Analysis of Formulation 4 of Langley for the Study of Noise From High Speed Surfaces

    NASA Technical Reports Server (NTRS)

    Farassat, F.; Farris, Mark

    1999-01-01

    There are several approaches to the prediction of the noise from sources on high speed surfaces. Two of these are the Kirchhoff and the Ffowcs williams-Hawkings methods. It can be shown that both of these methods depend on the solution of the wave equation with mathematically similar inhomogeneous source terms. Two subsonic solutions known as Formulation 1 and 1A of Langley are simple and efficient for noise prediction. The supersonic solution known as Formulation 3 is very complicated and difficult to code. Because of the complexity of the result, the computation time is longer than the subsonic formulas. Furthermore, it is difficult to assess the accuracy of noise prediction. We have been searching for a new and simpler supersonic formulation without these shortcomings. In the last AIAA Aeroacoustics Conference in Toulouse, Farassat, Dunn and Brentner presented a paper in which such a result was presented and called Formulation 4 of Langley. In this paper we will present two analytic tests of the validity this Formulation: 1) the noise from dipole distribution on the unit circle whose strength varies radially with the square of the distance from the center and 2) the noise from dipole distribution on the unit sphere whose strength varies with the cosine of the angle from the polar axis. We will discuss the question of singularities of Formulation 4.

  16. Human corpus luteum secretion of relaxin, oxytocin, and progesterone.

    PubMed

    Khan-Dawood, F S; Goldsmith, L T; Weiss, G; Dawood, M Y

    1989-03-01

    To determine whether the human corpus luteum is a source of relaxin and oxytocin, we measured the concentrations of these peptides in plasma obtained from the ovarian veins of ovaries with and without a corpus luteum and compared these to peripheral plasma levels. Peripheral and ovarian venous blood samples were obtained from 34 nonpregnant women, 13 during the luteal phase and 21 during the follicular phase of their cycles, and from a 6-week pregnant woman. Plasma relaxin, oxytocin, and progesterone concentrations were determined by sensitive and specific RIAs. Plasma relaxin levels were not detectable (less than 0.16 microgram/L) in peripheral or ovarian venous plasma not draining a corpus luteum. The mean relaxin concentration in plasma draining an ovary with a corpus luteum was 0.41 +/- 0.09 (+/- SE) microgram/L. Oxytocin levels also were significantly higher in plasma draining an ovary with a corpus luteum (6.70 +/- 1.86 pmol/L) than in that draining the ovary with no corpus luteum (1.58 +/- 0.09 pmol/L; P less than 0.01) or in peripheral plasma (1.58 +/- 0.09 pmol/L; P less than 0.025). The mean progesterone concentration also was highest in plasma draining an ovary with a corpus luteum (210.2 +/- 50.5 nmol/L) compared with those in plasma from the contralateral ovarian vein (40.3 +/- 16.5 nmol/L P less than 0.005) and peripheral plasma (30.2 +/- 5.7 nmol/L; P less than 0.005) during the luteal phase. In a woman who was 6 weeks pregnant, plasma draining the ovary with a corpus luteum had 1.9 micrograms relaxin/L, but only 0.49 pmol/L oxytocin; the latter was similar to concentrations in noncorpus luteum-bearing ovarian venous plasma. These findings indicate that the human corpus luteum secretes relaxin, oxytocin, and progesterone. Both ovarian oxytocin and relaxin may function as paracrine or autocrine modulators of luteal function.

  17. [The function of the oxytocin-synthesizing system of the hypothalamus in rats with diabetes mellitus undergoing hypoxic training].

    PubMed

    Kolesnyk, Iu M; Abramov, A V; Trzhetsyns'kyĭ, S D; Hancheva, O V

    1999-01-01

    The state of hypothalamic oxytocin-synthesizing system in Wistar rats were investigating. The morphometric measurements and immunocytochemical detection of oxytocin-containing cells was used for determining of the functional state of supraoptic nucleus, anterior and posterior-medialis magnocellular subdivisions of paraventricular nucleus. It was established intermittent hypoxic training exert positive influence on rats with experimental diabetes mellitus. This effects depending on increasing synthesis and secretion of hypothalamic oxytocin. Intermittent hypoxic training elevate contents of immunoreactive oxytocin without changing morphometric characteristics in neurons of supraoptic and paraventricular nuclei and median eminence of hypothalamus. In comparison oxytocin contents in these neurons elevade less significance in diabetic rats, but it was observed increasing of nucleolus volume in hypothalamic oxytocin-synthesizing neurons. Intermittent hypoxic training of diabetic rats stimulate more significance elevating oxytocin contents in hypothalamic neurons and median eminence that evidence high level activity of hypothalamic oxytocin-synthesizing system.

  18. 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

  19. Normal-phase LC method for simultaneous analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations.

    PubMed

    Al-Rimawi, Fuad

    2010-04-01

    A simple, precise, and accurate method is developed and validated for the analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulations. The method has shown adequate separation of the four ingredients from each other. Separation was achieved on a silica column (5 μm, 125 × 4.6 mm inner diameter) using a mobile phase consisting of methanol/ammonium dihydrogen phosphate buffer (90:10, v/v) at a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is validated in accordance with USP requirements for new methods for assay determination, which include accuracy, precision, selectivity, linearity and range, robustness and ruggedness. The current method demonstrates good linearity over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r (2) of 0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide with r (2) of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine maleate with r (2) of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol with r (2) of 0.991. The average recovery of the method is 99.7%, 98.6%, 98.1%, and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol, respectively. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operator has proven that the method is robust and rugged.

  20. A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome.

    PubMed

    Einfeld, Stewart L; Smith, Ellie; McGregor, Iain S; Steinbeck, Kate; Taffe, John; Rice, Lauren J; Horstead, Siân K; Rogers, Naomi; Hodge, M Antoinette; Guastella, Adam J

    2014-09-01

    Individuals with Prader-Willi syndrome (PWS) have a significant reduction in the number of oxytocin-producing neurons (42%) in the hypothalamic paraventricular nucleus. A number of animal studies and observations of humans show that lesions in this region can produce PWS-like symptoms. Given the evidence for potential oxytocin deficiency, we tested the effects of a course of intranasal oxytocin on PWS symptoms. Thirty individuals with PWS aged 12-30 years participated in an 18-week randomized double-blind placebo-controlled crossover trial. Participants received 8 weeks of oxytocin and 8 weeks of placebo with a minimum 2-week washout period. The first 11 participants received the following oxytocin doses: 24 IU (twice daily) B.I.D for participants 16 years and over and 18 IU B.I.D for participants 13-15 years. The dose was increased for the remaining 18 participants to 40 IU B.I.D for participants 16 years and over and 32 IU B.I.D for 13-15 years. Measures used to assess changes were standardized well-accepted measures, including the Developmental Behavior Checklist-Monitor, Parent, Teacher, and Adult; The Yale-Brown Obsessive Compulsive Scale; The Dykens Hyperphagia questionnaire; Reading The Mind in the Eyes Test; Epworth Sleepiness Scale and the Movie Stills. Oxytocin had little impact on any measure. The only significant difference found between the baseline, oxytocin, and placebo measures was an increase in temper outbursts (P = 0.023) with higher dose oxytocin. The lack of effect of oxytocin nasal spray may reflect the importance of endogenous release of oxytocin in response to exogenous oxytocin.

  1. [The uterine contraction stress test with oxytocin nasal spray in the diagnosis of hypoxemia].

    PubMed

    Hohmann, M; Künzel, W; Kirschbaum, M

    1986-01-01

    Deceleration of the fetal heart rate are indications of fetal distress, which are commonly seen in connection with uterine contractions. The aim of the investigation was, whether nasal application of oxytocin (Syntocinon, Sandoz AG) is sufficient for the induction of contractions for an oxytocin-challenge-test. 232 oxytocin-challenge-tests in 85 risk patients between 29th-42nd week of gestation were analyzed in a retrospective and prospective way. The amounts of oxytocin nasal spray necessary for stimulating contractions were compared to the gestational age and maternal body weight (1 spray snuff = 4 IU Oxytocin). 20 pregnant women were given 8 IU oxytocin nasal spray after 10 minutes CTG-registration without any contractions. The incidence of induced contractions per ten minutes period were calculated. The amount of oxytocin nasal spray necessary for the stimulation of contractions decreased in relation to the increased gestational age and maternal body weight (oxytocin spray = 2.751-0.051 X (gestational age)-0.014 X (body weight), p less than 0.01). After a single application of 8 IU oxytocin nasal spray at least one contraction occurred in 13 out of 20 cases within the first 10 minutes. Between the 20th-30th minute the induced uterine contractions reached a maximum of 3 contractions per 10 minutes. No persisting contractions were observed. The application of 8 IU of oxytocin nasal spray is sufficient to induce in about 95% of the cases an oxytocin-challenge-test which gives information concerning the actual state of the fetus at risk.

  2. Oxytocin's effect on resting-state functional connectivity varies by age and sex.

    PubMed

    Ebner, Natalie C; Chen, Huaihou; Porges, Eric; Lin, Tian; Fischer, Håkan; Feifel, David; Cohen, Ronald A

    2016-07-01

    The neuropeptide oxytocin plays a role in social cognition and affective processing. The neural processes underlying these effects are not well understood. Modulation of connectivity strength between subcortical and cortical regions has been suggested as one possible mechanism. The current study investigated effects of intranasal oxytocin administration on resting-state functional connectivity between amygdala and medial prefrontal cortex (mPFC), as two regions involved in social-cognitive and affective processing. Going beyond previous work that largely examined young male participants, our study comprised young and older men and women to identify age and sex variations in oxytocin's central processes. This approach was based on known hormonal differences among these groups and emerging evidence of sex differences in oxytocin's effects on amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective processing. In a double-blind design, 79 participants were randomly assigned to self-administer either intranasal oxytocin or placebo before undergoing resting-state functional magnetic resonance imaging. Using a targeted region-to-region approach, resting-state functional connectivity strength between bilateral amygdala and mPFC was examined. Participants in the oxytocin compared to the placebo group and men compared to women had overall greater amygdala-mPFC connectivity strength at rest. These main effects were qualified by a significant three-way interaction: while oxytocin compared to placebo administration increased resting-state amygdala-mPFC connectivity for young women, oxytocin did not significantly influence connectivity in the other age-by-sex subgroups. This study provides novel evidence of age-by-sex differences in how oxytocin modulates resting-state brain connectivity, furthering our understanding of how oxytocin affects brain networks at rest.

  3. Sedative effects of intranasal oxytocin in rabbits and rhesus monkeys.

    PubMed

    Hess, L; Votava, M; Málek, J; Kurzová, A; Slíva, J

    2016-12-21

    Oxytocin is a hormone therapeutically used mainly for its peripheral effects during pregnancy in the uterus and breasts. However, additional central effects, i.e. anxiolytic effect, decreased level of social stress and increased empathy have been also observed. Hence, the aim of our study was to evaluate if nasal oxytocin can be used as anxiolytic substance in rhesus monkeys (n=20) and rabbits (n=20). Simultaneously, mean arterial blood pressure, arterial oxygen saturation of hemoglobin and pulse rate were monitored in all the evaluated animals. While rabbits lost righting reflex, monkeys developed a dose-dependent loss of aggressiveness and/or anxiety as evaluated by behavioral methods (aggressive behavior was classified as non-sedated - sedated - strongly sedated).

  4. Relationship between Salivary Oxytocin Levels and Generosity in Preschoolers.

    PubMed

    Fujii, Takayuki; Schug, Joanna; Nishina, Kuniyuki; Takahashi, Taiki; Okada, Hiroyuki; Takagishi, Haruto

    2016-12-08

    This study examined the association between salivary oxytocin (sOT) levels and generosity in preschoolers. Fifty preschoolers played two dictator games (DG) by deciding how to allocate 10 chocolates between themselves and another child, who was either from the same class as the participant (ingroup member), or an unknown child from another class (outgroup member). sOT levels were assessed in saliva collected from the children immediately prior to the DG tasks. While sOT levels were negatively associated with allocations made to both ingroup and outgroup members by boys, among girl sOT levels were positively related to allocations made to ingroup members, and unrelated to allocations made to outgroup members. These results suggest sex differences in the association between salivary oxytocin and generosity.

  5. Relationship between Salivary Oxytocin Levels and Generosity in Preschoolers

    PubMed Central

    Fujii, Takayuki; Schug, Joanna; Nishina, Kuniyuki; Takahashi, Taiki; Okada, Hiroyuki; Takagishi, Haruto

    2016-01-01

    This study examined the association between salivary oxytocin (sOT) levels and generosity in preschoolers. Fifty preschoolers played two dictator games (DG) by deciding how to allocate 10 chocolates between themselves and another child, who was either from the same class as the participant (ingroup member), or an unknown child from another class (outgroup member). sOT levels were assessed in saliva collected from the children immediately prior to the DG tasks. While sOT levels were negatively associated with allocations made to both ingroup and outgroup members by boys, among girl sOT levels were positively related to allocations made to ingroup members, and unrelated to allocations made to outgroup members. These results suggest sex differences in the association between salivary oxytocin and generosity. PMID:27929138

  6. Oxytocin can impair memory for social and non-social visual objects: a within-subject investigation of oxytocin's effects on human memory.

    PubMed

    Herzmann, Grit; Young, Brent; Bird, Christopher W; Curran, Tim

    2012-04-27

    Oxytocin is important to social behavior and emotion regulation in humans. Oxytocin's role derives in part from its effect on memory performance. More specifically, previous research suggests that oxytocin facilitates recognition of social (e.g., faces), but not of non-social stimuli (e.g., words, visual objects). We conducted the first within-subject study to this hypothesis in a double-blind, placebo-controlled design. We administered oxytocin (24IU) and placebo (saline) in two separate sessions and in randomized order to healthy men. To obtain a baseline measure for session-dependent memory effects, which are caused by proactive interference, an additional group of male subjects in each session received placebo unbeknownst to them and the experimenter. After administration, participants studied faces and houses. Exactly one day after each study session, participants were asked to make memory judgments of new and old items. In the first study-test session, participants administered with oxytocin showed reduced recollection of previously studied faces and houses. Oxytocin also interacted with proactive-interference effects. By impeding memory in the first session, it reduced proactive interference in the second. But oxytocin contributed additionally to the memory-reducing effect of proactive interference when administered in the second session. These results demonstrate that oxytocin can have a memory-impairing effect on both social and non-social visual objects. The present study also emphasizes the necessity of including a non-treated, baseline group in within-subject designs when investigating oxytocin's effects on human memory.

  7. A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

    DTIC Science & Technology

    2013-10-01

    Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder PRINCIPAL INVESTIGATOR: John Gabrieli...SUBTITLE A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder 5a. CONTRACT NUMBER...dysfunctions and (2) oxytocin (OT) administration prior to CBT sessions will each enhance social function in young adults with autism spectrum disorders

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

    PubMed

    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.

  9. The use of oxytocin in nipple fluid aspiration.

    PubMed

    Zhang, Liping; Shao, Zhi-Ming; Beatty, Perrin; Sartippour, Maryam; Wang, He-Jing; Elashoff, Robert; Chang, Helena; Brooks, Mai N

    2003-01-01

    It has been shown that early detection of breast cancer saves lives. Recently there has been increasing interest in nipple aspirate fluid as a potential avenue for breast cancer diagnosis. One major challenge regarding studies of nipple aspirate fluid is the ability to obtain adequate samples. Here we describe the use of nasal oxytocin in a group of volunteer women in order to increase the yield of nipple aspirate fluid.

  10. Constitutive and ligand-induced nuclear localization of oxytocin receptor.

    PubMed

    Kinsey, Conan G; Bussolati, Gianni; Bosco, Martino; Kimura, Tadashi; Pizzorno, Marie C; Chernin, Mitchell I; Cassoni, Paola; Novak, Josef F

    2007-01-01

    Oxytocin receptor (OTR) is a membrane protein known to mediate oxytocin (OT) effects, in both normal and neoplastic cells. We report here that human osteosarcoma (U2OS, MG63, OS15 and SaOS2), breast cancer (MCF7), and primary human fibroblastic cells (HFF) all exhibit OTR not only on the cell membrane, but also in the various nuclear compartments including the nucleolus. Both an OTR-GFP fusion protein and the native OTR appear to be localized to the nucleus as detected by transfection and/or confocal immunofluorescence, respectively. Treatment with oxytocin causes internalization of OTR and the resulting vesicles accumulate in the vicinity of the nucleus and some of the perinuclear OTR enters the nucleus. Western blots indicate that OTR in the nucleus and on the plasma membrane are likely to be the same biochemical and immunological entities. It appears that OTR is first visible in the nucleoli and subsequently disperses within the nucleus into 4-20 spots while some of the OTR diffuses throughout the nucleoplasm. The behaviour and kinetics of OTR-GFP and OTR are different, indicating interference by GFP in both OTR entrance into the nucleus and subsequent relocalization of OTR within the nucleus. There are important differences among the tested cells, such as the requirement of a ligand for transfer of OTR in nuclei. A constitutive internalization of OTR was found only in osteosarcoma cells, while the nuclear localization in all other tested cells was dependent on ligand binding. The amount of OTR-positive material within and in the vicinity of the nucleus increased following a treatment with oxytocin in both constitutive and ligand-dependent type of cells. The evidence of OTR compartmentalization at the cell nucleus (either ligand-dependent or constitutive) in different cell types suggests still unknown biological functions of this protein or its ligand and adds this G-protein-coupled receptor to other heptahelical receptors displaying this atypical and unexpected

  11. 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

  12. OXYTOCIN INDUCES SOCIAL COMMUNICATION BY ACTIVATING ARGININEVASOPRESSIN V1A RECEPTORS AND NOT OXYTOCIN RECEPTORS

    PubMed Central

    SONG, Zhimin; MCCANN, Katharine E.; MCNEILL, John K.; LARKIN, Tony E.; HUHMAN, Kim L.; ALBERS, H. Elliott

    2014-01-01

    Arginine-vasopressin (AVP) and oxytocin (OT) and their receptors are very similar in structure. As a result, at least some of the effects of these peptides may be the result of crosstalk between their canonical receptors. The present study investigated this hypothesis by determining whether the induction of flank marking, a form of social communication in Syrian hamsters, by OT is mediated by the OT receptor or the AVP V1a receptor. Intracerebroventricular (ICV) injections of OT or AVP induced flank marking in a dose-dependent manner although the effects of AVP were approximately 100 times greater than those of OT. Injections of highly selective V1a receptor agonists but not OT receptor agonists induced flank marking, and V1a receptor antagonists but not OT receptor antagonists significantly inhibited the ability of OT to induce flank marking. Lastly, injection of alpha-melanocyte-stimulating hormone (α-MSH), a peptide that stimulates OT but not AVP release, significantly increased odor-induced flank marking, and these effects were blocked by a V1a receptor antagonist. These data demonstrate that OT induces flank marking by activating AVP V1a and not OT receptors, suggesting that the V1a receptor should be considered to be an OT receptor as well as an AVP receptor. PMID:25173438

  13. Neonatal manipulation of oxytocin alters oxytocin levels in the pituitary of adult rats.

    PubMed

    Young, E; Carter, C S; Cushing, B S; Caldwell, J D

    2005-07-01

    The neuropeptide oxytocin (OT) and its OT antagonists (OTA) in infant rats affect their behavior as adults. In this study we attempted to determine whether treating rats on the day of birth (postnatal day 1) with OT or OTA would affect brain OT levels of these rats as adults. Rat pups were injected with OT (3 microg), OTA (0.3 microg) or saline vehicle ip on postnatal day 1. As 60-day-old adults, treated rats were killed, and the OT content in their medial preoptic areas (MPOAs), medial hypothalami (MH) and pituitaries were assayed. In females, treatment with OTA on postnatal day 1 significantly decreased pituitary OT levels as adults. In males, by contrast, treatment with OTA on postnatal day 1 resulted in increased pituitary OT levels when they become adults compared to male rats treated with OT on postnatal day 1. There were no significant effects of neonatal treatment on OT levels in either the MH or MPOA. Day 1 postnatal treatment with OT or OTA had a long-term sexually dimorphic effect on OT levels in the pituitary.

  14. 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.

  15. Method for collecting mouse milk without exogenous oxytocin stimulation.

    PubMed

    Muranishi, Yuki; Parry, Laurent; Averous, Julien; Terrisse, Anne; Maurin, Anne-Catherine; Chaveroux, Cédric; Mesclon, Florent; Carraro, Valérie; Bruhat, Alain; Fafournoux, Pierre; Jousse, Céline

    2016-01-01

    It has been reported that breast-feeding more than 6 months strongly decreases the risk of allergy, diabetes, obesity, and hypertension in humans. In order to understand the mechanisms responsible for this benefit, it is important to evaluate precisely the composition of maternal milk, especially in response to environmental cues. Mouse models offer a unique opportunity to study the impact of maternal milk composition on the development and health of offspring. Oxytocin injection of the dam is usually used to stimulate milk ejection; however, exogenous oxytocin might have deleterious effects under some experimental conditions by modifying milk content as well as the physiology and behavior of the dam. Taking advantage of the natural stimulation of the mammary gland that occurs after the reunion of a dam that has been separated from her pups, we developed a new procedure to collect mouse milk without the injection of oxytocin. This method is easy to use, low-cost ,and non-invasive. Moreover, it provides a sufficient amount of milk for use in a wide range of biological analyses.

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

    PubMed

    Futagami, Hiroko; Sakuma, Yasuo; Kondo, Yasuhiko

    2016-04-08

    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.

  17. 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.

  18. 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.

  19. 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

  20. Treatment of inadequate lactation with oral sulpiride and buccal oxytocin.

    PubMed

    Ylikorkala, O; Kauppila, A; Kivinen, S; Viinikka, L

    1984-01-01

    Thirty-six puerperal women with inadequate lactation were treated with 50 mg sulpiride (N = 24) or placebo (N = 12) three times a day for two weeks. These treatments were supplemented with buccal oxytocin (100 IU, 300 IU, or 400 IU) or placebo preceding each breast-feeding on the sixth and 14th and on the seventh and 13th days of oral treatment, respectively. One woman treated with sulpiride and three women treated with placebo discontinued the trial because of the lack of the effect of treatment. The concentration of prolactin in maternal serum was higher (P less than .001) during sulpiride than placebo treatment at one week (380 +/- 43 ng/ml vs 23 +/- 7 ng/ml, mean +/- SE) and two weeks of treatment (381 +/- 38 ng/ml vs 34 +/- 10 ng/ml). Also, the daily breast milk yield, as measured objectively, was greater (P less than .05) during sulpiride than placebo treatment both at one week (628 +/- 51 ml vs 440 +/- 68 ml) and two weeks of treatment (684 +/- 67 ml vs 423 +/- 60 ml). Various doses of oxytocin failed to stimulate the milk secretion in the presence or absence of sulpiride-induced hyperprolactinemia. Thus, sulpiride improved inadequate lactation, whereas exogenous oxytocin alone or together with sulpiride had no effect on lactation in these mothers whose infants were able to suckle normally.

  1. 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.

  2. Differential Effects of Oxytocin on Agency and Communion for Anxiously and Avoidantly Attached Individuals.

    PubMed

    Bartz, Jennifer A; Lydon, John E; Kolevzon, Alexander; Zaki, Jamil; Hollander, Eric; Ludwig, Natasha; Bolger, Niall

    2015-08-01

    Oxytocin promotes prosocial behavior, especially in those individuals who are low in affiliation (e.g., avoidantly attached individuals), but can exacerbate interpersonal insecurities in those preoccupied with closeness (e.g., anxiously attached individuals). One explanation for these opposing observations is that oxytocin induces a communal, other-orientation. Becoming more other oriented should help those people who focus on the self to the exclusion of others, but could be detrimental to those who are other focused but have little sense of an agentic self. Using a within-subjects design, we administered intranasal oxytocin and placebo to 40 males and measured their agency (self-orientation) and communion (other-orientation). Oxytocin produced a slight increase in communion for the average participant; however, as predicted, avoidantly attached individuals were especially likely to perceive themselves as more communal ("kind," "warm," "gentle," etc.) after receiving oxytocin than after receiving the placebo. There was no main effect of oxytocin on agency for the average participant; however, anxiously attached individuals showed a selective decrease in agency ("independent," "self-confident," etc.) following administration of oxytocin. These data help explain the complex social effects of oxytocin.

  3. 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.

  4. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal.

    PubMed

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2013-10-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds.

  5. A brief history of oxytocin and its role in modulating psychostimulant effects.

    PubMed

    Carson, Dean S; Guastella, Adam J; Taylor, Emily R; McGregor, Iain S

    2013-03-01

    Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let-down reflex. Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia. In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity. We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes. Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects. Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents. Evidence also outlines a role for oxytocin in the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in both rodents and humans. Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated.

  6. Is oxytocin a maternal-foetal signalling molecule at birth? Implications for development.

    PubMed

    Kenkel, W M; Yee, J R; Carter, C S

    2014-10-01

    The neuropeptide oxytocin was first noted for its capacity to promote uterine contractions and facilitate delivery in mammals. The study of oxytocin has grown to include awareness that this peptide is a neuromodulator with broad effects throughout the body. Accumulating evidence suggests that oxytocin is a powerful signal to the foetus, helping to prepare the offspring for the extrauterine environment. Concurrently, the use of exogenous oxytocin or other drugs to manipulate labour has become common practice. The use of oxytocin to expedite labour and minimise blood loss improves both infant and maternal survival under some conditions. However, further investigations are needed to assess the developmental consequences of changes in oxytocin, such as those associated with pre-eclampsia or obstetric manipulations associated with birth. This review focuses on the role of endogenous and exogenous oxytocin as a neurochemical signal to the foetal nervous system. We also examine the possible developmental consequences, including those associated with autism spectrum disorder, that arise from exogenous oxytocin supplementation during labour.

  7. 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…

  8. 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.

  9. Oxytocin selectively moderates negative cognitive appraisals in high trait anxious males.

    PubMed

    Alvares, Gail A; Chen, Nigel T M; Balleine, Bernard W; Hickie, Ian B; Guastella, Adam J

    2012-12-01

    The mammalian neuropeptide oxytocin has well-characterized effects in facilitating prosocial and affiliative behavior. Additionally, oxytocin decreases physiological and behavioral responses to social stress. In the present study we investigated the effects of oxytocin on cognitive appraisals after a naturalistic social stress task in healthy male students. In a randomized, double-blind, placebo-controlled trial, 48 participants self-administered either an oxytocin or placebo nasal spray and, following a wait period, completed an impromptu speech task. Eye gaze to a pre-recorded video of an audience displayed during the task was simultaneously collected. After the speech, participants completed questionnaires assessing negative cognitive beliefs about speech performance. Whilst there was no overall effect of oxytocin compared to placebo on either eye gaze or questionnaire measures, there were significant positive correlations between trait levels of anxiety and negative self-appraisals following the speech. Exploratory analyses revealed that whilst higher trait anxiety was associated with increasingly poorer perceptions of speech performance in the placebo group, this relationship was not found in participants administered oxytocin. These results provide preliminary evidence to suggest that oxytocin may reduce negative cognitive self-appraisals in high trait anxious males. It adds to a growing body of evidence that oxytocin seems to attenuate negative cognitive responses to stress in anxious individuals.

  10. 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.

  11. Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study.

    PubMed

    Simeon, D; Bartz, J; Hamilton, H; Crystal, S; Braun, A; Ketay, S; Hollander, E

    2011-10-01

    Oxytocin has known stress-reducing and attachment-enhancing effects. We thus hypothesized that oxytocin would attenuate emotional and hormonal responses to stress in borderline personality disorder (BPD). Fourteen BPD and 13 healthy control (HC) adults received 40 IU intranasal oxytocin or placebo in double-blind randomized order followed by the Trier Social Stress Test. Subjective dysphoria (Profile of Mood Changes) and plasma cortisol levels were measured. Childhood trauma history, attachment style, and self-esteem were also rated. A significant "Group × Drug × Time" interaction effect for dysphoria (p=.04) reflected a proportionately greater attenuation of stress-induced dysphoria in the BPD group after oxytocin administration. Additionally, a marginally significant "Group × Drug" interaction effect for cortisol (p=.10) reflected a tendency toward greater attenuation of the stress-induced cortisol surge in the BPD group after oxytocin administration. In the combined sample, the oxytocin-placebo difference in the emotional stress reactivity was significantly predicted by childhood trauma alone (p=.037) and combined with self-esteem (p=.030), whereas the oxytocin-placebo difference in cortisol stress reactivity was predicted only by insecure attachment (p=.013). Results suggest that oxytocin may have a beneficial impact on emotional regulation in BPD, which merits further investigation and could have important treatment implications.

  12. 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.

  13. 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.

  14. Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

    DTIC Science & Technology

    2014-09-01

    AD_________________ Award Number: TITLE: Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism ...AUG 2013-7 Aug 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism ...Moy. . 14. ABSTRACT Currently, there are no established pharmaceutical strategies that effectively treat core autism spectrum disorder (ASD

  15. Restoration of angiogenic capacity of diabetes-insulted mesenchymal stem cells by oxytocin

    PubMed Central

    2013-01-01

    Background Angiogenesis is the main therapeutic mechanism of cell therapy for cardiovascular diseases, but diabetes is reported to reduce the function and number of progenitor cells. Therefore, we studied the effect of streptozotocin-induced diabetes on the bone marrow-mesenchymal stem cell (MSC) function, and examined whether diabetes-impaired MSC could be rescued by pretreatment with oxytocin. Results MSCs were isolated and cultured from diabetic (DM) or non-diabetic (non-DM) rat, and proliferation rate was compared. DM-MSC was pretreated with oxytocin and compared with non-DM-MSC. Angiogenic capacity was estimated by tube formation and Matrigel plug assay, and therapeutic efficacy was studied in rat myocardial infarction (MI) model. The proliferation and angiogenic activity of DM-MSC were severely impaired but significantly improved by pretreatment with oxytocin. Krüppel-like factor 2 (KLF2), a critical angiogenic factor, was dramatically reduced in DM-MSC and significantly restored by oxytocin. In the Matrigel plug assay, vessel formation of DM-BMSCs was attenuated but was recovered by oxytocin. In rat MI model, DM-MSC injection did not ameliorate cardiac injury, whereas oxytocin-pretreated DM-MSC improved cardiac function and reduced fibrosis. Conclusions Our results show that diabetes influenced MSC by reducing angiogenic capacity and therapeutic potential. We demonstrate the striking effect of oxytocin on stem cell dysfunction and suggest the use of oxytocin as a priming reagent in autologous stem cell therapy. PMID:24024790

  16. The Effect of Oxygen Inhalation Plus Oxytocin Compared with Oxytocin Only on Postpartum Haemorrhage: A Randomized Clinical Trial

    PubMed Central

    Suhrabi, Zainab; Taghinejad, Hamid; Direkvand-Moghadam, Ashraf

    2016-01-01

    Introduction Post Partum Haemorrhage (PPH) is the leading cause of maternal mortality across the world, mainly in the developing countries. Aim The present study was conducted with the aim to investigate effect of oxygen inhalation plus oxytocin compared with oxytocin only on PPH. Materials and Methods This study was a clinical trial which was performed in Shahid Mustafa Khomieni Teaching Hospital of Ilam (western Iran) from April 2012 to Nov 2013. One hundred and twenty pregnant women who were referred to delivery ward for normal vaginal delivery were selected with convenience sampling method and they were randomly assigned into two groups. For both groups management of the third stage of labour was done using 1000CC Ringer and 20 units of Oxytocin. In the intervention group, in addition to the routine administration, 8 liters of oxygen via face mask was used continuously until 2 hours after delivery. Blood loss was determined by regular weighing of the buttocks that were previously weighted. The difference was calculated before and after weighing (1 gram increasing of weight was considered to be equivalent to 1CC blood loss). Data were analysed by SPSS 16 version using Student- t and Chi-square tests. Results The two groups were homogenous in regard to all the base line variables. The study results indicated that the mean of blood loss were (256.16±97) ml at two hours after delivery in the control group and (149.5±46.49) ml in the intervention group. There was a significant difference between PPH of the two groups (p<0.006). Conclusion Research findings showed that the use of inspired oxygen during the third stage of labour and oxytocin infusion during 2hours later resulted in a significant decreasing in the amount of bleeding after normal vaginal delivery. PMID:27790522

  17. 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.

  18. 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.

  19. Size exclusion chromatography with evaporative light scattering detection as a method for speciation analysis of polydimethylsiloxanes. II. Validation of the method for analysis of pharmaceutical formulations.

    PubMed

    Mojsiewicz-Pieńkowska, Krystyna

    2011-12-05

    The aim of this study was to demonstrate the usefulness of the size exclusion chromatography with evaporative light scattering detection (SEC-ELSD) method in the identification and quantitative analysis of polydimethylsiloxanes (PDMS). The process of validation for the method was conducted, and the values obtained were compared with the acceptance criteria. Particularly important was the conclusion that SEC-ELSD method showed a high specificity for PDMS. PDMS is an organosilicon polymer and for this reason, it does not exist as a concrete chemical species. Depending on the length of the chain, PDMS can be toxic for organism. So far, the SEC-ELSD method has not been applied for the control of pharmaceutical products containing such PDMS as dimeticone or simeticone. The safety of use and effectiveness of such pharmaceutical products relies on the control of their quality. Therefore, the analytical methods and procedures that meet acceptance criteria for qualitative and quantitative analysis of the PDMS should be used. In the case of the analysis of pharmaceutical products, the acceptance criteria are established and recommended by, for example, the Pharmacopoeias, the U.S. Food and Drug Administration (FDA), the International Conference on Harmonisation (ICH) and the World Health Organization (WHO). The progress of knowledge, however, requires the development of new analytical tools which are able to solve incoming problems. In the case of pharmaceutical formulations containing PDMS, which are used not only by adults but also by children, it is necessary to use analytical methods which are characterized by a high specificity.

  20. 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.

  1. 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

  2. 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.

  3. A matter of distance-The effect of oxytocin on social discounting is empathy-dependent.

    PubMed

    Strang, Sabrina; Gerhardt, Holger; Marsh, Nina; Oroz Artigas, Sergio; Hu, Yang; Hurlemann, René; Park, Soyoung Q

    2017-04-01

    Generosity is an important behavior enriching human society and can be observed across cultures. However, generosity has been shown to be modulated as a function of social distance, also referred to as social discounting. Oxytocin and empathy are other factors that have been shown to play an important role in generous behavior. However, how exactly oxytocin and empathy impact social discounting is yet unknown. Here, we administered oxytocin or placebo in a double-blind design, and measured social discounting behavior. Additionally, individual differences in empathy were assessed. Our results show that the effect of oxytocin on generous behavior is modulated by trait empathy; only for those subjects who received oxytocin there was a positive correlation between individual trait empathy and their generous behavior towards close others.

  4. 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.

  5. 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

  6. Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.

    PubMed

    Baracz, Sarah J; Everett, Nicholas A; McGregor, Iain S; Cornish, Jennifer L

    2016-03-01

    The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) 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 in the NAc core. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5 pmol, 1.5 pmol, 4.5 pmol) or co-administration of oxytocin (1.5 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1 nmol, 3 nmol) in the NAc core (500 nl/side) was examined on METH-primed (1 mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking.

  7. Development of a highly specific enzyme immunoassay for oxytocin and its use in plasma samples.

    PubMed

    Haraya, Shiomi; Karasawa, Koji; Sano, Yoshihiro; Ozawa, Kimiko; Kato, Nobumasa; Arakawa, Hidetoshi

    2017-01-01

    Background The peptide hormone oxytocin acts in the central nervous system and plays an important role in various complex social behaviours. We report the production of a high affinity and specificity antibody for oxytocin and its use in a highly sensitive enzyme immunoassay. Biotin that was chemically bound to oxytocin derivative containing zero to six lysines as bridge was the labelled antigen. Seven labelled antigens were used to develop a highly sensitive enzyme immunoassay. Methods Antioxytocin antiserum was obtained by immunization of oxytocin-bovine thyrogloblin conjugate to rabbit. Oxytocin sample was added to the second antibody-coated microtitre plate and allowed to react overnight at 4℃, then biotinylated oxytocin was added 1 h at 4℃, and horseradish peroxidase-labelled avidin was added and incubated for 1 h at room temperature. The plate was then washed. Horseradish peroxidase activity was measured by a colorimetric method using o-phenylenediamine (490 nm). Results The sensitivity of the enzyme immunoassay improved as the number of lysine residues increased; consequently, biotinylated oxytocin bridged with five lysines was used. A standard curve for oxytocin ranged from 1.0 to 1000 pg/assay. The detection limit of the assay was 2.36 pg, and the reproducibility was 3.6% as CV% ( n = 6). Cross-reactivity with vasopressin and vasotocin was less than 0.01%. Conclusion The sensitivity of the enzyme immunoassay could be improved by increasing the number of lysine residues on the biotin-labelled antigen. The proposed method is sensitive and more specific than conventional immunoassays for oxytocin and can be used to determine plasma oxytocin concentrations.

  8. Inhibitory effect of oxytocin on accelerated colonic motility induced by water-avoidance stress in rats.

    PubMed

    Matsunaga, M; Konagaya, T; Nogimori, T; Yoneda, M; Kasugai, K; Ohira, H; Kaneko, H

    2009-08-01

    Recent studies have indicated that brain and gut activities are interrelated and exposure to several stressors, such as water-avoidance stress, stimulates the motor function of the gut through corticotropin-releasing factor (CRF)-signalling pathways in the brain. Central oxytocin is known to attenuate stress responses, including CRF expression in the brain. Here, we examined whether central oxytocin attenuated the acceleration of colonic motility induced by water-avoidance stress. A force transducer was attached to the distal colon of male rat, and the colonic motility and faecal pellet output were recorded while the rats were exposed to water-avoidance stress. Intracerebroventricular (i.c.v.) injections of oxytocin (5, 50 and 500 pmol) and the oxytocin receptor antagonist tocinoic acid (25 microg) were administered before exposure to water-avoidance stress, and the effect of oxytocin on colonic motor function was determined. Centrally administered oxytocin inhibited the accelerated colonic motility induced by water-avoidance stress. The effective dose ranged between 5 and 50 pmol on i.c.v. injection. Oxytocin also decreased the number of CRF-positive cells in the paraventricular nucleus and corticosterone release. The inhibitory effect of oxytocin on accelerated colonic motility was blocked by pretreatment with oxytocin receptor antagonist. Furthermore, centrally administered tocinoic acid enhanced the acceleration of colonic motility. These results suggested that endogenous central oxytocin may contribute to the regulation of colonic function and inhibit the brain CRF-signalling pathways targeting the gut, resulting in the inhibition of stress-induced colonic contractions.

  9. Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa

    PubMed Central

    Lawson, Elizabeth A.; Holsen, Laura M.; Santin, McKale; DeSanti, Rebecca; Meenaghan, Erinne; Eddy, Kamryn T.; Herzog, David B.; Goldstein, Jill M.; Klibanski, Anne

    2013-01-01

    Objective Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa (AN), and decreased levels in weight-recovered women with anorexia nervosa (ANWR) compared to healthy controls (HC). A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between post-prandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. Method We performed a cross-sectional study of 35 women (13 AN, 9 ANWR and 13 HC). Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120min after a standardized mixed meal. The area under the curve (AUC), and for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). Results In women with anorexia nervosa, oxytocin AUC and post-prandial nadir and peak levels were positively associated with STAI scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, most relationships remained significant. After controlling for leptin AUC, all of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of BDI-II scores. Conclusions Abnormal post-prandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This may represent an adaptive response of oxytocin secretion to food-related symptoms of anxiety and depression. PMID:23759466

  10. 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

  11. Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques.

    PubMed

    Freeman, Sara M; Samineni, Sridhar; Allen, Philip C; Stockinger, Diane; Bales, Karen L; Hwa, Granger G C; Roberts, Jeffrey A

    2016-04-01

    Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

  12. 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.

  13. 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.

  14. Oxytocin is expressed by both intrinsic sensory and secretomotor neurons in the enteric nervous system of guinea pig.

    PubMed

    Yu, Qiang; Ji, Ruihua; Gao, Xiaofei; Fu, Jiqiang; Guo, Wei; Song, Xianmin; Zhao, Xiaolin; Burnstock, Geoffrey; Shi, Xueyin; He, Cheng; Xiang, Zhenghua

    2011-05-01

    Single- and double-immunostaining techniques were used systematically to study the distribution pattern and neurochemical density of oxytocin-immunoreactive (-ir) neurons in the digestive tract of the guinea pig. Oxytocin immunoreactivity was distributed widely in the guinea pig gastrointestinal tract; 3%, 13%, 17%, 15%, and 10% of ganglion neurons were immunoreactive for oxytocin in the myenteric plexuses of the gastric corpus, jejunum, ileum, proximal colon, and distal colon, respectively, and 36%, 40%, 52%, and 56% of ganglion neurons were immunoreactive for oxytocin in the submucosal plexuses of the jejunum, ileum, proximal colon, and distal colon, respectively. In the myenteric plexus, oxytocin was expressed exclusively in the intrinsic enteric afferent neurons, as identified by calbindin 28 K. In the submucosal plexuses, oxytocin was expressed in non-cholinergic secretomotor neurons, as identified by vasoactive intestinal polypeptide. Oxytocin-ir nerve fibers in the inner circular muscle layer possibly arose from the myenteric oxytocin-ir neurons, and oxytocin-ir nerve fibers in the mucosa possibly arose from both the myenteric and submucosal oxytocin-ir neurons. Thus, oxytocin in the digestive tract might be involved in gastrointestinal tract motility mainly via the regulation of the inner circular muscle and the balance of the absorption and secretion of water and electrolytes.

  15. Antidepressant-like effects of oxytocin in mice are dependent on the presence of insulin-regulated aminopeptidase.

    PubMed

    Loyens, Ellen; De Bundel, Dimitri; Demaegdt, Heidi; Chai, Siew Yeen; Vanderheyden, Patrick; Michotte, Yvette; Gard, Paul; Smolders, Ilse

    2013-06-01

    Oxytocin is a neuromodulator with antidepressant-like effects. In vitro, oxytocin is rapidly cleaved by insulin-regulated aminopeptidase (IRAP). Oxytocin metabolites are known to exert strong central activities that are different from the effects of the parent molecule. Our goal is to investigate in vivo whether IRAP deletion modifies the antidepressant-like effects of oxytocin. Male and female C57Bl/6 mice, IRAP wild-type (IRAP(+/+)) and knock-out (IRAP(-/-)) mice were injected subcutaneously with saline, oxytocin or oxytocin combined with angiotensin IV. One hour after injection, immobility was timed during a 5 min forced swim that was preceded by an open field to study locomotor behaviour. Oxytocin induced antidepressant-like effects in male (0.25 mg/kg oxytocin) and female (0.15 mg/kg oxytocin) C57Bl/6 mice subjected to the forced swim test. Oxytocin did not influence locomotor behaviour in mice, as shown with the open field. These findings were reproduced in transgenic male (aged 3-6 months) and female (aged 12-18 months) IRAP(+/+) mice. However, the major findings of our study were that the antidepressant-like effect was reversed in angiotensin IV treated IRAP(+/+) mice and was completely absent in age- and gender-matched IRAP(-/-) mice. The lack of an antidepressant-like effect of oxytocin in young male and middle-aged female IRAP(-/-) mice attributes an important role to IRAP in mediating this effect.

  16. 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

  17. 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.

  18. 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.

  19. Defective oxytocin function: a clue to understanding the cause of autism?

    PubMed

    Gurrieri, Fiorella; Neri, Giovanni

    2009-10-22

    The autism spectrum disorders are a group of conditions with neurobehavioral impairment affecting approximately 0.6% of children. The clinical presentation is complex and the etiology is largely unknown, although a major role of genetic factors is widely accepted. A number of genetic studies led to the identification of genes and/or copy number variants whose alterations are associated with autism, but no specific factor has been found so far to be responsible for a substantial proportion of cases. Epigenetic modifications may also play a role, as demonstrated by the occurrence of autism in genetic conditions caused by mutations in imprinted genes or regions.The article by Gregory et al. published this month in BMC Medicine, reports on genomic and epigenetic alterations of OXTR, the gene encoding the receptor for oxytocin. The involvement of this gene was suggested by its deletion in an autistic patient. The subsequent analysis of a group of unrelated autistic subjects did not show an OXTR deletion, but rather hypermethylation of the gene promoter, with a reduced mRNA expression.These findings address two major points of the current debate on the etiology and pathogenesis of autism: the role of oxytocin, known to be involved in modeling human behavior, and the possible involvement of epigenetic mechanisms. The nature of this epigenetic dysregulation is unknown but, if proved to be true, might explain the failure to identify sequence alterations in a host of candidate genes. Practical implications of these findings may be forthcoming, however not before extension and validation on a larger scale have confirmed their value.See the associated research paper by Gregory et al: http://www.biomedcentral.com/1741-7015/7/62.

  20. Lack of stimulation of relaxin secretion in lactating sows by suckling in vivo or by oxytocin in vitro.

    PubMed

    Hunter, M G; Denning-Kendall, P; Boulton, M I; De Rensis, F; Wild, M L; Foxcroft, G R

    1992-01-01

    After parturition, eight sows were zero weaned by removing all piglets 6 h after birth; a further 18 sows suckled at least ten piglets each. Blood samples were collected on Day 4 after zero weaning or on Days 4, 14 and 21 of lactation and the sampling frequency increased during suckling bouts. Ovaries were recovered from sows on these days and corpora lutea were either extracted for estimation of relaxin and progesterone concentration, fixed for immunohistochemical analysis or incubated in vitro in the presence or absence of luteinizing hormone (LH) or oxytocin. Luteal weight and progesterone were higher in the zero-weaned sows than in lactating sows (P less than 0.05 and less than 0.001, respectively); relaxin content was below detection by Day 14. This was supported by immunohistochemical staining for relaxin, which showed limited immunostaining in zero-weaned and Day 4 sows, but none in the tissue recovered on Days 14 and 21, which showed typical signs of regression. Secretion of progesterone and relaxin by luteal tissue in vitro was highest in zero-weaned sows (P less than 0.05), decreased as lactation progressed and neither LH nor oxytocin had any significant effect. Concentrations of plasma relaxin were all less than 0.2 ng/ml in three of the four zero-weaned and Day-4-suckled sows assayed; there was no detectable increase during suckling bouts. It was concluded that during lactation the old corpus luteum of pregnancy is not able to release relaxin in response to suckling in vivo or to oxytocin treatment in vitro.

  1. Oxytocin receptors in dioestrous and anoestrous canine uteri.

    PubMed

    Tamminen, T M; Sahlin, L; Masironi, B; Taponen, J; Laitinen-Vapaavuori, O; Katila, T

    2017-02-01

    The aim of the study was to localize oxytocin receptors (OTR) and measure mRNA expression of OTR in the canine uterus with and without the influence of progesterone. Uterine samples were taken from nine anoestrous and eight dioestrous bitches during ovariohysterectomy. Histological changes were evaluated in haematoxylin and eosin (HE)-stained samples. Purified polyclonal antibody for OTR was used in immunohistochemistry to localize receptors in uterine layers. Relative mRNA concentration of OTR was evaluated with real-time PCR from full-thickness uterine samples taken from the middle horn and the body. Myometrial smooth muscle cells, endometrial luminal epithelium (LE) and deep and superficial glandular epithelium were positively stained for oxytocin receptors in non-pregnant animals. No significant difference in staining intensity was detected between uterine middle horn and body. However, the staining intensity of LE was significantly higher in dioestrous than in anoestrous uteri (p < .05). Leucocytes and endothelium of blood vessels were also positively stained for OTR. Real-time PCR showed no significant differences in OTR mRNA expression between the middle horn and the body of the uterus, or between anoestrous and dioestrous uterus. No correlation was noted between OTR mRNA expression and blood progesterone concentration. In conclusion, despite the apparent inactivity, the uterus of the non-pregnant bitch expresses OTR. The distribution or relative expression of OTR does not differ between uterine horn and body in dioestrus or anoestrus except in LE. LE may have more oxytocin-dependent activity during dioestrus than anoestrus.

  2. Oxytocin increases willingness to socially share one's emotions.

    PubMed

    Lane, Anthony; Luminet, Olivier; Rimé, Bernard; Gross, James J; de Timary, Philippe; Mikolajczak, Moïra

    2013-01-01

    Oxytocin (OT) is a neuropeptide that is attracting growing attention from researchers interested in human emotional and social behavior. There is indeed increasing evidence that OT has a calming effect and that it facilitates pair-bonding and social interactions. Some of OT's effects are thought to be direct, but it has been suggested that OT also may have indirect effects, mediated by changes in behavior. One potentially relevant behavioral change is an increased propensity for "emotional sharing" as this behavior, like OT, is known to have both calming and bonding effects. In this study, 60 healthy young adult men were randomly assigned to receive either intranasal placebo (PL; n = 30) or oxytocin (OT; n = 30). Participants were then instructed to retrieve a painful memory. Subsequently, OT and placebo participants' willingness to disclose to another person event-related facts (factual sharing) vs. event-related emotions (emotional sharing) was evaluated. Whereas the two groups were equally willing to disclose event-related facts, oxytocin was found to specifically increase the willingness to share event-related emotions. This study provides the first evidence that OT increases people's willingness to share their emotions. Importantly, OT did not make people more talkative (word counts were comparable across the two groups) but instead increased the willingness to share the specific component that is responsible for the calming and bonding effects of social sharing: emotions. Findings suggest that OT may shape the form of social sharing so as to maximize its benefits. This might help explain the calming and bonding effects of OT.

  3. 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

  4. Salubrious effects of oxytocin on social stress-induced deficits.

    PubMed

    Smith, Adam S; Wang, Zuoxin

    2012-03-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While positive social interactions can attenuate stress and promote health, the social environment can also be a major source of stress when it includes social disruption, confrontation, isolation, or neglect. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  5. Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons

    PubMed Central

    Ripamonti, Silvia; Ambrozkiewicz, Mateusz C; Guzzi, Francesca; Gravati, Marta; Biella, Gerardo; Bormuth, Ingo; Hammer, Matthieu; Tuffy, Liam P; Sigler, Albrecht; Kawabe, Hiroshi; Nishimori, Katsuhiko; Toselli, Mauro; Brose, Nils; Parenti, Marco; Rhee, JeongSeop

    2017-01-01

    Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons. Conversely, genetic elimination of oxytocin receptors increases the expression of protein components of excitatory synapses and excitatory synaptic transmission in vitro. In vivo, oxytocin-receptor-deficient hippocampal pyramidal neurons develop more complex dendrites, which leads to increased spine number and reduced γ-oscillations. These results indicate that oxytocin controls the development of hippocampal excitatory neurons and contributes to the maintenance of a physiological excitation/inhibition balance, whose disruption can cause neurobehavioral disturbances. DOI: http://dx.doi.org/10.7554/eLife.22466.001 PMID:28231043

  6. Ghrelin-Induced Enhancement of Vasopressin and Oxytocin Secretion in Rat Neurohypophyseal Cell Cultures.

    PubMed

    Gálfi, M; Radács, M; Molnár, Zs; Budai, I; Tóth, G; Pósa, A; Kupai, K; Szalai, Z; Szabó, R; Molnár, H A; Gardi, J; László, Ferenc A; Varga, Cs

    2016-12-01

    The effects of ghrelin on vasopressin and oxytocin secretion were studied in 13-14-day cell cultures of isolated rat neurohypophyseal tissue. The vasopressin and oxytocin contents of the supernatant were determined by radioimmunoassay after a 1- or 2-h incubation. Significantly increased levels of vasopressin and oxytocin production were detected in the cell culture media following ghrelin administration, depending on the ghrelin doses. The oxytocin level proved to be more elevated than that of vasopressin. The increase of vasopressin and oxytocin secretion could be totally blocked by previous administration of the ghrelin receptor antagonist ([D-Lys(3)]-growth hormone-releasing peptide-6). Application of the ghrelin receptor antagonist after ghrelin administration proved ineffective. The results indicate that vasopressin and oxytocin release is influenced directly by the ghrelin system, and the effects of ghrelin on vasopressin and oxytocin secretion from the neurohypophyseal tissue in rats can occur at the level of the posterior pituitary. Our observations lend support to the view that neurohypophysis contains ghrelin receptors.

  7. alpha-Melanocyte-stimulating hormone and oxytocin: a peptide signalling cascade in the hypothalamus.

    PubMed

    Sabatier, N

    2006-09-01

    alpha-Melanocyte-stimulating hormone (alpha-MSH) and oxytocin share remarkable similarities of effects on behaviour in rats; in particular, they both inhibit feeding behaviour and stimulate sexual behaviour. Recently, we showed that alpha-MSH interacts with the magnocellular oxytocin system in the supraoptic nucleus; alpha-MSH induces the release of oxytocin from the dendrites of magnocellular neurones but it inhibits the secretion of oxytocin from their nerve terminals in the posterior pituitary. This effect of alpha-MSH on supraoptic nucleus oxytocin neurones is remarkable for two reasons. First, it illustrates the capacity of magnocellular neurones to differentially regulate peptide release from dendrites and axons and, second, it emphasises the putative role of magnocellular neurones as a major source of central oxytocin release, and as a likely substrate of some oxytocin-mediated behaviours. The ability of peptides to differentially control secretion from different compartments of their targets indicates one way by which peptide signals might have a particularly significant effect on neuronal circuitry. This suggests a possible explanation for the striking way in which some peptides can influence specific, complex behaviours.

  8. Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers.

    PubMed

    Di Simplicio, M; Massey-Chase, R; Cowen, P J; Harmer, Catherine J

    2009-05-01

    Animal studies have shown the role of oxytocin in affiliation and attachment, and recent evidence suggests that oxytocin is also involved in human models of approach behaviour, possibly by modulating the processing of emotionally valenced stimuli. Although oxytocin administration has been reported to decrease neural responses to facial emotional information, the effects on a wider range of behavioural measures of emotional processing shown to be sensitive to antidepressant manipulation have not been examined. The aim of this study was to investigate whether intranasally administered oxytocin affects the processing of positive and negative affective information in healthy male volunteers across tasks measuring attention, perception and memory. Twenty-nine male healthy volunteers were randomly allocated to receive a single dose of oxytocin nasal spray (24 UI) or placebo. 50 min later, participants completed a battery of psychological tests measuring emotional processing. A single dose of intranasally administered oxytocin slowed reaction time to correctly identify fearful facial expressions and reduced the misclassification of positive emotions as negative ones. These effects occurred in the absence of significant differences in subjective ratings of mood and anxiety. These results suggest that oxytocin modulates emotion processing in healthy male volunteers. This action may contribute to the emerging role of the neuropeptide in promoting affiliative and approach behaviours by reducing the salience of potentially ambiguous and threatening social stimuli.

  9. Oxytocin and enhancement of the positive valence of social affiliation memories: an autobiographical memory study.

    PubMed

    Cardoso, Christopher; Orlando, Mark Anthony; Brown, Christopher A; Ellenbogen, Mark A

    2014-01-01

    Intranasal oxytocin has been shown to alter self-perceptions of personality (e.g., more trusting, increased extraversion). To follow up these findings, we examined the acute effects of two doses of intranasal oxytocin (24 IU and 48 IU) on another form of self-referential cognition: autobiographical memory. Changes in autobiographical memory (personal memories for the past) could conceivably effect change in self-perception and consequently alter social behaviors. We predicted that oxytocin would increase the number of specific personal memories recalled, and promote the recall of positive social affiliation memories. Seventeen male participants self-administered a placebo or oxytocin (24 IU, 48 IU) using a nasal spray on three separate occasions in a placebo-controlled, double-blind, and within-subject experiment. Participants completed the Autobiographical Memory Test (AMT) 110 minutes later. Analyses revealed a quadratic dose-response curve for the effects of intranasal oxytocin on autobiographical memory recall. The 24 IU dose, relative to the 48 IU dose and placebo, increased the number of specific personal memories recalled and promoted the recall of social affiliation memories that were rated more positively. The lack of effect with the 48 IU dose could be due to saturation of the oxytocin receptors at higher doses. Changes in autobiographical memory may be one mechanism by which oxytocin alters prosocial worldviews.

  10. PLASMA OXYTOCIN LEVELS PREDICT SOCIAL CUE RECOGNITION IN INDIVIDUALS WITH SCHIZOPHRENIA

    PubMed Central

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

    2015-01-01

    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

  11. Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men

    PubMed Central

    Thienel, M; Fritsche, A; Heinrichs, M; Peter, A; Ewers, M; Lehnert, H; Born, J; Hallschmid, M

    2016-01-01

    Background/Objectives: Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake, and raise the question of its potential to improve metabolic control in obesity. Subjects/Methods: We compared the effect of central nervous oxytocin administration (24 IU) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men. In double-blind, placebo-controlled experiments, ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration, followed by the assessment of postprandial, reward-driven snack intake. Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sampled to determine concentrations of blood glucose and hormones. Results: Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men, and led to a reduction in snack consumption in both groups, whereas energy expenditure remained generally unaffected. Hypothalamic–pituitary–adrenal axis secretion and the postprandial rise in plasma glucose were blunted by oxytocin in both groups. Conclusions: Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders. PMID:27553712

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

    PubMed Central

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

    2015-01-01

    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”), appears 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 two 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. In Study 1, 11 healthy adult volunteers attended three sessions during which they received methamphetamine (10mg or 20mg) or placebo under double blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin were measured at regular intervals throughout the sessions. In Study 2, 8 healthy adult volunteers attended a single session during which they received one beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither drug increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified. PMID:25853370

  14. 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.

  15. Population pharmacokinetic analysis of tacrolimus in Mexican paediatric renal transplant patients: role of CYP3A5 genotype and formulation

    PubMed Central

    Jacobo-Cabral, Carlos Orlando; García-Roca, Pilar; Romero-Tejeda, Elba Margarita; Reyes, Herlinda; Medeiros, Mara; Castañeda-Hernández, Gilberto; Trocóniz, Iñaki F

    2015-01-01

    Aims The aims of this study were (i) to develop a population pharmacokinetic (PK) model of tacrolimus in a Mexican renal transplant paediatric population (n = 53) and (ii) to test the influence of different covariates on its PK properties to facilitate dose individualization. Methods Population PK and variability parameters were estimated from whole blood drug concentration profiles obtained at steady-state using the non-linear mixed effect modelling software NONMEM® Version 7.2. Results Tacrolimus PK profiles exhibited high inter-patient variability (IPV). A two compartment model with first order input and elimination described the tacrolimus PK profiles in the studied population. The relationship between CYP3A5 genotype and tacrolimus CL/F was included in the final model. CL/F in CYP3A5*1/*1 and *1/*3 carriers was approximately 2- and 1.5-fold higher than in CYP3A5*3/*3 carriers (non-expressers), respectively, and explained almost the entire IPV in CL/F. Other covariates retained in the final model were the tacrolimus dose and formulation type. Limustin® showed markedly lower concentrations than the rest of the formulations. Conclusions Population PK modelling of tacrolimus in paediatric renal transplant recipients identified the tacrolimus formulation type as a significant covariate affecting the blood concentrations and confirmed the previously reported significant effect of CYP3A5 genotype on CL/F. It allowed the design of a proposed dosage based on the final model that is expected to help to improve tacrolimus dosing. PMID:25846845

  16. 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.

  17. Quantitation of acrylamide (and polyacrylamide): critical review of methods for trace determination/formulation analysis and future-research recommendations. Final report

    SciTech Connect

    Daughton, C.G.

    1988-01-01

    Polyacrylamides (esp. polyelectrolytes) have gained wide usage in water treatment (as flocculants/coagulants), tertiary oil recovery, and various other applications such as sewer grouts. Unreacted, residual acrylamide monomer (2-propenamide: CH2=CH-C(=O)-NH2) is usually present in the various bulk commercial formulations at low fractional percentages. Although the polymers are relatively nontoxic, acrylamide can elicit severe neurotoxicity and genotoxicity. For health concerns, use of polyacrylamides in drinking water has been subjected to closer evaluation during the last decade. Currently, dosage standards are indirectly based on the maximum concentration of acrylamide that would result from use of a commercial formulation of known acrylamide content. Although numerous methods of chemical analysis exist for determining the acrylamide content of a polyacrylamide formulation, no standardized method has been adopted for directly determining trace concentrations of acrylamide in water (e.g., at the sub-parts-per-billion level, ng-micrograms/L). This report represents the first in-depth literature review of methods for determining acrylamide monomer. Over 100 references were reviewed, and those that deal specifically with acrylamide determination are annotated in detail. The approach was to unify the general chemistry of acrylamide (and amides) with the published methods for quantitation.

  18. Salsolinol Up-Regulates Oxytocin Expression and Release During Lactation in Sheep.

    PubMed

    Górski, K; Marciniak, E; Zielińska-Górska, M; Misztal, T

    2016-03-01

    Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a dopamine-derived compound present in the central nervous system and pituitary gland. Several previous studies on lactating sheep and rats have reported that salsolinol plays a crucial role in the regulation of prolactin secretion. The present study investigated the effects of salsolinol, which was infused into the third ventricle of the brain, on oxytocin expression and release in lactating sheep, 48 h after weaning of 8-week-old lambs. Serial 30-min infusions of salsolinol and vehicle were performed at 30-min intervals from 10.00 to 15.00 h. Blood samples were collected every 10 min. The supraoptic nucleus (SON), paraventricular nucleus (PVN) and posterior pituitary were collected immediately after the experiment. Expression levels of mRNAs for oxytocin and peptidylglycine α-amidating monooxygenase (PAM), the terminal enzyme in the oxytocin synthesis pathway, were measured using a real-time polymerase chain reaction. Oxytocin peptide content in the posterior pituitary was measured by an enzyme-linked immunosorbent assay, and plasma oxytocin concentration was measured by radioimmunoassay. Salsolinol treatment significantly up-regulated oxytocin and PAM gene expression in the SON (P < 0.01 and P < 0.05, respectively), PVN (P < 0.01 and P < 0.05, respectively) and posterior pituitary (P < 0.05 and P < 0.05, respectively). Oxytocin peptide content in the posterior pituitary and the area under the response curve of plasma oxytocin were significantly (P < 0.05 and P < 0.01, respectively) higher in salsolinol-treated sheep than in control animals. The present study shows for the first time that salsolinol stimulates oxytocin secretion during lactation in sheep.

  19. Reduced circulating oxytocin and High-Molecular-Weight adiponectin are risk factors for metabolic syndrome.

    PubMed

    Yuan, Guoyue; Qian, Weiyun; Pan, Ruirong; Jia, Jue; Jiang, Dan; Yang, Qichao; Wang, Su; Liu, Yuanxin; Yu, Shuqin; Hu, Hao; Sun, Wenjun; Ye, Jingjing; Mao, Chaoming; Zhuang, Ruo; Zhou, Libin

    2016-07-30

    The neurohypophysial hormone, oxytocin, is involved in the regulation of energy metabolism. Adiponectin (APN) is an adipose tissue-specific serum protein that inversely associates with metabolic syndrome (MetS). High-molecular-weight adiponectin (HMW APN) is considered the active form. In the present study, we aimed to determine the relationships of oxytocin and HMW APN to MetS and investigate whether or not the combination of oxytocin and HMW APN is associated with further metabolic abnormalities compared to each of them alone. A total of 170 subjects (75 with MetS and 95 non-MetS) were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT), blood lipids, hs-CRP, oxytocin and HMW APN levels were measured. Compared with non-MetS subjects, serum oxytocin and HMW APN levels were significantly lower in subjects with MetS (P<0.01). We then classified the subjects into three groups: high oxytocin and high HMW APN levels (high score group), low oxytocin and low HMW APN levels (low score group) and others. Participants in low score group showed the worst metabolic profiles and were more likely to have MetS compared to the other two group. In Spearman rank correlation coefficient, the classification by the combination of oxytocin and HMW APN was significantly correlated with a larger number of metabolic risk factors compared with classification by each of them alone. Individuals with low circulating oxytocin levels coupled with low HMW APN levels were at significantly increased risk of MetS. The combination of both markers would be useful for identifying MetS high risk patients.

  20. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

    PubMed

    Baskerville, Tracey A; Douglas, Alison J

    2010-06-01

    Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

  1. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

    PubMed

    Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

    2016-09-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research.

  2. Breaking the loop: oxytocin as a potential treatment for drug addiction.

    PubMed

    McGregor, Iain S; Bowen, Michael T

    2012-03-01

    Drug use typically occurs within a social context, and social factors play an important role in the initiation, maintenance and recovery from addictions. There is now accumulating evidence of an interaction between the neural substrates of affiliative behavior and those of drug reward, with a role for brain oxytocin systems in modulating acute and long-term drug effects. Early research in this field indicated that exogenous oxytocin administration can prevent development of tolerance to ethanol and opiates, the induction of stereotyped, hyperactive behavior by stimulants, and the withdrawal symptoms associated with sudden abstinence from drugs and alcohol. Additionally, stimulation of endogenous oxytocin systems is a key neurochemical substrate underlying the prosocial and empathogenic effects of party drugs such as MDMA (Ecstasy) and GHB (Fantasy). Brain oxytocin systems exhibit profound neuroplasticity and undergo major neuroadaptations as a result of drug exposure. Many drugs, including cocaine, opiates, alcohol, cannabis, MDMA and GHB cause long-term changes in markers of oxytocin function and this may be linked to enduring deficits in social behavior that are commonly observed in laboratory animals repeatedly exposed to these drugs. Very recent preclinical studies have illustrated a remarkable ability of exogenously delivered oxytocin to inhibit stimulant and alcohol self-administration, to alter associated drug-induced changes in dopamine, glutamate and Fos expression in cortical and basal ganglia sites, and to prevent stress and priming-induced relapse to drug seeking. Oxytocin therefore has fascinating potential to reverse the corrosive effects of long-term drugs abuse on social behavior and to perhaps inoculate against future vulnerability to addictive disorders. The results of clinical studies examining intranasal oxytocin effects in humans with drug use disorders are eagerly awaited. This article is part of a Special Issue entitled Oxytocin, Vasopressin

  3. Prosocial effects of oxytocin in two mouse models of autism spectrum disorders.

    PubMed

    Teng, Brian L; Nonneman, Randal J; Agster, Kara L; Nikolova, Viktoriya D; Davis, Tamara T; Riddick, Natallia V; Baker, Lorinda K; Pedersen, Cort A; Jarstfer, Michael B; Moy, Sheryl S

    2013-09-01

    Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 h following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1-2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin.

  4. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion.

    PubMed

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

    2003-10-01

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

  5. Prosocial effects of oxytocin in two mouse models of autism spectrum disorders

    PubMed Central

    Teng, Brian L.; Nonneman, Randal J.; Agster, Kara L.; Nikolova, Viktoriya D.; Davis, Tamara T.; Riddick, Natallia V.; Baker, Lorinda K.; Pedersen, Cort A.; Jarstfer, Michael B.; Moy, Sheryl S.

    2013-01-01

    Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 hours following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1–2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin. PMID:23643748

  6. Finite element analysis of land subsidence above depleted reservoirs with pore pressure gradient and total stress formulations

    NASA Astrophysics Data System (ADS)

    Gambolati, Giuseppe; Ferronato, Massimiliano; Teatini, Pietro; Deidda, Roberto; Lecca, Giuditta

    2001-04-01

    The solution of the poroelastic equations for predicting land subsidence above productive gas/oil fields may be addressed by the principle of virtual works using either the effective intergranular stress, with the pore pressure gradient regarded as a distributed body force, or the total stress incorporating the pore pressure. In the finite element (FE) method both approaches prove equivalent at the global assembled level. However, at the element level apparently the equivalence does not hold, and the strength source related to the pore pressure seems to generate different local forces on the element nodes. The two formulations are briefly reviewed and discussed for triangular and tetrahedral finite elements. They are shown to yield different results at the global level as well in a three-dimensional axisymmetric porous medium if the FE integration is performed using the average element-wise radius. A modification to both formulations is suggested which allows to correctly solve the problem of a finite reservoir with an infinite pressure gradient, i.e. with a pore pressure discontinuity on its boundary.

  7. ToF-SIMS analysis of chemical heterogenities in inkjet micro-array printed drug/polymer formulations.

    PubMed

    Scoutaris, Nikolaos; Hook, Andrew L; Gellert, Paul R; Roberts, Clive J; Alexander, Morgan R; Scurr, David J

    2012-02-01

    Three different formulations comprising two drugs, felodipine and hydrochlorothiazide (HCT) and two polymers, poly(vinyl pyrolidone) (PVP) and poly(lactic-co-glycolic acid) (PLGA) were inkjet printed as micro-dot arrays and analysed on an individual micro-spot basis by time-of-flight secondary ion mass spectrometry (ToF-SIMS). For the HCT/PLGA formulation, the spots showed heterogeneity of the drug and other chemical constituents. To further investigate these heterogeneities, multivariate curve resolution was applied to the ToF-SIMS hyperspectral image datasets. This approach successfully identified distinct chemical components elucidating the HCT, PLGA, substrate material, and contaminants based on sulphur, phosphorous and sodium chloride. Spots printed using either of the drugs with PVP exhibited full substrate coverage and a uniform distribution of the active ingredient along with all other constituents within the printed spot area. This represents the preferred situation in terms of stability and controlling the release of a drug from a polymer matrix.

  8. Analysis of magnesium from magnesium stearate in pharmaceutical tablet formulations using hydrophilic interaction liquid chromatography with nano quantity analyte detection.

    PubMed

    Risley, Donald S; Magnusson, Lars-Erik; Morow, Paul R; Aburub, Aktham

    2013-05-05

    This study demonstrates the use of hydrophilic interaction liquid chromatography with a nano quantity analyte detector for the retention, separation and detection of magnesium from magnesium stearate in tablet formulations for a drug product formulation blend containing a hydrochloride salt of a weakly basic compound as the active ingredient. The nano quantity analyte detector can provide direct detection of inactive excipients and inorganic salts lacking ultraviolet chromophores, as well as, all non-volatile compounds. The separation was accomplished using a SeQuant ZIC-HILIC column and mobile phase consisting of 32.5:32.5:35 of acetone/methanol/ammonium formate buffer (150 mM, pH 4.5). Common validation parameters were evaluated to assess the method's quantitative potential for magnesium (from magnesium stearate) including: linearity, accuracy, specificity, solution stability, repeatability, and intermediate precision. Overall, the method described in this report proved to be very robust and represents a novel technique to conveniently separate and detect magnesium from magnesium stearate in pharmaceutical preparations both quickly and accurately.

  9. 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

  10. Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery.

    PubMed

    Tyzio, Roman; Cossart, Rosa; Khalilov, Ilgam; Minlebaev, Marat; Hübner, Christian A; Represa, Alfonso; Ben-Ari, Yehezkel; Khazipov, Rustem

    2006-12-15

    We report a signaling mechanism in rats between mother and fetus aimed at preparing fetal neurons for delivery. In immature neurons, gamma-aminobutyric acid (GABA) is the primary excitatory neurotransmitter. We found that, shortly before delivery, there is a transient reduction in the intracellular chloride concentration and an excitatory-to-inhibitory switch of GABA actions. These events were triggered by oxytocin, an essential maternal hormone for labor. In vivo administration of an oxytocin receptor antagonist before delivery prevented the switch of GABA actions in fetal neurons and aggravated the severity of anoxic episodes. Thus, maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery.

  11. Oxytocin Affects the Connectivity of the Precuneus and the Amygdala: A Randomized, Double-Blinded, Placebo-Controlled Neuroimaging Trial

    PubMed Central

    Kumar, Jyothika; Völlm, Birgit

    2015-01-01

    Background: Although oxytocin is one of the most widely studied neuropeptides in recent times, the mechanistic process by which it modulates social-affective behavior in the brain is not yet clearly understood. Thus, to understand the neurophysiological basis of oxytocin effects, we used resting-state functional MRI to examine the effects of intranasal oxytocin on brain connectivity in healthy males. Methods: Using a randomized, double-blinded, placebo-controlled, crossover design, 15 healthy male volunteers received 24 IU intranasal oxytocin or placebo prior to resting-state functional MRI acquisition at 3T. Results: We found that oxytocin significantly reduced the degree centrality of the right precuneus (P<.05). Oxytocin also reduced connectivity between the bilateral amygdalae and between the right precuneus and the right and left amygdala (P<.05). Although there were no significant changes in regional homogeneity at the whole brain level, posthoc results showed a reduction involving the right precuneus (P<.05). Conclusions: These results show that oxytocin affects one of the key centers in the brain for social cognition and introspective processing, the precuneus, and enhances our understanding of how oxytocin can modulate brain networks at rest. An improved understanding of the neurophysiological effects of oxytocin can be important in terms of evaluating the mechanisms that are likely to underlie the clinical responses observed upon long-term oxytocin administration. PMID:25522395

  12. Identification of a novel receptor for an invertebrate oxytocin/vasopressin superfamily peptide: molecular and functional evolution of the oxytocin/vasopressin superfamily.

    PubMed

    Kawada, Tsuyoshi; Kanda, Atsuhiro; Minakata, Hiroyuki; Matsushima, Osamu; Satake, Honoo

    2004-08-15

    Annetocin is structurally related to an OT (oxytocin)/VP (vasopressin) family peptide, which has been isolated from the earthworm Eisenia foetida and has been shown to induce OT-like egg-laying behaviour. We now report the identification of an endogenous AnR (annetocin receptor). The deduced AnR precursor displays high sequence similarity with OT/VP receptors. Genomic analysis of the AnR gene revealed that the intron-inserted position is conserved between the AnR gene and the mammalian OT/VP receptor genes. These results indicate that AnR and mammalian OT/VP receptors share a common ancestor gene. Administration of annetocin to the AnR expressed in Xenopus oocytes induced a calcium-dependent signal transduction. Reverse transcriptase-PCR analysis and in situ hybridization showed that the AnR gene is expressed specifically in the nephridia located in the clitellum region, although the nephridia are distributed throughout the worm body. This result suggests that annetocin induces egg-laying behaviour through its action on the nephridia. This is the first description concerning the functional correlation between an invertebrate OT/VP-related peptide and egg-laying behaviour.

  13. 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.

  14. Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS).

    PubMed

    Poklis, Justin L; Mohs, Amanda J; Wolf, Carl E; Poklis, Alphonse; Peace, Michelle R

    2016-10-01

    In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOF(TM) time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations.

  15. 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.

  16. Oxytocin receptor binding in the hypothalamus during gestation in rats.

    PubMed

    Bealer, Steven L; Lipschitz, David L; Ramoz, Gina; Crowley, William R

    2006-07-01

    Central oxytocin receptors (OTR) may be involved in adaptations of the brain oxytocin (OT) system during gestation, which are critical for systemic release of OT during parturition and lactation. We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat. Furthermore, to evaluate the importance of ovarian steroids in mediating pregnancy-related changes in OTR binding, we measured binding in ovariectomized animals treated with progesterone and/or estrogen, and in pregnant animals treated with exogenous progesterone during late gestation. We found that OTR binding was significantly increased in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by midgestation (day 15) compared with control. In addition, there was a further significant increase in OTR binding in these nuclei by late gestation (day 20). The bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA) also showed significant gestation-associated increases in OTR binding, which were similar during mid- and late pregnancy. Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites. Finally, estrogen treatment in ovariectomized animals resulted in increased OTR binding in the SON, BNST, and MPOA, but not the PVN. These data demonstrate that OTR binding in the hypothalamus is increased during mid- and late-gestation, compared with ovariectomized control animals, which may be mediated by increased estradiol.

  17. Salubrious effects of oxytocin on social stress-induced deficits

    PubMed Central

    Smith, Adam S.; Wang, Zuoxin

    2012-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

  18. Regulation of the macrophage oxytocin receptor in response to inflammation.

    PubMed

    Szeto, Angela; Sun-Suslow, Ni; Mendez, Armando J; Hernandez, Rosa I; Wagner, Klaus V; McCabe, Philip M

    2017-03-01

    It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/Gαq/11 signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages.

  19. Neonatal manipulation of oxytocin influences female reproductive behavior and success.

    PubMed

    Cushing, Bruce S; Levine, Karyn; Cushing, Nancy L

    2005-01-01

    During early neonatal development, oxytocin (OT) may influence the expression of adult behavior and physiology. Here we test the prediction that early postnatal exposure to OT or an oxytocin antagonist (OTA) can affect the subsequent expression of sexual receptivity and reproductive success of females. To test this hypothesis, female prairie voles (Microtus ochrogaster) received one of four treatments within 24 h of birth. Three groups received an intraperitoneal injection of OT, OTA, or isotonic saline. A fourth group was handled, but not injected. Around 75 days of age, females were paired with sexually experienced males for 72 h and sexual activity was recorded. Treatment had no effect on the probability of mating. Injection, regardless of treatment, reduced latency to mate compared with handled controls. OT and OTA treatment decreased mating bout frequency compared to saline and handled controls, while OTA treatment increased reproductive success, probability of successfully producing a litter. The results suggest that neonatally OT, both endogenous and exogenous, can affect the expression of adult female reproductive activity and that blocking the effects of endogenous OT during neonatal development can affect female reproductive success. Finally, the results suggest that a number of aspects of reproduction are regulated by OT during the postnatal period, but that the mechanism of action may differ depending upon the reproductive activity.

  20. Determination of lithium in pharmaceutical formulations used in the treatment of bipolar disorder by flow injection analysis with spectrophotometric detection.

    PubMed

    Silva, Cássia Maria L da; Almeida, Vanessa G K; Cassella, Ricardo J

    2007-10-15

    In this work, a flow injection system with spectrophotometric detection was developed for the determination of lithium in pharmaceutical formulations used in the treatment of bipolar disorder. Reaction between Quinizarine (1,4-dihydroxyanthraquinone) and Li(I) ion in alkaline medium containing dimethylsulfoxide (DMSO) was explored for this purpose. The flow system was optimized regarding to its chemical (DMSO, Quinizarine and NaOH concentrations and sample pH) and physical parameters (sample loop volume, carrier flow rate and reactor length) in order to establish better conditions in terms of sensitivity and sampling frequency. The results obtained showed that the concentration of DMSO in the reagent solution presents remarkable influence on the magnitude of analytical signal. Chemical species that could be found in the formulations such as Na(I), K(I), Mg(II), Ca(II), Ti(IV), Cl(-), CO(3)(2-) e sodium dodecylsulfate were tested as possible interfering ions. Among them, only non-monovalent cations presented noticeable interference on lithium signal. However, they were not found in concentrations high enough to cause interference in the determination of lithium in the samples. Sample preparation was performed by sonicating a slurry prepared by dispersing 100mg of powdered sample in 15mL of 0.10molL(-1) HCl solution. Results obtained by developed methodology were not statistically different from those obtained by flame emission spectrometry. In the optimized conditions the method presented a linear range of 5-40mgL(-1) and a relative standard deviation of 3.6% at 5mgL(-1) Li concentration. Detection and quantification limits were 0.54 and 1.8mgL(-1), respectively. Sampling frequency, calculated as the time interval passed between two consecutive injections, was 60 samples per hour. The methodology was successfully applied in the determination of lithium in three commercial samples.

  1. Chronic Methamphetamine Self-Administration Dysregulates Oxytocin Plasma Levels and Oxytocin Receptor Fibre Density in the Nucleus Accumbens Core and Subthalamic Nucleus of the Rat.

    PubMed

    Baracz, S J; Parker, L M; Suraev, A S; Everett, N A; Goodchild, A K; McGregor, I S; Cornish, J L

    2016-04-01

    The neuropeptide oxytocin attenuates reward and abuse for the psychostimulant methamphetamine (METH). Recent findings have implicated the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in oxytocin modulation of acute METH reward and relapse to METH-seeking behaviour. Surprisingly, the oxytocin receptor (OTR) is only modestly involved in both regions in oxytocin attenuation of METH-primed reinstatement. Coupled with the limited investigation of the role of the OTR in psychostimulant-induced behaviours, we primarily investigated whether there are cellular changes to the OTR in the NAc core and STh, as well as changes to oxytocin plasma levels, after chronic METH i.v. self-administration (IVSA) and after extinction of drug-taking. An additional aim was to examine whether changes to central corticotrophin-releasing factor (CRF) and plasma corticosterone levels were also apparent because of the interaction of oxytocin with stress-regulatory mechanisms. Male Sprague-Dawley rats were trained to lever press for i.v. METH (0.1 mg/kg/infusion) under a fixed-ratio 1 schedule or received yoked saline infusions during 2-h sessions for 20 days. An additional cohort of rats underwent behavioural extinction for 15 days after METH IVSA. Subsequent to the last day of IVSA or extinction, blood plasma was collected for enzyme immunoassay, and immunofluorescence was conducted on NAc core and STh coronal sections. Rats that self-administered METH had higher oxytocin plasma levels, and decreased OTR-immunoreactive (-IR) fibres in the NAc core than yoked controls. In animals that self-administered METH and underwent extinction, oxytocin plasma levels remained elevated, OTR-IR fibre density increased in the STh, and a trend towards normalisation of OTR-IR fibre density was evident in the NAc core. CRF-IR fibre density in both brain regions and corticosterone plasma levels did not change across treatment groups. These findings demonstrate that oxytocin systems, both centrally

  2. 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.

  3. Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.

    PubMed

    Tyzio, Roman; Nardou, Romain; Ferrari, Diana C; Tsintsadze, Timur; Shahrokhi, Amene; Eftekhari, Sanaz; Khalilov, Ilgam; Tsintsadze, Vera; Brouchoud, Corinne; Chazal, Genevieve; Lemonnier, Eric; Lozovaya, Natalia; Burnashev, Nail; Ben-Ari, Yehezkel

    2014-02-07

    We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naïve mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.

  4. 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.

  5. DNA damage after chronic oxytocin administration in rats: a safety yellow light?

    PubMed

    Leffa, Daniela D; Daumann, Francine; Damiani, Adriani P; Afonso, Arlindo C; Santos, Maria A; Pedro, Thayara H; Souza, Renan P; Andrade, Vanessa M

    2017-02-01

    Adjuvant therapy is a common therapeutic strategy used for schizophrenia management. Oxytocin has shown promising results as antipsychotic adjuvant in patients with schizophrenia. Although short-term clinical studies have indicated tolerability and no major side-effect manifestation, long-term studies remain needed. In this study, we investigated whether oxytocin chronic administration in rats may lead to brain DNA damage by comet assay. Our results suggest that 21 and 56-day treatment with once daily intraperitoneal oxytocin (0.1, 1.0 and 10.0 mg/kg) may cause substantial DNA damage in hippocampus. We have not found differences on body weight gain. Our findings also point that further clinical and preclinical studies evaluating oxytocin safety after chronic exposure are necessary.

  6. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter.

    PubMed

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2012-04-01

    Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.

  7. 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.

  8. Analysis of the impact of controlled release formulations on oral drug absorption, gut wall metabolism and relative bioavailability of CYP3A substrates using a physiologically-based pharmacokinetic model.

    PubMed

    Olivares-Morales, Andrés; Kamiyama, Yoshiteru; Darwich, Adam S; Aarons, Leon; Rostami-Hodjegan, Amin

    2015-01-25

    Controlled release (CR) formulations are usually designed to achieve similar exposure (AUC) levels as the marketed immediate release (IR) formulation. However, the AUC is often lower following CR compared to IR formulations. There are a few exceptions when the CR formulations have shown higher AUC. This study investigated the impact of CR formulations on oral drug absorption and CYP3A4-mediated gut wall metabolism. A review of the current literature on relative bioavailability (Frel) between CR and IR formulations of CYP3A substrates was conducted. This was followed by a systematic analysis to assess the impact of the release characteristics and the drug-specific factors (including metabolism and permeability) on oral bioavailability employing a physiologically-based pharmacokinetic (PBPK) modelling and simulation approach. From the literature review, only three CYP3A4 substrates showed higher Frel when formulated as CR. Several scenarios were investigated using the PBPK approach; in most of them, the oral absorption of CR formulations was lower as compared to the IR formulations. However, for highly permeable compounds that were CYP3A4 substrates the reduction in absorption was compensated by an increase in the fraction that escapes from first pass metabolism in the gut wall (FG), where the magnitude was dependent on CYP3A4 affinity. The systematic simulations of various interplays between different parameters demonstrated that BCS class 1 highly-cleared CYP3A4 substrates can display up to 220% higher relative bioavailability when formulated as CR compared to IR, in agreement with the observed data collected from the literature. The results and methodology of this study can be employed during the formulation development process in order to optimize drug absorption, especially for CYP3A4 substrates.

  9. A molecular mechanics study of the effect of substitution in position 1 on the conformational space of the oxytocin/vasopressin ring

    NASA Astrophysics Data System (ADS)

    Tarnowska, Monika; Liwo, Adam; Shenderovich, Mark D.; Liepiņa, Inta; Golbraikh, Alexander A.; Grzonka, Zbigniew; Tempczyk, Anna

    1993-12-01

    The effect of the substitution in position 1 on the low-energy conformations of the oxytocin/vasopressin 20-membered ring was investigated by means of molecular mechanics. Three representative substitutions were considered: β'-mercapto-β,β-dimethyl)propionic acid (Dmp), (β'-mercapto-β,β-cyclopentamethylene)propionic acid (Cpp), both forming strong antagonists, and (α,α-dimethyl-β-mercapto)propionic acid (α-Dmp), forming analogs of strongly reduced biological activity, with the β-mercaptopropionic (Mpa) residue taken as reference. Both ECEPP/2 (rigid valence geometry) and AMBER (flexible valence geometry) force fields were employed in the calculations. Three basic types of backbone conformations were taken into account which are distinguished by the type of β-turn at residues 3 and 4: β1/βIII, βII, and βI'/βIII', all types containing one or two intra-annular hydrogen bonds. The allowed (ring-closed) disulfide-bridge conformations were searched by an algorithm formulated in terms of scanning the disulfide-bridge torsional angle Cβ-S-S-Cβ. The ECEPP/2 and AMBER energies of the obtained conformations were found to be in reasonable agreement. Two of the low-energy conformers of the [Mpa1]-compound agreed very well with the cyclic part of the two conformers found in the crystal structure of [Mpa1]-oxytocin. An analysis of the effect of β-substitution on relative energies showed that the conformations with the N-C'-CH2-CH2 (ψ'1) and C'-CH2-CH2-S (ϰ'1) angles of the first residue around (-100°, 60°) and (100°, -60°) are not affected; this in most cases implies a left-handed disulfide bridge. In the case of α-substitution the allowed values of ψ'1 are close to ± 60°. This requirement, being in contradiction to the one concerning β-substitution, could explain the very low biological activity of the α-substituted analogs. The conformational preferences of substituted compounds can largely be explained by the analysis of local interactions

  10. 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

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

    PubMed

    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    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 functional magnetic resonance imaging 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.

  12. In vitro release and permeation of oxytocin from a mucoadhesive buccal patch.

    PubMed

    Li, C; Bhatt, P P; Johnston, T P

    1996-12-01

    A biocompatible, mucoadhesive patch was evaluated for potential use in the delivery of peptides. The model peptide oxytocin was incorporated into the polymeric patch matrix and the diffusion of oxytocin across excised rabbit buccal epithelium was studied following patch application. Penetration of oxytocin across excised mucosa from an applied patch did not exhibit a characteristic lag time for diffusion, with the steady-state flux of oxytocin being 0.062 +/- 0.019 microgram/cm2/hr. However, when finite-dose diffusion studies were conducted to quantitate transport of oxytocin across rabbit buccal mucosa, the mean apparent permeability coefficient (P), diffusion coefficient (D), partition coefficient (K), and lag time (tlag) were (1.94 +/- 0.74) x 10(-7) cm/sec, (9.20 +/- 1.65) x 10(-8) cm2/sec, 0.13 +/- 0.05 and 1.86 +/- 0.31 hr, respectively. The release of oxytocin from the mucoadhesive buccal patches in vitro proceeded very rapidly during the first 2 hr, with 72% of the amount initially incorporated into the patches released at 24 hr. The disappearance rate of intact, parent oxytocin when an oxytocin solution was placed in direct contact with the serosal and mucosal sides of freshly excised rabbit buccal mucosa was 0.74 +/- 0.34 microgram/cm2/hr and 3.38 +/- 1.07 micrograms/cm2/hr, respectively. Thus, the buccal patch evaluated in these studies appears to be suitable for transmucosal delivery of peptides.

  13. 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.

  14. Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers.

    PubMed

    Krause, Sabrina; Pokorny, Dan; Schury, Katharina; Doyen-Waldecker, Cornelia; Hulbert, Anna-Lena; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana; Gündel, Harald; Waller, Christiane; Buchheim, Anna

    2016-01-01

    Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the "hormone of affiliation" and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants (p = 0.004) and cortisol decreased in the significant majority of 73% participants (p = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as well as

  15. Non-peptide oxytocin receptor ligands and hamster circadian wheel running rhythms.

    PubMed

    Gannon, Robert L

    2014-10-17

    The synchronization of circadian rhythms in sleep, endocrine and metabolic functions with the environmental light cycle is essential for health, and dysfunction of this synchrony is thought to play a part in the development of many neurological disorders. There is a demonstrable need to develop new therapeutics for the treatment of neurological disorders such as depression and schizophrenia, and oxytocin is currently being investigated for this purpose. There are no published reports describing activity of oxytocin receptor ligands on mammalian circadian rhythms and that, then, is the purpose of this study. Non-peptide oxytocin receptor ligands that cross the blood brain barrier were systemically injected in hamsters to determine their ability to modulate light-induced phase advances and delays of circadian wheel running rhythms. The oxytocin receptor agonist WAY267464 (10 mg/kg) inhibited light induced phase advances of wheel running rhythms by 55%, but had no effect on light-induced phase delays. In contrast, the oxytocin receptor antagonist WAY162720 (10 mg/kg) inhibited light-induced phase delays by nearly 75%, but had no effect on light-induced phase advances. Additionally, WAY162720 was able to antagonize the inhibitory effects of WAY267464 on light-induced phase advances. These results are consistent for a role of oxytocin in the phase-delaying effects of light on circadian activity rhythms early in the night. Therefore, oxytocin may prove to be useful in developing therapeutics for the treatment of mood disorders with a concomitant dysfunction in circadian rhythms. Investigators should also be cognizant that oxytocin ligands may negatively affect circadian rhythms during clinical trials for other conditions.

  16. 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.

  17. Intranasal Oxytocin for the Treatment of Pain Associated with Interstitial Cystitis

    DTIC Science & Technology

    2013-09-01

    peripheral oxytocin has analgesic effects in other types of nociception making it a useful agent for chronic pain syndromes other than IC. Because the... Pain Associated with Interstitial Cystitis PRINCIPAL INVESTIGATOR: Meredith T. Robbins, Ph.D...Intranasal Oxytocin for the Treatment of Pain Associated with Interstitial Cystitis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0452 5c

  18. Research Review: Social motivation and oxytocin in autism – implications for joint attention development and intervention

    PubMed Central

    Stavropoulos, Katherine K. M.; Carver, Leslie J.

    2013-01-01

    Background and Scope The social motivation hypothesis (SMH) suggests that individuals with autism spectrum disorders (ASD) are less intrinsically rewarded by social stimuli than their neurotypical peers. This difference in social motivation has been posited as a factor contributing to social deficits in ASD. Social motivation is thought to involve the neuropeptide oxytocin. Here, we review the evidence for oxytocin effects in ASD, and discuss its potential role in one important social cognitive behavior. Methods Systematic searches were conducted using the PsychINFO and MEDLINE databases and the search terms “oxytocin”, and “autism”; the same databases were used for separate searches for “joint attention”, “intervention”, and “autism”, using the same inclusion criteria as an earlier 2011 review but updating it for the period 2010 to October 2012. Findings Several studies suggest that giving oxytocin to both individuals with ASD and typically developing individuals can enhance performance on social cognitive tasks. Studies that have attempted to intervene in joint attention in ASD suggest that social motivation may be a particular obstacle to lasting effects. Conclusions The review of the evidence for the SMH suggests a potential role for oxytocin in social motivation deficits in ASD. Because of its importance for later communicative and social development, the focus here is on implications of oxytocin and social motivation in the development of and interventions in joint attention. Joint attention is a central impairment in ASD, and as a result is the focus of several behavioral interventions. In describing this previous research on joint attention interventions in ASD, we pay particular attention to problems encountered in such studies, and propose ways that oxytocin may facilitate behavioral intervention in this area. For future research, integrating behavioral and pharmacological interventions (oxytocin administration) would be a worthwhile

  19. Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers

    PubMed Central

    Krause, Sabrina; Pokorny, Dan; Schury, Katharina; Doyen-Waldecker, Cornelia; Hulbert, Anna-Lena; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana; Gündel, Harald; Waller, Christiane; Buchheim, Anna

    2016-01-01

    Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the “hormone of affiliation” and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants (p = 0.004) and cortisol decreased in the significant majority of 73% participants (p = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

    DTIC Science & Technology

    2010-09-01

    disorder. Psychoneuroendocrinology 34: 917-923. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003). Social support and oxytocin interact to...TITLE: Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats PRINCIPAL...Annual 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Oxytocin and Social Support as Synergistic Inhibitors of 5a. CONTRACT NUMBER

  5. 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

  6. 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 t