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Sample records for oxytocin formulations analysis

  1. Towards heat-stable oxytocin formulations: analysis of degradation kinetics and identification of degradation products.

    PubMed

    Hawe, Andrea; Poole, Robert; Romeijn, Stefan; Kasper, Piotr; van der Heijden, Rob; Jiskoot, Wim

    2009-07-01

    To investigate degradation kinetics of oxytocin as a function of temperature and pH, and identify the degradation products. Accelerated degradation of oxytocin formulated at pH 2.0, 4.5, 7.0 and 9.0 was performed at 40, 55, 70 and 80 degrees C. Degradation rate constants were determined from RP-HPLC data. Formulations were characterized by HP-SEC, UV absorption and fluorescence spectroscopy. Degradation products were identified by ESI-MS/MS. The loss of intact oxytocin in RP-HPLC was pH- and temperature-dependent and followed (pseudo) first order kinetics. Degradation was fastest at pH 9.0, followed by pH 7.0, pH 2.0 and pH 4.5. The Arrhenius equation proved suitable to describe the kinetics, with the highest activation energy (116.3 kJ/mol) being found for pH 4.5 formulations. At pH 2.0 deamidation of Gln(4), Asn(5), and Gly(9)-NH2, as well as combinations thereof were found. At pH 4.5, 7.0 and 9.0, the formation of tri- and tetrasulfide-containing oxytocin as well as different types of disulfide and dityrosine-linked dimers were found to occur. Beta-elimination and larger aggregates were also observed. At pH 9.0, mono-deamidation of Gln(4), Asn(5), and Gly(9)-NH2 additionally occurred. Multiple degradation products of oxytocin have been identified unequivocally, including various deamidated species, intramolecular oligosulfides and covalent aggregates. The strongly pH dependent degradation can be described by the Arrhenius equation.

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

  4. Formation of amide- and imide-linked degradation products between the peptide drug oxytocin and citrate in citrate-buffered formulations.

    PubMed

    Poole, Robert A; Kasper, Piotr Tomasz; Jiskoot, Wim

    2011-07-01

    Citric acid is widely used to buffer pharmaceutical formulations including protein pharmaceuticals. In accelerated stability studies of the small cyclic peptide oxytocin, we have noted that additional degradation products form when oxytocin is formulated in citrate that do not form in other common buffers such as acetate and phosphate. Using high-pressure liquid chromatography combined with high-resolution and tandem mass spectrometry, we identified these degradation products as amide- and imide-linked adducts of oxytocin and citrate. The site of reaction was shown to be the N-terminal amine of cysteine. The adducts have been found to form for oxytocin formulated in citrate buffer over the pH range of 3-6; the extent of formation is greatest at a pH of 4-4.5. We have additionally identified these same adducts in samples of oxytocin formulated in citrate buffer that had been stored in the dark for 3 months at room temperature. Altogether, these results demonstrate that reaction between citrate and oxytocin leads to the formation of covalent amide- and imide-linked adducts. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  5. 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.

  6. 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).

  7. 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.

  8. [Obstetric outcomes in oxytocin-related and spontaneous deliveries--analysis of 2198 cases].

    PubMed

    Raba, Grzegorz; Baran, Piotr

    2009-07-01

    The aim of the work was to compare labour courses, ways of delivery, condition of the newborns in spontaneous and oxytocin-related labours and to analyse the indications for oxytocin administration. 2198 full-term deliveries (pregnant women qualified for elective caesarean section were excluded from the study) at the Provincial Hospital in Przemyśl, Poland. Labours with the adjunctive oxytocin infusion--1102 women. spontaneous labours (without oxytocin administration)--1096 women. The analysis of the compatibility of measured traits was carried out by the Chi2 test, p < 0.05 was assumed as statistically significant level. I. Indications for the oxytocin administration: secondary hypokinetic contractions of the uterus (642 labours--58.25%), premature rupture of membranes (176 labours - 15.97 %). II. Deliveries by caesarean section: 1. study group--187 women (16.97%). 2. control group--97 women (8.85%). Ch2 = 32.192; df = 1; p = 0.0000. III. Newborns after vaginal labours scored 7 or below according to the Apgar in the first minute after the delivery. 1. study group--35 newborns (8.7%); 2. control group--18 newborns (1.8%) ch2 = 5.493; df = 1; p = 0.0190. IV. Newborns hospitalised for over 48 hours: 1. study group--346 (31.39%); 2. control group--216 newborns (19.70%). Chi2 = 39.454; df = 1; p = 0.0000. (1) Hypokinetic uterine contractions were the most frequent indication for oxytocin administration during labour. (2) Oxytocin administration increases twice the risk of delivery by the caesarean section. (3) Newborns after vaginal oxytocin-related labours scored 7 or below on the Apgar score in the first minute after the birth when compared to the newborns after spontaneous labour. (4) Oxytocin administration during parturition elongates the time of newborns hospitalisation.

  9. Propranolol and oxytocin versus oxytocin alone for induction and augmentation of labor: a meta-analysis of randomized trials.

    PubMed

    Pergialiotis, Vasilios; Frountzas, Maximos; Prodromidou, Anastasia; Prapa, Sofia; Perrea, Despina N; Vlachos, Georgios D

    2016-04-01

    We sought to study the effect of propranolol co-administration with oxytocin during the latent and active phases of labor on labor outcomes. We searched Medline, Scopus, ClinicalTrials.gov and Cochrane Central Register databases. The meta-analysis was performed with the RevMan 5.1 software. Six studies were included in the present meta-analysis which enrolled 609 parturient. According to the findings of our study, propranolol administration during the latent phase effectively reduces the cesarean section rates (OR 0.49, 95 % CI 0.27, 0.89). However, this beneficial effect is not observed during the active phase of labor. The 5 min neonatal Apgar scores are not influenced by its administration (MD -0.07, 95 % CI -0.017, 0.02). Respectively, the neonatal admissions to a NICU are similar to those of neonates exposed only to oxytocin (OR 0.96, 95 % CI 0.36, 2.53). Propranolol's effect on the duration of the various stages of labor was underreported, however, evidence seem to support that it shortens the latent phase and possibly the total duration of labor. Firm results are, however, precluded due to the low number enrolled parturient and due to the significant methodological heterogeneity of included studies.

  10. 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 ...

  11. Analysis of malpractice claims with a focus on oxytocin use in labour.

    PubMed

    Jonsson, Maria; Nordén, Solveig Lindeberg; Hanson, Ulf

    2007-01-01

    The objective of this study was to analyse the motives behind disciplinary action in obstetric malpractice cases concerning delivery, and to evaluate the frequency of inappropriate oxytocin use in these cases. An analysis of all malpractice claims resulting in disciplinary action against physicians and midwives during the period 1996-2003. Investigations and decisions made by the Board of Medical Responsibility were reviewed with special focus on the use of oxytocin. Of 77 cases, 60 regarded patients in labour. In the majority, there had been a normal pregnancy and spontaneous start of labour (78%). At the beginning of labour, 87% showed a normal fetal heart rate (FHR) pattern, indicating fetal well-being. In 70%, there was adverse fetal outcome with brain damage or death. The most common reason for disciplinary action was improper interpretation of fetal monitor tracings and corresponding failure to recognise fetal distress (76%). Injudicious use of oxytocin was common (68.5%), and was the primary reason for disciplinary action in 33% of the cases. In a Swedish setting, a few common clinical problems pervade; interpretation of FHR patterns and the use of oxytocin account for the majority of rulings of negligence in malpractice cases regarding delivery. Analysis of the cases suggests that the adverse fetal outcomes could possibly have been prevented.

  12. 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.

  13. 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.

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

    PubMed Central

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

    2014-01-01

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

  15. [Transformation of genetically engineered oxytocinoyllysine into oxytocin].

    PubMed

    Mal'tsev, K V; Shvets, S V; Luk'ianova, N A; Grigor'ev, A V; Miroshnikov, A I

    1996-04-01

    Various methods for obtaining oxytocin from its recombinant precursor oxytocinoyllysine were studied. For splitting off the C-terminal lysine residue in oxytocinoyllysine, the carboxypeptidase B and an analogous carboxypeptidase from king crab hepatopancreas were used. Ammonolysis of oxytocinic acid methyl ester proved to be the most efficient method for the last stage of the oxytocin preparation. Reversed-phase HPLC was used for the product analysis at each stage of the recombinant oxytocinoyllysine conversion into oxytocin.

  16. 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…

  17. 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…

  18. 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

  19. The effect of early oxytocin augmentation in labor: a meta-analysis.

    PubMed

    Wei, Shu-Qin; Luo, Zhong-Cheng; Xu, Hairong; Fraser, William D

    2009-09-01

    To estimate the effects of early augmentation with oxytocin for slow progress of labor on the delivery method and on indicators of maternal and neonatal morbidity. We conducted electronic database searches of PubMed, MEDLINE, EMBASE, and the Cochrane Library for articles published through February 2009 using the keywords "oxytocin," "augmentation," "active management of labor," "cesarean section," and "labor." Primary authors were contacted directly if the data sought were unavailable. We included randomized controlled trials comparing early oxytocin augmentation with a more conservative approach to care in labor. We included only those studies in which membrane management was similar in the two groups. Early oxytocin augmentation was defined as immediate oxytocin administration when dystocia was identified. Data were extracted by two authors independently and evaluated for potential sources of bias. Relative risk (RR) and 95% confidence interval (CI) were calculated using fixed and random effects models. Nine trials with 1,983 women met the inclusion criteria. Early oxytocin was associated with an increase in the probability of spontaneous vaginal delivery (RR 1.09, 95% CI 1.03-1.17). For every 20 patients treated with early oxytocin augmentation, one additional spontaneous vaginal delivery is expected. Although the point estimate for the effect on cesarean delivery (RR 0.87, 95% CI 0.71-1.06) and on operative vaginal delivery (RR 0.84, 95% CI 0.70-1.00) showed modest protective effects, the CIs for both estimates included the null effect. A decrease in antibiotic use (RR 0.45, 95% CI 0.21-0.99) was observed with early intervention. Early oxytocin was associated with an increased risk of hyperstimulation (RR 2.90, 95% CI 1.21-6.94) without evidence of adverse neonatal effects. Women in the early oxytocin group reported higher levels of pain and discomfort in labor. Early oxytocin for augmentation in labor is associated with an increase in spontaneous vaginal

  20. State-space formulations for flutter analysis

    NASA Technical Reports Server (NTRS)

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

    1976-01-01

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

  1. 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.

  2. 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.

  3. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-08-21

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

  6. 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

  7. 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.

  8. 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

  9. Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

    PubMed

    Takayanagi, Yuki; Yoshida, Masahide; Takashima, Akihide; Takanami, Keiko; Yoshida, Shoma; Nishimori, Katsuhiko; Nishijima, Ichiko; Sakamoto, Hirotaka; Yamagata, Takanori; Onaka, Tatsushi

    2017-02-01

    Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  10. PGFM response to exogenous oxytocin and determination of the half-life of oxytocin in nonpregnant mares.

    PubMed

    Paccamonti, D L; Pycock, J F; Taverne, M A; Bevers, M; Van Der Weijden, G C; Gutjahr, S; Schams, D; Blouin, D

    1999-07-01

    We investigated the half-life of oxytocin in reproductively normal mares and the prostaglandin response after oxytocin administrations. Mares were given oxytocin, 10 or 25 iu, i.v., on the day of, or 2 days after, ovulation, and frequent jugular blood samples were collected for analysis of oxytocin and Prostaglandin F metabolite (PGFM) by RIA. Neither dose of oxytocin nor day of treatment affected the half-life of the exogenous oxytocin, which was determined to be 6.8 min. A significant increase in PGFM was observed within 6 min of oxytocin administration and peak values were observed within 10 min. PGFM response after oxytocin administration on the day of ovulation appeared elevated compared to the response 2 days after ovulation.

  11. Analysis of oxytocin in milk samples and intake pattern in different age groups of Indian population.

    PubMed

    Mishra, Manjari; Ali, Shakir; Das, Mukul

    2014-06-01

    Oxytocin (OT) injections have been indiscriminately used to milk cattle in dairy industries. There is no study available regarding surveillance of OT in market milk samples. OT from milk samples was extracted by precipitation with trichloroacetic acid and passed through the solid phase extraction column. OT was eluted and evaporated to dryness under a gentle stream of nitrogen. The residue was either dissolved in milli Q water or buffer for analysis through HPLC or EIA. The intake assessment of OT through milk was assessed through the Food Frequency Recall method employing a Food Frequency Questionnaire. On the basis of milk consumption and the values of OT in milk, the actual intake of OT was calculated. In the present study, a total of 55 milk samples (39 milkman and 16 branded) were analyzed for occurrence of OT by EIA and UV-HPLC from different locations of Lucknow, Uttar Pradesh (India). OT contamination in milkman samples was found to be 21 pg/mL to 18.9 ng/mL with the mean value of 8.9 ng/mL. The average daily intake of OT in terms of µg/day/person was highest (2.3-2.4 µg/day/person) in 1-3-year age group. Since there is no prescribed level of OT in milk and the intake of OT through this commodity is quite high there is need to implement regulatory laws so that non-physiological OT exposure may not occur in children which may have deleterious effects.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

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

    PubMed

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

    2015-08-30

    This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors and Editor-in-Chief of the journal. It was brought to the authors' attention that there were several significant data analytic errors linked to the data entry and the software program that was used in the published meta-analysis comparing the effect of intranasal oxytocin versus placebo administration on psychiatric symptoms. Correcting these errors changed the main result of this study. The authors greatly apologize to the journal, the reviewers, and readers for the errors in the original article, and would like to thank the readers who brought the errors to their attention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. 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.

  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. 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,

  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. 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.

  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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. Oxytocin and social functioning.

    PubMed

    Jones, Candace; Barrera, Ingrid; Brothers, Shaun; Ring, Robert; Wahlestedt, Claes

    2017-06-01

    Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.

  8. 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.

  9. [Oxytocin and postpartum depression].

    PubMed

    Cardaillac, C; Rua, C; Simon, E G; El-Hage, W

    2016-10-01

    Postpartum depression (PPD) is prevalent (about 10%) with a major impact on the mother and child health. At the hormonal level, poor regulation of oxytocin rate has a key role in depression. Recently, oxytocin has been used on psychiatric therapy, intranasal or intravenously, particularly in mood disorders. But, in obstetrics, this molecule is administered during childbirth. The objective of this study was to determine if intravenous administration of oxytocin could influence thymic state of the mother in the postpartum period. Literature review, after consultation of Pubmed and Sciencedirect databases, with the following keywords: oxytocin, postpartum depression, pregnancy, social behavior. The effects of oxytocin in the PPD are part of a multifactorial mechanism (hormonal and social) that influences the hormonal effects of oxytocin. Oxytocin use in therapeutic was able to give conclusive results in psychiatry, the way and the optimal method of administration are not known. PPD is associated with administrated oxytocin during labour. Physiopathology remains unknown. It is possible that oxytocin administered during childbirth is related with the onset or worsening of the PPD without defining if it's a cause or a consequence. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    PubMed

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

    2016-12-01

    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. 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. 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). 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.

  12. Can Oxytocin Enhance the Placebo Effect?

    ClinicalTrials.gov

    2017-07-29

    Oxytocin Effect on Memory Performance During Phase 1; Oxytocin Effect on Memory Performance During Phase 2; Oxytocin Effect on Memory Performance During Phase 3; Oxytocin Effect on Memory Performance During Phase 4

  13. Oxytocin promotes human ethnocentrism

    PubMed Central

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

    2011-01-01

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

  14. Oxytocin promotes human ethnocentrism.

    PubMed

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

    2011-01-25

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

  15. Oxytocin and social functioning

    PubMed Central

    Jones, Candace; Barrera, Ingrid; Brothers, Shaun; Ring, Robert; Wahlestedt, Claes

    2017-01-01

    Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed. PMID:28867943

  16. 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

  17. Detection of Salivary Oxytocin Levels in Lactating Women

    PubMed Central

    White-Traut, Rosemary; Watanabe, Kaoru; Pournajafi-Nazarloo, Hossein; Schwertz, Dorie; Bell, Aleeca; Carter, C. Sue

    2009-01-01

    Oxytocin is a neuropeptide with widespread influence on many physiological and social functions including: labor and birth, lactation, sexual behavior, nurturing maternal behaviors, and stress reduction. However, our understanding of oxytocin’s roles has been hampered by lack of noninvasive methods for assessing oxytocin levels. The goal of the present study was to assess whether oxytocin could be detected in saliva and whether changes occurred in the pattern of oxytocin release among lactating women from before, at initiaton and after breast feeding. Using a prospective repeated measures design, 11 research participants each provided 18 saliva samples during three feeding cycles (before, at initiation and after breast feeding) for two 24-hour data collection periods (Day 1 and 2). Within each day, saliva was collected at late evening, early morning, and late morning. Salivary samples were concentrated four-fold by dehydration prior to analysis and oxytocin was measured in saliva using an enzyme immunoassay (EIA). Salivary oxytocin values, when reconverted to their original levels, ranged from 6.44 – 61.05 pg/ml. Oxytocin values in saliva varied significantly as a function of the breast feeding cycle, but did not show reliable differences as a function of the time of feeding. Oxytocin was highest before feeding, followed by a decrease at initiation of feeding, and an increase at 30 minutes after feeding. The findings suggest that oxytocin release into saliva increases in anticipation of feedings. This study also supports the potential usefulness of salivary measures of oxytocin as a noninvasive index of changes in this peptide. PMID:19365797

  18. Analysis of FGM beams by means of a unified formulation

    NASA Astrophysics Data System (ADS)

    Giunta, G.; Belouettar, S.; Carrera, E.

    2010-06-01

    This paper proposes several axiomatic refined theories for the linear static analysis of beams made of functionally graded materials. A bi-directional variation upon the cross-section is accounted for. Via a unified formulation, a generic N-order approximation is assumed for the displacement unknown variables over the beam cross-section. The governing differential equations and the boundary conditions are derived in terms of a fundamental nucleo that does not depend upon the approximation order. A Navier type, closed form solution is adopted. Beams undergo bending and torsional loadings. Deep beams are investigated. Comparisons with three-dimensional finite element models are given. The numerical investigation shows that the proposed unified formulation yields the complete three-dimensional displacement and stress fields as long as the appropriate approximation order is considered.

  19. 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.

  20. 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.

  1. 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.

  2. Functional characterization of an oxytocin receptor gene variant (rs2268498) previously associated with social cognition by expression analysis in vitro and in human brain biopsy.

    PubMed

    Reuter, Martin; Montag, Christian; Altmann, Steffen; Bendlow, Fabian; Elger, Christian; Kirsch, Peter; Becker, Albert; Schoch-McGovern, Susanne; Simon, Matthias; Weber, Bernd; Felten, Andrea

    2017-10-01

    The oxytocin system plays a prominent role in social behavior across species, and numerous genetic studies in humans have reported associations between polymorphisms on the oxytocin receptor (OXTR) gene and phenotypes related to social cognition, affiliation, perspective taking, and sociability in healthy subjects and in patients with atypical social behavior, such as in autism spectrum disorders (ASD). Recently, the first study demonstrating altered agonist-induced OXTR internalization and recycling for the exonic variant rs35062132 emerged. Beside this, there has been no further demonstration of the functionality of the OXTR variants especially there does not exist any for the regulatory units. To address this gap in the literature, we tested the functionality of the promoter flanking single nucleotide polymorphism (SNP) rs2268498, which has proven an interesting candidate for predicting social behavior in recent association studies. Results of genetic expression analyses in human hippocampal tissue showed a twofold difference in messenger RNA transcription, dependent on the presence or absence of the C-allele. This finding was corroborated by cloning, i.e., in vitro reporter gene expression analysis after transfection of OXTR promoter plasmids into HEK-293 cells. Our results underline the importance of OXTR rs2268498 for genetic research in social behavior and ASD.

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

    PubMed

    Sun, Wendell Q

    2015-01-01

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

  4. 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.

  5. 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.

  6. Factors Associated with Higher Oxytocin Requirements in Labor

    PubMed Central

    Frey, Heather A.; Tuuli, Methodius G.; England, Sarah K.; Roehl, Kimberly A.; Odibo, Anthony O.; Macones, George A.; Cahill, Alison G.

    2014-01-01

    Objective To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. Methods A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004-2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Results Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birth weight >4000 gm, intrapartum fever, administration of magnesium, and induction of labor. Conclusions Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients. PMID:25204333

  7. Factors associated with higher oxytocin requirements in labor.

    PubMed

    Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

    2015-09-01

    To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

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

    PubMed

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

    2006-11-01

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

  9. [Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage].

    PubMed

    Loscul, C; Chantry, A-A; Caubit, L; Deneux-Tharaux, C; Goffinet, F; Le Ray, C

    2016-09-01

    To study the association between the duration of oxytocin augmentation intervals and the risk of postpartum haemorrhage (PPH) among primiparous women in spontaneous labour. Retrospective cohort including primiparous women in spontaneous labour who received oxytocin during labour (n=454). Oxytocin augmentation intervals were dichotomized in intervals<20minutes and≥20minutes. Obstetrical and neonatal issues were analyzed according to the duration oxytocin augmentation intervals. The association between oxytocin augmentation intervals and PPH was analyzed using univariate and multivariate analysis. Oxytocin augmentation intervals were shorter than 20minutes for 43.8% of the study population. The rate of PPH was higher (9.1% vs 3.5%; P=0.014), and the use of sulprostone was more frequent (6.5% vs 3.5%; P=0.013) if oxytocin augmentation intervals were shorter than 20minutes in comparison with intervals≥20minutes. The association between oxytocin augmentation intervals and PPH remains significant after adjustment on other PPH risk factors (adjusted OR=3.48, 95% CI [1.45-8.34]). The rate of adverse neonatal issue, defined by arterial pH at birth≤7.10 and/or 5minutes score d'Apgar≤7, was higher if oxytocin augmentation intervals were<20minutes (12.1% vs 4.3%; P=0.002). Our study demonstrated an increased risk of PPH for primiparous women in spontaneous labour who received oxytocin with augmentation intervals shorter than 20minutes. Copyright © 2016. Published by Elsevier Masson SAS.

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

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. Tinnitus Treatment with Oxytocin: A Pilot Study.

    PubMed

    Azevedo, Andreia Aparecida; Figueiredo, Ricardo Rodrigues; Elgoyhen, Ana Belen; Langguth, Berthold; Penido, Norma De Oliveira; Schlee, Winfried

    2017-01-01

    Tinnitus is the perception of sound in the absence of an external stimulus. It is a frequent condition for which there is as yet no pharmacological treatment approved. Auditory and non-auditory pathways are involved in tinnitus' pathophysiology. Oxytocin is a neurohormone and eventual neurotransmitter that plays a complex role in social cognition and behavior. To evaluate the potential of oxytocin as a tinnitus treatment. Two studies were performed. Study 1 was a long-term open pilot study, while study 2 investigated short-term effects with a double-blinded placebo-controlled cross-over study. Ambulatory ENT care. In study 1, 15 patients were investigated over a 10-week period in an open pilot study. In study 2, 16 patients were included in a placebo-controlled crossover trial to investigate short-term effects following a single dose. For the long-term study (study 1), analysis of variance revealed a significant decrease in tinnitus sensation, both for the Tinnitus Handicap Inventory and Clinical Global Impression (CGI). Also, the short-term effects in study 2 revealed a significant reduction of tinnitus because of the oxytocin nasal spray as measured with the Visual Analog Scale and the CGI Scale. These preliminary studies demonstrated that oxytocin may represent a helpful tool for treating tinnitus and further larger controlled studies are warranted.

  13. Elevated plasma levels of oxytocin in women taking low-dose oral contraceptives. Identification of the plasma oxytocin with high performance liquid chromatography.

    PubMed

    Stock, S; Silber, M; Uvnäs-Moberg, K

    1989-01-01

    The aim of the present study was to investigate whether low-dose oral contraceptives affect oxytocin concentrations in plasma. Twenty women participated in an open cross-over study. Six consecutive blood samples were drawn twice, with a 4-week interval, in the luteal phase of the menstrual cycle when the women were/were not taking oral contraceptives. Plasma levels of oxytocin were analysed with a radio-immunoassay specific for oxytocin. A significant increase in oxytocin concentrations was observed following ingestion of oral contraceptives (p less than 0.02). Women with the highest oxytocin levels during a normal menstrual cycle increased their levels the most when on oral contraceptives. Analysis with high performance liquid chromatography demonstrated that immunoreactive oxytocin found in plasma, whether with or without oral contraceptives, co-eluted with synthetic oxytocin standard. An interesting possibility could be that the mental side effects and effects on glucose metabolism occurring after treatment with oral contraceptives might be related to elevated oxytocin levels, since metabolic and CNS effects of oxytocin are known.

  14. 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.

  15. Problem Formulation and Analysis of the 1-Hop ARQ Links

    NASA Astrophysics Data System (ADS)

    Cheung, K.-M.

    2013-08-01

    In space communications, standard link analysis assumes that messages are sent once. For a communication link that uses an error-correction coding scheme, bit-error rate (BER) or frame-error rate (FER), and link margins are common metrics that characterize the quality of a link, and they are used to determine the supportable data rate. With the advent of Automatic Repeat-reQuest (ARQ) protocols, when messages are corrupted during transmission, they can be resent multiple times automatically until they are correctly received and acknowledged. The concept of BER, FER, and link margin cannot be directly applied, and the link analysis approach for ARQ links needs to be reexamined. In this article, we provide the problem formulation and extend the standard link analysis approach to a 1-hop ARQ link (no routing), under the assumption that code-block errors occur independently as in the case of space communications. We develop analytical models that describe the statistical behavior of standard 1-hop ARQ links. By integrating these analytical ARQ protocol models into the standard link analysis, we bypass the need to simulate or emulate the ARQ protocol operations, and generate relevant statistics on effective data rate, effective throughput, latency, and FER.

  16. 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

  17. 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

  18. 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

  19. Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells

    PubMed Central

    Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Wada, Koh-ichi; Kusayama, Toshiyuki; Ishii, Noe; Yatsu, Takeyuki; Uchida, Wataru; Tanaka, Akihiro

    2000-01-01

    [3H]-oxytocin was used to characterize the oxytocin receptor found in human uterine smooth muscle cells (USMC). Specific binding of [3H]-oxytocin to USMC plasma membranes was dependent upon time, temperature and membrane protein concentration. Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high-affinity binding sites with an apparent equilibrium dissociation constant (Kd) of 0.76 nM and a maximum receptor density (Bmax) of 153 fmol mg−1 protein. The Hill coefficient (nH) did not differ significantly from unity, suggesting binding to homogenous, non-interacting receptor populations. Competitive inhibition of [3H]-oxytocin binding showed that oxytocin and vasopressin (AVP) receptor agonists and antagonists displaced [3H]-oxytocin in a concentration-dependent manner. The order of potencies for peptide agonists and antagonists was: oxytocin>[Asu1,6]-oxytocin>AVP= atosiban>d(CH2)5Tyr(Me)AVP>[Thr4,Gly7]-oxytocin>dDAVP, and for nonpeptide antagonists was: L-371257>YM087>SR 49059>OPC-21268>SR 121463A>OPC-31260. Oxytocin significantly induced concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i) and hyperplasia in USMC. The oxytocin receptor antagonists, atosiban and L-371257, potently and concentration-dependently inhibited oxytocin-induced [Ca2+]i increase and hyperplasia. In contrast, the V1A receptor selective antagonist, SR 49059, and the V2 receptor selective antagonist, SR 121463A, did not potently inhibit oxytocin-induced [Ca2+]i increase and hyperplasia. The potency order of antagonists in inhibiting oxytocin-induced [Ca2+]i increase and hyperplasia was similar to that observed in radioligand binding assays. In conclusion, these data provide evidence that the high-affinity [3H]-oxytocin binding site found in human USMC is a functional oxytocin receptor coupled to [Ca2+]i increase and cell growth. Thus human USMC may prove to be a valuable tool in further investigation of the

  20. Analysis of a Commercial Marijuana e-Cigarette Formulation

    PubMed Central

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

    2016-01-01

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

  1. 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. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    PubMed

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

    2014-09-01

    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. 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. 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. 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 social cognition, and support the exploration of

  3. 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

  4. Oxytocin as an Indicator of Psychological and Social Well-Being in Domesticated Animals: A Critical Review

    PubMed Central

    Rault, Jean-Loup; van den Munkhof, Marleen; Buisman-Pijlman, Femke T. A.

    2017-01-01

    Oxytocin is often portrayed as a hormone specific to social behavior, reflective of positive welfare states, and linked to mental states. Research on oxytocin in domesticated animal species has been few to date but is rapidly increasing (in dog, pig, cattle, sheep), with direct implications for animal welfare. This review evaluates the evidence for the specificity of oxytocin as an indicator of: 1. Social, 2. Positive, and 3. Psychological well-being. Oxytocin has most often been studied in socially relevant paradigms, with a lack of non-social control paradigms. Oxytocin research appears biased toward investigating positive valence, with a lack of control in valence or arousal. Oxytocin actions are modulated by the environmental and social contexts, which are important factors to consider. Limited evidence supports that oxytocin's actions are linked to psychological states; nevertheless whether this is a direct effect of oxytocin per se remains to be demonstrated. Overall, it is premature to judge oxytocin's potential as an animal welfare indicator given the few and discrepant findings and a lack of standardization in methodology. We cover potential causes for discrepancies and suggest solutions through appropriate methodological design, oxytocin sampling or delivery, analysis and reporting. Of particular interest, the oxytocinergic system as a whole remains poorly understood. Appreciation for the differences that social contact and group living pose in domesticated species and the way they interact with humans should be key considerations in using oxytocin as a psychosocial indicator of well-being. PMID:28955264

  5. 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.

  6. Texture analysis of cosmetic/pharmaceutical raw materials and formulations.

    PubMed

    Tai, A; Bianchini, R; Jachowicz, J

    2014-08-01

    The purpose of this work was to quantify textural properties of cosmetic and pharmaceutical raw materials. Textural parameters such as hardness, consistency, cohesiveness, index of viscosity, stickiness and resilience were evaluated. The measurements were performed using texture analyser - a tensile metre equipped with special probes (in the form of acrylic cylinder and stainless steel sphere), which can penetrate the measured sample of a product recording the force, distance and time. The instrument simulates the action of a human finger touching the surface and probing the properties of an object. The set-up has been previously shown to quantify the rheological/textural properties of cosmetic and pharmaceutical products such as creams, lotion and gels as well as rheological behaviour of human skin. The results include the analysis of water, glycerine and mineral oil as well as aqueous solutions of thickeners such as Acrylates/C10-30 Alkyl Acrylate Crosspolymer (Ultrez-20 obtained from Noveon) and carbomer. Solutions of common surfactants and complex surfactant formulations such as shampoos have also been investigated. The results, in the form plots of force as a function of time or distance, resulting from slow bidirectional probe movement (submergence and desubmergence) in the analysed fluid, were interpreted by considering buoyancy, drag and viscous drag force given by Stokes equation. The data can be used to correlate with tactile evaluations of products by trained panel evaluations. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  7. 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.

  8. 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.

  9. [Study on the biological assay of Herba Leonuri--analysis the dosage response curve of Herba Leonuri and oxytocin and establishment of adequate potency pattern].

    PubMed

    Yang, Minghua; Yang, Subei; Jin, Zuhan; Zhu, Shuangyou

    2002-06-01

    To establish the effective patten of Herba Leonuri to be suitable for biological assay. By comparing the dosage-effect curve of Herba Leonuri and oxytocin the suitable effective pattern was set up. The experiment suggest that the uterus contract height from 20 mm to 85 mm is the adequate effective range. In this range, the effect both Herba Leonuri and oxytocin should plot as a straight line against the log dose and two lines are basically parallel. In the light of establishing effective pattern, the biological assay of Herba Leonuri may pattern the method of oxytocin biological assay to regard oxytocin as standard. The result error of Herba Leonuri assay is under 20%, not exceed the demand limits of biological assay.

  10. 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

  11. The function of oxytocin: a potential biomarker for prostate cancer diagnosis and promoter of prostate cancer

    PubMed Central

    Chen, Qi; Gu, Meng; Zhou, Juan; Liu, Chong; Chen, Yanbo; Wang, Zhong

    2017-01-01

    Purpose To measure the level of oxytocin in serum and prostate cancer (PCa) tissue and study its effect on the proliferation of PCa cells. Results Oxytocin level in serum was significantly increased in PCa patients compared with the no-carcinoma individuals. Additionally, the levels of oxytocin and its receptor were also elevated in the PCa tissue. However, no significant difference existed among the PCa of various Gleason grades. Western blot analysis confirmed the previous results and revealed an increased expression level of APPL1. Materials and methods The level of oxytocin in serum was measured by ELISA analysis. The expression of oxytocin and its receptor in prostate was analyzed by immunohistochemistry. The proliferation and apoptosis of PCa cells were assessed by the Cell Counting Kit 8 (CCK8) assay, cell cycle analysis and caspase3 activity analysis, respectively. Western blot analysis was used for the detection of PCNA, Caspase3 and APPL1 protein levels. Conclusions Serum and prostatic oxytocin levels are increased in the PCa subjects. Serum oxytocin level may be a biomarker for PCa in the future. Oxytocin increases PCa growth and APPL1 expression. PMID:28415720

  12. Social support, oxytocin, and PTSD.

    PubMed

    Olff, Miranda; Koch, Saskia B J; Nawijn, Laura; Frijling, Jessie L; Van Zuiden, Mirjam; Veltman, Dick J

    2014-01-01

    A lack of social support and recognition by the environment is one of the most consistent risk factors for posttraumatic stress disorder (PTSD), and PTSD patients will recover faster with proper social support. The oxytocin system has been proposed to underlie beneficial effects of social support as it is implicated in both social bonding behavior and reducing stress responsivity, notably amygdala reactivity (Koch et al., 2014; Olff et al., 2010; Olff, 2012). The amygdala is found to be hypersensitive in people with PTSD. In order to investigate neurobiological mechanisms underlying potential preventive and therapeutic effects of intranasal oxytocin, we performed a series of fMRI studies (funded with a prestigious NWO TOP grant): BONDS standing for "Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology" in acutely traumatized persons admitted to the emergency department (Frijling et al., 2014); BOOSTER "Boosting oxytocin after trauma: the effects of intranasal oxytocin administration on emotional and motivational processing and neural activity in PTSD" in police officers with and without PTSD. In this presentation, we present the BOOSTER results on the effects of a single oxytocin administration on amygdala reactivity in response to emotional faces in PTSD patients versus traumatized controls. We found significantly decreased bilateral amygdala reactivity towards emotional faces in PTSD patients compared to traumatized controls. These promising results call for intervention studies such as studying the effects of medication (oxytocin) enhanced psychotherapy in PTSD patients.

  13. 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

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

    PubMed

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

    2016-07-30

    A large array of studies have investigated peripheral oxytocin (OT) and vasopressin (ADH) as potential biomarkers of psychiatric disorders, with highly conflicting and heterogenous findings. We searched Web of KnowledgeSM and Scopus® for English original articles investigating OT and/or ADH levels in different biological fluids (plasma/serum, saliva, urine and cerebrospinal fluid) across several psychiatric disorders. Sixty-four studies were included. We conducted 19 preliminary meta-analyses addressing OT alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 7 psychiatric disorders and ADH alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 6 psychiatric disorders compared to controls. Hedge's g was used as effect size measure, together with heterogeneity analyses, test of publication biases and quality control. None of them (except serum OT in anorexia nervosa) revealed significant differences. There is no convincing evidence that peripheral ADH or OT might be reliable biomarkers in psychiatric disorders. However, the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies, which need to be validated and standardized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Chemical and functional analysis of generic hydroxyurea formulations.

    PubMed

    Harrod, Virginia L; Howard, Thad; Abboud, Miguel R; Hankins, Jane; Lobo, Clarisse; Ware, Russell E

    2008-06-01

    Hydroxyurea has documented laboratory and clinical efficacy for children with sickle cell anemia (SCA), and has potential to become an effective and inexpensive treatment option for patients in countries with limited resources. Concerns exist, however, regarding product quality and manufacturing variability among different international vendors, particularly for generic formulations. To address these concerns, hydroxyurea capsules from 8 different pharmaceutical sources were analyzed using quantitative chemical and functional assays. All samples had measured values within 20% of expected results, with no significant differences observed among vendors. Generic hydroxyurea formulations represent a potent yet inexpensive therapeutic option for children with SCA worldwide.

  16. 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

  17. Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder.

    PubMed

    Mitchell, Jennifer M; Arcuni, Peter A; Weinstein, Dawn; Woolley, Josh D

    2016-01-01

    A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4 Edition criteria) to evaluate therapeutic potential and assess tolerability. Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures. Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed. Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

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

    USDA-ARS?s Scientific Manuscript database

    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-...

  19. Formulation and Analysis of the Quantum Radar Cross Section

    NASA Astrophysics Data System (ADS)

    Brandsema, Matthew J.

    in this document includes re-deriving the QRCS formula to be a general bistatic formula, as the current equation is only valid for monostatic radar geometries. This re-derivation process also leads to the addition of terms that capture the effect of photon polarization, something that is not properly taken into account in the current literature. Most importantly, a new formulation of the QRCS formula will be derived that includes writing the equation in terms of Fourier transforms. This has a profound impact on the analysis of the theory of the QRCS as it allows for the derivation of closed form solutions of certain geometries, something that has never been possible due to the form of the current QRCS equation. All together, this document will provide a complete and general theory of the QRCS. After deriving the necessary equations, there will be extensive work in the utilization of these equations in deriving geometry dependent responses and comparing the closed form solutions to the classical solutions as well as comparing the solutions to the numerical simulations. The current literature relies exclusively on numerical simulations to analyze the behavior of the QRCS. The simulations done do not take into account the macroscopic nature of the target. Because the atoms are so numerous, and because of the underlying Fourier transform relationship, there are many issues of sampling that must be taken into account when performing simulations. Simulating an object with too few samples results in an aliased and incorrect version of the QRCS response. An extensive error analysis is presented which ensures an accurate simulation result based on sample number. Finally, possible future work endeavors will be presented which include QRCS diffraction, shadowing, more accurate simulation concepts, and the effect of quantum tunneling on the QRCS response.

  20. 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).

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. 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.

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

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

    USDA-ARS?s Scientific Manuscript database

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

  7. Oxytocin 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.

  8. 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

  9. 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.

  10. New Formulation of Artificial Viscosity for Lagrangian Analysis of Shocks

    NASA Astrophysics Data System (ADS)

    Zhou, Haibing; Xiong, Jun; Zhang, Shudao

    2009-06-01

    We have developed a new artificial viscosity that satisfies a set of conditions set out by Caramana. ootnotetextE. J. Caramana, M. J. Shashkov and P. P. Whalen, J. Comp. Physics, 144, 70-97, 1998. This is based on Lew’sootnotetextA. Lew, R. Radovitzky and M. Ortiz, J. Computer-Aided Materials Design, 8, 213-231, 2001. artificial viscosity. Due to the tensor nature of the new artificial viscosity, it reduces the dependence of the numerical solution on the grid. Central to this formulation is an eigenvalue viscosity limiter to control the magnitude of the artificial viscosity. This is effected in a simple and straightforward manner to obtain forms of artificial viscosity that are able to distinguish between adiabatic and shock compression. The formulation is applicable to any number of dimensions and for grids that are either logically rectangular or unstructured. The viscous stress is simply computed with respect to a given element of grid that always yields the compression condition and with limiter functions computed with respect to neighbor element.

  11. Oxytocin reduces caloric intake in men

    PubMed Central

    Lawson, Elizabeth A.; Marengi, Dean A.; DeSanti, Rebecca L.; Holmes, Tara M.; Schoenfeld, David A.; Tolley, Christiane J.

    2015-01-01

    Objective Preclinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects. Oxytocin effects on nutrition and metabolism in humans are not well defined. We hypothesized that oxytocin would reduce caloric intake and appetite, and alter levels of appetite-regulating hormones. We also explored metabolic effects of oxytocin. Methods We performed a randomized, placebo-controlled crossover study of single-dose intranasal oxytocin (24 IU) in 25 fasting healthy men. After oxytocin/placebo, subjects selected breakfast from a menu, and were given double portions. Caloric content of food consumed was measured. Visual analogue scales were used to assess appetite and blood was drawn for appetite-regulating hormones, insulin, and glucose before and after oxytocin/placebo. Indirect calorimetry assessed resting energy expenditure (REE) and substrate utilization. Results Oxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones. There was no effect of oxytocin on REE. Oxytocin resulted in a shift from carbohydrate to fat utilization and improved insulin sensitivity. Conclusions Intranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects. The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation. PMID:25865294

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

    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

    2015-01-01

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

  14. Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.

    PubMed

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

    2014-10-31

    Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 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.

  16. Oxytocin and vulnerable romantic relationships.

    PubMed

    Grebe, Nicholas M; Kristoffersen, Andreas Aarseth; Grøntvedt, Trond Viggo; Emery Thompson, Melissa; Kennair, Leif Edward Ottesen; Gangestad, Steven W

    2017-04-01

    Oxytocin (OT) has been implicated in the formation and maintenance of various social relationships, including human romantic relationships. Competing models predict, alternatively, positive or negative associations between naturally-occurring OT levels and romantic relationship quality. Empirical tests of these models have been equivocal. We propose a novel hypothesis ('Identify and Invest') that frames OT as an allocator of psychological investment toward valued, vulnerable relationships, and test this proposal in two studies. In one sample of 75 couples, and a second sample of 148 romantically involved individuals, we assess facets of relationships predicting changes in OT across a thought-writing task regarding one's partner. In both studies, participants' OT change across the task corresponded positively with multiple dimensions of high relationship involvement. However, increases in participants' OT also corresponded to their partners reporting lower relationship involvement. OT increases, then, reflected discrepancies between assessments of self and partner relationship involvement. These findings are robust in a combined analysis of both studies, and do not significantly differ between samples. Collectively, our findings support the 'Identify and Invest' hypothesis in romantic couples, and we argue for its relevance across other types of social bonds. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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

  4. Oxytocin and Interpersonal Relationships.

    PubMed

    Patin, Alexandra; Scheele, Dirk; Hurlemann, Rene

    2017-08-16

    The neuropeptide oxytocin (OT) has emerged as a potent modulator of diverse aspects of interpersonal relationships. OT appears to work in close interaction with several other neurotransmitter networks, including the dopaminergic reward circuit, and to be dependent on sex-specific hormonal influences. In this chapter, we focus on four main domains of OT and interpersonal relationships, including (1) the protective effect of OT on an individual's ability to withstand stress (i.e., stress buffering), (2) the effect of OT on emotion recognition and empathy, (3) OT's ability to enhance social synchrony and cooperation among individuals, and (4) the effect of OT on an individual's perception of social touch. We then illustrate the connection between OT and loneliness while grieving the loss of a loved one. We finish by discussing the clinical potential of OT, focusing on its potential role as an adjunct to psychotherapy, its enhancement through sex-specific hormonal influences, and the difficulties that present themselves when considering OT as a therapy. Overall, we argue that OT continues to hold strong therapeutic promise, but that it is strongly dependent on internal and external influences, for instance the patient's personal past experiences and interaction with the therapist in order to provide the best possible therapy.

  5. Oxytocin and Aggression.

    PubMed

    de Jong, Trynke R; Neumann, Inga D

    2017-09-02

    The neuropeptide oxytocin (OT) has a solid reputation as a facilitator of social interactions such as parental and pair bonding, trust, and empathy. The many results supporting a pro-social role of OT have generated the hypothesis that impairments in the endogenous OT system may lead to antisocial behavior, most notably social withdrawal or pathological aggression. If this is indeed the case, administration of exogenous OT could be the "serenic" treatment that psychiatrists have for decades been searching for.In the present review, we list and discuss the evidence for an endogenous "hypo-oxytocinergic state" underlying aggressive and antisocial behavior, derived from both animal and human studies. We furthermore examine the reported effects of synthetic OT administration on aggression in rodents and humans.Although the scientific findings listed in this review support, in broad lines, the link between a down-regulated or impaired OT system activity and increased aggression, the anti-aggressive effects of synthetic OT are less straightforward and require further research. The rather complex picture that emerges adds to the ongoing debate questioning the unidirectional pro-social role of OT, as well as the strength of the effects of intranasal OT administration in humans.

  6. 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…

  7. Outcome of misoprostol and oxytocin in induction of labour.

    PubMed

    Acharya, Trishna; Devkota, Ramesh; Bhattarai, Bimbishar; Acharya, Radha

    2017-01-01

    Induction of labour is the process of initiating the labour by artificial means from 24 weeks of gestation. The main aim of this study is to find out the maternal and foetal outcomes after induction of labour with misoprostol and oxytocin beyond 37 weeks of gestation. This was a hospital-based observational study carried out at Paropakar Maternity and Women's Hospital, Nepal. Misoprostol of 25 µg was inserted in posterior fornix of vagina or oxytocin infusion was started from 2.5 units on whom induction was decided. Maternal and foetal/neonatal outcomes were observed. Collected data were analysed using SPSS and MS Excel. General induction rate was found to be 7.2%. In this study, post-term pregnancy was found to be the most common reason for induction of labour. Analysis of onset of labour led to the finding that mean onset of labour was much rapid in oxytocin (6.6 h) than misoprostol (13.6 h). However, there is similarity in induction-delivery interval in both groups. Overall, the rate of normal delivery and caesarean section was found to be 64.9% and 33.2%, respectively. Similarly, normal delivery within 12 h was seen in 18.4% of the patients given with misoprostol and 43.5% in oxytocin group. Foetal distress was found as the most common reason for caesarean section. The overall occurrence of maternal complication was found to be similar in misoprostol and oxytocin groups, nausea/vomiting being the most common (36.7%) complication followed by fever (24.1%). Besides this, the most common neonatal complication found in overall cases was meconium stained liquor (49.2%). It was found that misoprostol was used most frequently for induction of labour compared to oxytocin. The onset of labour was found to be rapid in oxytocin than misoprostol. However, the occurrence of side effects was found to be similar in both misoprostol and oxytocin groups.

  8. 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.

  9. [Water intoxication following oxytocin perfusion].

    PubMed

    Borg, G; Seligmann, G; Sournies, G; Thoulon, J M

    1983-01-01

    The authors report a case of water intoxication in a woman who received 140 I.U. of oxytocin in 3 litres of glucose serum in 15 hours to induce a therapeutic abortion. This water intoxication led to loss of consciousness with increase in weight and hyponatraemia. The treatment consisted in restricting fluid intake, giving sodium and 20% Mannitol. A short review of the literature with an explanation of the physiopathology is given. This is the antidiuretic action of oxytocin when it is given with too much fluid without electrolytes.

  10. 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.

  11. Oxytocin administered during labor and breast-feeding: a retrospective cohort study.

    PubMed

    García-Fortea, Pedro; González-Mesa, Ernesto; Blasco, Marta; Cazorla, Olga; Delgado-Ríos, M; González-Valenzuela, María J

    2014-10-01

    The relationship between labor physiology and the onset of lactation leads to assess the potential correlation between oxytocin administration during labor and duration of breast-feeding. This study was designed as a retrospective cohort study where patients given synthetic oxytocin during labor induction were considered as the exposed cohort, and patients not given oxytocin formed the non-exposed cohort. Four hundred of the 7465 children born at our maternity during 2006 were randomly selected. Information about breast-feeding was available for 316 of these children. Eventual confounding or adjustment factors were analyzed using stratified and multivariate analysis. Oxytocin was used for delivery of 189 (59.8%) newborns, multiplying the risk of bottle-feeding by 1.451 (95% CI 1.28-1.63). The best-fit regression model of oxytocin use effect on bottle-feeding included sex and gestational age of the newborn. The use of oxytocin also multiplies the risk of breast-feeding withdrawal at 3 months by 2.29 (95% CI 1.41-3.74). This effect is confounded by maternal age, being higher for mothers under 27 years. Oxytocin administration during labor had some impact on both onset and duration of breast-feeding, particularly in mothers under 27 years of age and newborns delivered at term. Clinical Study registered at U.S. NCT01951040.

  12. 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

  13. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Oxytocin and bone

    PubMed Central

    Sun, Li; Zaidi, Mone; Zallone, Alberta

    2014-01-01

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

  15. Trends and morbidity associated with oxytocin use in labour in nulliparas at term.

    PubMed

    Buchanan, Sarah L; Patterson, Jillian A; Roberts, Christine L; Morris, Jonathan M; Ford, Jane B

    2012-04-01

    To determine the trends in oxytocin use at a population level within New South Wales and to assess the maternal and neonatal morbidities associated with the use of oxytocin. Trends in oxytocin use were assessed for women in NSW who were nulliparas at term with a singleton, cephalic fetus between 1998 and 2008. Maternal and neonatal morbidities were assessed in 2007-2008 using linked hospital and birth data with regression analysis. Oxytocin was also assessed by indication for use being either induction or augmentation of labour. The overall use of oxytocin increased from 10,291 (36.5%) of births in 1998 to 14,440 (45.4%) of births in 2008 (P < 0.0001) with the increase entirely because of the increased use for induction of labour. The use of oxytocin was associated with an increase in regional analgesia (65 to 22%), instrumental delivery (21 to 18%) and caesarean section (29 to 14%) as compared to women who did not receive oxytocin in labour. Oxytocin was also associated with an increase in severe maternal adjusted odds ratios ((aOR) 1.48, 95% CI 1.30-1.68) and neonatal morbidity (aOR 1.29, 95% CI 1.17-1.41). This increase in morbidity was maintained when both augmentation and induction were assessed separately. Oxytocin has an important role in the management of labour. However, its use should be carefully monitored with standardised treatment regimes to minimise maternal and neonatal morbidity. © 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  16. 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.

  17. 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.

  18. 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.

  19. Vasopressin and oxytocin in stress.

    PubMed

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

    1995-12-29

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

  20. Analysis of argentinated peptide complexes using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Peptide = oxytocin, arg(8) -vasopressin, bradykinin, bombesin, somatostatin, neurotensin.

    PubMed

    Gupta, Shyam L; Dhiman, Vikas; Jayasekharan, T; Sahoo, N K

    2016-06-15

    The increased use of silver nanoparticles (AgNPs) for various biological applications, and over-expression of various peptide receptors in different tumors/cancer cells, necessitate the need for dedicated investigations on the intrinsic binding ability of Ag with various biologically important peptides for better understanding of AgNPs-peptide interactions and for the future development of contrasting agents as well as drugs for imaging/biomedical applications. The [M+(Ag)n ](+) complexes are prepared and characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Silver complexes of the peptides [M+(Ag)n ](+) , where M = oxytocin, arg(8) -vasopressin, bradykinin, bombesin, somatostatin, and neurotensin, have been investigated for their intrinsic Ag(+) -binding ability. Unusual binding of up to seven Ag(+) with these small peptides is observed. The mass spectra show n = 1-5 for bombesin and somatostatin, n = 1-6 for bradykinin and arg(8) -vasopressin, and n = 1-7 for oxytocin and neurotensin. In addition, oxytocin and arg(8) -vasopressin show the formation of dimers and their complexes [M2 +(Ag)n ](+) with n = 1-8 and n = 1-5, respectively. The possible amino acid residues responsible for Ag(+) binding in each peptide have been identified on the basis of density functional theory (DFT)-calculated binding energy values of Ag(+) towards individual amino acids. Mass spectrometric evidence indicates that the peptides, viz., oxytocin, arg(8) -vasopressin, bradykinin, bombesin, somatostatin, and neurotensin, show greater affinity for Ag(+) . Hence, they may be used as carriers for AgNPs in targeted drug delivery as well as an alternative for iodinated contrasting agents in dual energy X-ray imaging techniques. Radio-labeled Ag with these peptides can also be used in radio-pharmaceuticals for diagnostic and therapeutic applications. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. 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

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

    NASA Technical Reports Server (NTRS)

    Gupta, K. K.

    1986-01-01

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

  3. Oxytocin regimen for labor augmentation, labor progression, and perinatal outcomes.

    PubMed

    Zhang, Jun; Branch, D Ware; Ramirez, Mildred M; Laughon, S Katherine; Reddy, Uma; Hoffman, Mathew; Bailit, Jennifer; Kominiarek, Michelle; Chen, Zhen; Hibbard, Judith U

    2011-08-01

    To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes. Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing of 1, 2, and 4 milliunits/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders. Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared with 1 milliunit/min, the regimens starting with 2 milliunits/min and 4 milliunits/min reduced the duration of first stage by 0.8 hours (95% confidence interval 0.5-1.1) and 1.3 hours (1.0-1.7), respectively, in nulliparous women. No effect was observed on the second stage of labor. Similar patterns were observed in multiparous women. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparous women. High-dose oxytocin regimen (starting dose at 4 milliunits/min and increment of 4 millliunits/min) is associated with a shorter duration of first-stage of labor for all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. II.

  4. Topical oxytocin reverses vaginal atrophy in postmenopausal women: a double-blind randomized pilot study.

    PubMed

    Jonasson, Aino Fianu; Edwall, Lena; Uvnäs-Moberg, Kerstin

    2011-12-01

    Oxytocin is a peptide hormone produced in the hypothalamus and it is best known for its role in labour and lactation. This double-blind, randomized study was performed at Huddinge Hospital of Karolinska Institutet, Stockholm in order to test the effectiveness of topical oxytocin gel in women with postmenopausal vaginal atrophy. Twenty postmenopausal women (at least two years after menopause) with symptoms of vaginal atrophy such as vaginal dryness, pain, itching, discomfort and bleeding during intercourse were enrolled in the study when visual inspection of the vagina had confirmed that their mucosa was atrophic. The participants were randomized to intravaginal treatment with either oxytocin or placebo gel for seven days. Before and after treatment, a gynaecological examination and a visual and colposcopic inspection of the vagina were performed, biopsies from the vaginal mucosa were taken and blood samples were collected for analysis of circulating levels of estradiol and oxytocin. Prior to treatment, visual and colposcopic inspection showed that all of the 20 participants had an atrophic vaginal mucosa. After treatment with the oxytocin gel, the examination showed that the vaginal epithelium of seven of the 10 participants in the oxytocin group had become healthier and normalized. No change in these parameters was observed among the 10 participants in the placebo group. This difference between the oxytocin and placebo groups was significant (P= 0.003). Seven participants in the active group and four in the placebo group reported relief of symptoms of vaginal atrophy after seven days of applying the gel. The effect of oxytocin to normalize the morphological appearance of the vaginal mucosa was almost significant when compared with the placebo group (P= 0.07). There was no significant difference between the circulating levels of estradiol and oxytocin in both the oxytocin and placebo groups before and after treatment. None of the participants reported any side

  5. 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

  6. 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.

  7. Oxytocin in cesarean-sections. What's new?

    PubMed

    Yamaguchi, Eduardo Tsuyoshi; Siaulys, Mônica Maria; Torres, Marcelo Luis Abramides

    2016-01-01

    Oxytocin is the uterotonic agent of choice in the prevention and treatment of postpartum uterine atony. Nevertheless, there is no consensus on the optimal dose and rate for use in cesarean sections. The use of high bolus doses (e.g., 10IU of oxytocin) can determine deleterious cardiovascular changes for the patient, especially in situations of hypovolemia or low cardiac reserve. Furthermore, high doses of oxytocin for prolonged periods may lead to desensitization of oxytocin receptors in myometrium, resulting in clinical inefficiency. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  8. [Oxytocin in cesarean-sections. What's new?].

    PubMed

    Yamaguchi, Eduardo Tsuyoshi; Siaulys, Mônica Maria; Torres, Marcelo Luis Abramides

    2016-01-01

    Oxytocin is the uterotonic agent of choice in the prevention and treatment of postpartum uterine atony. Nevertheless, there is no consensus on the optimal dose and rate for use in cesarean sections. The use of high bolus doses (e.g., 10 IU of oxytocin) can determine deleterious cardiovascular changes for the patient, especially in situations of hypovolemia or low cardiac reserve. Furthermore, high doses of oxytocin for prolonged periods may lead to desensitization of oxytocin receptors in myometrium, resulting in clinical inefficiency. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  9. 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

  10. 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

  11. 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.

  12. Integrating gene set analysis and nonlinear predictive modeling of disease phenotypes using a Bayesian multitask formulation.

    PubMed

    Gönen, Mehmet

    2016-12-13

    Identifying molecular signatures of disease phenotypes is studied using two mainstream approaches: (i) Predictive modeling methods such as linear classification and regression algorithms are used to find signatures predictive of phenotypes from genomic data, which may not be robust due to limited sample size or highly correlated nature of genomic data. (ii) Gene set analysis methods are used to find gene sets on which phenotypes are linearly dependent by bringing prior biological knowledge into the analysis, which may not capture more complex nonlinear dependencies. Thus, formulating an integrated model of gene set analysis and nonlinear predictive modeling is of great practical importance. In this study, we propose a Bayesian binary classification framework to integrate gene set analysis and nonlinear predictive modeling. We then generalize this formulation to multitask learning setting to model multiple related datasets conjointly. Our main novelty is the probabilistic nonlinear formulation that enables us to robustly capture nonlinear dependencies between genomic data and phenotype even with small sample sizes. We demonstrate the performance of our algorithms using repeated random subsampling validation experiments on two cancer and two tuberculosis datasets by predicting important disease phenotypes from genome-wide gene expression data. We are able to obtain comparable or even better predictive performance than a baseline Bayesian nonlinear algorithm and to identify sparse sets of relevant genes and gene sets on all datasets. We also show that our multitask learning formulation enables us to further improve the generalization performance and to better understand biological processes behind disease phenotypes.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. The LC/MS analysis of glycation of IgG molecules in sucrose containing formulations.

    PubMed

    Gadgil, Himanshu S; Bondarenko, Pavel V; Pipes, Gary; Rehder, Doug; McAuley, Arnold; Perico, Natalie; Dillon, Tom; Ricci, Margaret; Treuheit, Michael

    2007-10-01

    Glycation of a recombinant monoclonal IgG2 molecule, in sucrose containing liquid formulations, was studied using reversed-phase LC/MS analysis of the intact IgG, the F(ab')2 fragments and after complete tryptic digestion. The extent of glycation in sucrose containing formulations was monitored at different temperatures over a period of 21 months using the Hexose index (Hex(I)). Hex(I) represents the average number of hexose molecules per molecule of IgG and was calculated by using the intensity values of peaks corresponding to hexose isoforms in the deconvoluted mass spectra. The rate of glycation in mildly acidic sucrose containing formulations was proportional to the incubation temperature. No glycation was observed in sucrose containing formulations incubated at 4 degrees C even after 18 months. However, when the same formulations were incubated at 37 degrees C glycation was observed after just 1 month. The glycation sites were mapped to 10 lysine residues distributed throughout the molecule. The amino terminal end of the light chain was also shown to contain glycation. The surface accessibility of the lysine side chain could influence its susceptibility to glycation. (c) 2007 Wiley-Liss, Inc.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart

    PubMed Central

    Gutkowska, Jolanta; Jankowski, Marek; Lambert, Chantal; Mukaddam-Daher, Suhayla; Zingg, Hans H.; McCann, Samuel M.

    1997-01-01

    Previous studies indicated that the central nervous system induces release of the cardiac hormone atrial natriuretic peptide (ANP) by release of oxytocin from the neurohypophysis. The presence of specific transcripts for the oxytocin receptor was demonstrated in all chambers of the heart by amplification of cDNA by the PCR using specific oligonucleotide primers. Oxytocin receptor mRNA content in the heart is 10 times lower than in the uterus of female rats. Oxytocin receptor transcripts were demonstrated by in situ hybridization in atrial and ventricular sections and confirmed by competitive binding assay using frozen heart sections. Perfusion of female rat hearts for 25 min with Krebs–Henseleit buffer resulted in nearly constant release of ANP. Addition of oxytocin (10−6 M) significantly stimulated ANP release, and an oxytocin receptor antagonist (10−7 and 10−6 M) caused dose-related inhibition of oxytocin-induced ANP release and in the last few minutes of perfusion decreased ANP release below that in control hearts, suggesting that intracardiac oxytocin stimulates ANP release. In contrast, brain natriuretic peptide release was unaltered by oxytocin. During perfusion, heart rate decreased gradually and it was further decreased significantly by oxytocin (10−6 M). This decrease was totally reversed by the oxytocin antagonist (10−6 M) indicating that oxytocin released ANP that directly slowed the heart, probably by release of cyclic GMP. The results indicate that oxytocin receptors mediate the action of oxytocin to release ANP, which slows the heart and reduces its force of contraction to produce a rapid reduction in circulating blood volume. PMID:9326674

  5. 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.

  6. [Oxytocin administration during labor. Results from the 2010 French National Perinatal Survey].

    PubMed

    Belghiti, J; Coulm, B; Kayem, G; Blondel, B; Deneux-Tharaux, C

    2013-11-01

    To estimate the frequency of oxytocin administration during labor, in all women in labor, in low-risk women, and in women with a previous cesarean delivery. Our objectives were also to identify characteristics of women and of maternity units associated with this practice in France. Analysis of the 2010 French Perinatal Survey data (n=14,681 women who delivered in continental France). The frequency of oxytocin administration during labor was estimated in all women in labor (n=12,845) and in low-risk women (n=9798). The independent associations between oxytocin administration during labor and characteristics of women and units were quantified with multivariate logistic regression modeling. Sixty-four percent of laboring women received oxytocin during labor, and 58% of women with a spontaneous onset of labor. In the population of low-risk women with spontaneous labor and epidural, nulliparity and over-weight, as well as the private status and small size of the maternity unit, were independently associated with a more frequent administration of oxytocin during labor. Oxytocin administration during labor is very frequent in France, probably beyond classical indications. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. [Effect of oxytocin on human pain perception].

    PubMed

    Pfeifer, A-C; Ditzen, B; Neubauer, E; Schiltenwolf, M

    2016-10-01

    Over the years the effect of the neuropeptide oxytocin and its possible utilization for pain management has been increasingly more investigated and discussed. Initial results emphasized the effects of oxytocin with respect to labor and breastfeeding. Diverse animals studies were also able to demonstrate the effectiveness of the peptide in attachment behavior and pain perception; however, it is still unclear how oxytocin affects pain perception in humans. The potential therapeutic effectiveness of oxytocin could be particularly important for primary and secondary treatment of pain patients because chronification of pain can occur more frequently in this area. For this review the databases PubMed, Medline und PsycINFO were searched using the terms oxytocin, pain, human and analgesic. The search resulted in a total of 89 original articles after excluding articles regarding labor pain, breastfeeding and animal studies. Only those studies were included which were carried out between 1994 and 2015. A total of 17 articles remained for inclusion in this review and included 13 studies on the exogenous application of oxytocin and 4 on measurement of oxytocin levels in plasma. This review article gives a summary of the current state of research on oxytocin and its direct and indirect association with human pain perception and emphasizes its relevance for the multimodal management of pain.

  8. 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.

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

    NASA Technical Reports Server (NTRS)

    Lisano, Michael E.

    2006-01-01

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

  10. 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.

  11. 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.

  12. Oxytocin improves "mind-reading" in humans.

    PubMed

    Domes, Gregor; Heinrichs, Markus; Michel, Andre; Berger, Christoph; Herpertz, Sabine C

    2007-03-15

    The ability to "read the mind" of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals. In a double-blind, placebo-controlled, within-subject design, 30 healthy male volunteers were tested for their ability to infer the affective mental state of others using the Reading the Mind in the Eyes Test (RMET) after intranasal administration of 24 IU oxytocin. Oxytocin improved performance on the RMET compared with placebo. This effect was pronounced for difficult compared with easy items. Our data suggest that oxytocin improves the ability to infer the mental state of others from social cues of the eye region. Oxytocin might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.

  13. Oxytocin Enhances Social Persuasion during Hypnosis

    PubMed Central

    Bryant, Richard A.; Hung, Lynette

    2013-01-01

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

  14. 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.

  15. Oxytocin in mares: lack of evidence for oxytocin production by or action on preovulatory follicles.

    PubMed

    Stock, A E; Emeny, R T; Sirois, J; Fortune, J E

    1995-04-01

    It is not known whether the equine preovulatory follicle produces oxytocin or is a target tissue for oxytocin, as has been reported for other species, especially ruminants. Bovine granulosa cells secrete oxytocin, and oxytocin modulates the production of progesterone by granulosa cells in vitro. We examined whether oxytocin plays a comparable role in the equine preovulatory follicle. To test the hypothesis that the equine preovulatory follicle produces oxytocin during estrus and that its production increases in late estrus, preovulatory follicles were isolated during early (Days 1 to 2; n = 4) and late (Days 4 to 5; n = 4) estrus. Granulosa cells, pieces of theca interna and pieces of follicle wall (theca with attached granulosa cells) were cultured for 3 d with or without equine gonadotropins. Culture media were collected, replaced at 3, 6, 12, 24, 48, and 72 hr of culture, and assayed for oxytocin. Granulosa cells from preovulatory follicles secreted negligible amounts of oxytocin during 3 d of culture, irrespective of gonadotropin treatment or stage of estrus. Likewise, negligible amounts of oxytocin were measured in theca and follicle wall cultures at both developmental stages, in the presence or absence of gonadotropins. Furthermore, follicular fluid from early or late estrous follicles contained only negligible amounts of oxytocin. To determine if oxytocin affects steroidogenesis by equine granulosa cells, granulosa cells from follicles obtained on Day 2 of estrus were cultured with graded doses of oxytocin (0, 1, 10, 100, and 1,000 ng/ml) in defined medium supplemented with testosterone (0.5 microM) and culture media were assayed for estradiol-17 beta and progesterone. Estradiol was secreted throughout the culture period, and its production was not significantly affected by oxytocin treatment (P > 0.05). Progesterone secretion was relatively low during the first 24 hr of culture, increased dramatically on the second day of culture, and remained high through

  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. 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

  18. 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

  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. PMID:28405575

  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. A Symbolic Formulation for Analytical Compliance Analysis and Synthesis of Flexure Mechanisms.

    PubMed

    Su, Hai-Jun; Shi, Hongliang; Yu, Jingjun

    2012-05-01

    This paper presents a symbolic formulation for analytical compliance analysis and synthesis of flexure mechanisms with serial, parallel, or hybrid topologies. Our approach is based on the screw theory that characterizes flexure deformations with motion twists and loadings with force wrenches. In this work, we first derive a symbolic formulation of the compliance and stiffness matrices for commonly used flexure elements, flexure joints, and simple chains. Elements of these matrices are all explicit functions of flexure parameters. To analyze a general flexure mechanism, we subdivide it into multiple structural modules, which we identify as serial, parallel, or hybrid chains. We then analyze each module with the known flexure structures in the library. At last, we use a bottom-up approach to obtain the compliance/stiffness matrix for the overall mechanism. This is done by taking appropriate coordinate transformation of twists and wrenches in space. Four practical examples are provided to demonstrate the approach. A numerical example is employed to compare analytical compliance models against a finite element model. The results show that the errors are sufficiently small (2%, compared with finite element (FE) model), if the range of motion is limited to linear deformations. This work provides a systematical approach for compliance analysis and synthesis of general flexure mechanisms. The symbolic formulation enables subsequent design tasks, such as compliance synthesis or sensitivity analysis.

  2. Multi-Pathway Cellular Analysis on Crude Natural Drugs/Herbs from Japanese Kampo Formulations

    PubMed Central

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

    2015-01-01

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

  3. 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.

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

    PubMed Central

    Lenz, Kathryn M.; Sengelaub, Dale R.

    2010-01-01

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

  5. Carbetocin versus oxytocin to reduce additional uterotonic use at non-elective caesarean section: a double-blind, randomised trial (.).

    PubMed

    Whigham, Carole-Anne; Gorelik, Alexandra; Loughnan, Terrence E; Trivedi, Amar

    2016-12-01

    We compared the efficacy of Carbetocin (long-acting oxytocin receptor agonist) versus Oxytocin given at non-elective caesarean section. We performed a double-blind, randomised, single-centre study. Eligible women were ≥37 weeks of gestation undergoing emergency caesarean section. Participants received either carbetocin of 100 μg or oxytocin 5 international units. The primary outcome was the need to administer additional uterotonics, as determined by the clinician. Secondary outcomes included estimated blood loss, haemoglobin drop pre-post operation and the need for a blood transfusion Results: From August 2012 to February 2013, 114 women were enroled. Two were excluded from analysis as they received a general anaesthetic. Fifty-nine patients received 100-μg carbetocin; 53 received 5 international units oxytocin. There was no statistically significant difference in the number of women requiring additional uterotonics between the two groups: Carbetocin group 22% and Oxytocin group 13% (p = 0.323). There were no significant differences in the fall in haemoglobin, estimated blood loss, rates of post-partum haemorrhage or blood transfusions. Oxytocin and carbetocin have similar requirements for additional uterotonics, estimated blood loss, haemoglobin drop and blood transfusions. There was a trend towards requiring additional uterotonics in patients receiving Carbetocin which was not statistically significant. This study found no benefits in using carbetocin over oxytocin.

  6. Oxytocin for frontotemporal dementia: a systematic review.

    PubMed

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

    2017-01-01

    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). 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. 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. 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.

  7. 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.

  8. 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

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

    PubMed

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

    2012-09-01

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

  10. 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.

  11. 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.

  12. 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.

  13. Oxytocin for labour and caesarean delivery: implications for the anaesthesiologist.

    PubMed

    Dyer, Robert A; Butwick, Alexander J; Carvalho, Brendan

    2011-06-01

    The implications of the obstetric use of oxytocin for obstetric anaesthesia practice are summarised. The review focuses on recent research on the uterotonic effects of oxytocin for prophylaxis and management of uterine atony during caesarean delivery. Oxytocin remains the first-line agent in the prevention and management of uterine atony. In-vitro and in-vivo studies show that prior exposure to oxytocin induces uterine muscle oxytocin receptor desensitization. This may influence oxytocin dosing for adequate uterine tone following delivery. Oxytocin has important cardiovascular side-effects (hypotension, tachycardia and myocardial ischaemia). Recent studies suggest that the effective dose of oxytocin for prophylaxis against uterine atony during caesarean delivery is significantly lower than the 5-10 IU historically used by anaesthesiologists. Slow administration of small bolus doses of oxytocin minimises maternal haemodynamic disturbance. Continuous oxytocin infusions are recommended for maintaining uterine tone after bolus administration, although ideal infusion rates are still to be established. The efficacy of the long-acting oxytocin analogue carbetocin requires further investigation. Recommendations are presented for oxytocin dosing during caesarean delivery. Oxytocin remains the first-line uterotonic after vaginal and caesarean delivery. Recent research elucidates the therapeutic range of oxytocin during caesarean delivery, as well as receptor desensitization. Evidenced-based protocols for the prevention and treatment of uterine atony during caesarean delivery are recommended.

  14. Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks.

    PubMed

    Saa, Pedro A; Nielsen, Lars K

    2017-09-12

    Kinetic models are critical to predict the dynamic behaviour of metabolic networks. Mechanistic kinetic models for large networks remain uncommon due to the difficulty of fitting their parameters. Recent modelling frameworks promise new ways to overcome this obstacle while retaining predictive capabilities. In this review, we present an overview of the relevant mathematical frameworks for kinetic formulation, construction and analysis. Starting with kinetic formalisms, we next review statistical methods for parameter inference, as well as recent computational frameworks applied to the construction and analysis of kinetic models. Finally, we discuss opportunities and limitations hindering the development of larger kinetic reconstructions. Copyright © 2017. Published by Elsevier Inc.

  15. Pinhão starch and coat extract as new natural cosmetic ingredients: Topical formulation stability and sensory analysis.

    PubMed

    Daudt, Renata Moschini; Back, Patrícia Inês; Cardozo, Nilo Sérgio Medeiros; Marczak, Ligia Damasceno Ferreira; Külkamp-Guerreiro, Irene Clemes

    2015-12-10

    The objective of this study was to use pinhão derivatives, starch and coat extract, as new natural ingredients to develop cosmetic formulations. Two types of formulation, gel and emulgel, and their controls were developed. The formulations were characterized by stability studies using thermal stress. The parameters analyzed were resistance to centrifugation, pH, spreadability, rheology, content of phenolic compounds and antioxidant activity. Sensory analysis was also performed to verify the acceptability of the ingredients to potential consumers. The pH was kept the same after heating/freezing cycles for all formulations, and the formulations showed stability by resistance to centrifugation. The formulations did not induce any skin irritation or cutaneous pH alteration. The pinhão starch addition improved spreadability stability and increased viscosity when compared with control formulations. The pinhão coat extract used in these formulations is a good source of phenolic compounds and antioxidant activity. Moreover, sensory analysis indicates that the emulgel formulation is the best vehicle for adding pinhão starch and pinhão coat extract. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Oxytocin Regimen for Labor Augmentation, Labor Progression, Perinatal Outcomes

    PubMed Central

    Zhang, Jun; Branch, D. Ware; Ramirez, Mildred M.; Laughon, S. Katherine; Reddy, Uma; Hoffman, Mathew; Bailit, Jennifer; Kominiarek, Michelle; Chen, Zhen; Hibbard, Judith U.

    2013-01-01

    Objective To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes. Methods Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing: 1, 2, and 4 mU/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders. Results Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared to 1 mU/min, the regimens starting with 2 mU/min and 4 mU/min reduced the duration of 1st stage by 0.8 hours (95% confidence interval 0.5 – 1.1) and 1.3 hours (1.0 – 1.7), respectively, in nulliparas. No effect was observed on the second stage of labor. Similar patterns were observed in multiparas. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparas. Conclusion High-dose oxytocin regimen (starting dose at 4 mU/min and increment of 4 mU/min) is associated with a shorter duration of first stage of labor in all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. PMID:21775839

  17. 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

  18. Fetal Release of Copeptin in Response to Maternal Oxytocin Administration: A Randomized Controlled Trial.

    PubMed

    Wellmann, Sven; Koslowski, Andrea; Spanaus, Katharina; Zimmermann, Roland; Burkhardt, Tilo

    2016-10-01

    To test whether an oxytocin challenge test raises neonatal levels of copeptin, the C-terminal portion of proarginine vasopressin, a sensitive stress marker elevated in neonates born by vaginal delivery as opposed to elective cesarean delivery. In a randomized controlled trial in women with a singleton pregnancy undergoing elective cesarean delivery at greater than 36 weeks of gestation and no contractions or rupture of membranes, we compared arterial umbilical cord plasma concentrations of copeptin between neonates exposed to an oxytocin challenge test before elective cesarean delivery and those administered saline infusion (placebo group). Women randomized to an oxytocin challenge test received 5 international units/500 mL oxytocin Ringer lactate infused at a rate of 12 mL/h and doubled every 10 minutes until it induced three uterine contractions per 10-minute interval, at which point it was discontinued. Neonatal copeptin levels were the primary endpoint. Secondary endpoints included biochemical and physiologic parameters of fetal and maternal well-being. From January 2012 to October 2012 and from September 2013 to January 2015, 78 women underwent an oxytocin challenge test and 78 placebo infusion, of whom 12 and 11, respectively, were excluded as a result of insufficient blood sample volume for analysis. Umbilical cord plasma copeptin levels [median (range)] were higher in neonates who underwent an oxytocin challenge test than those who underwent placebo infusion: 22.2 (3.22-2,319) compared with 7.39 (2.5-344.6) pmol/L (P<.001). There were no statistically significant differences between the two groups in secondary outcomes. Oxytocin challenge test-induced contractions before elective cesarean delivery trigger fetal copeptin release. ClinicalTrials.gov, https://clinicaltrials.gov, NCT01962701.

  19. Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9.

    PubMed

    Manturewicz, Michał; Grzonka, Zbigniew; Borovicková, Lenka; Slaninová, Jirina

    2007-01-01

    Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole analogues of amino acids were prepared using solid-phase peptide synthesis method and tested for rat uterotonic in vitro and pressor activities, as well as for their affinity to human oxytocin receptor. The tetrazolic group has been used as a bioisosteric substitution of carboxylic, ester or amide groups in structure-activity relationship studies of biologically active compounds. Replacement of the amide groups of Gln(4) and Asn(5) in oxytocin by tetrazole analogues of aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities. Oxytocin analogues in which the glycine amide residue in position 9 was substituted by tetrazole analogues of glycine had diminished activities as well. The analysis of differences in rat uterotonic activity and in the affinity to human oxytocin receptors of analogues containing either an acidic 5-substituted tetrazolic group or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new conclusions concerning the role of the amide group of amino acids in positions 4, 5 and 9 of oxytocin for its activity. The data suggest that the interaction of the side chain of Gln(4) with the oxytocin receptor is influenced mainly by electronic effects and the hydrogen bonding capacity of the amide group. Steric effects of the side chain are minor. Substitution of Asn(5) by its tetrazole derivative gave an analogue of very low activity. The result suggests that in the interaction between the amide group of Asn(5) and the binding sites of oxytocic receptor hydrogen bonds are of less importance than the spatial requirements for this group.

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

    PubMed

    Freeman, Sara M; Young, Larry J

    2016-04-01

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

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

    PubMed

    Zheng, Jack Y; Keeney, Melissa P

    2006-03-09

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

  2. Structural meta-analysis of regular human insulin in pharmaceutical formulations.

    PubMed

    Fávero-Retto, Maely P; Palmieri, Leonardo C; Souza, Tatiana A C B; Almeida, Fábio C L; Lima, Luís Mauricio T R

    2013-11-01

    We have studied regular acting, wild-type human insulin at potency of 100 U/mL from four different pharmaceutical products directly from their final finished formulation by the combined use of mass spectrometry (MS), dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR), and single-crystal protein crystallography (PX). All products showed similar oligomeric assembly in solution as judged by DLS and SAXS measurements. The NMR spectra were compatible with well folded proteins, showing close conformational identity for the human insulin in the four products. Crystallographic assays conducted with the final formulated products resulted in all insulin crystals belonging to the R3 space group with two a dimer in the asymmetric unit, both with the B-chain in the T configuration. Meta-analysis of the 24 crystal structures solved from the four distinct insulin products revealed close similarity between them regardless of variables such as biological origin, product batch, country origin of the product, and analytical approach, revealing a low conformational variability for the converging insulin structural ensemble. We propose the use of MS, SAXS, NMR fingerprint, and PX as a precise chemical and structural proof of folding identity of regular insulin in the final, formulated product.

  3. 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

  4. Analysis of thiamine concentrations in commercial canned foods formulated for cats.

    PubMed

    Markovich, Jessica E; Freeman, Lisa M; Heinze, Cailin R

    2014-01-15

    To measure thiamine concentrations in commercial canned foods formulated for cats as an initial assessment of the variation among canned foods and to determine the effects of flavor (fish vs nonfish) of the food, texture (paté vs nonpaté) of the food, country of manufacture, and size of the company on thiamine concentration. Prospective cross-sectional study. 90 canned, nontherapeutic diets formulated for cats (1 fish and 1 nonfish flavor for each of 45 brands). Each canned food was homogenized, and thiamine concentration was analyzed with a fluorometric method. Thiamine concentration was below the minimums of the Association of American Feed Control Officials in 12 of 90 (13.3%) foods and below the recommended allowance of the National Research Council in 14 of 90 (15.6%) foods. Paté foods had significantly lower thiamine concentrations than did nonpaté foods, and foods from smaller companies had significantly lower thiamine concentrations, compared with concentrations in foods from larger companies. Flavor of food and country of manufacture were not significantly associated with thiamine concentration. A wide range of thiamine concentrations was found in the foods evaluated. Thiamine concentration in a substantial percentage of commercially available canned foods was below the amount recommended for adult cats. Additional research on interlot and intralot variation in thiamine concentrations of foods formulated for cats is warranted. Companies should implement strict quality control and analysis practices regarding food products. Clinicians should consider thiamine deficiency as a differential diagnosis in a cat with acute neurologic dysfunction.

  5. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. 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.

  9. 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.

  10. 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.

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

    PubMed

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

    2016-09-07

    The electrochemical detection of oxytocin using boron-doped diamond (BDD) electrodes was studied. Cyclic voltammetry of oxytocin in a phosphate buffer solution exhibits an oxidation peak at +0.7 V (vs. Ag/AgCl), which is attributable to oxidation of the phenolic group in the tyrosyl moiety. Furthermore, the linearity of the current peaks obtained in flow injection analysis (FIA) using BDD microelectrodes over the oxytocin concentration range from 0.1 to 10.0 μM with a detection limit of 50 nM (S/N = 3) was high (R(2) = 0.995). Although the voltammograms of oxytocin and vasopressin observed with an as-deposited BDD electrode, as well as with a cathodically-reduced BDD electrode, were similar, a clear distinction was observed with anodically-oxidized BDD electrodes due to the attractive interaction between vasopressin and the oxidized BDD surface. By means of this distinction, selective measurements using chronoamperometry combined with flow injection analysis at an optimized potential were demonstrated, indicating the possibility of making selective in situ or in vivo measurements of oxytocin.

  12. Cost-effectiveness analysis of oral fentanyl formulations for breakthrough cancer pain treatment.

    PubMed

    Cortesi, Paolo Angelo; D'Angiolella, Lucia Sara; Vellucci, Renato; Allegri, Massimo; Casale, Giuseppe; Favaretti, Carlo; Kheiraoui, Flavia; Cesana, Giancarlo; Mantovani, Lorenzo Giovanni

    2017-01-01

    Breakthrough cancer Pain (BTcP) has a high prevalence in cancer population. Patients with BTcP reported relevant health care costs and poor quality of life. The study assessed the cost-effectiveness of the available Oral Fentanyl Formulations (OFFs) for BTcP in Italy. A decision-analytical model was developed to estimate costs and benefits associated with treatments, from the Italian NHS perspective. Expected reductions in pain intensity per BTcP episodes were translated into, percentage of BTcP reduction, resource use and Quality-Adjusted-Life-Years (QALYs). Relative efficacy, resources used and unit costs data were derived from the literature and validated by clinical experts. Probabilistic and deterministic sensitivity analyses were performed. At base-case analysis, Sublingual Fentanyl Citrate (FCSL) compared to other oral formulations reported a lower patient's cost (€1,960.8) and a higher efficacy (18.7% of BTcP avoided and 0.0507 QALYs gained). The sensitivity analyses confirmed the main results in all tested scenarios, with the highest impact reported by BTcP duration and health care resources consumption parameters. Between OFFs, FCSL is the cost-effective option due to faster reduction of pain intensity. However, new research is needed to better understand the economic and epidemiologic impact of BTcP, and to collect more robust data on economic and quality of life impact of the different fentanyl formulations. Different fentanyl formulations are available to manage BTcP in cancer population. The study is the first that assesses the different impact in terms of cost and effectiveness of OFFs, providing new information to better allocate the resources available to treat BTcP and highlighting the need of better data.

  13. 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.

  14. 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.

  15. 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

  16. 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.

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

    PubMed

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

    2016-07-01

    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.

  18. 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

  19. 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.

  20. Making room for oxytocin in understanding depression.

    PubMed

    McQuaid, Robyn J; McInnis, Opal A; Abizaid, Alfonso; Anisman, Hymie

    2014-09-01

    Depression is accompanied by an array of neurobiological variations, including altered HPA axis activity, monoamine, growth factor and inflammatory immune functioning. In addition, a recent perspective has entertained the possible role for oxytocin in depressive disorders. Given the involvement of oxytocin in prosocial behaviors such as attachment, affiliation, trust, and social support seeking, it is not surprising this neuropeptide might be involved in the development or maintenance of depressive disorders. This view is supported by evidence that oxytocin interacts with various neuroendocrine, neurotransmitter, and inflammatory processes that have previously been implicated in depression. Thus, it might be profitable to consider the contribution of oxytocin in the context of several neurobiological changes provoked by stressors. The current review examines the relation between oxytocin and depression with a specific focus on the interactions between the oxytocinergic system and stressor-provoked biological and psychosocial responses. The possibility is also considered that oxytocin might increase the salience of social cues, such that positive or negative experiences result in exaggerated responses that may influence affective states.

  1. 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.

  2. 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

  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. 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.

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

    PubMed

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

    2014-09-01

    Behavioral and neuroplastic changes occurring in the development of addiction parallel those that occur in social bonding. This has led to speculation that drugs of abuse co-opt systems that subserve social attachment to shift attachment to drugs of abuse. Oxytocin, a neuropeptide that is important in social bonding, has been shown in rodents to decrease psychostimulant self-administration, locomotor activity, and conditioned place preference, it is unclear what role it may play in human drug addiction. In this double-blind, placebo-controlled crossover study, 23 cocaine-dependent inpatients in court-ordered treatment completed 4 task sessions measuring desire to use cocaine, cue-induced craving, monetary reward decisions and social cognition. Before each session, subjects administered 24 IU of intranasal oxytocin or placebo. Oxytocin increased desire to use cocaine and cue-induced excitability with no effect on cue-induced desire to use. Oxytocin also removed the effect of state anger on several measures of cue reactivity. Response to monetary reward increased under oxytocin and measures of social cognition worsened. The significant increase in the desire for drug and monetary reward as well as the significant decrease in measures of social cognition was small but warrant further study of the effect of oxytocin׳s effect in cocaine dependent subjects. The effect of oxytocin to modulate the relationship between state anger and cue reactivity should be explored further for potential therapeutic use of oxytocin in cocaine dependent patients. These findings are discussed in light of the human and rodent oxytocin literature. Copyright © 2014. Published by Elsevier B.V.

  6. [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.

  7. 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

  8. A general approach-avoidance hypothesis of oxytocin: accounting for social and non-social effects of oxytocin.

    PubMed

    Harari-Dahan, Osnat; Bernstein, Amit

    2014-11-01

    We critically reexamine extant theory and empirical study of Oxytocin. We question whether OT is, in fact, a "social neuropeptide" as argued in dominant theories of OT. We critically review human and animal research on the social and non-social effects of Oxytocin, including behavioral, psychophysiological, neurobiological, and neuroimaging studies. We find that extant (social) theories of Oxytocin do not account for well-documented non-social effects of Oxytocin. Furthermore, we find a range of evidence that social and non-social effects of Oxytocin may be mediated by core approach-avoidance motivational processes. We propose a General Approach-avoidance Hypothesis of Oxytocin (GAAO). We argue that the GAAO may provide a parsimonious account of established social and non-social effects of Oxytocin. We thus re-conceptualize the basic function(s) and mechanism(s) of action of Oxytocin. Finally, we highlight implications of the GAAO for basic and clinical research in humans

  9. Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

    PubMed

    Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

    2017-08-01

    Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ(2) tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value < .05 was considered statistically significant. The high-dose-requiring women had greater rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P

  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. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Artificial neural network as an alternative to multiple regression analysis in optimizing formulation parameters of cytarabine liposomes.

    PubMed

    Subramanian, Narayanaswamy; Yajnik, Archit; Murthy, Rayasa S Ramachandra

    2004-02-02

    The objective of the study was to optimize the formulation parameters of cytarabine liposomes by using artificial neural networks (ANN) and multiple regression analysis using 3(3) factorial design (FD). As model formulations, 27 formulations were prepared. The formulation variables, drug (cytarabine)/lipid (phosphatidyl choline [PC] and cholesterol [Chol]) molar ratio (X1), PC/Chol in percentage ratio of total lipids (X2), and the volume of hydration medium (X3) were selected as the independent variables; and the percentage drug entrapment (PDE) was selected as the dependent variable. A set of causal factors was used as tutorial data for ANN and fed into a computer. The optimization was performed by minimizing the generalized distance between the predicted values of each response and the optimized one that was obtained individually. In case of 3(3) factorial design, a second-order full-model polynomial equation and a reduced model were established by subjecting the transformed values of independent variables to multiple regression analysis, and contour plots were drawn using the equation. The optimization methods developed by both ANN and FD were validated by preparing another 5 liposomal formulations. The predetermined PDE and the experimental data were compared with predicted data by paired t test, no statistically significant difference was observed. ANN showed less error compared with multiple regression analysis. These findings demonstrate that ANN provides more accurate prediction and is quite useful in the optimization of pharmaceutical formulations when compared with the multiple regression analysis method.

  19. 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.

  20. 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.

  1. 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.

  2. Micellar liquid chromatographic analysis of benzyl alcohol and benzaldehyde in injectable formulations.

    PubMed

    Rizk, Mohamed; Ibrahim, Fawzia; Hefnawy, Mohamed; Nasr, Jenny Jeehan

    2007-06-01

    An accurate, sensitive and selective reversed-phase micellar liquid chromatographic method was developed for simultaneous determination of benzyl alcohol and benzaldehyde. This method was applied in different injectable formulations containing diclofenac, piroxicam, lincomycin and clindamycin. The method showed excellent linearity in the range of 10-100 microg mL(-1) and 1-20 microg mL(-1) with the limit of detection (S/N = 3) 0.25 microg mL(-1) (2.3 x 10(-6) mol L(-1)) and 0.12 microg mL(-1) (1.13 x 10(-6) mol L(-1)) for benzyl alcohol and benzaldehyde, respectively. The suggested method was successfully applied to the analysis of the studied drugs in bulk with average recoveries of 100.1 +/- 1.0% for benzyl alcohol and 100.4 +/- 1.6% for benzaldehyde, and to the determination of benzyl alcohol and benzaldehyde in injectable formulations with the respective average recoveries of 99.8 +/- 0.3 and 100.0 +/- 0.4%.

  3. Comparison of low-dose oxytocin and dinoprostone for labor induction in postterm pregnancies: a randomized controlled prospective study.

    PubMed

    Akay, Nezahat Öztürk; Hızlı, Deniz; Yılmaz, Saynur Sarıcı; Yalvaç, Serdar; Kandemir, Omer

    2012-01-01

    The aim of this study was to compare the efficacy of oxytocin and dinoprostone in achieving successful labor induction and vaginal delivery in postterm women with an unfavorable cervix. Postterm women with an uncomplicated pregnancy and a Bishop score of ≤6 were randomized to receive either dinoprostone vaginal pessary (Propess®) or low-dose oxytocin. The primary outcomes were the length of the induction-to-delivery period and the incidence of vaginal delivery. A total of 144 women were available for the analysis. The overall vaginal delivery rates were 75% (54/72) for the dinoprostone group and 80.6% (58/72; p = 0.35) for the oxytocin group; the mean induction-to-vaginal delivery interval was 13.3 and 10.3 h in the dinoprostone and the oxytocin group, respectively (p = 0.003). Uterine hyperstimulation was 7.4% compared with 6.8% (p = 0.8), and abnormal fetal heart rate was 26.4% compared with 18% (p = 0.2), respectively. Both oxytocin and dinoprostone seem to have similar obstetric outcomes in postterm pregnancies with an unfavorable cervix, except for a significant superiority of oxytocin for delivery in a shorter period. Copyright © 2012 S. Karger AG, Basel.

  4. 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

  5. Oxytocin attenuates social and non-social avoidance: Re-thinking the social specificity of Oxytocin.

    PubMed

    Harari-Dahan, Osnat; Bernstein, Amit

    2017-07-01

    Re-examining decades of the social construal of Oxytocin, the General Approach-Avoidance Hypothesis of Oxytocin (GAAO) predicts that Oxytocin will modulate responding to emotionally-evocative and personally-relevant social and non-social stimuli due to its action on the neural substrate of approach and avoidance motivation. We report the first critical experimental test of GAAO predictions by means of a double-blind intra-nasal administration of Oxytocin vs. placebo in 90 healthy adults (N=90, 50% women). As predicted, we found that among men and women for whom negative emotion (anxious arousal) is motivationally-relevant, intra-nasal administration of Oxytocin reduced behavioral avoidance of emotionally-evocative negatively-valenced social and non-social stimuli, but not closely matched emotionally-neutral stimuli. Findings cannot be explained by extant social theories of Oxytocin. We discuss the implications of the present findings for basic and translational clinical Oxytocin research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. In vitro evaluation of novel mucoadhesive buccal tablet of oxytocin prepared with Diospyros peregrina fruit mucilages.

    PubMed

    Metia, Pulak Kumar; Bandyopadhyay, Amal Kumar

    2008-04-01

    Novel mucoadhesive buccal tablets (NMBTs) of oxytocin were prepared as cores in cup fashion to release and permeate the drug unidirectionally toward the buccal mucosa to reach the systemic circulation directly. Adhesive cups for NMBTs were prepared with mucilage (DPM) isolated from edible Diospyros peregrina fruit. Mucoadhesive properties like shear and tensile and peel strengths of the adhesive cups were estimated on freshly excised bovine buccal mucosa. Core tablets were formulated with oxytocin using two penetration enhancers, sodium taurocholate and sodium thioglycollate. In vitro permeability studies of NMBTs were conducted in a Franz diffusion cell containing 50 ml of phosphate buffer, pH 6.6, at 37+/-0.2 degrees C through excised bovine buccal mucosa, and the amount of drug permeated was estimated at 220 nm on reverse-phase HPLC using a BDS Hypersil C(8) column with acetonitrile and potassium dihydrogen orthophosphate buffer 0.05 M, pH 6.6, (20 : 80 v/v) as the mobile phase, at flow rate of 1.25 ml/m. The NMBTs containing 0.75% w/w sodium taurocholate showed 26% permeability without damaging the histology of the buccal mucosa. The results suggest that this formulation may be a suitable alternative to oxytocin injections.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. The role of oxytocin in cardiovascular regulation.

    PubMed

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

    2014-03-18

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

  13. The role of oxytocin in cardiovascular regulation.

    PubMed

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

    2014-02-01

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

  14. The role of oxytocin in cardiovascular regulation

    PubMed Central

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

    2014-01-01

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

  15. Validation of a LC method for the analysis of zafirlukast in a pharmaceutical formulation.

    PubMed

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

    2000-08-01

    A reversed-phase high-performance liquid chromatographic (HPLC) method was developed and validated for estimation of zafirlukast in a pharmaceutical formulation. Assay samples were extracted utilizing acetonitrile. Drug and internal standard were chromatographed on reversed-phase C18 columns, using mixtures of acetonitrile/water and the eluents were monitored at different wavelengths. The method was validated statistically for its linearity, accuracy, robustness and precision. Experimental design was used during validation to evaluate method robustness and for the determination of intermediate precision. Factors examined for statistical approaches include laboratory, day, analyst, instrument, different percentage of organic modifier, temperature, wavelength and flow-rate. Due to its simplicity and accuracy, the method may be used for routine quality control analysis.

  16. Evaluation of finite element formulations for transient conduction forced-convection analysis

    NASA Technical Reports Server (NTRS)

    Thornton, E. A.; Wieting, A. R.

    1979-01-01

    Numerical studies clarifying the advantages and disavantages of conventional versus upwind convective finite elements are presented along with lumped versus consistent formulations for practical conduction forced-convection analysis. A finite-element procedure for treatment of negligible capacitance fluid nodes is presented. The procedure is based on procedures used in finite-element structural dynamics to treat nodes with negligible structural mass. Two finite-element programs and a finite-difference lumped-parameter program used in the studies are discussed. Evaluation studies utilizing three convection and two combined conduction-convection problems are then presented and discussed. Additionally, the computational time saving offered by the finite element procedure is considered for a practical combined conduction-convection problem.

  17. 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

  18. 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.

  19. 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.

  20. Postpartum uterine response to oxytocin and carbetocin.

    PubMed

    Amsalem, Hagai; Aldrich, Clive J; Oskamp, Marilynne; Windrim, Rory; Farine, Dan

    2014-01-01

    To obtain quantitative data on uterine contractility postpartum and compare the response of intramuscular oxytocin to carbetocin. A prospective study using an intrauterine pressure transducer (IUPT) to measure frequency, amplitude, and duration of contractions following the administration of either oxytocin (10 U) or carbetocin (30 microg). The IUPT was tolerated by all subjects and generated useful data 90% of the time in most subjects (12/16). Both drugs generated hypertonic uterine activity with contractions of similar duration. However, carbetocin resulted in contractions of sustained higher amplitude and frequency and therefore higher uterine performance as expressed by Montevideo units. This uterotonic effect of carbetocin lasted for 3 hours. IUPT monitoring generated quantitative data on postpartum uterine activity. When compared to high-dose oxytocin, a low dose of carbetocin has a more prolonged effect on uterine activity both in terms of a higher amplitude and frequency of contractions.

  1. Oxytocin and Schizophrenia Spectrum Disorders.

    PubMed

    Ettinger, Ulrich; Hurlemann, René; Chan, Raymond C K

    2017-09-02

    In this chapter, we present an overview of studies of oxytocin (OXT) in schizophrenia and the schizophrenia spectrum. We first outline the current state of pharmacological treatment of the symptoms of schizophrenia and point to unmet clinical needs. These relate particularly to the debilitating negative symptoms and social cognitive deficits that are frequently observed in patients suffering from schizophrenia. We argue that new treatments are needed to alleviate these impairments. As OXT has been proposed and investigated as a putative treatment, we will then summarise evidence from studies in patients with schizophrenia that have investigated the effects of OXT at several levels, i.e. at the levels of clinical symptoms, social cognitive function as assessed with experimental and neuropsychological tasks, and brain function as assessed using functional magnetic resonance imaging (fMRI). Finally, we will introduce the concept of the schizophrenia spectrum and highlight the importance of studying OXT effects in subclinical spectrum samples, such as in people with high levels of schizotypal personality. We conclude that the evidence of beneficial effects of OXT in schizophrenia is inconsistent, calling for further research in this field.

  2. Oxytocin: Old Hormone, New Drug

    PubMed Central

    Gutkowska, Jolanta; Jankowski, Marek

    2009-01-01

    Oxytocin (OT), traditionally associated with reproductive functions, was revisited recently, and several new functions in cardiovascular regulation were discovered. These functions include stimulation of the cardioprotective mediators nitric oxide (NO) and atrial natriuretic peptide. OT’s cardiovascular outcomes comprise: (i) natriuresis, (ii) blood pressure reduction, (iii) negative inotropic and chronotropic effects, (iv) parasympathetic neuromodulation, (v) NO pathway involvement in vasodilatation and endothelial cell growth, (vi) anti-inflammatory and (vii) antioxidant activities as well as (viii) metabolic effects. In addition, we have reported abundant OT in the early developing heart with its capacity to generate cardiomyocytes (CMs) from mouse embryonic stem cells and stem cells residing in the heart. OT increases glucose uptake by cultured CMs, in normal, hypoxic and even in insulin resistance conditions. In experimentally-induced myocardial infarction in rats, continuous in vivo OT delivery improves the cardiac healing process and cardiac work, diminishes inflammation, and stimulates angiogenesis. Therefore, in pathological situations, OT plays an anti-inflammatory and cardioprotective role, enhancing vascular and metabolic functions, with potential therapeutic application(s). PMID:27713231

  3. 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.

  4. Annexin A1 Complex Mediates Oxytocin Vesicle Transport

    PubMed Central

    Makani, Vishruti; Sultana, Rukhsana; Sie, Khin Sander; Orjiako, Doris; Tatangelo, Marco; Dowling, Abigail; Cai, Jian; Pierce, William; Butterfield, D. Allan; Hill, Jennifer; Park, Joshua

    2013-01-01

    Oxytocin is a major neuropeptide that modulates the brain functions involved in social behavior and interaction. Despite of the importance of oxytocin for neural control of social behavior, little is known about the molecular mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin is synthesized in the cell bodies of hypothalamic neurons in the supraoptic and paraventricular nuclei and processed to a 9-amino-acid mature form during post-Golgi transport to the secretion sites at the axon terminals and somatodendritic regions. Oxytocin secreted from the somatodendritic regions diffuses throughout the hypothalamus and its neighboring brain regions. Some oxytocin-positive axons innervate and secrete oxytocin to the brain regions distal to the hypothalamus. Brain oxytocin binds to its receptors in the brain regions involved in social behavior. Oxytocin is also secreted from the axon terminal at the posterior pituitary gland into the blood circulation. We have discovered a new molecular complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150), and microtubule motor, that controls the distribution of oxytocin vesicles between the axon and the cell body in a protein kinase A (PKA)- and protein kinase C (PKC)-sensitive manner. ANXA1 showed significant co-localization with oxytocin vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1, thus increasing the axon-localization of oxytocin vesicles. Conversely, activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating the axon-localization of oxytocin vesicles. Our study suggests that ANXA1 complex coordinates the actions of PKA and PKC to control the distribution of oxytocin vesicles between the axon and the cell body. PMID:24118254

  5. Man and the chimaera. Selective versus neutral oxytocin evolution.

    PubMed

    Acher, R; Chauvet, J; Chauvet, M T

    1995-01-01

    The oxytocin/vasopressin superfamily encompasses vertebrate and invertebrate peptides and therefore the ancestral gene encoding the precursor protein antedates the divergence between the two groups, about 700 million years ago. The preserved nonapeptide pattern indicates that both the precursor structures and the processing enzymatic machinery were greatly conserved to ensure the building of a specific conformation. Substitutions, which may be neutral or selective, occurred in precise positions. Virtually all vertebrate species possess an oxytocin-like and a vasopressin-like peptide so that two evolutionary lineages can be traced. Because a single peptide, vasotocin ([Ile3]-vasopressin or [Arg8]-oxytocin) has been found in the most primitive Cyclostomata, a primordial gene duplication and subsequent mutations are assumed to have given rise to the two lineages. They started with vasotocin and isotocin ([Ser4,Ile8]-oxytocin) in bony fishes and culminated with vasopressin and oxytocin in placental mammals. Mesotocin ([Ile3]-oxytocin), found in lungfishes, amphibians, reptiles, birds and marsupials, appears as an evolutionary intermediate. The change from isotocin ([Ser4,Ile8]-oxytocin) into mesotocin ([Ile8]-oxytocin), can be observed in African and Australian lungfishes, species making the transition from bony fishes to land vertebrates. On the other hand the replacement of mesotocin by oxytocin can be detected in marsupials, particularly in the North-American opossum and the Australian Northern bandicoot that have both mesotocin and oxytocin whereas placental mammals possess only oxytocin. The invariability of this peptide in placentals can be explained by receptor-fitting selective pressure. In contrast to bony vertebrates in which neurohypophysial hormones revealed a remarkable structural stability, cartilaginous fishes displayed an unique oxytocin-like hormone evolution with variability and duality. Aside from vasotocin, in the subclass Selachii, rays have

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

    PubMed

    Klimas, Rimantas; Baranauskas, Algirdas; Gendrolis, Antanas

    2002-01-01

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

  7. Use of high resolution mass spectrometry for analysis of polymeric excipients in drug delivery formulations.

    PubMed

    Perez Hurtado, Pilar; Lam, Pui Yiu; Kilgour, David; Bristow, Anthony; McBride, Eileen; O'Connor, Peter B

    2012-10-16

    Two polymeric excipients, typically used in enabling drug delivery approaches, are Gelucire 44/14 (a product of Gattefosse s.a, St Priest, France) and polysorbate 80; these are known to improve solubility of poorly water-soluble drugs and, hence, increase their effective bioavailability. In addition to the use of Gelucire 44/14 and polysorbate 80 as excipients in drugs, they are also widely used as cosmetic and food additives. In general, complex structures and compositions of drug excipients impact performance of the formulation in vivo and consequently affect drug absorption. Therefore, a comparison between excipients from different suppliers and batches to batch would provide an indication of the impact on drug product performance and also the study of the effectiveness of the system and any problems associated with the formulation. In this study, high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) is used to compare two different batches of Gelucire 44/14 and polysorbate 80. With the high resolving power of FTICR MS, it was possible to differentiate between batches of excipients from differences in the identified components. The improved resolution offered by FTICR MS allowed assignment of four polymeric series differences in the two batches of polysorbate 80 and the presence of one compound and three polymeric series differences in the two batches of Gelucire 44/14. The increase in the number of components assigned in the excipients batch using FTICR-MS, compared to the numbers previously assigned by lower resolution TOF MS, underlines the importance of high resolution techniques in analysis of highly complex mixtures.

  8. Oxytocin discontinuation during active labor in women who undergo labor induction.

    PubMed

    Diven, Liany C; Rochon, Meredith L; Gogle, Julia; Eid, Sherrine; Smulian, John C; Quiñones, Joanne N

    2012-12-01

    The purpose of this study was to determine whether there is an increase in the cesarean delivery rate in women who undergo induction when oxytocin is discontinued in the active phase of labor. We conducted a prospective randomized controlled trial of women who underwent induction of labor at term; they were assigned randomly to either routine oxytocin use (routine) or oxytocin discontinuation (DC) once in active labor. Analysis was by intention to treat. Two hundred fifty-two patients were eligible for study analysis: 127 patients were assigned randomly to the routine group and 125 patients were assigned randomly to the DC group. Cesarean delivery rate was similar between the groups (routine, 25.2% [n = 32] vs the DC group, 19.2% [n = 24]; P = .25). There was a higher chorioamnionitis rate and slightly longer active phase in those women who were assigned to the DC group. In adjusted analysis, the rate of chorioamnionitis was not different by randomization group but was explained by the duration of membrane rupture and intrauterine pressure catheter placement. Discontinuation of oxytocin in active labor after labor induction does not increase the cesarean delivery rate significantly. Copyright © 2012 Mosby, Inc. All rights reserved.

  9. 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.

  10. Determination of oxytocin in milk of cows administered oxytocin.

    PubMed

    Prakash, B S; Paul, Vijay; Kliem, Heike; Kulozik, Ulrich; Meyer, Heinrich H D

    2009-03-16

    To address people's concerns of exogenous oxytocin (OT) administration to lactating bovines, a study was undertaken to (a) establish an enzyme immunoassay (EIA) for OT determination in milk, (b) quantify OT in milk of cows administered OT, and (c) study influence of pasteurization on OT stability in milk. A sensitive EIA validated according to the criteria of European Union-Decision 2002/657/EC was developed for OT in skim milk in an analytical range of 10-250pgmL(-1) with a decision limit (CCalpha) of 30pgmL(-1) and detection capability (CCbeta) of 41.5pgmL(-1). Milk samples collected from cows (n=38) administered either 25 or 50IU OT prior to milking were investigated for the presence of OT. There was no significant difference among both groups with the mean concentrations of OT being 15.8 and 14.9pgmL(-1) for cows subjected to 25 and 50IU OT administration, respectively. The OT levels in skim milk of control cows (n=30; untreated) were basal (around 10pgmL(-1)). All the analyzed milk samples were below the CCalpha value of 30pgmL(-1). Pasteurization of OT spiked milk samples at different temperature and sample holding conditions reduced the immunological activity of OT to 43% at 110 degrees C. However, no further decline occurred in the immunological activity with increased pasteurization temperature and time. It was concluded that the milk OT concentrations after OT administrations were minimal and below the assay decision limit. However, OT was quite stable to pasteurization in OT spiked milk.

  11. 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.

  12. Combining multiple single-reference transmissibility functions in a unique matrix formulation for operational modal analysis

    NASA Astrophysics Data System (ADS)

    Devriendt, C.; Weijtjens, W.; De Sitter, G.; Guillaume, P.

    2013-10-01

    In recent years, the authors have proposed an innovative approach for Operational Modal Analysis based on transmissibility measurements. A method was proposed based on combining 2 single-reference transmissibility functions that were obtained during 2 different loading conditions. However in practice one in general has access to multiple transmissibility functions and perhaps even multiple loading conditions. In this paper a new method is introduced that combines all the measured single-reference transmissibility functions in a unique matrix formulation in order to identify system poles. It will be shown that each element of the pseudo-inverse of this matrix is a rational function with poles equal to the system poles. The proposed method reduces the risk to miss system poles and to identify extra non-physical poles. Therefore the method increases the usability and reliability of transmissibility based operational modal analysis (TOMA). The method will be demonstrated and validated by means of an experiment on a beam excited at multiple inputs for three different loading conditions.

  13. 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.

  14. 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.

  15. Wavelet-like efficient analysis of two-dimensional arbitrarily shaped radomes using a surface formulation

    NASA Astrophysics Data System (ADS)

    Quesada-Pereira, F. D.; Vidal, A.; Boria, V. E.; Alvarez-Melcón, A.; Gimeno, B.

    2007-10-01

    Radomes are usually made of lossy dielectric materials, and their accurate analysis is often cumbersome because of their typical large electrical size and geometrical complexity. In real reflector antenna structures, there are always complex interactions between the radome, the reflector surfaces and the directional feeds, which are typically neglected for the sake of simplicity. In this paper we will consider all such interactions in a very accurate way, thus requiring a high number of unknowns for the numerical solution of the problem. To overcome such drawback, an integral equation formulation based on the Equivalence Principle in combination with the wavelet transform has been employed, obtaining finally a robust and accurate CAD tool for the rigorous analysis of arbitrarily shaped radomes containing continuous and discrete electromagnetic sources. It will be shown that the use of wavelet-like bases substantially improves the numerical efficiency and memory requirements of the original integral equation method. For verification purposes, the results obtained with the new technique are successfully compared with examples taken from the literature. Complex antenna structures are then discussed in order to prove the usefulness of the new method.

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

    PubMed

    Madari, Hamta; Jacobs, Robert S

    2004-08-01

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

  17. 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

  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. 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. © IMechE 2014.

  20. 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.

  1. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage.

    PubMed

    Westhoff, Gina; Cotter, Amanda M; Tolosa, Jorge E

    2013-10-30

    ; heterogeneity not applicable); and in trials that gave oxytocin at a dose of 10 IU (RR 0.48; 95% CI 0.33 to 0.68; two trials, 2901 women; T² = 0.02, I² = 27%). Prophylactic oxytocin versus ergot alkaloids. Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL (RR 0.76; 95% CI 0.61 to 0.94; five trials, 2226 women; T² = 0.00, I² = 0%). The benefit of oxytocin over ergot alkaloids to prevent PPH greater than 500 mL only persisted in the subgroups of quasi-randomised trials (RR 0.71, 95% CI 0.53 to 0.96; three trials, 1402 women; T² = 0.00, I² = 0%) and in trials that performed active management of the third stage of labour (RR 0.58; 95% CI 0.38 to 0.89; two trials, 943 women; T² = 0.00, I² = 0%). Use of prophylactic oxytocin was associated with fewer side effects compared with use of ergot alkaloids; including decreased nausea between delivery of the baby and discharge from the labour ward (RR 0.18; 95% CI 0.06 to 0.53; three trials, 1091 women; T² = 0.41, I² = 41%) and vomiting between delivery of the baby and discharge from the labour ward (RR 0.07; 95% CI 0.02 to 0.25; three trials, 1091 women; T² = 0.45, I² = 30%). Prophylactic oxytocin + ergometrine versus ergot alkaloids: There was no benefit seen in the combination of oxytocin and ergometrine versus ergometrine alone in preventing PPH greater than 500 mL (RR 0.90; 95% CI 0.34 to 2.41; five trials, 2891 women; T² = 0.89, I² = 80%). The use of oxytocin and ergometrine was associated with increased mean blood loss (MD 61.0 mL; 95% CI 6.00 to 116.00 mL; fixed-effect analysis; one trial, 34 women; heterogeneity not applicable).In all three comparisons, there was no difference in mean length of the third stage or need for manual removal of the placenta between treatment arms. Prophylactic oxytocin at any dose decreases both PPH greater than 500 mL and the need for therapeutic uterotonics compared to placebo alone. Taking into account the subgroup analyses from both primary

  2. 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.

  3. 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.

  4. Benefits of Oxytocin Administration in Obstructive Sleep Apnea.

    PubMed

    Jain, Vivek; Marbach, Joseph; Kimbro, Shawn; Andrade, David C; Jain, Arad; Capozzi, Eleanor; Mele, Kyle; Del Rio, Rodrigo; Kay, Matthew W; Mendelowitz, David

    2017-08-10

    Activation of oxytocin receptors has shown benefits in animal models of Obstructive Sleep Apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. 8 patients diagnosed with OSA were administered intranasal oxytocin (40 i.u.). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability were assessed. Oxytocin significantly increased indices of parasympathetic activity, including heart rate variability, total sleep time, and the Post-Polysommogram Sleep Assessment (PPSA) score, an index of self-reported sleep satisfaction. Although the Apnea-Hypopnea Index (AHI) was not significantly changed with oxytocin administration, when apnea and hypopnea events were compared independently, the frequency of hypopneas, but not apneas, were significantly (p<.005) decreased with oxytocin treatment. Both apneas and hypopneas were significantly shortened in duration with oxytocin treatment. Oxytocin treatment significantly decreased the percent of apnea and hypopnea events that were accompanied with an arousal. Oxytocin administration has the potential to restore cardiorespiratory homeostasis and reduce some clinically important (objective and patient-reported) adverse events that occur with OSA. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory and autonomic function in OSA patients. Copyright © 2017, American Journal of Physiology-Lung Cellular and Molecular Physiology.

  5. Use and abuse of oxytocin for augmentation of labor.

    PubMed

    Selin, Lotta; Almström, Elisabeth; Wallin, Gunnar; Berg, Marie

    2009-01-01

    To investigate the use of oxytocin for augmentation of labor and its relation to labor progress and delivery outcome. A retrospective observational study undertaken in a Swedish hospital during 2000-2001. Singleton pregnancies at > or = 37 weeks of gestation with cephalic presentation and spontaneous onset of labor. Data were collected from 1,263 clinical records. The partogram was used to diagnose labor dystocia (LD). Prevalence of oxytocin administration, LD and operative delivery. Oxytocin was administered to 55% of the women (75% of primiparas and 38.1% of multiparas); a majority did not meet LD criteria. LD frequency was 19.8% (32.7% in primiparas and 7.4% in multiparas). Oxytocin was started both 'too early' and 'too late' in relation to the diagnosis of LD. Cesarean section (CS) was performed on 17.1% of primiparous and 2.4% of multiparous oxytocin recipients with LD, compared to 2.3 and 1.5%, respectively, of oxytocin recipients without diagnosed LD. Oxytocin augmentation was undertaken in an unstructured manner; some women were inadequately treated and others were treated unnecessarily. Oxytocin recipients with LD underwent operative delivery to a higher extent than oxytocin recipients without LD, suggesting that the main reason for CS was the underlying problem of LD rather than the oxytocin augmentation itself.

  6. 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

  7. Oxytocin mediates stress-induced analgesia in adult mice

    PubMed Central

    Robinson, D A; Wei, F; Wang, G D; Li, P; Kim, S J; Vogt, S K; Muglia, L J; Zhuo, M

    2002-01-01

    As a neurohormone and as a neurotransmitter, oxytocin has been implicated in the stress response. Descending oxytocin-containing fibres project to the dorsal horn of the spinal cord, an area important for processing nociceptive inputs. Here we tested the hypothesis that oxytocin plays a role in stress-induced analgesia and modulates spinal sensory transmission. Mice lacking oxytocin exhibited significantly reduced stress-induced antinociception following both cold-swim (10 °C, 3 min) and restraint stress (30 min). In contrast, the mice exhibited normal behavioural responses to thermal and mechanical noxious stimuli and morphine-induced antinociception. In wild-type mice, intrathecal injection of the oxytocin antagonist dOVT (200 μm in 5 μl) significantly attenuated antinociception induced by cold-swim. Immunocytochemical staining revealed that, in the mouse, oxytocin-containing neurones in the paraventricular nucleus of the hypothalamus are activated by stress. Furthermore, oxytocin-containing fibres were present in the dorsal horn of the spinal cord. To test whether descending oxytocin-containing fibres could alter nociceptive transmission, we performed intracellular recordings of dorsal horn neurones in spinal slices from adult mice. Bath application of oxytocin (1 and 10 μm) inhibited excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. This effect was reversed by the oxytocin antagonist dOVT (1 μm). Whole-cell recordings of dorsal horn neurones in postnatal rat slices revealed that the effect of oxytocin could be blocked by the addition of GTP-γ-S to the recording pipette, suggesting activation of postsynaptic oxytocin receptors. We conclude that oxytocin is important for both cold-swim and restraint stress-induced antinociception, acting by inhibiting glutamatergic spinal sensory transmission. PMID:11956346

  8. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  9. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  10. 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 and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680...

  11. 21 CFR 522.1680 - Oxytocin injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  12. 21 CFR 522.1680 - Oxytocin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin. (a.... It will contract smooth muscle cells of the mammary gland for milk letdown if the udder is in proper...

  13. 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

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

    PubMed

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

    2012-02-01

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

  15. Enantiomeric separation of bupropion enantiomers by electrokinetic chromatography: quantitative analysis in pharmaceutical formulations.

    PubMed

    Castro-Puyana, María; García, Ma Angeles; Marina, Ma Luisa

    2008-11-01

    The first CE method enabling the quantitation of the two enantiomers of bupropion was developed in this work. Electrokinetic chromatography (EKC) mode using cyclodextrins as chiral selectors was employed. A study on the enantiomeric separation ability of different neutral and anionic CDs was carried out. Sulfated-beta-CD was shown to provide the highest values for the enantiomeric resolution. The influence of some experimental conditions, such as pH, chiral selector concentration, temperature, and separation voltage on the enantiomeric separation of bupropion was also studied. The use of 10 mM sulfated-beta-CD in 50 mM borate buffer (pH 9.0) with an applied voltage of 30 kV and a temperature of 30 degrees C enabled the separation of the enantiomers of bupropion with high resolution (Rs > 7) and short analysis time (approximately 3.5 min). Finally, the method was successfully applied to the quantitation of bupropion in two pharmaceutical formulations.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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. © Thieme Medical Publishers.

  1. 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

  2. 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.

  3. Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome.

    PubMed

    Di Napoli, Agnese; Warrier, Varun; Baron-Cohen, Simon; Chakrabarti, Bhismadev

    2014-01-01

    Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs2268490-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS.

  4. 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.

  5. 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

  6. Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

    PubMed

    Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

    2015-09-01

    To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. [Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis].

    PubMed

    Iwao, Yasunori

    2015-01-01

    With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg-St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5% showed downward curvature indicating a gradual decrease in surface area over time. Conversely, with TR-FB, even when its concentration was increased, the S(t) profile for APAP had a maximum value. The differences between Mg-St and TR-FB could be explained by the differences in extensibility deriving from their morphology. Next, we evaluated the effect of disintegtant concentration using five disintegrants. When disintegrant was added to ethenzamide tablet formulation, an increase in the dissolution rate and S(t) dependent on disintegrant concentration was observed, according to the type of disintegrant. It was found that the water absorption ability of disintegrants had strong correlations with the parameters of S(t). Taken together, this study demonstrates that analysis of S(t) can directly provide useful information, especially about the functionality of pharmaceutical excipients.

  8. 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.

  9. 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.

  10. On the stability analysis of hyperelastic boundary value problems using three- and two-field mixed finite element formulations

    NASA Astrophysics Data System (ADS)

    Schröder, Jörg; Viebahn, Nils; Wriggers, Peter; Auricchio, Ferdinando; Steeger, Karl

    2017-05-01

    In this work we investigate different mixed finite element formulations for the detection of critical loads for the possible occurrence of bifurcation and limit points. In detail, three- and two-field formulations for incompressible and quasi-incompressible materials are analyzed. In order to apply various penalty functions for the volume dilatation in displacement/pressure mixed elements we propose a new consistent scheme capturing the non linearities of the penalty constraints. It is shown that for all mixed formulations, which can be reduced to a generalized displacement scheme, a straight forward stability analysis is possible. However, problems based on the classical saddle-point structure require a different analyses based on the change of the signature of the underlying matrix system. The basis of these investigations is the work from Auricchio et al. (Comput Methods Appl Mech Eng 194:1075-1092, 2005, Comput Mech 52:1153-1167, 2013).

  11. Analysis of different innovative formulations of curcumin for improved relative oral bioavailability in human subjects.

    PubMed

    Purpura, Martin; Lowery, Ryan P; Wilson, Jacob M; Mannan, Haider; Münch, Gerald; Razmovski-Naumovski, Valentina

    2017-02-16

    The optimal health benefits of curcumin are limited by its low solubility in water and corresponding poor intestinal absorption. Cyclodextrins (CD) can form inclusion complexes on a molecular basis with lipophilic compounds, thereby improving aqueous solubility, dispersibility, and absorption. In this study, we investigated the bioavailability of a new γ-cyclodextrin curcumin formulation (CW8). This formulation was compared to a standardized unformulated curcumin extract (StdC) and two commercially available formulations with purported increased bioavailability: a curcumin phytosome formulation (CSL) and a formulation of curcumin with essential oils of turmeric extracted from the rhizome (CEO). Twelve healthy human volunteers participated in a double-blinded, cross-over study. The plasma concentrations of the individual curcuminoids that are present in turmeric (namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were determined at baseline and at various intervals after oral administration over a 12-h period. CW8 showed the highest plasma concentrations of curcumin, demethoxycurcumin, and total curcuminoids, whereas CSL administration resulted in the highest levels of bisdemethoxycurcumin. CW8 (39-fold) showed significantly increased relative bioavailability of total curcuminoids (AUC0-12) in comparison with the unformulated StdC. The data presented suggest that γ-cyclodextrin curcumin formulation (CW8) significantly improves the absorption of curcuminoids in healthy humans.

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

    PubMed Central

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

    2014-01-01

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

  13. Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

    PubMed

    Bugg, George J; Siddiqui, Farah; Thornton, Jim G

    2011-07-06

    neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

  14. Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

    PubMed

    Bugg, George J; Siddiqui, Farah; Thornton, Jim G

    2013-06-23

    of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

  15. Inhaled oxytocin increases positive social behaviors in newborn macaques

    PubMed Central

    Simpson, Elizabeth A.; Sclafani, Valentina; Paukner, Annika; Hamel, Amanda F.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.; Ferrari, Pier Francesco

    2014-01-01

    Early caregiver–infant interactions are critical for infants’ socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults—including expression recognition and affiliation—it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants’ social skills, measured earlier in development. We also hypothesized that oxytocin’s effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants’ facial gesturing at a human caregiver increased, and infants’ salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants’ imitative skill (measured earlier in development: 1–7 d of age) predicted oxytocin-associated increases in affiliative behaviors—lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver—suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder. PMID:24778211

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

    PubMed Central

    Ross, Heather E.; Young, Larry J.

    2009-01-01

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

  17. Role of oxytocin in the initiation of term and preterm labor in rats: changes in oxytocin receptor density and plasma oxytocin concentration and the effect of an oxytocin antagonist, L-366,509.

    PubMed

    Kobayashi, M; Akahane, M; Minami, K; Moro, M; Ajisawa, Y; Inoue, Y; Kawarabayashi, T

    1999-03-01

    Our purpose was to compare the functional roles of oxytocin in term and preterm labor in rats by both biochemical and pharmacologic means. We determined the myometrial oxytocin receptor density and the maternal plasma concentrations of oxytocin and progesterone on gestational days 18, 20, and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm labor induced by the combined use of bilateral ovariectomy and estradiol injection. We also evaluated the effects of an oxytocin antagonist, L-366,509, on the initiation of both term and preterm labor. The number of tritiated oxytocin binding sites in myometrial membranes rapidly increased on gestational day 22 (morning) in rats with term labor. Plasma progesterone level decreased in an inverse fashion. A rapid increase in circulating oxytocin concentration was observed at the onset of delivery in rats in labor at term. Both the plasma oxytocin concentration and the receptor density had the same values in rats with preterm labor as in rats with term labor. L-366,509 delayed the initiation of labor in rats with term and preterm labor in a dose-dependent manner. It is confirmed biochemically and pharmacologically that oxytocin plays an important role in the initiation of both term and preterm labor in rats. The oxytocin antagonist examined was able to delay term and preterm labor, so it might prove useful in clinical practice for the treatment of preterm labor.

  18. 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

  19. 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.

  20. 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

  1. 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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Giribabu, D.; Shankar, V.

    2016-07-01

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

  4. Oxytocin-induced postinhibitory rebound firing facilitates bursting activity in oxytocin neurons

    PubMed Central

    Israel, Jean-Marc; Poulain, Dominique A.; Oliet, Stéphane H.R.

    2008-01-01

    During parturition and lactation, neurosecretory oxytocin (OT) neurons in the hypothalamus achieve pulsatile hormone secretion by coordinated bursts of firing that occur throughout the neuronal population. This activity is partly controlled by somatodendritic release of OT which facilitates the onset and recurrence of synchronized bursting. To further investigate the cellular mechanisms underlying the control exerted by OT on the activity of its own neurons, we studied the effects of the peptide on membrane potential and synaptic activity in OT neurons in hypothalamic organotypic slice cultures. Bath application of low concentrations of OT (<100 nM) facilitated GABA-A receptor-mediated inhibitory transmission through a presynaptic mechanism without affecting membrane potential and excitatory glutamatergic synaptic activity. The facilitatory action of OT on GABAergic transmission was dose-dependent, starting at 25 nM and disappearing at concentrations above 100 nM. As previously shown, higher concentrations of OT (>500 nM) had the opposite effect, inhibiting GABA-A receptors via a postsynaptic mechanism. Surprisingly, OT-mediated facilitation of GABAergic transmission promoted action potential firing in 40% of the neurons. Each action potential occurred at the end of the repolarizing phase of an inhibitory potential. Pharmacological dissection revealed that this firing involved the activation of low-threshold activated calcium channels. Detailed statistical analysis showed that OT-mediated firing up-regulated bursting activity in OT neurons. It is thus likely to optimize OT secretion and, as a consequence, facilitate delivery and milk ejection in mammals. PMID:18184781

  5. Proficiency test for chemical laboratories for the analysis of a pesticide in a formulated product: interlaboratory study.

    PubMed

    Sanyal, Doyeli; Rani, Anita

    2009-01-01

    A multilaboratory proficiency testing program was conducted by the National Accreditation Board for Testing and Calibration Laboratories (India) and coordinated by the Institute of Pesticide Formulation Technology. This program was conducted to compare the performance of individual laboratories in the area of pesticide formulation (Chlorpyrifos 20 EC) analysis. A total of 24 laboratories in India participated. Analysis of 2 parameters (i.e., estimation of the active ingredient and the acidity) of 2 samples of Chlorpyrifos 20 EC was the objective of this program. Homogeneity tests were performed before sample distribution. Performance of the participating laboratories was evaluated by using new robust statistics given in the guidelines of the National Association of Testing Authorities, Australia. Results were collated and statistically computed to calculate the value of 2 types of Z-scores (Zwi and Zbi). In addition to the statistical analysis, a graphical representation such as the Youden plot was also generated to evaluate the performance of participating laboratories.

  6. Gastroprotective strategies in chronic NSAID users: a cost-effectiveness analysis comparing single-tablet formulations with individual components.

    PubMed

    de Groot, N L; Spiegel, B M R; van Haalen, H G M; de Wit, N J; Siersema, P D; van Oijen, M G H

    2013-01-01

    To evaluate the cost-effectiveness of competing gastroprotective strategies, including single-tablet formulations, in the prevention of gastrointestinal (GI) complications in patients with chronic arthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs). We performed a cost-utility analysis to compare eight gastroprotective strategies including NSAIDs, cyclooxygenase-2 inhibitors, proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol, and single-tablet formulations. We derived estimates for outcomes and costs from medical literature. The primary outcome was incremental cost per quality-adjusted life-year gained. We performed sensitivity analyses to assess the effect of GI complications, compliance rates, and drug costs. For average-risk patients, NSAID + PPI cotherapy was most cost-effective. The NSAID/PPI single-tablet formulation became cost-effective only when its price decreased from €0.78 to €0.56 per tablet, or when PPI compliance fell below 51% in the NSAID + PPI strategy. All other strategies were more costly and less effective. The model was highly sensitive to the GI complication risk, costs of PPI and NSAID/PPI single-tablet formulation, and compliance to PPI. In patients with a threefold higher risk of GI complications, both NSAID + PPI cotherapy and single-tablet formulation were cost-effective. NSAID + PPI cotherapy is the most cost-effective strategy in all patients with chronic arthritis irrespective of their risk for GI complications. For patients with increased GI risk, the NSAID/PPI single-tablet formulation is also cost-effective. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  7. Chapman-Enskog analysis for finite-volume formulation of lattice Boltzmann equation

    NASA Astrophysics Data System (ADS)

    Patil, D. V.

    2013-06-01

    The classical Chapman-Enskog expansion is performed for the recently proposed finite-volume formulation of lattice Boltzmann equation (LBE) method [D.V. Patil, K.N. Lakshmisha, Finite volume TVD formulation of lattice Boltzmann simulation on unstructured mesh, J. Comput. Phys. 228 (2009) 5262-5279]. First, a modified partial differential equation is derived from a numerical approximation of the discrete Boltzmann equation. Then, the multi-scale, small parameter expansion is followed to recover the continuity and the Navier-Stokes (NS) equations with additional error terms. The expression for apparent value of the kinematic viscosity is derived for finite-volume formulation under certain assumptions. The attenuation of a shear wave, Taylor-Green vortex flow and driven channel flow are studied to analyze the apparent viscosity relation.

  8. 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.

  9. 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.

  10. 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.

  11. [The oxytocin signal cascade during premature labor].

    PubMed

    Friebe-Hoffmann, U

    2003-05-01

    Since 30 years the rate of preterm deliveries of 7% remained unchanged. This is due to a lack of understanding of the underlying pathomechanisms of preterm labor. Oxytocin (OT) as well as its receptor (OTR) play a key role in the process of (preterm) labor as part of a paracrine system that regulates myometrial contractility. Binding of OT to its corresponding receptor, OTR, leads to activation of actin-myosin interactions and therewith myometrial contractions as well as production of intrauterine prostaglandins (PGE(2), PGF(2 alpha)) mainly in decidua and myometrium. Oxytocin expression increases significantly at time of parturition, as does the expression of its receptor. Both can be influenced by diverse cellular substrates. The focus of our research group is based on the exploration of the influence of cytokines on OTR signaling.

  12. 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.

  13. 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. © 2015 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

  14. 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

  15. 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

  16. 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.

  17. 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.

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

    PubMed Central

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

    2014-01-01

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

  19. 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

  20. Factors Related to Intimidation During Oxytocin Administration.

    PubMed

    Beckmann, Claudia A; Cannella, Barbara L

    2015-01-01

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

  1. 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

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

    PubMed

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

    2002-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Sheppard, Cheyenne J.

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

  4. Hypothalamic oxytocin mediates social buffering of the stress response

    PubMed Central

    Smith, Adam S.; Wang, Zuoxin

    2013-01-01

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

  5. Oxytocin's fingerprint in personality traits and regional brain volume.

    PubMed

    Andari, Elissar; Schneider, Fabien C; Mottolese, Raphaëlle; Vindras, Philippe; Sirigu, Angela

    2014-02-01

    Oxytocin has a fundamental role in social behavior. In humans, supporting evidence shows that oxytocin enhances people's ability to trust or affiliate with others. A key question is whether differences in plasma oxytocin concentration in humans are related to people's differences in their social traits of personality and if such differences are reflected in the structural organization of brain areas responsive to the action of this hormone. We examined the correlation between oxytocin plasma levels and personality traits in 30 healthy subjects, tested with the Inventory revised neuroticism-extroversion-openness personality inventory (NEO-PI-R). By using the voxel-based morphometry technique, we also investigated changes in gray matter volume as a function of the plasma oxytocin level and NEO-PI-R scores. A positive correlation was found between plasma oxytocin and extraversion scores, a dimension that captures social affiliative tendencies. Moreover, we found an inverse correlation between plasma oxytocin and the volume of the right amygdala and the right hippocampus, 2 brain areas implicated in fear and anxiety. Finally, we showed that the amygdala-hippocampal complex correlate negatively with extraversion scores. Our findings provide evidence for a neural mechanism linking physiological oxytocin's variability and structural variation of brain regions relevant for emotion regulation to individual differences in affiliative personality traits.

  6. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. 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.

  9. Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior.

    PubMed

    Proctor, Darby; Calcutt, Sarah E; Burke, Kimberly; de Waal, Frans B M

    2016-08-01

    Oxytocin has been suggested as a treatment to promote positive social interactions in people with Autism Spectrum Disorders (ASD). However, it is difficult to test this effect outside of the laboratory in realistic social situations. One way to resolve this issue is to study behavioral changes in closely related species with complex social relationships, such as chimpanzees. Here, we use captive, socially housed chimpanzees to evaluate the effects of oxytocin in a socially complex environment. After administering intranasal oxytocin or a placebo to an individual chimpanzee (total n = 8), she was returned to her social group. An experimenter blind to the condition measured the subject's social behavior. We failed to find a behavioral difference between conditions. As one of the goals for oxytocin administration as a treatment for ASD is increasing prosocial behaviors during 'real world' encounters, it is problematic that we failed to detect behavioral changes in our closest living relatives. However, our null findings may be related to methodological challenges such as determining an effective dose of oxytocin for chimpanzees and how long oxytocin takes to cross the blood-brain barrier. Thus, more research on intranasal oxytocin dosing and uptake are needed to continue exploring whether oxytocin changes social behavior in naturalistic settings and as a treatment for ASD.

  10. 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.

  11. 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.

  12. 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.

  13. In vitro and in vivo evaluation of a novel mucoadhesive buccal oxytocin tablet prepared with Dillenia indica fruit mucilage.

    PubMed

    Metia, P K; Bandyopadhyay, A K

    2008-04-01

    Novel mucoadhesive buccal tablets (NMBT) of oxytocin were prepared as core in cup fashion to release the drug unidirectionally towards the buccal mucosa. Adhesive cups were prepared with a mucilage isolated from edible Dillenia indica fruits (DIM). Shear, tensile and peel strengths of prepared adhesive cups were estimated on freshly excised bovine buccal mucosa. Core tablets were formulated with oxytocin using permeation enhancers viz. sodium taurocholate and sodium thioglycollate. In vitro permeability studies of NMBT were conducted in a Franz diffusion cell containing 50 mL of phosphate buffer pH 6.6 at 37 +/- 0.2 degrees C through excised bovine buccal mucosa. In vivo studies on anaesthetized New Zealand albino male rabbits were conducted and drug levels in plasma were estimated at 220 nm by reverse phase HPLC using BDS Hypersil C8 column using acetonitrile and 0.05 M potassium dihydrogen orthophosphate buffer pH 6.6 (20:80 v/v) as mobile phase, at a flow rate of 1.25 mL/ min. Optimized formulation showed C(max), T(max), t1/2 and AUC(total), 688 pg/mL, 2 h, 0.079 h, and 1999.72 h x pg/mL respectively. The NMBT containing 0.75% w/w sodium taurocholate showed 27% bioavailability without damaging the buccal mucosasuggesting its suitability as an alternative to noninvasive administration of oxytocin.

  14. 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

  15. Sex differences in methamphetamine seeking in rats: Impact of oxytocin

    PubMed Central

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

    2013-01-01

    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 (1 mg/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 1 mg/kg, IP) 30 min before a meth priming injection (1 mg/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

  16. 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

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

    SciTech Connect

    Martinez, M.J.

    1995-06-01

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

  18. 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

  19. 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.

  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. Human Neuroimaging of Oxytocin and Vasopressin in Social Cognition

    PubMed Central

    Zink, Caroline F; Meyer-Lindenberg, Andreas

    2012-01-01

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

  3. 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

  4. 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.

  5. 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. A single MCR-ALS model for drug analysis in different formulations: Application on diazepam commercial preparations.

    PubMed

    De Luca, Michele; Ioele, Giuseppina; Spatari, Claudia; Ragno, Gaetano

    2017-02-05

    A multivariate curve resolution - alternating least squares (MCR-ALS) analysis was used to quantify diazepam (DZP) in thirty commercial liquid formulations. MCR calibration was run on the UV spectrophotometric data of the commercial DZP samples over the range 200-400nm, allowing the resolution of the drug signal and then the excipients contained in all the formulations. A single model MCR for the determination of the drug in all samples was then built through the adoption of the correlation constraint. This model was optimized by an appropriate selection of the most useful wavelength ranges and then validated on external samples. DZP concentrations in the pharmaceutical formulations were measured by HPLC-DAD analysis. The performance of the MCR model was compared with that from application of classical partial least squares regression (PLSR). The results, in terms of error of prediction, were very satisfactory, reaching a relative error below of 1.66% against 2.56%, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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.

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

    PubMed Central

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

    2010-01-01

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

  10. 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.

  11. The usefulness of 2D DOSY and 3D DOSY-COSY 1H NMR for mixture analysis: application to genuine and fake formulations of sildenafil (Viagra).

    PubMed

    Trefi, Saleh; Gilard, Véronique; Balayssac, Stéphane; Malet-Martino, Myriam; Martino, Robert

    2009-12-01

    Two-dimensional diffusion ordered spectroscopy (DOSY) (1)H NMR is proposed to analyze drugs that are complex mixtures in order to discriminate genuine from fake formulations. The method was applied to the analysis of 17 formulations of sildenafil, one being genuine Viagra and the others illegally manufactured formulations of this drug coming from India, Syria and China. It enabled (i) distinguishing imitations or counterfeit from the authentic formulation, (ii) detecting the presence of sildenafil or adulterants, (iii) gaining information on the formulation process by detection of various excipients, thus giving a precise and global 'signature' of the manufacturer. Even though some samples are slightly overdosed, the quality of products manufactured in India and Syria was better than that of Chinese formulations which were adulterated with vardenafil and homosildenafil. This study also presents a three-dimensional DOSY-COSY (1)H NMR experiment that provides both virtual separation and structural information.

  12. 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.

  13. The comparison of brand-name and generic formulations of venlafaxine: a therapeutic drug monitoring analysis.

    PubMed

    Unterecker, Stefan; Proft, Florian; Riederer, Peter; Lauer, Martin; Deckert, Jürgen; Pfuhlmann, Bruno

    2014-04-01

    Venlafaxine (VEN) is a widely used antidepressant drug, which is available in both brand-name and generic formulations. Bioequivalence studies indicate some pharmacokinetic variability. However, naturalistic therapeutic drug monitoring studies of different generic formulations are lacking. In 2010, inpatients of the Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, were treated with either slow-release brand-name VEN (Trevilor) or slow-release generic VEN (Venlafaxin Hexal) depending on the respective inpatient ward. Routine therapeutic drug monitoring analyses of both groups were compared after matching samples regarding dose of VEN, gender, age, smoking habits, and evaluation of co-medication. Both groups did not differ in mean values of VEN, O-desmethyl-VEN (ODV), VEN + ODV serum concentrations, and ODV/VEN ratio. No difference in dose-corrected serum concentrations between generic and brand-name VEN was revealed for males, females, smokers, or nonsmokers. In both groups, Spearman Rho correlation between VEN dose and VEN + ODV serum concentration was moderate but significant (P < 0.001; generic: r = 0.554; brand name: r = 0.668). Within the generic subgroup, females had a significantly higher dose-corrected serum concentration of VEN (U test, P < 0.05), whereas within brand name, no gender influence was detected. Spearman Rho correlation of age and dose-corrected ODV (P < 0.05) and VEN + ODV (P < 0.05) was significant only in the generic group. In the brand-name sample, smokers had significantly lower dose-corrected serum concentrations of ODV (U test, P < 0.01) and VEN + ODV (P < 0.01). In the generic group, smoking habit was without any influence. No differences in serum concentrations in dependence of either VEN formulations suggest a safe and efficient treatment of patients using the evaluated generic VEN. However, differences within one formulation regarding gender, age, and smoking status suggest variability of

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

    PubMed Central

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

    2016-01-01

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

  15. 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.

  16. Oxytocin release in magnocellular nuclei: neurochemical mediators and functional significance during gestation

    PubMed Central

    Armstrong, William E.; Crowley, William R.

    2010-01-01

    When released from dendrites within the supraoptic (SON) and paraventricular (PVN) nuclei (intranuclear release) during suckling, oxytocin exerts autocrine and paracrine effects on oxytocin neurons that are necessary for the unique timing and episodic pattern of oxytocin release into the systemic circulation that is characteristic of lactation. Recent reports have shown that stimulation of central noradrenergic and histaminergic receptors are both necessary for intranuclear release of oxytocin in response to suckling. In addition, in vitro studies indicate that excitatory amino acids may also be critical for central oxytocin secretion, although in vivo experiments have not provided direct support for this hypothesis. In addition to a critical role in intranuclear oxytocin release during lactation, norepinephrine has also been shown to stimulate central oxytocin during gestation. Stimulation of central oxytocin receptors during gestation appears critical for normal systemic oxytocin secretion in responses to suckling during the subsequent period of lactation. Oxytocin receptor blockade during pregnancy alters normal timing of systemic oxytocin release during suckling and reduces milk delivery. Several adaptations occur in the central oxytocin system that are necessary for determining the unique response characteristic observed during parturition and gestation. Central oxytocin receptor stimulation during gestation has been implicated in pregnancy-related morphological changes in magnocellular oxytocin neurons, disinhibition of oxytocin neurons to GABA, and adaptations in membrane response characteristics of oxytocin neurons. In conclusion, intranuclear oxytocin release during gestation and lactation are critical for establishing, and then evoking the unique pattern of systemic oxytocin secretion in response to the suckling offspring necessary for adequate milk delivery. Furthermore, activation of central noradrenergic receptors appears to be critical for release of

  17. 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).

  18. 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.

  19. 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.

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

    ERIC Educational Resources Information Center

    Ho, Hsuan-Fu; Hung, Chia-Chi

    2008-01-01

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

  1. 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…

  2. Oxytocin pathways and the evolution of human behavior.

    PubMed

    Carter, C Sue

    2014-01-01

    This review examines the hypothesis that oxytocin pathways--which include the neuropeptide oxytocin, the related peptide vasopressin, and their receptors--are at the center of physiological and genetic systems that permitted the evolution of the human nervous system and allowed the expression of contemporary human sociality. Unique actions of oxytocin, including the facilitation of birth, lactation, maternal behavior, genetic regulation of the growth of the neocortex, and the maintenance of the blood supply to the cortex, may have been necessary for encephalization. Peptide-facilitated attachment also allows the extended periods of nurture necessary for the emergence of human intellectual development. In general, oxytocin acts to allow the high levels of social sensitivity and attunement necessary for human sociality and for rearing a human child. Under optimal conditions oxytocin may create an emotional sense of safety. Oxytocin dynamically moderates the autonomic nervous system, and effects of oxytocin on vagal pathways, as well as the antioxidant and anti-inflammatory effects of this peptide, help to explain the pervasive adaptive consequences of social behavior for emotional and physical health.

  3. 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.

  4. Oxytocin specifically enhances valence-dependent parasympathetic responses.

    PubMed

    Gamer, Matthias; Büchel, Christian

    2012-01-01

    The evolutionarily highly conserved neuropeptide oxytocin seems to be involved in the regulation of complex forms of social behavior. It enhances the processing of positive social stimuli, reduces behavioral and neuroendocrine stress responses and modulates amygdala activity in humans. Moreover, it has been proposed that oxytocin dampens sympathetic nervous system activity. This hypothesis was tested in a double-blind, placebo-controlled study with 38 men either receiving 24 IU oxytocin intranasally or a placebo spray. While accomplishing an emotion classification task, electrodermal responses were measured as an index of sympathetic activity. Moreover, heart rate changes were recorded that are additionally mediated by the parasympathetic nervous system. Oxytocin enhanced differential heart rate responses to facial expressions as a function of the emotional valence, but had no effect on electrodermal activity or tonic measures of physiological arousal. These results indicate that oxytocin specifically modulates phasic activity of the parasympathetic nervous system which potentially reflects an increased motivational value of facial expressions following oxytocin treatment. Findings suggest that anxiolytic effects of oxytocin are not reflected in short-term sympathetic responses and may even be a consequence of rather than a prerequisite for improved social information processing. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. 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

  6. 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

  7. Gender moderates the effect of oxytocin on social judgments.

    PubMed

    Hoge, Elizabeth A; Anderson, Eric; Lawson, Elizabeth A; Bui, Eric; Fischer, Laura E; Khadge, Shradha D; Barrett, Lisa Feldman; Simon, Naomi M

    2014-05-01

    The neuropeptide oxytocin is implicated in social processing, and recent research has begun to explore how gender relates to the reported effects. This study examined the effects of oxytocin on social affective perception and learning. Forty-seven male and female participants made judgments of faces during two different tasks, after being randomized to either double-blinded intranasal oxytocin or placebo. In the first task, "unseen" affective stimuli were presented in a continuous flash suppression paradigm, and participants evaluated faces paired with these stimuli on dimensions of competence, trustworthiness, and warmth. In the second task, participants learned affective associations between neutral faces and affective acts through a gossip learning procedure and later made affective ratings of the faces. In both tasks, we found that gender moderated the effect of oxytocin, such that male participants in the oxytocin condition rated faces more negatively, compared with placebo. The opposite pattern of findings emerged for female participants: they rated faces more positively in the oxytocin condition, compared with placebo. These findings contribute to a small but growing body of research demonstrating differential effects of oxytocin in men and women. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Oxytocin modulates human communication by enhancing cognitive exploration.

    PubMed

    de Boer, Miriam; Kokal, Idil; Blokpoel, Mark; Liu, Rui; Stolk, Arjen; Roelofs, Karin; van Rooij, Iris; Toni, Ivan

    2017-09-08

    Oxytocin is a neuropeptide known to influence how humans share material resources. Here we explore whether oxytocin influences how we share knowledge. We focus on two distinguishing features of human communication, namely the ability to select communicative signals that disambiguate the many-to-many mappings that exist between a signal's form and meaning, and adjustments of those signals to the presumed cognitive characteristics of the addressee ("audience design"). Fifty-five males participated in a randomized, double-blind, placebo controlled experiment involving the intranasal administration of oxytocin. The participants produced novel non-verbal communicative signals towards two different addressees, an adult or a child, in an experimentally-controlled live interactive setting. We found that oxytocin administration drives participants to generate signals of higher referential quality, i.e. signals that disambiguate more communicative problems; and to rapidly adjust those communicative signals to what the addressee understands. The combined effects of oxytocin on referential quality and audience design fit with the notion that oxytocin administration leads participants to explore more pervasively behaviors that can convey their intention, and diverse models of the addressees. These findings suggest that, besides affecting prosocial drive and salience of social cues, oxytocin influences how we share knowledge by promoting cognitive exploration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. [Genetic engineering of oxytocin: isolation of oxytocinoyllysine].

    PubMed

    Ovchinnikova, T V; Murav'eva, T I; Chupova, L A; Tagaev, A A; Martynova, N Iu; Miroshnikov, A I

    1995-12-01

    A hybrid protein, Il-Ox-K, was obtained from cells of E. coli TG1/pTOTEilox strain. The N-terminal sequence of this protein (63 amino acid residues) is a fragment of human interleukin-3, and the C-terminal sequence represents the full amino acid sequence of oxytocin flanked by a lysine residue. The modified oxytocinoyl-Lys containing S-sulfocysteine residues was isolated after tryptic digestion of S-sulfoderivative of the hybrid protein. The modified peptide was converted into the cyclic form containing the disulfide bonds [formula: see text]. Obtaining the oxytocinoyl-Lys proves the possibility of preparing short peptides using the microbiological synthesis.

  10. Discontinuation of oxytocin in the active phase of labor.

    PubMed

    Girard, Bénédicte; Vardon, Delphine; Creveuil, Christian; Herlicoviez, Michel; Dreyfus, Michel

    2009-01-01

    To show that early discontinuation of oxytocin will not increase the mean duration of the active labor phase in a clinically significant way. Controlled non-inferiority study. Department of Obstetrics and Gynecology, University of Caen, Clemenceau Hospital, France. A total of 138 women with singleton pregnancy and a vertex presentation of over 34 gestational weeks, presenting a medical indication of induction of labor or a dystocia at onset of labor, from May 2005 to June 2006. Two parallel groups were compared: continuation of oxytocin until delivery versus discontinuation of oxytocin at the onset of the active phase. The clinically acceptable increase in mean duration of the active phase of labor (non-inferiority margin) was set at 60 minutes. Primary outcome measure was duration of the active labor phase. Secondary outcome measures included total duration of labor, parameters concerning oxytocin use, rates of uterine hyperstimulation and fetal heart rate (FHR) abnormalities, and mode of delivery. Some neonatal outcomes were also analyzed. Equivalence of the two strategies (continuation vs. discontinuation of oxytocin) was not demonstrated (p=0.97 testing for non-inferiority), the active phase even being significantly longer by a mean of 113 minutes (p=0.0001 testing for superiority). The rates of cesarean sections, alterations of FHR and delivery hemorrhage were higher when oxytocin was continued, but not significantly. There were significantly more infants hospitalized in neonatology when oxytocin was continued (p=0.028). Discontinuation of oxytocin at the onset of the active phase prolongs labor. We found no argument for discontinuing the infusion of oxytocin at the onset of the active phase.

  11. Acute intranasal oxytocin improves positive self-perceptions of personality.

    PubMed

    Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

    2012-04-01

    Research suggests the experimental manipulation of oxytocin facilitates positive interactions, cooperation, and trust. The mechanism by which oxytocin influences social behavior is not well understood. We explored the hypothesis that oxytocin alters how people perceive themselves, which could be one mechanism by which oxytocin promotes prosocial behavior. In a between-subject, randomized, and double-blind experiment, 100 university students received a 24 I.U. dose of intranasal oxytocin or placebo, and then completed the Revised NEO Personality Inventory (NEO-PI-R) and other self-report measures 90 min later. Intranasal oxytocin increased ratings of NEO-PI-R extraversion and openness to experiences [F(1,98) = 4.910, p = .025, partial η (2) = .05; F(1,98) = 6.021, p = .016, partial η (2) = .06], particularly for the following facets: positive emotions (d = 0.48, p < .05), warmth (d = 0.47, p < .05), openness to values (d = 0.45, p < .05) and ideas (d = 0.40, p < .05), trust (d = 0.44, p < .05), and altruism (d = 0.40, p < .05). Oxytocin had no influence on ratings of negative emotionality, conscientiousness, rejection sensitivity, depression, worry, self-esteem, and perceived social support. The administration of oxytocin improved participants' self-perceptions of their personality, at least for certain traits important for social affiliation. Increased positive self-referential processing may be one mechanism by which oxytocin promotes positive social behaviors.

  12. Oxytocin in survivors of childhood-onset craniopharyngioma.

    PubMed

    Daubenbüchel, Anna M M; Hoffmann, Anika; Eveslage, Maria; Özyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M; Martens, Henri; Geenen, Vincent; Müller, Hermann L

    2016-11-01

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

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

    PubMed

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  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 analysis of delays in simulator digital computing systems. Volume 1: Formulation of an analysis approach using a central example simulator model

    NASA Technical Reports Server (NTRS)

    Heffley, R. K.; Jewell, W. F.; Whitbeck, R. F.; Schulman, T. M.

    1980-01-01

    The effects of spurious delays in real time digital computing systems are examined. Various sources of spurious delays are defined and analyzed using an extant simulator system as an example. A specific analysis procedure is set forth and four cases are viewed in terms of their time and frequency domain characteristics. Numerical solutions are obtained for three single rate one- and two-computer examples, and the analysis problem is formulated for a two-rate, two-computer example.

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

    NASA Technical Reports Server (NTRS)

    Sadler, S. G.

    1972-01-01

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

  17. 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.

  18. 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.

  19. 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.

  20. Dynamic analysis of the tether transportation system using absolute nodal coordinate formulation

    NASA Astrophysics Data System (ADS)

    Sun, Xin; Xu, Ming; Zhong, Rui

    2017-10-01

    Long space tethers are becoming a rising concern as an alternate way for transportation in space. It benefits from fuel economizing. This paper focuses on the dynamics of the tether transportation system, which consists of two end satellites connected by a flexible tether, and a movable vehicle driven by the actuator carried by itself. The Absolute Nodal Coordinate Formulation is applied to the establishment of the equation of motion, so that the influence caused by the distributed mass and elasticity of the tether is introduced. Moreover, an approximated method for accelerating the calculation of the generalized gravitational forces on the tether is proposed by substituting the volume integral every step into summation of finite terms. Afterwards, dynamic evolutions of such a system in different configurations are illustrated using numerical simulations. The deflection of the tether and the trajectory of the crawler during the transportation is investigated. Finally, the effect on the orbit of the system due to the crawler is revealed.

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

    NASA Technical Reports Server (NTRS)

    Felippa, Carlos A.; Ohayon, Roger

    1991-01-01

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

  2. 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.

  3. Exogenous oxytocin modulates human myometrial microRNAs.

    PubMed

    Cook, Joanna R; MacIntyre, David A; Samara, Eleni; Kim, Sung Hye; Singh, Natasha; Johnson, Mark R; Bennett, Phillip R; Terzidou, Vasso

    2015-07-01

    MicroRNAs (miRNAs) play a modulatory role in pathways that lead to labor onset, although oxytocin is known to modulate gene expression within the myometrium. We aimed to identify miRNAs whose expression is regulated by oxytocin in pregnant human myometrium. Myometrial miRNA expression profiles were compared between samples collected from women at term before the onset of labor (no labor; n = 8) and after labor onset after early exogenous oxytocin treatment (n = 8). Multivariate modelling was used to assess differences in miRNA profiles. Biologic validation was undertaken on 3 independent patient cohorts (no labor, n = 10; labor induced with oxytocin, n = 8; and spontaneous labor with no oxytocin treatment, n = 10). In vitro studies that used primary myocytes were undertaken to assess target miRNA expression after oxytocin treatment. Target genes of candidate miRNAs were identified in silico and cross-referenced with genes that are known to be associated with labor or expressed in myometrium. In total, 1309 miRNAs were analyzed by microarray, of which 494 were detected in human myometrium. Multivariate modeling identified 12 target miRNAs the differential expression of which was most responsible for the observed separation of the 2 patient populations in the primary discovery cohorts. Biologic validation in the independent secondary sample cohorts showed that oxytocin independently regulated 5 miRNAs (hsa-miR-146b-3p, hsa-miR-196b-3p, hsa-miR-223-3p, hsa-miR-873-5p, and hsa-miR-876-5p). Additionally, hsa-miR-146b-3p was increased both in labor that was induced with oxytocin and in myometrium from spontaneous labor with no oxytocin treatment compared with no labor samples. Four of the validated miRNAs (hsa-miR-146a-5p, hsa-miR-146b-3p, hsa-miR-196b-3p, and hsa-miR-876-5p) were expressed in primary human myocytes; oxytocin treatment of these cells replicated the directional changes that were observed in vivo. Oxytocin alters the expression of a unique set of

  4. 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.

  5. 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

  6. 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.

  7. 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…

  8. 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…

  9. A comparison between the effect of oxytocin only and oxytocin plus propranolol on the labor (a double blind randomized trial).

    PubMed

    Kashanian, Maryam; Fekrat, Mohsen; Zarrin, Zahra; Ansari, Narges S

    2008-06-01

    The comparison between the effect of oxytocin alone or in combination with propranolol on labor. A double blind randomized controlled trial was performed on 150 nulliparas with a gestational age of 39-41 weeks of pregnancy and a Bishop score of < or =5. In the first group (oxytocin group = 75), oxytocin alone was used for induction of labor. In the second group (propranolol group = 75 cases), before the beginning of oxytocin, 2 mg propranolol was slowly injected intravenously then the oxytocin was initiated. The number of patients who delivered in the first day showed no difference between the two groups. The mean duration for obtaining good contractions was shorter in the propranolol group in both the first and second day of induction The mean interval between the beginning of induction until the beginning of active phase at the first day of induction was shorter in the propranolol group. The mean interval between the beginning of induction until delivery at the first day of induction was shorter in the propranolol group. The amount of necessary oxytocin for the first day of induction was less in the propranolol group. Propranolol may shorten the induction duration and labor and reduce the amount of necessary oxytocin.

  10. 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.

  11. 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.

  12. The role of oxytocin in neuropsychiatric disorders.

    PubMed

    Marazziti, D; Catena Dell'osso, M

    2008-01-01

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

  13. Unintended clinical consequences of the implementation of a checklist-based, low-dose oxytocin protocol.

    PubMed

    Rohn, Amanda E; Bastek, Jamie A; Sammel, Mary D; Wang, Eileen; Srinivas, Sindhu K

    2015-03-01

    Standardized oxytocin protocols have been used to improve the safety and quality of obstetric care. We examined rates of chorioamnionitis and labor dystocia requiring cesarean delivery as unintended consequences of the implementation of a low-dose, checklist-based oxytocin protocol. We performed a retrospective cohort study of live singleton deliveries that underwent a trial of labor in two 15-month periods, comparing outcomes in those who delivered before to after protocol implementation. Patients and outcomes were identified using a combination of electronic medical records and International Classification of Diseases, 9th Revision, Clinical Modification codes. Time trend analysis was performed to evaluate for secular trends. A total of 8,717 women were included; 5,077 received oxytocin. Despite an unchanged rate of cesarean deliveries from before to after initiation of the protocol (15.15 vs. 14.75%, p = 0.60), deliveries after protocol implementation were generally characterized by higher rates of chorioamnionitis (7.48 vs. 5.97%, p < 0.001), longer median time from admission to delivery (524 vs. 462 minutes, p < 0.001), more cesarean deliveries performed for labor dystocia (50.62 vs. 40.92%, p < 0.001), and fewer cesarean deliveries performed for fetal distress (32.52 vs. 38.67%, p = 0.02). Low-dose oxytocin protocols are intended to increase safety, but they may have unintended consequences related to prolonged labor, and should be studied before widespread use. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. [Active management of the third stage of labor: Three schemes of oxytocin: randomised clinical trial].

    PubMed

    Neri-Mejía, M; Pedraza-Avilés, A G

    2016-05-01

    To compare the effectiveness of intramuscular oxytocin against intravenous oxytocin against intravenous traditional oxytocin infusion, in the active management of the third period of the delayed impingement labor work and controlled cord traction. Randomized controlled blinded clinical trial. In women age 14 to 40 with full term pregnancy, childbirth attended by ISSSTE's Regional Hospital "Gral. Ignacio Zaragoza", in the period from August to December 2015. 152 deliveries were attended, from which 66 fulfill with selection criteria. Group 1 = 22 patients, group 2 = 21 patients and Group 3 = 23 patients. The total age average was 26.92 + 5.8. For blood volume, statistical differences were significant among the three groups (p = 0.000). Adverse reactions were presented in 1 .5%, without difference between the groups. (P = 0.337). The differences in hemoglobin values and final and initial hematocrit presented differences with statistical significance (p = 0.000 for both). Nonetheless, the differences obtained in the analysis of the diverse variables among the three types of treatment, the three schemes are effective on the obstetrical hemorrhage prevention.

  16. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth.

    PubMed

    Anagnostou, Evdokia; Soorya, Latha; Brian, Jessica; Dupuis, Annie; Mankad, Deepali; Smile, Sharon; Jacob, Suma

    2014-09-11

    There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. Fifteen children and adolescents with verbal IQs≥70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. 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.

  18. 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

  19. High-dose versus low-dose oxytocin for augmentation of delayed labour.

    PubMed

    Kenyon, Sara; Tokumasu, Hironobu; Dowswell, Therese; Pledge, Debbie; Mori, Rintaro

    2013-07-13

    of these outcomes there were inconsistencies between studies in the size of effect. When we carried out sensitivity analysis (temporarily removing a study at high risk of bias) the differences between groups were no longer statistically significantThere were no significant differences between high- and low-dose regimens for instrumental vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage, chorioamnionitis or women's perceptions of experiences. For neonatal outcomes, there was no significant difference between groups for Apgar scores, umbilical cord pH, admission to special care baby unit, or neonatal mortality. The following outcomes were not evaluated in the included studies: perinatal mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. Higher-dose regimens of oxytocin (4 mU per minute or more) were associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence to recommend that high-dose regimens are advised routinely for women with delay in the first stage of labour. Further research should evaluate the effect of high-dose regimens of oxytocin for women delayed in labour and should include maternal and neonatal outcomes as well as the effects on women.

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

    PubMed Central

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

    2013-01-01

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

  1. 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

  2. Discrimination of orange beverage emulsions with different formulations using multivariate analysis.

    PubMed

    Mirhosseini, Hamed; Tan, Chin Ping

    2010-06-01

    The constituents in a food emulsion interact with each other, either physically or chemically, determining the overall physico-chemical and organoleptic properties of the final product. Thus, the main objective of present study was to investigate the effect of emulsion components on beverage emulsion properties. In most cases, the second-order polynomial regression models with no significant (P > 0.05) lack of fit and high adjusted coefficient of determination (adjusted R(2), 0.851-0.996) were significantly fitted to explain the beverage emulsion properties as function of main emulsion components. The main effect of gum arabic was found to be significant (P < 0.05) in all response regression models. Orange beverage emulsion containing 222.0 g kg(-1) gum arabic, 2.4 g kg(-1) xanthan gum and 152.7 g kg(-1) orange oil was predicted to provide the desirable emulsion properties. The present study suggests that the concentration of gum arabic should be considered as a primary critical factor for the formulation of orange beverage emulsion. This study also indicated that the interaction effect between xanthan gum and orange oil showed the most significant (P < 0.05) effect among all interaction effects influencing all the physicochemical properties except for density. Copyright (c) 2010 Society of Chemical Industry.

  3. 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.

  4. 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.

  5. 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.

  6. Oxytocin and the Biopsychology of Performance in Team Sports

    PubMed Central

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

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

  7. Synthetic oxytocin and breastfeeding: reasons for testing an hypothesis.

    PubMed

    Odent, M R

    2013-11-01

    Synthetic oxytocin is widely used in developed countries and in emerging countries as well. It is the most common medical intervention in childbirth. A great variety of side effects are plausible. There are in particular theoretical reasons to test the hypothesis that the increasing incidence of breastfeeding difficulties and the frequent earlier than desired cessation of breastfeeding are related to the use of synthetic oxytocin during labour. There have already been some studies that tend to support this hypothesis. Four hundred of the 7465 children born in 2006 at the Carlos Haya University Hospital (Malaga, Spain) were randomly selected. By interviewing the mothers, information about feeding type and duration was obtained in 2011 for 316 children. Among the 189 children who were born after labours induced or augmented with synthetic oxytocin, the odds ratio for bottle-feeding was 1.451 and the odds ratio for withdrawal at 3 months was 2.294. In addition, the Battelle Developmental Inventory was used to assess at age five 148 children (84 born with synthetic oxytocin): the odds ratio for neuropsychological development disorders after use of oxytocin was 1.46. The main limitation of such a preliminary study is that in the context of a tertiary Spanish hospital the possible effects of synthetic oxytocin on the quality and duration of breastfeeding cannot be easily dissociated from the effects of other components of pharmacological assistance during labour, particularly epidural fentanyl (a synthetic opioid analgesic). This comment is valid for all studies exploring the side effects of synthetic oxytocin in obstetric units of developed countries, including explorations through videotapes of the effects of synthetic oxytocin on primitive neonatal reflexes. It is also valid for studies exploring the side effects of obstetric analgesia without taking into account the use of synthetic oxytocin. This is why we underline the importance of conducting such studies in

  8. Acidemia at birth, related to obstetric characteristics and to oxytocin use, during the last two hours of labor.

    PubMed

    Jonsson, Maria; Nordén-Lindeberg, Solveig; Ostlund, Ingrid; Hanson, Ulf

    2008-01-01

    Evaluate obstetric characteristics during the last two hours of labor in neonates born with acidemia. Case-control study. Delivery units at two university hospitals in Sweden. Out of 28,486 deliveries during 1994-2004, 305 neonates had an umbilical artery pH value <7.05 at birth. neonates with an umbilical artery pH < 7.05. Controls were neonates with pH > or = 7.05 and an Apgar score > or =7 at 5 minutes. Obstetric characteristics, cardiotocographic patterns and oxytocin treatment during the last two hours of labor were recorded. In the univariate analysis, > or =6 contractions/10 minutes (odds ratio (OR) 4.94, 95% confidence interval (CI) 3.25-7.49), oxytocin use (OR 2.20, 95% CI 1.66-2.92), bearing down > or =45 minutes (OR 1.77, 95% CI 1.31-2.38) and occipito-posterior position (OR 2.18, 95% CI 1.19-3.98) were associated with acidemia at birth. In the multivariate analysis, only > or =6 contractions/10 minutes (OR 5.36, 95% CI 3.32-8.65) and oxytocin use (OR 1.89, 95% CI 1.21-2.97) were associated with acidemia at birth. Among cases with > or =6 contractions/10 minutes, 75% had been treated with oxytocin. Pathological cardiotocographic patterns occurred in 68.8% of cases and in 26.1% of controls (p<0.001). A hyperactive uterine contraction pattern and oxytocin use are the most important risk factors for acidemia at birth. The increased uterine activity was related to overstimulation in the majority of cases. The duration of bearing down is less important when uterine contraction frequency has been considered.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Oxytocin for preventing postpartum haemorrhage (PPH) in non-facility birth settings.

    PubMed

    Pantoja, Tomas; Abalos, Edgardo; Chapman, Evelina; Vera, Claudio; Serrano, Valentina P

    2016-04-14

    event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on

  17. 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

  18. Effect of oxytocin discontinuation during the active phase of labor.

    PubMed

    Öztürk, Filiz Halıcı; Yılmaz, Saynur Sarıcı; Yalvac, Serdar; Kandemir, Ömer

    2015-01-01

    To observe the progression of labor when oxytocin use is limited to the onset of the active stage of labor. A randomized, prospective controlled study was performed to address the issue of oxytocin infusion after the onset of active labor in 140 patients. In the study group, infusion of oxytocin was discontinued at the onset of the active phase of labor, which was accepted as a cervical dilatation of 5 cm. In the control group, incremental oxytocin infusion was administered until 5 cm cervical dilatation, and then was maintained at the same level until delivery. The primary outcome variable was duration from the beginning of the active phase to delivery. In the study group, the duration of the active phase of labor was about 30 min longer than in the control group and this difference was significant. The secondary outcomes of the study were maternal-fetal complications of oxytocin and in both groups there were no significant differences. It is not reasonable to discontinue oxytocin infusion at the beginning of active labor. Nevertheless, for an accurate conclusion expanded investigations are needed.

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

    PubMed

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

    2016-01-01

    to evaluate the effects of labor stimulation with oxytocin on maternal and neonatal outcomes. 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. 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. 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.

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

    PubMed Central

    2013-01-01

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

  1. Intranasal oxytocin enhances positive self-attribution in healthy men.

    PubMed

    Colonnello, Valentina; Heinrichs, Markus

    2014-11-01

    A growing body of studies consistently demonstrates that social responsiveness toward others is influenced by the neurohormone oxytocin. However, the potential role of oxytocin for self-perception remains relatively unexplored. Thus, we investigated whether oxytocin administration influences the self-attribution of positive and negative adjectives at the early, effortful stage of self-related information processing. Sixty healthy male participants received either 24I.U. oxytocin or a placebo in a randomized double-blind study before completing a sorting task, in which they were instructed to co-classify, as fast as possible, positive and negative adjectives into either self or non-self categories. Oxytocin-treated participants reported stronger positive attitudes toward themselves compared to placebo. The present findings demonstrate that oxytocin administration influences the early stage of self-related information processing and suggests that the oxytocinergic system might be involved in psychopathological conditions characterized by a negative representation of self. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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

  3. Effect of oxytocin during labor on neonatal acidemia.

    PubMed

    Mussi, Serena; Incerti, Maddalena; Plevani, Cristina; Ghidini, Alessandro; Pezzullo, John C; Locatelli, Anna

    2016-10-01

    To assess the factors affecting neonatal acidemia, including occurrence of tachysystole/hypertonus in fetuses exposed to oxytocin during labour and with continuously-monitored fetal heart rate (FHR) tracings. Prospective observational study of all women with term pregnancies who received oxytocin for induction/augmentation of labour. FHR tracings were prospectively classified using ACOG classification. Independent predictors of neonatal acidemia were identified using multivariate linear regression with p < 0.05 considered significant. We included 430 women, 236 of whom (54.9%) had spontaneous onset of labour. The duration of active phase of the second stage of labour and the presence of abnormal FHR tracing during labour were significantly associated with UA pH (p < 0.001) and BE (p < 0.001), while maximum dose of oxytocin (p < 0.17; p < 0.7) and tachysystole (p < 0.9; p < 0.8) were not. At logistic regression, the duration of active phase of the second stage of labour was independently predictive of neonatal acidemia (p < 0.009) while abnormal FHR tracing approached significance (p < 0.088). In women receiving oxytocin during labour, the duration of active phase of the second stage of labour correlates with neonatal acidemia, whereas maximum dose of oxytocin, duration of oxytocin administration and occurrence of tachysystole during labour do not.

  4. "Lie to me"-Oxytocin impairs lie detection between sexes.

    PubMed

    Pfundmair, Michaela; Erk, Wiebke; Reinelt, Annika

    2017-10-01

    The hormone oxytocin modulates various aspects of social behaviors and even seems to lead to a tendency for gullibility. The aim of the current study was to investigate the effect of oxytocin on lie detection. We hypothesized that people under oxytocin would be particularly susceptible to lies told by people of the opposite sex. After administration of oxytocin or a placebo, male and female participants were asked to judge the veracity of statements from same- vs. other-sex actors who either lied or told the truth. Results showed that oxytocin decreased the ability of both male and female participants to correctly classify other-sex statements as truths or lies compared to placebo. This effect was based on a lower ability to detect lies and not a stronger bias to regard truth statements as false. Revealing a new effect of oxytocin, the findings may support assumptions about the hormone working as a catalyst for social adaption. Copyright © 2017. Published by Elsevier Ltd.

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

    PubMed

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

    2016-07-05

    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.

  6. Memory response to oxytocin predicts relationship dissolution over 18 months.

    PubMed

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

    2016-06-01

    Oxytocin is known for its role in pair bonding in non-human animals. To examine the role of oxytocin in human romantic bonding, we examined its effect on recall of memories of past and current romantic experiences as predictors of relationship dissolution. In a placebo-controlled, within-subject, randomized experiment, 48 participants (24♀; 16 single) self-administered intranasal oxytocin and completed an autobiographical memory test. Participants in a current romantic relationship reported on their relationship status 18 months later. Participants in a relationship recalled fewer memories of past romantic partners following oxytocin administration relative to placebo. Participants who responded to oxytocin by recalling more conflict memories of their current romantic partner, relative to placebo, were more likely to have ended their relationship over 18 months than those who did not show this response. These results suggest that the memory response to an intranasal oxytocin challenge may represent an index of relationship outcome over time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. An oxytocin receptor in anococcygeus muscles isolated from male mice.

    PubMed Central

    Gibson, A.

    1986-01-01

    The nature of the neurohypophyseal peptide receptor in the anococcygeus muscles from male mice was investigated. The rank order of potency of naturally occurring peptides was oxytocin greater than Arg-vasotocin greater than Arg-vasopressin greater than Lys-vasopressin, which is similar to that found in the uterus and mammary gland. Selective agonists on the oxytocin (OT) receptors of the uterus and mammary gland (Thr4-OT; Gly7-OT; Thr4-Gly7-OT) were also potent agonists in the mouse anococcygeus. Competitive antagonists of uterine responses to oxytocin (dP-TyrMe-Thr4-OT; dP-TyrMe-OT; dP-Thr4-OT; dp-Orn8-OT) were also competitive antagonists of oxytocin-induced contractions of the mouse anococcygeus. It is concluded that the neurohypophyseal peptide receptor of the male mouse anococcygeus is of the oxytocin type; antagonist pA2 values suggest that this receptor resembles, but may not be identical to, the uterine oxytocin receptor. Possible physiological and pharmacological implications of these observations are discussed. PMID:3011170

  8. 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.

  9. A novel spectroscopic analysis to detect photochemical reaction of the bronchodilator - Doxofylline and its estimation in pharmaceutical formulation.

    PubMed

    Sasi Rekha, P; Gunasekaran, S

    2017-09-11

    Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy and safety of the formulated products during manufacture, storage and use. In this investigation, a novel spectroscopic approach has been adopted by employing the FTIR-ATR and UV/Visible techniques to detect the photochemical reactions of the drug Doxofylline, chemically designated as 7-(1, 3 dioxolane-2-yl methyl) theophylline, in its raw (pure) form. Significant changes were observed in terms of optical density of the absorption bands and a satisfactory analysis has been performed using ANOVA Statistics. It highlights the role of the photochemistry of drugs with respect to its spectral profiles and also explains photo physical processes. In addition; the drug compatibility study was also undertaken by using FTIR-ATR technique which indicated that there were no interactions occurring between the raw sample of the drug and the excipients used in the preparation of the pharmaceutical formulation. With this, UV-visible spectroscopic method was validated for the quantitative estimation of Doxofylline in pharmaceutical dosage forms and was performed with λmax at 274nm. Calibration curves were linear between the concentration range 10-50μg/ml. The various parameters such as linearity, precision, accuracy, recovery and specificity were studied according to ICH guidelines (Ahmed et al., 2016; Jain et al., 2011; ICH, 1996). Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 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

  11. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 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

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

    PubMed

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

    2016-08-23

    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.

  14. 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.

  15. 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

  16. Oxytocin-dependent consolation behavior in rodents.

    PubMed

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

    2016-01-22

    Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human. Copyright © 2016, American Association for the Advancement of Science.

  17. Oxytocin is an anabolic bone hormone

    PubMed Central

    Tamma, Roberto; Colaianni, Graziana; Zhu, Ling-ling; DiBenedetto, Adriana; Greco, Giovanni; Montemurro, Gabriella; Patano, Nicola; Strippoli, Maurizio; Vergari, Rosaria; Mancini, Lucia; Colucci, Silvia; Grano, Maria; Faccio, Roberta; Liu, Xuan; Li, Jianhua; Usmani, Sabah; Bachar, Marilyn; Bab, Itai; Nishimori, Katsuhiko; Young, Larry J.; Buettner, Christoph; Iqbal, Jameel; Sun, Li; Zaidi, Mone; Zallone, Alberta

    2009-01-01

    We report that oxytocin (OT), a primitive neurohypophyseal hormone, hitherto thought solely to modulate lactation and social bonding, is a direct regulator of bone mass. Deletion of OT or the OT receptor (Oxtr) in male or female mice causes osteoporosis resulting from reduced bone formation. Consistent with low bone formation, OT stimulates the differentiation of osteoblasts to a mineralizing phenotype by causing the up-regulation of BMP-2, which in turn controls Schnurri-2 and 3, Osterix, and ATF-4 expression. In contrast, OT has dual effects on the osteoclast. It stimulates osteoclast formation both directly, by activating NF-κB and MAP kinase signaling, and indirectly through the up-regulation of RANK-L. On the other hand, OT inhibits bone resorption by mature osteoclasts by triggering cytosolic Ca2+ release and NO synthesis. Together, the complementary genetic and pharmacologic approaches reveal OT as a novel anabolic regulator of bone mass, with potential implications for osteoporosis therapy. PMID:19369205

  18. Oxytocin is an anabolic bone hormone.

    PubMed

    Tamma, Roberto; Colaianni, Graziana; Zhu, Ling-ling; DiBenedetto, Adriana; Greco, Giovanni; Montemurro, Gabriella; Patano, Nicola; Strippoli, Maurizio; Vergari, Rosaria; Mancini, Lucia; Colucci, Silvia; Grano, Maria; Faccio, Roberta; Liu, Xuan; Li, Jianhua; Usmani, Sabah; Bachar, Marilyn; Bab, Itai; Nishimori, Katsuhiko; Young, Larry J; Buettner, Christoph; Iqbal, Jameel; Sun, Li; Zaidi, Mone; Zallone, Alberta

    2009-04-28

    We report that oxytocin (OT), a primitive neurohypophyseal hormone, hitherto thought solely to modulate lactation and social bonding, is a direct regulator of bone mass. Deletion of OT or the OT receptor (Oxtr) in male or female mice causes osteoporosis resulting from reduced bone formation. Consistent with low bone formation, OT stimulates the differentiation of osteoblasts to a mineralizing phenotype by causing the up-regulation of BMP-2, which in turn controls Schnurri-2 and 3, Osterix, and ATF-4 expression. In contrast, OT has dual effects on the osteoclast. It stimulates osteoclast formation both directly, by activating NF-kappaB and MAP kinase signaling, and indirectly through the up-regulation of RANK-L. On the other hand, OT inhibits bone resorption by mature osteoclasts by triggering cytosolic Ca(2+) release and NO synthesis. Together, the complementary genetic and pharmacologic approaches reveal OT as a novel anabolic regulator of bone mass, with potential implications for osteoporosis therapy.

  19. 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.

  20. 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.

  1. Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour.

    PubMed

    McDonald, S J; Prendiville, W J; Blair, E

    1993-11-06

    To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. Double blind, randomised controlled trial. Two metropolitan teaching hospitals in Perth, Western Australia. All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. Postpartum haemorrhage, nausea, vomiting, and increased blood pressure. 3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure. There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose