ResearchPad - oxytocin https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The Childbirth Experience Questionnaire (CEQ)—Validation of its use in a Danish-speaking population of new mothers stimulated with oxytocin during labour]]> https://www.researchpad.co/article/elastic_article_14579 When determining optimal treatment regimens, patient reported outcomes including satisfaction are increasingly appreciated. It is well established that the birth experience may affect the postnatal attachment to the newborn and the management of subsequent pregnancies and deliveries. As we have no robust validated Danish tool to evaluate the childbirth experience exists, we aimed to perform a transcultural adaptation of the Childbirth Experience Questionnaire (CEQ) to a Danish context.MethodsIn accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN), we translated the Swedish-CEQ to Danish. The Danish-CEQ was tested for content validity among 10 new mothers. In a population of women who have had their labour induced, we then assessed the electronic questionnaire for validity and reliability using factor analytical design, hypothesis testing, and internal consistency. Based on these data, we determined criterion and construct responsiveness in addition to floor and ceiling effects.ResultsThe content validation resulted in minor adjustments in two items. This improved the comprehensibility. The electronic questionnaire was completed by 377 of 495 women (76.2%). The original Swedish-CEQ was four-dimensional, however an exploratory factor analysis revealed a three-dimensional structure in our Danish population (Own capacity, Participation, and Professional support). Parous women, women who delivered vaginally, and women with a labour duration <12 hours had a higher score in each domain. The internal consistency (Cronbach’s alpha) ranged between 0.75 and 0.89 and the ICC between 0.68–0.93. We found ceiling effects of 57.6% in the domain Professional support and of 25.5% in the domain Participation.ConclusionThis study offers transcultural adaptation of the Swedish-CEQ to a Danish context. The 3-dimensional Danish-CEQ demonstrates construct validity and reliability. Our results revealed significant ceiling effect especially in the domain Professional support, which needs to be acknowledged when considering implementing the Danish-CEQ into trials and clinical practice. ]]> <![CDATA[Predicting resource-dependent maternal health outcomes at a referral hospital in Zanzibar using patient trajectories and mathematical modeling]]> https://www.researchpad.co/article/5c8823d5d5eed0c4846390ee

Poor intra-facility maternity care is a major contributor to maternal mortality in low- and middle-income countries. Close to 830 women die each day due to preventable maternal complications, partly due to the increasing number of women giving birth in health facilities that are not adequately resourced to manage growing patient populations. Barriers to adequate care during the ‘last mile’ of healthcare delivery are attributable to deficiencies at multiple levels: education, staff, medication, facilities, and delays in receiving care. Moreover, the scope and multi-scale interdependence of these factors make individual contributions of each challenging to analyze, particularly in settings where basic data registration is often lacking. To address this need, we have designed and implemented a novel systems-level and dynamic mathematical model that simulates the impact of hospital resource allocations on maternal mortality rates at Mnazi Mmoja Hospital (MMH), a referral hospital in Zanzibar, Tanzania. The purpose of this model is to provide a rigorous and flexible tool that enables hospital administrators and public health officials to quantitatively analyze the impact of resource constraints on patient outcomes within the maternity ward, and prioritize key areas for further human or capital investment. Currently, no such tool exists to assist administrators and policy makers with effective resource allocation and planning. This paper describes the structure and construct of the model, provides validation of the assumptions made with anonymized patient data and discusses the predictive capacity of our model. Application of the model to specific resource allocations, maternal treatment plans, and hospital loads at MMH indicates through quantitative results that medicine stocking schedules and staff allocations are key areas that can be addressed to reduce mortality by up to 5-fold. With data-driven evidence provided by the model, hospital staff, administration, and the local ministries of health can enact policy changes and implement targeted interventions to improve maternal health outcomes at MMH. While our model is able to determine specific gaps in resources and health care delivery specifically at MMH, the model should be viewed as an additional tool that may be used by other facilities seeking to analyze and improve maternal health outcomes in resource constrained environments.

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<![CDATA[The availability, prices and affordability of essential medicines in Malawi: A cross-sectional study]]> https://www.researchpad.co/article/5c6c75d2d5eed0c4843d025a

Introduction

The Malawian government recently introduced cost-covering consultation fees for self-referral patients in tertiary public hospitals. Previously, patients received medicines free of charge in government-owned health facilities, but must pay elsewhere. Before the government implements a payment policy in other areas of health care, it is important to investigate the prices, affordability and availability of essential medicines in Malawi.

Methods

Data on availability and prices of 50 essential medicines were collected in 44 health facilities in two major cities and two districts. These included 12 public facilities, 11 facilities of the Christian Health Association of Malawi (CHAM), nine retail pharmacies, eight wholesalers and four private clinics/hospitals. Price, availability and affordability were assessed based on the methodology developed by the World Health Organization and Health Action International, which compares local prices to international reference prices.

Results and discussion

The overall availability of medicines was 48.5% in public facilities, 71.1% in retail pharmacies, 62.9% in CHAM facilities and 57.5% in private clinics. The availability of essential medicines varied from 0% for ethosuximide to 100% for amoxicillin and cotrimoxazole tablets. Antibiotic formulations for adults were widely available, in contrast to the low availability of pediatric formulations. Several medicines for non-communicable diseases like sodium valproate, phenytoin, paraldehyde, captopril and simvastatin showed poor availability and affordability. The overall median price ratio compared to the international reference price was 1.11 for wholesalers, 2.54 in CHAM facilities, 2.70 in retail pharmacies, and 4.01 in private clinics, which is low compared to other countries. But nevertheless, for 18 out of 32 medicines assessed, the cost of one course exceeded the statutory minimum daily wage, making them unaffordable to a majority of the population. Therefore, continued provision of free public health care is still of critical importance for the foreseeable future until other financing mechanisms have been explored.

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<![CDATA[Interactive effects of OXTR and GAD1 on envy-associated behaviors and neural responses]]> https://www.researchpad.co/article/5c4243a2d5eed0c4845e0913

Inequity aversion (negative feelings induced by outcome differences between the self and other) plays a key role in human social behaviors. The neurotransmitters oxytocin and GABA have been implicated in neural responses to inequity. However, it remains poorly understood not only how individual genetic factors related to oxytocin and GABA affect the neural mechanisms behind inequity aversion, but also how these genes interact. To address these issues, we examined relationships between genotypes, behavioral decisions and brain activities during the ultimatum game. We identified interactive effects between the polymorphisms of the oxytocin receptor gene (OXTR) and glutamate decarboxylase 1 gene for GABA synthesis (GAD1) on envy aversion (i.e., disadvantageous inequity aversion) and on envy-induced activity in the dorsal ACC (dACC). Thus, our integrated approach suggested interactive genetic effects between OXTR and GAD1 on envy aversion and the underlying neural substrates.

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<![CDATA[Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism]]> https://www.researchpad.co/article/5c40f77dd5eed0c48438626a

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social interactions, difficulty with communication, and repetitive behavior patterns. In humans affected by ASD, there is a male pre-disposition towards the condition with a male to female ratio of 4:1. In part due to the complex etiology of ASD including genetic and environmental interplay, there are currently no available medical therapies to improve the social deficits of ASD. Studies in rodent models and humans have shown promising therapeutic effects of oxytocin in modulating social adaptation. One pharmacological approach to stimulating oxytocinergic activity is the melanocortin receptor 4 agonist Melanotan-II (MT-II). Notably the effects of oxytocin on environmental rodent autism models has not been investigated to date. We used a maternal immune activation (MIA) mouse model of autism to assess the therapeutic potential of MT-II on autism-like features in adult male mice. The male MIA mice exhibited autism-like features including impaired social behavioral metrics, diminished vocal communication, and increased repetitive behaviors. Continuous administration of MT-II to male MIA mice over a seven-day course resulted in rescue of social behavioral metrics. Normal background C57 male mice treated with MT-II showed no significant alteration in social behavioral metrics. Additionally, there was no change in anxiety-like or repetitive behaviors following MT-II treatment of normal C57 mice, though there was significant weight loss following subacute treatment. These data demonstrate MT-II as an effective agent for improving autism-like behavioral deficits in the adult male MIA mouse model of autism.

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<![CDATA[Variation in severe postpartum hemorrhage management: A national vignette-based study]]> https://www.researchpad.co/article/5c1c0ac6d5eed0c484426a7b

Objectives

To assess variations in management of severe postpartum hemorrhage: 1) between obstetricians in the same situation 2) by the same obstetrician in different situations.

Study design

A link to a vignette-based survey was emailed to obstetricians of 215 maternity units; the questionnaire asked them to report how they would manage the PPH described in 2 previously validated case-vignettes of different scenarios of severe PPH. Vignette 1 described a typical immediate, severe PPH, and vignette 2 a less typical case of severe but gradual PPH. They were constructed in 3 successive steps and included multiple-choice questions proposing several types of clinical practice options at each step. Variations in PPH were assessed in a descriptive analysis; agreement about management and its timing between vignette 1 and vignette 2 was assessed with the Kappa coefficient.

Results

Analysis of complete responses from 119 (43.4%) obstetricians from 53 (24.6%) maternity units showed delayed or inadequate management in both vignettes. While 82.3% and 83.2% of obstetricians (in vignettes 1 and 2, respectively) would administer oxytocin 15 minutes after PPH diagnosis, only 52.9% and 29.4% would alert other team members. Management by obstetricians of the two vignette situations was inconsistent in terms of choice of treatment and timing of almost all treatments.

Conclusion

Case vignettes demonstrated inadequate management as well as variations in management between obstetricians and in different PPH situations. Protocols or procedures are necessary in all maternity units to reduce the variations in practices that may explain a part of the delay in management that leads to PPH-related maternal mortality and morbidity.

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<![CDATA[Improved clinical management but not patient outcome in women with postpartum haemorrhage—An observational study of practical obstetric team training]]> https://www.researchpad.co/article/5bb530e440307c24312bb0b8

Objective

Postpartum haemorrhage (PPH) is the most common obstetric emergency. A well-established postpartum haemorrhage protocol in the labour ward is crucial for effective treatment. The aim of the study was to investigate if practical obstetric team training improves the patient outcome and clinical management of PPH.

Setting

The practical obstetric team training (PROBE) at Linköping University Hospital, Sweden, with approximate 3000 deliveries annually, was studied between the years of 2004–2011. Each team consisted of one or two midwives, one obstetrician or one junior doctor and one nurse assistant. Emergency obstetrics cases were trained in a simulation setting. PROBE was scheduled during work hours at an interval of 1.5 years.

Population

Pre-PROBE women (N = 419 were defined as all women with vaginal birth between the years of 2004–2007 with an estimated blood loss of ≥1000 ml within the first 24 hours of delivery. Post-PROBE women (N = 483) were defined as all women with vaginal birth between the years of 2008–2011 with an estimated blood loss of ≥1000 ml within the first 24 hours of delivery. The two groups were compared regarding blood loss parameters and management variables using retrospective data from medical records.

Results

No difference was observed in estimated blood loss, haemoglobin level, blood transfusions or the incidence of postpartum haemorrhage between the two groups. Post-PROBE women had more often secured venous access (p<0.001), monitoring of vital signs (p<0.001) and received fluid resuscitation (p<0.001) compared to pre-PROBE women. The use of uterine massage was also more common among the post-PROBE women compared with the pre-PROBE women (p<0.001).

Conclusion

PROBE improved clinical management but not patient outcome in women with postpartum haemorrhage in the labour ward. These new findings may have clinical implications since they confirm that training was effective concerning the management of postpartum haemorrhage. However, there is still no clear evidence that simulation training improve patient outcome in women with PPH.

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<![CDATA[Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects]]> https://www.researchpad.co/article/5b498f9a463d7e0897c6e016

Methylenedioxymethamphetamine (MDMA) increases oxytocin, empathy, and prosociality. Oxytocin plays a critical role in emotion processing and social behavior and has been shown to mediate the prosocial effects of MDMA in animals. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the oxytocin receptor (OXTR) may influence the emotional and social effects of MDMA in humans. The effects of common genetic variants of the OXTR (rs53576, rs1042778, and rs2254298 SNPs) on the emotional, empathogenic, and prosocial effects of MDMA were characterized in up to 132 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. In a subset of 53 subjects, MDMA produced significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. The rs53576 and rs225498 SNPs did not moderate the subjective effects of MDMA in up to 132 subjects. None of the SNPs moderated MDMA-induced impairments in negative facial emotion recognition or enhancements in emotional empathy in the Multifaceted Empathy Test in 69 subjects. MDMA significantly increased plasma oxytocin concentrations. MDMA and oxytocin concentrations did not differ between OXTR gene variants. The present results provide preliminary evidence that OXTR gene variations may modulate aspects of the prosocial subjective effects of MDMA in humans. However, interpretation should be cautious due to the small sample size. Additionally, OXTR SNPs did not moderate the subjective overall effect of MDMA (any drug effect) or feelings of “closeness to others”.

Trial registration: ClinicalTrials.gov: http://www.clinicaltrials.gov, No: NCT00886886, NCT00990067, NCT01136278, NCT01270672, NCT01386177, NCT01465685, NCT01771874, and NCT01951508.

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<![CDATA[Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces]]> https://www.researchpad.co/article/5989daa4ab0ee8fa60ba6d57

Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.

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<![CDATA[CSF and Blood Oxytocin Concentration Changes following Intranasal Delivery in Macaque]]> https://www.researchpad.co/article/5989db48ab0ee8fa60bd9205

Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

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<![CDATA[Using Misoprostol for Primary versus Secondary Prevention of Postpartum Haemorrhage – Do Costs Matter?]]> https://www.researchpad.co/article/5989da6cab0ee8fa60b93446

Background

Postpartum heammorrhage (PPH), defined as blood loss greater than or equal to 500 ml within 24 hours after birth, is the leading cause of maternal deaths globally and in India. Misoprostol is an important option for PPH management in setting where oxytocin (the gold standard for PPH prevention and treatment) in not available or not feasible to use. For the substantial number of deliveries which take place at home or at lower level heatlh facilities in India, misoprostol pills can be adminstered to prevent PPH. The standard approach using misoprostol is to administer it prophylactically as primary prevention (600 mcg). An alternative strategy could be to administer misoprostol only to those who are at high risk of having PPH i.e. as secondary prevention.

Methods

This study reports on the relative cost per person of a strategy involving primary versus secondary prevention of PPH using misoprostol. It is based on a randomized cluster trial that was conducted in Bijapur district in Karnataka, India between December 2011 and March 2014 among pregnant women to compare two community-level strategies for the prevention of PPH: primary and secondary. The analysis was conducted from the government perspective using an ingredient approach.

Results

The cluster trial showed that there were no significant differences in clinical outcomes between the two study arms. However, the results of the cost analysis show that there is a difference of INR 6 (US$ 0.1) per birth for implementing the strategies primary versus secondary prevention. In India where 14.9 million births take place at sub-centres and at home, this additional cost of INR 6 per birth translates to an additional cost of INR 94 (US$ 1.6) million to the government to implement the primary prevention compared to the secondary prevention strategy.

Conclusion

As clinical outcomes did not differ significantly between the two arms in the trial, taking into account the difference in costs and potential issues with sustainability, secondary prevention might be a more strategic option.

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<![CDATA[Effects of early postnatal environment on hypothalamic gene expression in OLETF rats]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be02f3

Previous reports have shown that the early postnatal environment has the ability to modify the obesity phenotype of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. To determine whether this early postnatal environment affects hypothalamic signaling systems involved in energy balance, OLETF pups and lean Long-Evans Tokushima Otsuka (LETO) pups were cross-fostered to same or opposite strain Dams (designated as LdLp: LETO pups with LETO dams; LdOp: OLETF pups with LETO dams; OdLp: LETO pups with OLETF dams; and OdOp: OLETF pups with OLETF dams). Hypothalamic gene expression was examined at postnatal day 23 (PND 23) and PND 90 as OdOp rats started to gain more body weight at PND 23 and developed obesity at PND 90 relative to lean control LdLp rats. On PND 23, neuropeptide Y (Npy) gene expression was significantly increased in the dorsomedial hypothalamus (DMH) in both LdOp and OdOp pups compared to LdLp pups. Maternal environment did not affect DMH Npy expression in LETO weanlings. On PND 90, maternal environment during the cross-fostering period had a major effect on DMH Npy expression. Levels were significantly increased in both OdOp and OdLp rats relative to those in LdOp rats and LdLp controls. Reduced expression of Npy in the DMH of LdOp rats was consistent with their reduction of body weight compared to OdOp rats. In contrast to DMH Npy, gene expression for Npy and proopiomelanocortin in the arcuate nucleus appeared to appropriately respond to alterations in body weight and plasma leptin levels. Levels of oxytocin gene expression in the paraventricular nucleus were lower in offspring raised by LETO dams apparently responding to the higher DMH NPY levels. Together, our results demonstrate effects of both genotype and early postnatal environment on obesity of OLETF rats and further suggest an important role of DMH NPY in the development of obesity of OLETF rats.

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<![CDATA[Deficiency of Antinociception and Excessive Grooming Induced by Acute Immobilization Stress in Per1 Mutant Mice]]> https://www.researchpad.co/article/5989daa3ab0ee8fa60ba6bb9

Acute stressors induce changes in numerous behavioral parameters through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Several important hormones in paraventricular nucleus of the hypothalamus (PVN) play the roles in these stress-induced reactions. Corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) and corticosterone are considered as molecular markers for stress-induced grooming behavior. Oxytocin in PVN is an essential modulator for stress-induced antinociception. The clock gene, Per1, has been identified as an effecter response to the acute stresses, but its function in neuroendocrine stress systems remains unclear. In the present study we observed the alterations in grooming and nociceptive behaviors induced by acute immobilization stress in Per1 mutant mice and other genotypes (wild types and Per2 mutant). The results displayed that stress elicited a more robust effect on grooming behavior in Per1 mutant mice than in other genotypes. Subsequently, the obvious stress-induced antinociception was observed in the wild-type and Per2 mutant mice, however, in Per1 mutant, this antinociceptive effects were partially-reversed (mechanical sensitivity), or over-reversed to hyperalgesia (thermal sensitivity). The real-time qPCR results showed that in PVN, there were stress-induced up-regulations of Crh, Avp and c-fos in all of genotypes; moreover, the expression change of Crh in Per1 mutant mice was much larger than in others. Another hormonal gene, Oxt, was up-regulated induced by stress in wild-type and Per2 mutant but not in Per1 mutant. In addition, the stress significantly elevated the serum corticosterone levels without genotype-dependent differences, and accordingly the glucocorticoid receptor gene, Nr3c1, expressed with a similar pattern in PVN of all strains. Taken together, the present study indicated that in acute stress treated Per1 mutant mice, there are abnormal hormonal responses in PVN, correlating with the aberrant performance of stress-induced behaviors. Therefore, our findings suggest a novel functional role of Per1 in neuroendocrine stress system, which further participates in analgesic regulation.

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<![CDATA[Novel Oxytocin Gene Expression in the Hindbrain Is Induced by Alcohol Exposure: Transgenic Zebrafish Enable Visualization of Sensitive Neurons]]> https://www.researchpad.co/article/5989dacbab0ee8fa60bb44f2

Background

Fetal Alcohol Spectrum Disorders (FASD) are a collection of disorders resulting from fetal ethanol exposure, which causes a wide range of physical, neurological and behavioral deficits including heightened susceptibility for alcoholism and addictive disorders. While a number of mechanisms have been proposed for how ethanol exposure disrupts brain development, with selective groups of neurons undergoing reduced proliferation, dysfunction and death, the induction of a new neurotransmitter phenotype by ethanol exposure has not yet been reported.

Principal Findings

The effects of embryonic and larval ethanol exposure on brain development were visually monitored using transgenic zebrafish expressing cell-specific green fluorescent protein (GFP) marker genes. Specific subsets of GFP-expressing neurons were highly sensitive to ethanol exposure, but only during defined developmental windows. In the med12 mutant, which affects the Mediator co-activator complex component Med12, exposure to lower concentrations of ethanol was sufficient to reduce GFP expression in transgenic embryos. In transgenic embryos and larva containing GFP driven by an oxytocin-like (oxtl) promoter, ethanol exposure dramatically up-regulated GFP expression in a small group of hindbrain neurons, while having no effect on expression in the neuroendocrine preoptic area.

Conclusions

Alcohol exposure during limited embryonic periods impedes the development of specific, identifiable groups of neurons, and the med12 mutation sensitizes these neurons to the deleterious effects of ethanol. In contrast, ethanol exposure induces oxtl expression in the hindbrain, a finding with profound implications for understanding alcoholism and other addictive disorders.

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<![CDATA[Oxytocin Motivates Non-Cooperation in Intergroup Conflict to Protect Vulnerable In-Group Members]]> https://www.researchpad.co/article/5989da79ab0ee8fa60b97b49

Intergroup conflict is often driven by an individual's motivation to protect oneself and fellow group members against the threat of out-group aggression, including the tendency to pre-empt out-group threat through a competitive approach. Here we link such defense-motivated competition to oxytocin, a hypothalamic neuropeptide involved in reproduction and social bonding. An intergroup conflict game was developed to disentangle whether oxytocin motivates competitive approach to protect (i) immediate self-interest, (ii) vulnerable in-group members, or (iii) both. Males self-administered oxytocin or placebo (double-blind placebo-controlled) and made decisions with financial consequences to themselves, their fellow in-group members, and a competing out-group. Game payoffs were manipulated between-subjects so that non-cooperation by the out-group had high vs. low impact on personal payoff (personal vulnerability), and high vs. low impact on payoff to fellow in-group members (in-group vulnerability). When personal vulnerability was high, non-cooperation was unaffected by treatment and in-group vulnerability. When personal vulnerability was low, however, in-group vulnerability motivated non-cooperation but only when males received oxytocin. Oxytocin fuels a defense-motivated competitive approach to protect vulnerable group members, even when personal fate is not at stake.

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<![CDATA[Long Chain Polyunsaturated Fatty Acids Alter Oxytocin Signaling and Receptor Density in Cultured Pregnant Human Myometrial Smooth Muscle Cells]]> https://www.researchpad.co/article/5989dac8ab0ee8fa60bb31fb

Epidemiological studies and interventional clinical trials indicate that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms are not well understood, prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor. In animal studies, modest DHA provision has been shown to reduce placental and uterine PGE2 and PGF, matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase activity. However, modulation of PG biosynthesis may not account for all the effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent mechanism of LC PUFA action using cultured pregnant human myometrial smooth muscle cells. Our goal was to characterize the effect of LC PUFA treatment on oxytocin signaling, a potent uterotonic hormone involved in labor. The addition of 10 µM–100 µM DHA or arachidonic acid (AA) to the culture media for 48 h resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA and AA significantly inhibited phosphatidylinositol turnover and [Ca2+]i mobilization with oxytocin stimulation compared to bovine serum albumin control and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor membrane concentration without altering binding affinity or rate of receptor internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation of oxytocin signaling and provide new insight into additional mechanisms pertaining to reports of dietary fish and fish oil consumption prolonging gestation.

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<![CDATA[Increased Serum Levels of Oxytocin in ‘Treatment Resistant Depression in Adolescents (TRDIA)’ Group]]> https://www.researchpad.co/article/5989db10ab0ee8fa60bcbeea

Objective

‘Treatment-resistant depression’ is depression that does not respond to an adequate regimen of evidence-based treatment. Treatment-resistant depression frequently becomes chronic. Children with treatment-resistant depression might also develop bipolar disorder (BD). The objective of this study was to determine whether serum levels of oxytocin (OXT) in treatment-resistant depression in adolescents (TRDIA) differ from non-treatment-resistant depression in adolescents (non-TRDIA) or controls. We also investigated the relationships between serum OXT levels and the clinical symptoms, severity, and familial histories of adolescent depressive patients.

Methods

We measured serum OXT levels: TRDIA (n = 10), non-TRDIA (n = 27), and age- and sex- matched, neurotypical controls (n = 25). Patients were evaluated using the Children’s Depression Rating Scale-Revised (CDRS-R) and the Depression Self-Rating Scale for Children-Japanese Version (DSRS-C-J). The patients were also assessed retrospectively using the following variables: familial history of major depressive disorder and BD (1st degree or 2nd degree), history of disruptive mood dysregulation disorder, recurrent depressive disorder (RDD), history of antidepressant activation.

Results

Serum levels of OXT among the TRDIA and non-TRDIA patients and controls differed significantly. Interestingly, the rates of a family history of BD (1st or 2nd degree), RDD and a history of antidepressant activation in our TRDIA group were significantly higher than those of the non-TRDIA group.

Conclusions

Serum levels of OXT may play a role in the pathophysiology of TRDIA.

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<![CDATA[Oxytocin and Vasopressin Involved in Restraint Water-Immersion Stress Mediated by Oxytocin Receptor and Vasopressin 1b Receptor in Rat Brain]]> https://www.researchpad.co/article/5989db34ab0ee8fa60bd29d9

Aims

Vasopressin (AVP) and oxytocin (OT) are considered to be related to gastric functions and the regulation of stress response. The present study was to study the role of vasopressinergic and oxytocinergic neurons during the restraint water-immersion stress.

Methods

Ten male Wistar rats were divided into two groups, control and RWIS for 1h. The brain sections were treated with a dual immunohistochemistry of Fos and oxytocin (OT) or vasopressin (AVP) or OT receptor or AVP 1b receptor (V1bR).

Results

(1) Fos-immunoreactive (Fos-IR) neurons dramatically increased in the hypothalamic paraventricular nucleus (PVN), the supraoptic nucleus (SON), the neucleus of solitary tract (NTS) and motor nucleus of the vagus (DMV) in the RWIS rats; (2) OT-immunoreactive (OT-IR) neurons were mainly observed in the medial magnocellular part of the PVN and the dorsal portion of the SON, while AVP-immunoreactive (AVP-IR) neurons mainly distributed in the magnocellular part of the PVN and the ventral portion of the SON. In the RWIS rats, Fos-IR neurons were indentified in 31% of OT-IR neurons and 40% of AVP-IR neurons in the PVN, while in the SON it represented 28%, 53% respectively; (3) V1bR-IR and OTR-IR neurons occupied all portions of the NTS and DMV. In the RWIS rats, more than 10% of OTR-IR and V1bR-IR neurons were activated in the DMV, while lower ratio in the NTS.

Conclusion

RWIS activates both oxytocinergic and vasopressinergic neurons in the PVN and SON, which may project to the NTS or DMV mediating the activity of the neurons by OTR and V1bR.

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<![CDATA[Mechanisms of the Anti-Obesity Effects of Oxytocin in Diet-Induced Obese Rats]]> https://www.researchpad.co/article/5989da84ab0ee8fa60b9bb0b

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.

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<![CDATA[Pregnancy-Associated Risk Factors of Postpartum Breast Cancer in Korea: A Nationwide Health Insurance Database Study]]> https://www.researchpad.co/article/5989d9efab0ee8fa60b6e068

Patients with postpartum breast cancer have been reported to have a poor prognosis. The present study aimed to evaluate the pregnancy-related risk factors of postpartum breast cancer in Korea. We collected patient data from the Korea National Health Insurance (KNHI) Claims Database of the Health Insurance Review and Assessment Service (HIRA) for the 2009–2013 period. We evaluated the pregnancy-related risk factors for postpartum breast cancer in two population groups. For Group 1 (women who had given birth during the 2010–2012 period), data on those who were diagnosed with breast cancer from childbirth to 1-year postpartum were extracted. For Group 2, we extracted the data of women who gave birth in 2010 and traced them until December 31, 2013. In Group 1, 1,384,551 deliveries and 317 postpartum breast cancer patients were recorded in Korea between January 1, 2010, and December 31, 2012. Women aged ≥35 years (Odds Ratio [OR], 2.003; 95% Confidence Interval [CI], 1.567–2.560) and those who gave birth via cesarean delivery (OR, 1.237; 95% CI, 0.986–1.553) were considered to be at a higher risk for breast cancer. Lower risk was noted in primiparous women (OR, 0.737; 95% CI, 0.585–0.928). In Group 2, the data of 457,924 women who gave birth in 2010 were traced until December 31, 2013. Among them, 655 patients were diagnosed with breast cancer, and age ≥35 years and cesarean delivery were associated with an higher risk of breast cancer, whereas primiparous status was associated with a lower risk of breast cancer. In conclusion, older age (≥35 years) and cesarean delivery are significant risk factors for postpartum breast cancer, and primiparous women have a lower risk of developing postpartum breast cancer.

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