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Lancet (London, England) Dec 2023Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity.
METHODS
STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091.
FINDINGS
Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population.
INTERPRETATION
Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin.
FUNDING
French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Oxytocin; Oxytocics; Labor, Induced; Labor, Obstetric; Morbidity
PubMed: 37952548
DOI: 10.1016/S0140-6736(23)01803-2 -
Journal of Periodontal Research Apr 2024The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of...
OBJECTIVE
The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis.
BACKGROUND DATA
Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen-reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature-induced periodontitis. Therefore, anti-inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease.
METHODS
We used an animal model of ligature-induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 μg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement-enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF-α levels in plasma were determined using specific rat enzyme-linked immunosorbent assays (ELISA). OXT receptors, IL-6, IL-1β, and TNF-α expression were determined in gingival tissues by semiquantitative or real-time PCR.
RESULTS
We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis-induced increased gum expression of oxytocin receptors, TNF-α, IL-6, and IL-1β (p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model.
CONCLUSIONS
Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature-induced periodontitis.
Topics: Rats; Male; Animals; Oxytocin; Tumor Necrosis Factor-alpha; Receptors, Oxytocin; Disease Models, Animal; Periodontitis; Gingiva; Alveolar Bone Loss; Alveolar Process; Inflammation Mediators
PubMed: 38226427
DOI: 10.1111/jre.13212 -
Neuroscience and Biobehavioral Reviews Jun 2024This review delves into the phenomenon of positive emotional contagion (PEC) in rodents, an area that remains relatively understudied compared to the well-explored realm... (Review)
Review
This review delves into the phenomenon of positive emotional contagion (PEC) in rodents, an area that remains relatively understudied compared to the well-explored realm of negative emotions such as fear or pain. Rodents exhibit clear preferences for individuals expressing positive emotions over neutral counterparts, underscoring the importance of detecting and responding to positive emotional signals from others. We thoroughly examine the adaptive function of PEC, highlighting its pivotal role in social learning and environmental adaptation. The developmental aspect of the ability to interpret positive emotions is explored, intricately linked to maternal care and social interactions, with oxytocin playing a central role in these processes. We discuss the potential involvement of the reward system and draw attention to persisting gaps in our understanding of the neural mechanisms governing PEC. Presenting a comprehensive overview of the existing literature, we focus on food-related protocols such as the Social Transmission of Food Preferences paradigm and tickling behaviour. Our review emphasizes the pressing need for further research to address lingering questions and advance our comprehension of positive emotional contagion.
Topics: Emotions; Animals; Humans; Social Behavior; Social Interaction; Social Learning; Behavior, Animal; Oxytocin
PubMed: 38614451
DOI: 10.1016/j.neubiorev.2024.105674 -
Neuroscience and Biobehavioral Reviews Aug 2023Oxytocin is gaining traction in the treatment of various substance use disorders (SUD). We performed a systematic review assessing the efficacy of oxytocin for treating... (Review)
Review
Oxytocin is gaining traction in the treatment of various substance use disorders (SUD). We performed a systematic review assessing the efficacy of oxytocin for treating different SUD. The electronic databases MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials examining the effects of oxytocin vs. placebo in SUD samples. Quality assessment was conducted using a Cochrane validated checklist. A total of 17 trials with unique samples were identified. These were conducted on participants with SUD involving alcohol (n = 5), opioids (n = 3), opioids and/or cocaine/other stimulants (n = 3), cannabis (n = 2), or nicotine (n = 4). Across the SUD-groups, oxytocin reduced withdrawal symptoms (3/5 trials), negative emotional states (4/11 trials), cravings (4/11 trials), cue-induced cravings (4/7 trials), and consumption (4/8 trials). Sixteen trials had an overall considerable risk of bias. In conclusion, although oxytocin showed some promising therapeutic effects, the findings are too inconsistent and the trials too heterogeneous to derive any firm conclusions. Sounder methodological and well-powered trials are warranted.
Topics: Humans; Oxytocin; Analgesics, Opioid; Substance-Related Disorders; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 37119993
DOI: 10.1016/j.neubiorev.2023.105185 -
Psychoneuroendocrinology Aug 2023Eating disorders continue to be a major public health issue and important cause of morbidity and premature mortality, particularly for young people. Yet in a concerning... (Review)
Review
Eating disorders continue to be a major public health issue and important cause of morbidity and premature mortality, particularly for young people. Yet in a concerning dialectic, this occurs in the context of an epidemic of obesity which, with its medical complications, constitutes another vexing public health challenge. While it is not an eating disorder per se obesity is often comorbid with eating disorders. Effective treatment for both eating disorders and obesity has proven to be elusive and in the search for novel therapeutic interventions, the prosocial, anxiolytic, brain plasticity and metabolic effects of oxytocin (OT) have been examined from this perspective. The availability of intranasal oxytocin (IN-OT) has led to a number of interventional treatment studies in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), their atypical and subclinical forms and in medical and psychiatric conditions co-occurring or comorbid with these, obesity with BED would be included here. The aim of this mini review is to collate recent findings on OT as a novel therapeutic intervention in eating disorders and obesity and to identify and address some of the knowledge gaps in the use of IN-OT. The wider clinical perspective utilised here might better address some of the gaps and identify future directions of research. Clearly much remains to be done for OT to fulfil its therapeutic promise in eating disorders. OT might yet be of therapeutic promise and will be appreciated where treatment advances have been hard to come by and prevention challenging for these disorders.
Topics: Humans; Anorexia Nervosa; Binge-Eating Disorder; Bulimia Nervosa; Feeding and Eating Disorders; Obesity; Oxytocin
PubMed: 37178641
DOI: 10.1016/j.psyneuen.2023.106290 -
Neuropeptides Oct 2023Neurodegeneration is progressive cell loss in specific neuronal populations, often resulting in clinical consequences with significant medical, societal, and economic... (Review)
Review
BACKGROUND
Neurodegeneration is progressive cell loss in specific neuronal populations, often resulting in clinical consequences with significant medical, societal, and economic implications. Because of its antioxidant, anti-inflammatory, and anti-apoptotic properties, oxytocin has been proposed as a potential neuroprotective and neurobehavioral therapeutic agent, including modulating mood disturbances and cognitive enchantment.
METHODS
Literature searches were conducted using the following databases Web of Science, PubMed, Elsevier Science Direct, Google Scholar, the Core Collection, and Cochrane from January 2000 to February 2023 for articles dealing with oxytocin neuroprotective properties in preventing or treating neurodegenerative disorders and diseases with a focus on oxidative stress, inflammation, and apoptosis/cell death.
RESULTS
The neuroprotective effects of oxytocin appears to be mediated by its anti-inflammatory properties, inhibition of neuro inflammation, activation of several antioxidant enzymes, inhibition of oxidative stress and free radical formation, activation of free radical scavengers, prevent of mitochondrial dysfunction, and inhibition of apoptosis.
CONCLUSION
Oxytocin acts as a neuroprotective agent by preventing neuro-apoptosis, neuro-inflammation, and neuronal oxidative stress, and by restoring mitochondrial function.
Topics: Humans; Antioxidants; Oxytocin; Oxidative Stress; Anti-Inflammatory Agents; Inflammation; Neuroprotective Agents; Apoptosis
PubMed: 37354708
DOI: 10.1016/j.npep.2023.102352 -
Journal of Neuroendocrinology Sep 2023Oxytocin is a peptide-hormone extensively studied for its multifaceted biological functions and has recently gained attention for its role in eating behavior, through... (Review)
Review
Oxytocin is a peptide-hormone extensively studied for its multifaceted biological functions and has recently gained attention for its role in eating behavior, through its action as an anorexigenic neuropeptide. Moreover, the gut microbiota is involved in oxytocinergic signaling through the brain-gut axis, specifically in the regulation of social behavior. The gut microbiota is also implicated in appetite regulation and is postulated to play a role in central regulation of hedonic eating. In this review, we provide an overview on oxytocin and its individual links with the microbiome, the homeostatic and non-homeostatic regulation of eating behavior as well as social behavior and stress.
Topics: Oxytocin; Feeding Behavior; Peptide Hormones; Neuropeptides; Appetite Regulation; Eating; Brain
PubMed: 36872624
DOI: 10.1111/jne.13243 -
Frontiers in Endocrinology 2023Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in...
INTRODUCTION
Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.
METHODS
Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.
RESULTS
The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.
DISCUSSION
In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.
Topics: Infant, Newborn; Female; Humans; Dinoprost; NF-kappa B; Calcium; Premature Birth; Cyclooxygenase 2; Myometrium; Inflammation; Obstetric Labor, Premature; Cytokines; RNA, Messenger
PubMed: 37547305
DOI: 10.3389/fendo.2023.1150125 -
The European Journal of Contraception &... Oct 2023To explore women's perception of the need for an ultrasound scan before medical abortion provided by telemedicine services.
PURPOSE
To explore women's perception of the need for an ultrasound scan before medical abortion provided by telemedicine services.
METHODS
We have analysed women's requests for medical abortion through the website www.womenonweb.org from the 1st of January 2019 to the 5th of October 2020. Before receiving abortion drugs for self-managed medical abortion, women received online counselling and were asked to complete an online survey on pre-abortion ultrasound scan and the reasons for having or not having one. The initial dataset included 62641 entries from 207 countries. Each entry corresponded to a person's request for medical abortion. Women reported only one or multiple reasons for not having a pre-abortion ultrasound scan.
RESULTS
Among 59648 women requesting a medical abortion, 45653 (76,54%) did not have any pre-abortion ultrasound scan and specified a reason for that. The countries with the highest rates of women not having a pre-abortion ultrasound scan were Thailand, Poland, Northern Ireland, Mexico, South Korea, Japan, Chile, Indonesia, Germany, and Brazil. The main reasons for not having a pre-abortion ultrasound scan were being confident regarding pregnancy length; and thus, no need for a scan stated by 10910/34390 women (31.7%), lack of resources stated by 10589/34390 women (30.8%), and privacy issues stated by 6472/34390 women (18.8%).
CONCLUSION
Most women opting for medical abortion through telemedicine did not undergo a pre-abortion ultrasound scan. The main reason stated was that women did not find it necessary, lack of resources and privacy issues.
Topics: Pregnancy; Female; Humans; Mifepristone; Misoprostol; Abortion, Induced; Northern Ireland; Surveys and Questionnaires
PubMed: 37698511
DOI: 10.1080/13625187.2023.2249158 -
Reproduction (Cambridge, England) Aug 2023Inappropriate uterine contractions are a matter of concern during pregnancy or menses. We identified the transient receptor potential melastatin 4 (TRPM4) ion channel as...
IN BRIEF
Inappropriate uterine contractions are a matter of concern during pregnancy or menses. We identified the transient receptor potential melastatin 4 (TRPM4) ion channel as a new actor in mouse uterine contractions highlighting this protein as a potential pharmacological target for a better control of myometrial activity.
ABSTRACT
Control of uterine contractions is of interest in the context of inappropriate myometrial activity during pregnancy and at time of delivery, but it is also a matter for menstrual pain. While several molecular determinants of myometrial contractions have been described, the complete distribution of roles to the various actors is far from understood. A key phenomenon is a variation in cytoplasmic Ca2+ which leads to the activation of calmodulin in smooth muscle and also in the phosphorylation of myosin allowing contraction. The Ca2+ - TRPM4 channel which is known to modulate Ca2+- fluxes in several cell types was shown to participate in vascular as well as detrusor muscle contraction. We thus designed a study to determine whether it also participates in myometrial contraction. Uterine rings were isolated from Trpm4+/+ and Trpm4-/- non-pregnant adult mice and contractions were recorded using an isometric force transducer. In basal conditions, spontaneous contractions were similar in both groups. Application of 9-phenanthrol, a pharmacological TRPM4 inhibitor, dose-dependently reduced contraction parameters in Trpm4+/+ rings with an IC50 around 2.10-6 mol/L. The effect of 9-phenanthrol was significantly reduced in Trpm4-/- rings. The effect of oxytocin was tested and was found to be stronger in Trpm4+/+ rings compared to Trpm4-/-. Under a constant stimulation by oxytocin, 9-phenanthrol still reduced contraction parameters in Trpm4+/+ rings with a smaller effect on Trpm4-/-. Altogether it indicates that TRPM4 participates in uterine contractions in mice and may thus be evaluated as a new target to control such contractions.
Topics: Female; Pregnancy; Mice; Animals; Uterine Contraction; Calcium; Oxytocin; TRPM Cation Channels; Myometrium
PubMed: 37204208
DOI: 10.1530/REP-22-0484