A single administration of carbetocin before electroejaculation increases the insemination doses produced from each ejaculate in rams.

The aim of the study was to determine the effect of carbetocin administration (a long-acting analog of oxytocin) 20 or 10 min before electroejaculation (EE) on the duration of semen collection procedure, quantitative and qualitative characteristics of the ejaculate, and stress biomarkers in rams. Semen was collected from 12 Corriedale rams (age, 2.5-5.5 years old) with EE, in a Latin-square design, administrating carbetocin (0.2 mg/100 kg of body weight i.v.) 20 or 10 min before EE, or without carbetocin administration (CB-20, CB-10, and CON treatments, respectively). Each treatment was applied to different rams every 3-4 days, allowing all the rams to receive all three treatments. Carbetocin administered 20 or 10 min before EE increased the number of sperm ejaculated (P = 0.01), the semen concentration (P = 0.02), the number of insemination doses collected in a single collection (P = 0.01), and the number of insemination doses collected/electrical pulses administered (P = 0.05) compared to control rams. Carbetocin administered 20 or 10 min before semen collection prolonged the time required for EE and the number of pulses administered during EE compared to CON rams (P < 0.03 for both). The CB-10 rams required the administration of more electrical pulses during ejaculation than CON rams (P = 0.001), and CB-20 treatment tended to require more electrical pulses than CON rams (P = 0.06). The volume of the ejaculate was greater in CB-10 than in CON rams (P = 0.01), and that of CB-20 treatment tended to be greater than CON rams (P = 0.08). The percentage of sperm with intact membrane was greater in CB-20 than in CON rams (P = 0.01). Total protein, albumin, and globulin concentrations were lower immediately after carbetocin administration 20 or 10 min before EE. The treatments did not affect cortisol concentration, glycemia, rectal and surface temperatures, heart rate, and facial expressions. Carbetocin administration before EE of rams improved the quantitative and qualitative characteristics of the ejaculate, duplicating the number of insemination doses collected. It can be a promising treatment to obtain a greater quantity of doses to inseminate with a lower frequency of semen collections, reducing the negative impacts of EE on animal welfare.

Hypothalamic Paraventricular Stimulation Inhibits Nociceptive Wide Dynamic Range Trigeminocervical Complex Cells via Oxytocinergic Transmission.

Oxytocinergic transmission blocks nociception at the peripheral, spinal, and supraspinal levels through the oxytocin receptor (OTR). Indeed, a neuronal pathway from the hypothalamic paraventricular nucleus (PVN) to the spinal cord and trigeminal nucleus caudalis (Sp5c) has been described. Hence, although the trigeminocervical complex (TCC), an anatomical area spanning the Sp5c, C1, and C2 regions, plays a role in some pain disorders associated with craniofacial structures (e.g., migraine), the role of oxytocinergic transmission in modulating nociception at this level has been poorly explored. Hence, in vivo electrophysiological recordings of TCC wide dynamic range (WDR) cells sensitive to stimulation of the periorbital or meningeal region were performed in male Wistar rats. PVN electrical stimulation diminished the neuronal firing evoked by periorbital or meningeal electrical stimulation; this inhibition was reversed by OTR antagonists administered locally. Accordingly, neuronal projections (using Fluoro-Ruby) from the PVN to the WDR cells filled with Neurobiotin were observed. Moreover, colocalization between OTR and calcitonin gene-related peptide (CGRP) or OTR and GABA was found near Neurobiotin-filled WDR cells. Retrograde neuronal tracers deposited at the meningeal (True-Blue, TB) and infraorbital nerves (Fluoro-Gold, FG) showed that at the trigeminal ganglion (TG), some cells were immunopositive to both fluorophores, suggesting that some TG cells send projections via the V1 and V2 trigeminal branches. Together, these data may imply that endogenous oxytocinergic transmission inhibits the nociceptive activity of second-order neurons via OTR activation in CGRPergic (primary afferent fibers) and GABAergic cells.

The influence of parity, body condition, litter size and carbetocin administration on colostrum production and immunoglobulin levels in highly productive sows within a tropical environment.

The aim of this study was to explore the factors contributing to colostrum production and the levels of colostrum immunoglobulins (IgG and IgA) in contemporary highly productive sows within a tropical climate. We focused on variables such as parity number, litter size, sow body condition score (BCS), the timing of sample collection following the commencement of farrowing and the use of carbetocin during the birthing process. A total of 100 colostrum samples were collected from a group of 50 Danish Landrace × Yorkshire crossbred sows. These samples were taken at two distinct time intervals: right after farrowing (0 h) and 6 h later. The colostrum samples were classified according to the sows' parity numbers, with 33 samples originating from primiparous sows and 67 from multiparous ones. Additionally, the number of live-born piglets were categorized into three groups: 7-13, 14-17 and ≥ 18 piglets per litter. Moreover, the samples were categorized based on the use of carbetocin during the birthing process, with 34 sows experiencing natural farrowing and 66 sows receiving carbetocin. The sow's BCS was assessed through visual evaluation and palpation. The piglet colostrum consumption and the amount of colostrum produced by the sows were determined. The concentrations of IgG and IgA were determined by using the enzyme-linked immunosorbent assay (ELISA) technique. On average, the colostrum production averaged 5.5 ± 1.7 kg, with IgG and IgA concentrations averaging 54.9 ± 24.6 mg/ml and 7.6 ± 3.5 mg/ml, respectively. Primiparous sows exhibited a significant 25.2% decrease in IgG concentration within 6 h of parturition (P < 0.05), whereas no such decline was observed in multiparous sows. Furthermore, multiparous sows displayed higher colostrum yields (6.2 ± 1.5 kg and 4.3 ± 1.5 kg, respectively, P < 0.001) and IgA concentrations compared to primiparous sows (8.3 ± 3.8 mg/ml and 6.3 ± 2.6 mg/ml, respectively, P = 0.002). Furthermore, a positive correlation was observed between IgA concentrations in colostrum and the sow's BCS at both the 0-h and 6-h post-farrowing time points (r = 0.425, P = 0.002 and r = 0.315, P = 0.031, respectively). The administration of carbetocin did not yield a significant impact on the concentrations of IgG and IgA in the sows' colostrum (P > 0.05). In conclusion, during the initial 6 h after birth, colostrum IgA levels remained stable, whereas there was a noticeable decline in IgG levels, particularly among primiparous sows. The production volume of colostrum and the concentration of IgA in sows within tropical conditions were influenced by both parity number and body condition score.

Delivery-Dependent Shift in Oxytocin-Responsive Cell Population in the Central Amygdala of the Female Rat.

INTRODUCTION: Despite its recent reputation as prosocial neurohormone, the most important physiological role of oxytocin (OT) is stimulating uterine contractions. Though it is well known that plasma OT concentrations change drastically during delivery, it remains unexplored whether and how OT receptors in the maternal brain are activated. We examined whether the responses of cells in the central amygdala (CeA), an OT receptor-rich limbic site involved in pain and fear memory regulation, to exogenously applied OT analogue, Thr-Gly-OT (TGOT), vary depending on delivery. METHODS: Intracellular Ca2+ dynamics of the CeA cells were visualized in brain slices from female rats at virgin (VG), during pregnancy term (PT) days 16-21, within 24 h after delivery (G0), and within 1-3 days after delivery (G3). The Ca2+ responses to 1 µM TGOT, 20 mM KCl (high K), and 300 µM ADP were compared. RESULTS: We found that fraction of cells responding to TGOT, high K, and ADP differed significantly between the four delivery-associated terms. In particular, the fraction of cells responding to TGOT (TGOT responders) significantly increased from VG and PT at G0 and G3. Furthermore, the significant positive correlation between TGOT and high K response in TGOT and high K responders was reduced at G0, while that between TGOT and ADP responses in TGOT and ADP responders was increased at G0. CONCLUSION: These results indicate that the responses of CeA cells to an OT receptor agonist markedly change around delivery, which might play a role in controlling the labor-related pain and post-delivery emotional complications.

Is there a role for carbetocin in the prophylaxis of postpartum obstetric haemorrhage?

Postpartum haemorrhage is a common complication of pregnancy, most commonly due to uterine atony. Uterotonics have a vital role in preventing postpartum haemorrhage but the choice of the most effective agent with the fewest adverse effects is a subject of debate. Carbetocin, a synthetic analogue of oxytocin has been available in the UK since 2007 but is not currently widely used. It has a longer duration of action than oxytocin, which avoids the need for an infusion and as it is heat-stable it can be stored at room temperature. Current UK clinical guidelines, based on the results of older meta-analyses, do not recommend carbetocin as a first-line agent. A Cochrane review, published in 2018, ranked carbetocin in the top three drug regimens for preventing postpartum haemorrhage and an international consensus statement on uterotonic use for caesarean birth concluded that carbetocin may become the preferred drug for caesarean birth, by reducing the need for additional uterotonics. The higher cost of carbetocin when compared with oxytocin is a limiting factor, but the significant healthcare costs of a postpartum haemorrhage and the physiological impact of this event suggests it a reasonable alternative to consider, especially if ergometrine is contraindicated or in those who are undergoing a caesarean birth or are at high risk of bleeding.

Teleost Nonapeptides, Isotocin and Vasotocin Administration Released the Milt by Abdominal Massage in Male Catfish, Clarias magur.

In the present work the nonapeptides i.e., isotocin and vasotocin alone or in a combination were tested in C. magur to evaluate their effect on stripping by abdominal massage. Also, we used chitosan-carbon nanotube nanocomposites to conjugate the nonapetides isotocin (abbreviated as COOH-SWCNTCSPeP) and isotocin and vasotocin (COOH-SWCNTCSPePs) with the aim of sustaining the effect for a longer duration. The conjugation of nonapeptides with nanocomposites was confirmed by Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). Two experiments were conducted to study the effect of naked (without nanoparticles) and conjugated nonapeptides on the milt release by stripping. Both the experiments consisted of eight treatments which included four naked groups two nanoconjugated groups and two controls. Both naked and nonconjugated formulations were successful in stripping the male catfish. The mRNA expression of selected reproductive genes was analysed to decipher the effect of nanopeptides at the molecular level. Nonapeptide treatment either naked or nanoconjugated, resulted in the upregulation of the transcript level of genes. Histological analysis revealed the concentration of spermatozoa was more in peptide injected groups than in the controls. The synergistic effects of nonapeptides and Ovatide had a positive impact on GSI. Thus, the present formulations were successful in stripping the male catfish to obtain the milt with significant reproductive success. Even though the naked groups perform better but the number of males required to fertilize the eggs in nanoconjuagted groups was smaller making it worth using for the delivery of nonapeptides.

Effect of Carbetocin on Postpartum Hemorrhage after Vaginal Delivery: A Meta-Analysis.

Background: The efficacy of oxytocin and carbetocin in preventing postpartum hemorrhage (PPH) in women with vaginal delivery has been controversial. This study is aimed at conducting a meta-analysis that compares the efficacy of carbetocin and oxytocin in the prevention of PPH among women with vaginal delivery. Methods: Literature was retrieved from PubMed, Medline, Embase, CENTRAL, and CNKI databases. The randomized controlled trials (RCTs) that compare the efficacy of carbetocin and oxytocin to prevent PPH were searched. Data from the included literatures were extracted by two researchers, including author, title, publication date, study type, study number, the incidence of PPH, number of patients requiring additional uterotonics, and number of patients requiring blood transfusion. Jadad scale was used to evaluate the quality of the included RCTs. The Chi-square test was adopted for the heterogeneity test. A fixed-effect model was used for analysis if heterogeneity did not exist between literatures. If heterogeneity exists between literatures, a random-effect model was used for analysis. The source of heterogeneity was explored by subgroup analysis and sensitivity analysis. Results: The incidence of PPH in the carbetocin group was lower than that in the oxytocin group (OR = 0.62, 95% CI (0.46, 0.84), Z = 3.14, P = 0.002). There was no heterogeneity among studies (χ 2 = 7.29, P = 0.12, I 2 = 45%) and no significant publication bias (P > 0.05). The proportion of women requiring additional uterotonics in the carbetocin group was lower than that in the oxytocin group (OR = 0.41, 95% CI (0.29, 0.56), Z = 5.34, P < 0.00001). There was no heterogeneity among studies (χ 2 = 0.82, P = 0.84, I 2 = 0%) and no significant publication bias (P > 0.05). There was no significant difference in the proportion of women needing blood transfusion between the carbetocin group and the oxytocin group (OR = 0.92, 95% CI (0.66, 1.29), Z = 0.46, P = 0.64). There was no heterogeneity among studies (χ 2 = 3.06, P = 0.55, I 2 = 0%) and no significant publication bias (P > 0.05). Conclusion: Carbetocin is superior to oxytocin in preventing PPH among women with vaginal delivery and can be widely used in clinical practice.

Circulating isotocin, not angiotensin II, is the major dipsogenic hormone in eels.

Angiotensin II (AngII) is generally known as the most important dipsogenic hormone throughout vertebrates, while two other neurohypophysial hormones, vasopressin and oxytocin, are not dipsogenic in mammals. In this study, we found that systemic isotocin, but not vasotocin, is the potent dipsogenic hormone in eels. When injected intra-arterially into conscious eels, isotocin, vasotocin and AngII equally increased ventral aortic pressure dose dependently at 0.03-1.0 nmol kg-1, but only isotocin induced copious drinking. The dipsogenic effect was dose dependent and occurred significantly at as low as 0.1 nmol kg-1. By contrast, a sustained inhibition of drinking occurred after AngII injection, probably due to baroreflexogenic inhibition. No such inhibition was observed after isotocin injection despite similar concurrent hypertension. The baroreceptor may exist distal to the gill circulation because the vasopressor effect occurred at both ventral and dorsal aorta after AngII but only at ventral aorta after isotocin. By contrast, intra-cerebroventricular (i.c.v.) injection of isotocin had no effect on drinking or blood pressure, but AngII increased drinking and aortic pressure dose dependently at 0.03-0.3 nmol per eel. Lesioning of the area postrema (AP), a sensory circumventricular organ, abolished drinking induced by peripheral isotocin, but not i.c.v. AngII. Collectively, isotocin seems to be a major circulating hormone that induces swallowing through its action on the AP, while AngII may be an intrinsic brain peptide that induces drinking through its action on a different circumventricular site, possibly a recently identified blood-brain barrier-deficient structure in the antero-ventral third ventricle of eels, as shown in birds and mammals.

An Octopus-Derived Peptide with Antidiuretic Activity in Rats.

Discovering new drug candidates with high efficacy and few side effects is a major challenge in new drug development. The two evolutionarily related peptides oxytocin (OXT) and arginine vasopressin (AVP) are known to be associated with a variety of physiological and psychological processes via the association of OXT with three types of AVP receptors. Over decades, many synthetic analogs of these peptides have been designed and tested for therapeutic applications; however, only a few studies of their natural analogs have been performed. In this study, we investigated the bioactivity and usefulness of two natural OXT/AVP analogs that originate from the marine invertebrate Octopus vulgaris, named octopressin (OTP) and cephalotocin (CPT). By measuring the intracellular Ca2+ or cyclic AMP increase in each OXT/AVP receptor subtype-overexpressing cell, we found that CPT, but not OTP, acts as a selective agonist of human AVP type 1b and 2 receptors. This behavior is reminiscent of desmopressin, the most widely prescribed antidiuretic drug in the world. Similar to the case for desmopressin, a single intravenous tail injection of CPT into Sprague-Dawley rats reduced urine output and increased urinary osmolality. In conclusion, we suggest that CPT has a significant antidiuretic effect and that CPT might be beneficial for treating urological conditions such as nocturia, enuresis, and diabetes insipidus.

The neural distribution of the avian homologue of oxytocin, mesotocin, in two songbird species, the zebra finch and the canary: A potential role in song perception and production.

The avian homologue of oxytocin (OT), formerly called mesotocin, influences social behaviors in songbirds and potentially song production. We sought to characterize the distribution of OT peptide in the brain of two songbird species: canaries (Serinus canaria) and zebra finches (Taeniopygia guttata). To visualize OT, we performed immunocytochemistry using an antibody previously shown to identify OT in avian species. In both canaries and zebra finches, dense OT-ir perikarya were located in the paraventricular nucleus (PVN), preoptic area (POA), supraoptic nucleus (SON), and medial bed nucleus of the stria terminalis (BNSTm). We also observed morphologically distinct OT-ir cells scattered throughout the mesopallium. OT-ir fibers were observed in the PVN, ventral medial hypothalamus (VMH), periaqueductal gray (PAG), intercollicular nucleus (ICo), and ventral tegmental area (VTA). We also observed punctate OT-ir fibers in the song control nucleus HVC. In both male and female canaries, OT-ir fibers were present in the lateral septum (LS), but innervation was greater in males. We did not observe this sex difference in zebra finches. Much of the OT staining observed is consistent with general distributions within the vertebrate hypothalamus, indicating a possible conserved function. However, some extra-hypothalamic distributions, such as perikarya in the mesopallium, may be specific to songbirds and play a role in song perception and production. The presence of OT-ir fibers in HVC and song control nuclei projecting dopaminergic regions provides anatomical evidence in support of the idea that OT can influence singing behavior-either directly via HVC or indirectly via the PAG, VTA, or POA.

Implementing Heat-Stable Carbetocin for Postpartum Haemorrhage Prevention in Low-Resource Settings: A Rapid Scoping Review.

Heat-stable carbetocin (HSC), a long-acting oxytocin analogue that does not require cold-chain transportation and storage, is effective in preventing postpartum haemorrhage (PPH) in vaginal and caesarean deliveries in tertiary-care settings. We aimed to identify literature documenting how it is implemented in resource-limited and lower-level maternity care settings to inform policies and practices that enable its introduction in these contexts. A rapid scoping review was conducted with an 8-week timeframe by two reviewers. MEDLINE, EMBASE, Emcare, the Joanna Briggs Institute Evidence-Based Practice Database, the Maternity and Infant Care Database, and the Cochrane Library were searched for publications in English, French, and Spanish from January 2011 to September 2021. Randomized and non-randomized studies examining the feasibility, acceptability, and health system considerations in low-income and lower-middle-income countries were included. Relevant data were extracted using pretested forms, and results were synthesized descriptively. The search identified 62 citations, of which 12 met the eligibility criteria. The review did not retrieve studies focusing on acceptability and health system considerations to inform HSC implementation in low-resource settings. There were no studies located in rural or lower-level maternity settings. Two economic evaluations concluded that HSC is not feasible in terms of cost-effectiveness in lower-middle-income economies with private sector pricing, and a third one found superior care costs in births with PPH than without. The other nine studies focused on demonstrating HSC effectiveness for PPH prevention in tertiary hospital settings. There is a lack of evidence on the feasibility (beyond cost-effectiveness), acceptability, and health system considerations related to implementing HSC in resource-constrained and lower-level maternity facilities. Further implementation research is needed to help decision-makers and practitioners offer an HSC-inclusive intervention package to prevent excessive bleeding among pregnant women living in settings where oxytocin is not available or of dubious quality.

Comparison of carbetocin as a bolus or an infusion with prophylactic phenylephrine on maternal heart rate during Cesarean delivery under spinal anesthesia: a double-blinded randomized controlled trial.

PURPOSE: Carbetocin, an oxytocin analog, given as a postpartum hemorrhage prophylaxis in elective Cesarean deliveries, frequently causes tachycardia and hypotension. Phenylephrine infusion has been shown to prevent spinal anesthesia-induced hypotension. The goal of this study was to evaluate if a slow infusion of carbetocin would reduce maternal heart rate variation and hemodynamic disturbances compared with a rapid bolus in parturients receiving a prophylactic phenylephrine infusion during elective Cesarean delivery. METHODS: In this double-blinded randomized controlled trial, 70 healthy parturients were allocated to either a bolus group or an infusion group. At cord clamping, participants in the bolus group received carbetocin 100 µg as a rapid intravenous bolus, while participants in the infusion group received carbetocin 100 µg over 10 min. The primary outcome was the variation in maternal heart rate from baseline during the 20 min following cord clamping. Secondary outcomes included blood pressure, cardiac output, and stroke volume variations during the study period, measured with the ClearSight™ hemodynamic monitor. RESULTS: Maximum heart rate variation was not different between the groups: bolus group, mean (standard deviation) 29.8 (25.2)% vs infusion group, 27.2 (23.3)%; P = 0.67. The increase in heart rate occurred significantly earlier in the bolus group than in the infusion group (median [interquartile range] time, 105 [69-570] sec vs 485 [255-762] sec; P = 0.02; group × time interaction: two-way repeated measures ANOVA, P = 0.04). There was no significant difference in maximum variations for the other hemodynamic parameters between the groups. CONCLUSION: Carbetocin infused over ten minutes did not reduce the magnitude of maternal heart rate variation but delayed its occurrence. This finding could be relevant to the anesthesiologist caring for parturients in whom a slight increase in maternal heart rate is clinically undesirable. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03404544); registered 19 January 2018.

RéSUMé: OBJECTIF: Lorsque la carbétocine, un analogue de l'ocytocine, est administrée à titre de prophylaxie pour les hémorragies du post-partum dans les accouchements par césarienne programmée, cet agent provoque fréquemment une tachycardie et une hypotension. Il a été démontré qu'une perfusion de phényléphrine prévenait l'hypotension induite par la rachianesthésie. L'objectif de cette étude était d'évaluer si une perfusion lente de carbétocine réduirait la variation de fréquence cardiaque maternelle et les perturbations hémodynamiques par rapport à un bolus rapide chez les parturientes recevant une perfusion prophylactique de phényléphrine pendant un accouchement par césarienne programmée. MéTHODE: Dans cette étude randomisée contrôlée à double insu, 70 parturientes en bonne santé ont été allouées à un groupe bolus ou à un groupe perfusion. Lors du clampage du cordon, les participantes du groupe bolus ont reçu 100 µg de carbétocine sous forme de bolus intraveineux rapide, tandis que les participantes du groupe perfusion ont reçu 100 µg de carbétocine sur dix minutes. Le critère d'évaluation principal était la variation de la fréquence cardiaque maternelle par rapport aux valeurs de base au cours des 20 minutes suivant le clampage du cordon. Les critères secondaires comprenaient la tension artérielle, le débit cardiaque et les variations du volume d'éjection au cours de la période d'étude, tels que mesurés avec le moniteur hémodynamique ClearSight™. RéSULTATS: La variation maximale de fréquence cardiaque n'était pas différente entre les groupes : groupe bolus, moyenne (écart type) 29,8 (25,2) % vs groupe perfusion, 27,2 (23,3) %; P = 0,67. L'augmentation de la fréquence cardiaque s'est produite significativement plus tôt dans le groupe bolus que dans le groupe perfusion (temps médian [écart interquartile], 105 [69-570] sec vs 485 [255-762] sec; P = 0,02;× interaction groupe x temps : ANOVA bidirectionnelle à mesures répétées, P = 0,04). Il n'y avait pas de différence significative dans les variations maximales pour les autres paramètres hémodynamiques entre les groupes. CONCLUSION: La carbétocine perfusée pendant dix minutes n'a pas réduit l'ampleur de la variation de la fréquence cardiaque maternelle, mais a retardé son apparition. Cette découverte pourrait être pertinente pour l'anesthésiologiste qui prend soin de parturientes chez qui une légère augmentation de la fréquence cardiaque maternelle serait cliniquement indésirable. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03404544); enregistrée le 19 janvier 2018.

Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 µg; carbetocin 100 µg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 µg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 µg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 µg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 µg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.

Measurement of urinary mesotocin in large-billed crows by enzyme-linked immunosorbent assay.

Mesotocin (MT) is an avian homologue of oxytocin (OT). Behavioral pharmacological studies in birds have suggested the involvement of MT in socially affiliative behavior. However, investigations of peripheral MT levels associated with social behavior are lacking because non-invasive methods to measure surrogate plasma MT have yet to be established. This study aimed to measure urinary MT in crows using a commercially available OT enzyme-linked immunosorbent assay kit. Urine samples were collected after intravenous injection of MT and centrifuged to separate urine and fecal components. We found that urinary MT was significantly elevated 15-30 min after MT injection. These results validate our method for the use of urine samples for the measurement of peripheral MT levels in crows.

Non-invasive method of obtaining milk from mice using carbetocin, a synthetic analogue of oxytocin.

INTRODUCTION: The mouse is an important laboratory animal in pharmacological and toxicological research. However, there is a limited ability to analyse the penetration of tested substances in mouse breastmilk, which is technically difficult to obtain in sufficient quantities. The aim of the study is to verify the use of carbetocin for this purpose. METHODS: The effect of carbetocin (20 and 40 µg per animal) was tested in nursing ICR females that had milk collected for 15 min, started 1.5 min after administration. At a higher dose, carbetocin was also tested with a 20-min collection, started 7 min after application. Oxytocin (2 IU per animal) and saline were used as positive and negative controls, respectively. RESULTS: Milk yield using a lower dose of carbetocin was comparable to oxytocin. However, the duration of action of carbetocin was longer than that of oxytocin. A higher doses of carbetocin resulted in significantly higher milk volumes. DISCUSSION: The use of carbetocin has proven to be an effective non-invasive method to obtain up to 0.89 g of milk from one mouse in 20 min.

Cost-effectiveness analysis of carbetocin versus oxytocin for the prevention of postpartum hemorrhage following vaginal birth in the United Kingdom.

AIMS: To assess the cost-effectiveness of carbetocin versus oxytocin for the prevention of postpartum hemorrhage (PPH) following vaginal birth from the perspective of the UK National Health Service (NHS). MATERIALS AND METHODS: A decision tree model was designed to analyze the cost per PPH event avoided associated with utilizing carbetocin versus oxytocin for prophylactic treatment of PPH in women following vaginal birth from a UK perspective. It modelled the potential for women to require an additional uterotonic after prophylaxis, and to still experience a PPH event and receive associated treatment. Inpatient recovery and follow-up periods post-PPH were also included in the model. Costs associated with drug acquisition and administration, PPH management (i.e. additional staffing and possible operating theater and high dependency unit utilization), inpatient hospitalization, and follow-up visits were all considered. Adverse event management costs were not included. Resource utilization varied depending on the severity of the PPH event (as defined by the amount of blood lost). PPH events avoided were estimated. In an exploratory analysis, quality adjusted life years (QALYs) were estimated as well. RESULTS: In the deterministic base case, costs were £55 lower and PPH events were 0.0342 lower per woman with carbetocin use compared to oxytocin use. Across the cohort of 100 women the reduction in PPH events led to the largest cost savings (£4,233 saved) out of all cost categories, with total cost savings of £5,495. Carbetocin utilization amongst the entire cohort led to 3.42 avoided PPH events compared to oxytocin utilization, comprised of 3.03 fewer mild/moderate PPH events and 0.39 fewer severe PPH events. Carbetocin utilization led to 0.0001 additional QALYs per woman. CONCLUSION: Carbetocin utilization leads to lower prophylactic treatment costs and less PPH events versus oxytocin when utilized for the prevention of PPH following vaginal birth in the UK.

Efficacy of Carbetocin versus Oxytocin for the Prevention of Primary Post Partum Haemorrhage after Caesarean Section in Mymensingh Medical College Hospital, Bangladesh.

Prevention of postpartum haemorrhage has been a major issue for its life threatening impact on maternal morbidity and mortality worldwide. Conventional continuous infusion of oxytocin has been employed for this condition. Apparently, in place of conventional oxytocics, application of carbetocin with longer half-life shows the same clinical benefits. This requires doing this present study. To compare the effectiveness of I/V bolus cabetocin and oxytocin infusion used for prevention of primary PPH after caesarean section. This descriptive cross-sectional comparative study was carried out in Department of Obstetrics and Gynaecology, Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from November 2015 to April 2016. A total of 100 pregnant women undergoing elective or emergency caesarean section were enrolled and divided into two groups on the basis of exclusion and inclusion criteria. Group I (n=50) received bolus of 100µgm IV carbetocin after delivery of the baby & Group II (n=50) received 20 IU of oxytocin in 1000ml of Hartman solution I/V in 8 hours continuous infusion after delivery of the baby. Baseline demographic and obstetric profile, indications for C/S, estimated blood loss, hemoglobin level, additional uterotonic agents, blood pressure and the diuresis were compared immediate postoperatively and 24 hours after operation. The patients were followed up for 24 hours after operation regarding outcomes variables. Baseline profiles were similar between two groups. Regarding haemodynamic effects, both drugs have a hypotensive effect but a greater reduction in blood pressure is found in oxytocin group. There was no significant difference in respect of estimated blood loss, blood transfusion, additional oxytocics and diuresis between two groups. It can be concluded that a single injection of carbetocin is as effective as continuous oxytocin infusion to prevent postpartum haemorrhage, with similar haemodynamic profile. So, carbetocin as a uterotonic agent is an acceptable alternative for prevention of postpartum haemorhage after caesarean section.

Social partner cooperativeness influences brain oxytocin transcription in Trinidadian guppies (Poecilia reticulata).

For non-kin cooperation to be maintained, individuals need to respond adaptively to the cooperative behaviour of their social partners. Currently, however, little is known about the biological responses of individuals to experiencing cooperation. Here, we quantify the neuroregulatory response of Trinidadian guppies (Poecilia reticulata) experiencing cooperation or defection by examining the transcriptional response of the oxytocin gene (oxt; also known as isotocin), which has been implicated in cooperative decision-making. We exposed wild-caught females to social environments where partners either cooperated or defected during predator inspection, or to a control (non-predator inspection) context, and quantified the relative transcription of the oxt gene. We tested an experimental group, originating from a site where individuals are under high predation threat and have previous experience of large aquatic predators (HP), and a control group, where individuals are under low predation threat and naïve to large aquatic predators (LP). LP, but not HP, fish showed different behavioural responses to the behaviour of their social environment, cooperating with cooperative partners and defecting when paired with defecting ones. In HP, but not LP, fish brain mid-section oxt relative transcription varied depending on social partner behaviour. HP fish experiencing cooperation during predator inspection had lower oxt transcription than those experiencing defection. This effect was not present in the control population or in the control context, where the behaviour of social partners did not affect oxt transcription. Our findings provide insight into the neuromodulation underpinning behavioural responses to social experiences, and ultimately to the proximate mechanisms underlying social decision-making.

Effect of heat stable carbetocin vs oxytocin for preventing postpartum haemorrhage on post delivery hemoglobin-a randomized controlled trial.

OBJECTIVE: To compare the effect of heat-stable carbetocin 100 µg IM versus oxytocin 10 IU IM on post-delivery hemoglobin level. SETTING: Hospital based study in Southern India. POPULATION: Women delivering vaginally who were enrolled in the WHO CHAMPION trial in a single facility in India. WHO CHAMPION Trial was a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin with oxytocin administered immediately after vaginal birth in women across 23 sites in 10 countries. METHODS: This was a nested randomized controlled trial designed to compare the effect of heat-stable carbetocin 100 µg IM versus oxytocin 10 IU IM, administered within one minute of vaginal delivery of the baby for prevention of postpartum hemorrhage, on post-delivery 48-72 h hemoglobin level, adjusted for pre-delivery hemoglobin level. 1,799 women from one hospital in India participated in this study. RESULTS: Pre-delivery hemoglobin and postpartum blood loss were not significantly different between carbetocin and oxytocin. Post-delivery hemoglobin, unadjusted or adjusted for pre-delivery hemoglobin, was slightly lower for carbetocin (10.09 g/dL) compared to oxytocin (10.21) (p value of 0.0432). The drop in hemoglobin was slightly higher for carbetocin, although the difference was very small (1.2 g/dL for carbetocin, 1.1 g/dL for oxytocin) (p value of .0786). The proportion of participants with a drop in hemoglobin of 2 g/dL or more, adjusted for pre-delivery hemoglobin, was higher for carbetocin (RR = 1.29, 95% CI 1.02-1.63). From the regression coefficients it can be derived that post-delivery hemoglobin, adjusted for pre-delivery hemoglobin, decreases on average 0.12 g/dL for each dL of blood lost, for the two treatments combined. CONCLUSION: The present ancillary study showed that intramuscular administration of 100 µg of heat stable carbetocin can result in a slightly lower post-delivery hemoglobin, slightly higher drop and higher percentage of women having a drop of 2 g/dL or larger, compared to 10 IU of oxytocin.