Comparative study between oxytocin and combination of tranexamic acid and ethamsylate in reducing intra-operative bleeding during emergency and elective cesarean section after 38 weeks of normal pregnancy.

OBJECTIVE: Cesarean Section (CS) is associated with an increased risk of hemorrhage. Many drugs are used to decrease this risk. We aim to compare the combination of ethamsylate and tranexamic acid, oxytocin, and placebo in women undergoing CS. METHODS: We conducted a double-blinded, randomized, placebo-controlled trial between October and December 2020 in four university hospitals in Egypt. The study included all pregnant women in labor without any complications who accepted to participate in the study between October and December 2020. The participants were divided into three groups. The subjects were randomly allocated to receive either oxytocin (30 IU in 500 ml normal saline during cesarean section), combined one gram of tranexamic acid with 250 mg of ethamsylate once before skin incision, or distilled water. Our main outcome was the amount of blood loss during the operation. The secondary outcomes were the need for blood transfusion, hemoglobin and hematocrit changes, hospital stay, operative complications, and the need for a hysterectomy. The one-way ANCOVA test was used to compare the quantitative variables between the three groups while the Chi-square test was used to compare the qualitative variables. Post hoc analysis then was performed to compare the difference between every two groups regarding the quantitative variables. RESULTS: Our study included 300 patients who were divided equally into three groups. Tranexamic acid with ethamsylate showed the least intra-operative blood loss (605.34 ± 158.8 ml) compared to oxytocin (625.26 ± 144.06) and placebo (669.73 ± 170.69), P = 0.015. In post hoc analysis, only tranexamic acid with ethamsylate was effective in decreasing the blood loss compared to placebo (P = 0.013); however, oxytocin did not reduce blood loss compared to saline (P = 0.211) nor to tranexamic acid with ethamsylate (P = 1). Other outcomes and CS complications showed no significant difference between the three groups except for post-operative thrombosis which was significantly higher in the tranexamic and ethamsylate group, P < 0.00001 and the need for a hysterectomy which was significantly increased in the placebo group, P = 0.017. CONCLUSION: The combination of tranexamic acid and ethamsylate was significantly associated with the least amount of blood loss. However, in pairwise comparisons, only tranexamic acid with ethamsylate was significantly better than saline but not with oxytocin. Both oxytocin and tranexamic acid with ethamsylate were equally effective in reducing intra-operative blood loss and the risk of hysterectomy; however, tranexamic acid with ethamsylate increased the risk of thrombotic events. Further research with a larger number of participants is needed. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202009736186159 and was approved on 04/09/2020.

Oxytocin infusion rates for maintaining uterine tone during non-elective cesarean section in laboring patients: a randomized, controlled trial.

PURPOSE: Oxytocin infusions for uterine tone maintenance are recommended following initial low oxytocin doses during cesarean section. Very limited literature is available on the optimal infusion rates in laboring patients who have been earlier exposed to oxytocin. METHODS: 105 patients, having received oxytocin for induction/augmentation of labor, received oxytocin infusions at rates of 2.5 IU/h (Group 2.5), 5 IU/h (Group 5) or 10 IU/h (Group 10) following 3 IU slow bolus. The primary outcome measure was estimated intraoperative blood loss; secondary outcome measures included uterine tone adequacy, requirements for additional uterotonics, and any side effects. Minor postpartum hemorrhage (PPH) was defined as blood loss > 500 ml and major/severe hemorrhage as blood loss > 1000 ml. RESULTS: Group 10 had minimum blood loss (311.1 ± 44.9 ml) and uterotonic requirements compared to other groups (p < 0.001). Group 2.5 had maximum blood loss (549.4 ± 74.3 ml) and uterotonic requirements; Group 5 had intermediate values (402.0 ± 49.5 ml). Twenty-six patients in group 2.5 had minor PPH against only one in group 5 and none in group 10 (p < 0.001). No patient in either group had major PPH. The incidence of hypotension was higher in group 10 than in group 2.5 (p = 0.004). Nausea and vomiting were also more frequent in group 10 than in the other two groups. CONCLUSION: Oxytocin infusions at 5 IU/h and 10 IU/h are more effective in reducing blood loss and preventing PPH than 2.5 IU/h. The dose of 10 IU/h, although the most efficacious, is associated with a high incidence of side effects. Hence, further studies are needed to find out the optimal maintenance infusion rate of oxytocin during cesarean section in laboring patients who have received oxytocin earlier.

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

Oxytocin suppresses epithelial cell-derived cytokines production and alleviates intestinal inflammation in food allergy.

Food allergy is a growing healthcare problem worldwide, but prophylactic options and regulatory therapies are limited. Oxytocin (OXT), conventionally acknowledged as a hormone, was recently proven to have potent anti-inflammatory and immunomodulatory activities in certain diseases. Here, we reported the novel function and its underlying mechanisms of OXT on food allergy in vivo and in vitro. We showed that the levels of OXT were elevated in ovalbumin (OVA)-allergic mice and patients with food allergy. In HT-29 cells, OXT inhibited the production of the epithelial cell-derived cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 by suppressing NF-κB signaling, in which ß-arrestin2 participated. These functions of OXT were abolished by oxytocin receptor (OXTR) depletion. Treating OVA-induced BALB/c mice with OXT suppressed TSLP, IL-25 and IL-33 production and attenuated systemic anaphylaxis and intestinal inflammation. OXTR-/- mice showed extreme increases in TSLP, IL-25 and IL-33 levels as well as severe systemic anaphylaxis and intestinal inflammation. In conclusion, through OXTRs, OXT has a promising antiallergic effect on experimental food allergy by suppressing epithelial TSLP, IL-25 and IL-33 production via inhibiting NF-κB signaling and upregulating ß-arrestin2 expression. Our study provides a new therapeutic perspective for food allergy in humans.

Transcriptional profiling of equine endometrium before, during and after capsule disintegration during normal pregnancy and after oxytocin-induced luteostasis in non-pregnant mares.

The current study used RNA sequencing to determine transcriptional profiles of equine endometrium collected 14, 22, and 28 days after ovulation from pregnant mares. In addition, the transcriptomes of endometrial samples obtained 20 days after ovulation from pregnant mares, and from non-pregnant mares which displayed and failed to display extended luteal function following the administration of oxytocin, were determined and compared in order to delineate genes whose expressions depend on the presence of the conceptus as opposed to elevated progesterone alone. A mere fifty-five transcripts were differentially expressed between samples collected from mares at Day 22 and Day 28 of pregnancy. This likely reflects the longer-term exposure to a relatively constant, progesterone-dominated environment with little change in factors secreted by the conceptus that would affect endometrial gene expression. The complement system was amongst the canonical pathways significantly enriched in transcripts differentially expressed between Day 14 and Day 22/28 of pregnancy. The expression of complement components 7 and 8 was confirmed using in situ hybridization. The expression of SERPING1, an inhibitor of the complement system, was confirmed by immunohistochemistry. In line with the resumed capacity of the endometrium to produce prostaglandin, prostaglandin G/H synthase 1 was expressed at higher levels at Days 22 and 28 than at Day 14 of pregnancy. Our data suggest that this up-regulation is enhanced by the presence of the conceptus; samples obtained from mares at Day 20 of pregnancy had significantly higher levels of prostaglandin G/H synthase 1 transcript than mares with extended luteal function.

Effect of exogenous administration of oxytocin on postpartum follicular dynamics, oestrous rate and ovulation in Nili-Ravi buffaloes.

Based on different surveys, dairy farmers are concerned about extensive use of exogenous oxytocin in buffaloes, which is being held responsible for reproductive problems including irregular oestrous cycle and delayed ovulation. For these concerns, effects of oxytocin injection on postpartum follicular dynamics, postpartum oestrous interval (PEI), oestrous length, the interval from onset of estrus to ovulation and blood progesterone (P4) were studied in Nili-Ravi buffaloes. For this purpose, 23 animals within 1 week after calving were randomly divided into three groups: without oxytocin (CON; n = 7), 10 i.u. oxytocin (LOW; n = 8), 30 i.u. oxytocin - (HIGH; n = 8) and used to record the PEI for the study period of 154 days. At subsequent estrus, three buffaloes from each group (not served) were selected randomly to monitor two cycles for 6 weeks. Transrectal ultrasonography was performed to evaluate follicular and corpus luteum (CL) development, and blood sampling was done for progesterone (P4) analysis. These results revealed that postpartum oestrous interval (PEI) decreased significantly in oxytocin-treated groups. The number of small, medium and total follicles on the left ovary was significantly higher in the HIGH group. However, an overall number of small and total follicles on both right and left ovaries was significantly higher in CON and HIGH groups. On the other hand, there was no difference in the number of follicles on the right ovary among all treatment groups. The same was true for the size of pre-ovulatory follicles, CL, P4 concentrations and oestrous cycle length. The intervals from onset of estrus to ovulation and from standing estrus to ovulation were increased considerably in the HIGH group. It is concluded that exogenous oxytocin administration resulted in the shortening of PEI but triggered a delay in ovulation. Moreover, a higher dose of oxytocin could stimulate the growth of small, medium, and total follicles in postpartum Nili-Ravi buffaloes.

Analytical and physiological validation of an enzyme immunoassay to measure oxytocin in dog, wolf, and human urine samples.

Oxytocin (OT) promotes pro-sociality, bonding, and cooperation in a variety of species. Measuring oxytocin metabolite (OTM) concentrations in urine or saliva provides intriguing opportunities to study human and animal behaviour with minimal disturbance. However, a thorough validation of analytical methods and an assessment of the physiological significance of these measures are essential. We conducted an analytical validation of a commercial Enzyme Immunoassay (EIA; Arbor OT assay kit) to measure OTM concentrations in dog, wolf, and human urine samples. To test the assay's ability to detect changes in OTM concentrations, we administered oxytocin intranasally to 14 dogs. Assay performance with regard to parallelism was acceptable. Assay accuracy and extraction efficiency for dog and wolf samples were comparable to a previously validated assay (Enzo OT assay kit) but variation was smaller for human samples. Binding sensitivity and antibody specificity were better in the Arbor assay. Average OTM concentrations were more than twice as high as in comparable samples measured with the Enzo assay, highlighting a lack of comparability of absolute values between different assays. Changes in OTM concentrations after intranasal treatment were detected reliably. The Arbor assay met requirements of a "fit-for-purpose" validation with improvement of several parameters compared to the Enzo assay.

Oxytocin administration modulates the complex type of ultrasonic vocalisation of mice pups prenatally exposed to valproic acid.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by communication disability with no curative treatment. Maternal separation-induced ultrasonic vocalisation (USV) was widely used to assess communication disability between pups and dams. Particularly, USV calls in many genetically modified ASD model mice were altered. Previously, we demonstrated that mice pups exposed to valproic acid in utero (VPA pups) showed decreased number of USV calls on postnatal day 11 and were rescued by subcutaneous injection of oxytocin. However, the qualitative change of USV calls by oxytocin has not been evaluated in VPA pups. In the present study, we examined the duration of oxytocin effect and analysed the altered pattern of USV calls using VPA pups. The oxytocin administration increased the total number of USV calls and the effect persisted up to 120 min in VPA pups. The pattern analysis revealed that the increase in the number of complex calls also persisted up to 120 min. These results suggested that oxytocin had a prolonged effect on USV calls, mainly on complex calls, in VPA pup, showing that oxytocin could recover their social modality to respond to maternal separation.

Management of prolonged first stage of labour in a low-resource setting: lessons learnt from rural Malawi.

BACKGROUND: Caesarean sections without medical indication cause substantial maternal and perinatal ill-health, particularly in low-income countries where surgery is often less safe. In presence of adequate labour monitoring and by appropriate use of evidence-based interventions for prolonged first stage of labour, unnecessary caesarean sections can be avoided. We aim to describe the incidence of prolonged first stage of labour and the use of amniotomy and augmentation with oxytocin in a low-resource setting in Malawi. METHODS: Retrospective analysis of medical records and partographs of all women who gave birth in 2015 and 2016 in a rural mission hospital in Malawi. Primary outcomes were incidence of prolonged first stage of labour based on partograph tracings, caesarean section indications and utilization of amniotomy and oxytocin augmentation. RESULTS: Out of 3246 women who gave birth in the study period, 178 (5.2%) crossed the action line in the first stage of labour, of whom 21 (11.8%) received oxytocin to augment labour. In total, 645 women gave birth by caesarean section, of whom 241 (37.4%) with an indication 'prolonged first stage of labour'. Only 113 (46.9%) of them crossed the action line and in 71/241 (29.5%) membranes were still intact at the start of caesarean section. Excluding the 60 women with prior caesarean sections, 14/181 (7.7%) received oxytocin prior to caesarean section for augmentation of labour. CONCLUSION: The diagnosis prolonged first stage of labour was often made without being evident from labour tracings and two basic obstetric interventions to prevent caesarean section, amniotomy and labour augmentation with oxytocin, were underused.

Using shear wave elastography to assess uterine tonicity after vaginal delivery.

This study aims to evaluate the feasibility and clinical interest of shear wave elastography, by quantitatively estimating the baseline stiffness of the myometrium before and after placental expulsion. We conducted a prospective cohort study of women at term, without known risk factors for postpartum hemorrhage, who gave birth via spontaneous labor in our tertiary center. Myometrium tonicity was evaluated based on measurements of shear wave speed (SWS) in the anterior uterine corpus. All data points were collected by a single operator. Measurements were carried out at three different time points: after fetal delivery (T1), after placental delivery (T2) and 30 min after placental delivery (T3). Our primary objective was to assess the feasibility of this new imaging technique. Ten valid SWS measurements obtained at each of the three different time points were considered as a positive primary outcome. Our secondary objectives were to evaluate the difference in median myometrial shear wave velocity between each time point, as well as to determine the correlation between myometrial shear wave velocity and patients' characteristics. 38 women were recruited during the study period, of whom 34 met the study criteria. 1017 SWS measurements were obtained. The median time to perform measurements was 16 s for one value, and 2 min 56 s for ten. For 11 women (32%) it was not possible to achieve ten SWS at T1 as placental expulsion immediately followed the birth of the newborn. One patient experienced placental retention and only measurements at T1 were performed. For all other patients, we were successfully able to obtain all measures as intended. There was no difference in the mean shear wave speed between the three time points. After adjustments for confounders, we observed a significant correlation for total blood loss (correlation coefficient = - 0.26, p < 0.001, units of oxytocin (correlation coefficient = - 0.34, p = 0.03), and newborn weight (correlation coefficient = - 0.08, p = 0.001). It is feasible to assess uterine tonicity by shear wave imaging, after placental expulsion. We did not observe a variance in uterine tonicity between the three time points. Women who had higher blood loss, received more units of oxytocin and/or those with newborns of a higher weight exhibited lower shear wave speed measures.

Oxytocin and Misoprostol With Diclofenac in the Preparation for Magnetic Resonance-Guided High-Intensity Ultrasound Treatment of Symptomatic Uterine Fibroids: A Prospective Cohort Study.

Uterine fibroids (UFs) are very common benign tumors of the female reproductive tract. According to recent reports, magnetic resonance-guided high-intensity ultrasound (MR-HIFU) appears to be a well-tolerated and efficient treatment option for UFs. However, MR-HIFU still presents several limitations. The treatment is rarely associated with achieving complete non-perfused volume (NPV). Not all patients are qualified for a final procedure, and selected women obtain very good results in such treatment. The primary objective of this experimental study was to assess the effect of transvaginal misoprostol and intravenous oxytocin preparation on UF volume change, sonication time and NPV after MR-HIFU procedure in women of reproductive age with symptomatic UFs. Secondary outcomes included the effect on the peri-procedural effectiveness of misoprostol and oxytocin. This study enrolled 247 women with symptomatic UFs; based on gynecologic examinations and magnetic resonance imaging (MRI) scans, 128 women qualified for MR-HIFU without pharmacologic treatment, 57 women qualified for the misoprostol/diclofenac group and 62 women qualified for the oxytocin group. Pharmacologic pre-treatment improved NPV compared with non-pharmacologic treatment (average NPV: controls 61.9% ± 25.8%; oxytocin 76.8% ± 20.7%; misoprostol/diclofenac 85.2% ± 15.1%; average sonication time: controls 120 min ± 56.4%; oxytocin 111 min ± 45.4%; misoprostol/diclofenac 80 min ± 47.7%). Statistical analysis did not reveal significant intergroup differences in UF volume changes after 6 mo (controls: n = 40, 37.4% ± 27.5%; oxytocin n = 25, 45.8% ± 31%; misoprostol/diclofenac n = 19, 33.4% ± 23.2%). The misoprostol/diclofenac group, which achieved the highest NPV immediately after the MR-HIFU procedure, was characterized by the lowest UF volume change percentages 6 mo later. The administration of vasoconstrictor drugs (oxytocin and misoprostol/diclofenac) to support MR-HIFU in UF treatment is a new issue that may improve the total effectiveness of this method. Randomized controlled trials are necessary to estimate the real effect of vasoconstrictors on MR-HIFU.

Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial.

OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN: Multicentre, double-blind, randomised placebo-controlled trial. SETTING: 30 French hospitals. POPULATION: Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS: Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES: Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity-mortality within 6 ± 2 weeks after delivery. RESULTS: 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66-1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group. CONCLUSIONS: As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events. TWEETABLE ABSTRACT: Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.

Evaluating efficacy of intravenous carbetocin in reducing blood loss during abdominal myomectomy: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of carbetocin versus placebo in decreasing intraoperative blood loss and the need for blood transfusion during abdominal myomectomy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Tertiary university hospital from September 2019 to February 2020. PATIENT(S): A total of 138 women with symptomatic leiomyoma who were candidates for abdominal myomectomy (n = 69 in each group). INTERVENTION(S): We randomized the study participants in a 1:1 ratio to carbetocin and placebo groups. Intravenous 100 µg carbetocin or placebo was administered slowly after induction of anesthesia. MAIN OUTCOME MEASURE(S): Intraoperative blood loss, need for blood transfusion, postoperative hemoglobin, operative time, length of hospitalization, and drug side-effects. RESULT(S): The baseline characteristics were similar among all groups. Carbetocin had significantly lower intraoperative blood loss compared with placebo (mean difference 184 mL). Hemoglobin level 24 hours after surgery was significantly lower in the placebo group than in the carbetocin group (9.1 ± 0.8 vs. 10.3 ± 0.6 g/dL). Eight women in the carbetocin group needed blood transfusion compared with 17 in placebo group. Operative time, length of hospitalization, and side-effects were similar in both groups. CONCLUSION(S): A single preoperative intravenous dose of 100 µg carbetocin is a simple, practical, and effective method of decreasing intraoperative blood loss and the need for blood transfusion during abdominal myomectomy, with tolerable, few, nonsignificant side-effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT04083625.

Induced prostaglandin release alters steroid concentrations but not pregnancy survival in cows.

Embryonic mortality (EM) is a major factor limiting reproductive efficiency in cattle, and despite negative connotations related to reproductive performance, prostaglandin F2α (PGF2α) is capable of being released by the uterus by Day 30 of gestation. Therefore, the objective was to evaluate differences in PGF2α release after an oxytocin challenge between cows with high circulating concentrations of pregnancy-associated glycoproteins (PAGs) vs low PAG because of the association of increased PAG concentrations with pregnancy success. At Day 30 of gestation, pregnant cows were divided into oxytocin treatment (OT; n = 13) and control (CON; n = 12) groups. Treatment cows were further subdivided by circulating PAG concentration (high PAG, n = 7; and low PAG, n = 6). Blood samples were collected every 30 min beginning 1 h before oxytocin administration and continuing for 4 h. Prostaglandin F2α metabolite (PGFM), progesterone, estradiol-17ß (E2), and PAG concentrations were quantified. The peak concentration of PGFM occurred 2 h after oxytocin injection in treatment animals and returned to baseline levels by 4 h. No correlations were observed between PAG and PGFM, progesterone, or E2 concentrations (P > 0.05). There was no difference in initial or final PGFM concentrations between groups (P > 0.05). Progesterone and E2 concentrations decreased in cows after treatment of oxytocin (P < 0.05); however, only progesterone returned to basal concentrations by the end of the sampling period. In summary, cows with high vs low PAG concentrations at Day 30 of gestation have a similar PGFM response to oxytocin challenge.

Oxytocin and cabergoline alleviate ovarian hyperstimulation syndrome (OHSS) by suppressing vascular endothelial growth factor (VEGF) in an experimental model.

PURPOSE: Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication of ovarian stimulation in reproductive medicine. Here, we aimed to investigate the role of oxytocin (OT) and cabergoline in the prevention and alleviation of the OHSS in an animal model. METHODS: Thirty-five female immature Wistar rats were randomly assigned to five groups. The control group (n = 7) received saline only for five consecutive days. Remaining twenty-eight rats received 10 IU of pregnant mare serum gonadotropin (PMSG) followed by 30 IU of human chorionic gonadotropin (hCG) to induce OHSS. Group 2 (n = 7) was managed with no additional intervention after the induction of OHSS. Group 3 (n = 7) received 100 µg/kg cabergoline 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Group 4 (n = 7) and group 5 (n = 7) received 80 µg/kg and 160 µg/kg OT after induction of OHSS, respectively. Oxytocin was administered 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Body and ovary weight, vascular permeability (VP), VEGF expression in the ovaries, and levels of VEGF in the peritoneal fluids were examined in all animals. RESULTS: Cabergoline and OT reduced body weight, ovary weight, and VP compared to that of the OHSS group (p < 0.05). VEGF expressions in ovaries and peritoneal VEGF levels were decreased in cabergoline and OT groups compared to that of the OHSS groups (p < 0.001 for cabergoline and OT-80 µg/kg; p < 0.00001 for OT-160 µg/kg). However, there was no statistically significant difference in these parameters between the OT and cabergoline groups. CONCLUSION: Both OT and cabergoline were active in the alleviation of OHSS through suppression of VEGF and VP. Overall, we conclude that OT is effective for downregulation for VEGF and improvement in vascular permeability in OHSS.

Predicting Postpartum Hemorrhage After Low-Risk Vaginal Birth by Labor Characteristics and Oxytocin Administration.

OBJECTIVE: To determine the odds of postpartum hemorrhage (PPH) in low-risk women who gave birth vaginally and were exposed to different durations and dosages of oxytocin across a range of labor durations during spontaneous or induced labor. DESIGN: A retrospective cross-sectional analysis of data from the Consortium for Safe Labor. SETTING: Data were gathered from 12 clinical institutions across the United States from 2002 to 2008. PARTICIPANTS: After exclusion of high-risk conditions associated with PPH, we examined data from 27,072 women who gave birth vaginally. METHODS: PPH was defined as estimated blood loss of greater than 500 ml at the time of birth and/or a diagnostic code for PPH before hospital discharge. We included covariates were if they were associated with oxytocin use and PPH and did not mediate oxytocin use. We used regression models to determine the likelihood of PPH overall and within the induced and spontaneous labor groups separately. We used subgroup analyses within specific durations of labor to clarify the findings. RESULTS: The overall rate of PPH was 3.9%. Women with induced labor experienced PPH more frequently than women who labored spontaneously. Labor augmentation was associated with greater adjusted odds for PPH when oxytocin was infused for more than 4 hours. Longer duration of spontaneous labor and the second stage of labor did not change this association. Oxytocin use during labor induction increased the odds for PPH when administered for more than 7 hours. The odds further increased when induction lasted longer than 12 hours and/or the second stage of labor was longer than 3 hours. CONCLUSION: Strategies for judicious oxytocin administration may help mitigate PPH in low-risk women having vaginal birth.

Inducción de trabajo de parto en pacientes COVID-19: experiencia en el Hospital San Juan de Dios / Labor induction in COVID-19 patients: experience in the San Juan de Dios Hospital

INTRODUCCIÖN Y OBJETIVOS: Describir la experiencia de los partos en gestantes con diagnóstico confirmado de COVID 19 mediante RT-PCR asintomáticas o con sintomatología leve y aquellas sin la enfermedad, y determinar la tasa de éxito de parto vaginal en inducción de trabajo de parto. MÉTODOS: Análisis retrospectivo de pacientes que tuvieron su parto entre 15 de Abril y 03 de Julio del 2020 en el Hospital San Juan de Dios. Se incluyeron las pacientes inducidas con Dinoprostona, Oxitocina o ambas de manera secuencial y se dividieron según estatus COVID 19 mediante RT-PCR al ingreso. Se caracterizó demográficamente el grupo de pacientes positivas y se determinaron los datos de ambos grupos en relación a la necesidad de inducción de trabajo de parto y su éxito para parto vaginal. RESULTADOS: De un total de 657 nacimientos, hubo un 9.7% (n=64) de pacientes con COVID 19, de las cuales un 23.4% (n=15) requirió inducción de trabajo de parto, con una tasa de éxito para parto vaginal de un 66.7% (n=10). De estas pacientes, un 50% recibió Oxitocina, un 40% Dinosprostona y un 10% ambos medicamentos de forma secuencial. En las pacientes negativas, hubo un total de 568 nacimientos, con un 29.8% (n=169) de usuarias que requirieron inducción. La tasa de éxito para parto vaginal en este grupo fue de 72.2% (n=122), utilizando un 50% Oxitocina; un 27% Dinoprostona; un 14.8% ambas; y un 8.2% Balón de Cook. CONCLUSIONES: Sabemos que los resultados de este estudio están limitados por el bajo número de pacientes incluidas, sin embargo, podemos observar que, en nuestra experiencia con las pacientes que arrojaron PCR SARS-CoV-2 positivas, asintomáticas o con enfermedad leve, se logró realizar la inducción de trabajo de parto según protocolos habituales, obteniendo porcentajes de éxito para partos vaginales, similares a las pacientes sin la enfermedad.

INTRODUCTION AND OBJECTIVES: Describe the experience of deliveries in pregnant women with a confirmed diagnosis of COVID 19 by asymptomatic RT-PCR or with mild symptoms and those without the disease, and determine the success rate of vaginal delivery in the induction of labor. METHODS: Retrospective study of patients who had their delivery between 15th April and 03rd of July, 2020 in the San Juan de Dios Hospital. Patients induced with Dinoprostone, Oxytocin or both sequentially were included, and were divided according to COVID 19 status by RT-PCR on their admission process. The group of positive patients was demographically characterized and the data of both groups was determined in relation to the need for labor induction and its success for vaginal delivery. RESULTS: Of a total of 657 births, there were 9.7% (n = 64) of patients with COVID 19, of which 23.4% (n = 15) required labor induction, with a success rate for vaginal delivery of 66.7% (n = 10). Of these patients, 50% received Oxytocin, 40% Dinosprostone and 10% both drugs sequentially. In the negative patients, there were a total of 568 births, with 29.8% (n = 169) of users requiring labor induction. The success rate for vaginal delivery in this group was 72.2% (n = 122); 50% using Oxytocin; 27% Dinoprostone; 14.8% using both; and 8.2% using Cook's Catheter. CONCLUSIONS: We know that the results of this study are limited by the low number of patients included, however, in our experience, we can observe that, in patients with SARS-CoV-2 PCR positive, asymptomatic or with mild disease, it was possible to perform induction of labor according to standard protocols, achieving success rates for vaginal deliveries, similar to patients without the disease.

Oxytocin in the anterior cingulate cortex is involved in helping behaviour.

Empathy toward the distress of others is thought to motivate helping behaviour, in the form of voluntary action to eliminate that distress. Neuropeptide oxytocin is associated with various social cognitive abilities, including empathy and prosocial behaviour. The anterior cingulate cortex is known to be one of the brain regions underlying empathy, and one in which oxytocin receptors are expressed. However, the relationship between helping behaviour and oxytocin in the anterior cingulate cortex is still unclear. The present study investigated whether oxytocin in the anterior cingulate cortex is involved in rats' helping behaviour. In Experiment 1, we examined the influence of blockading the oxytocin receptors in the anterior cingulate cortex on helping behaviour. Impeding oxytocin in the anterior cingulate cortex delayed learning of the helping behaviour. In Experiment 2, we examined immunofluorescent colocalization of oxytocin receptors and c-fos proteins in the anterior cingulate cortex, the anterior insular cortex, and the amygdala in rats that acquired helping behaviour. We found increased c-fos expression in oxytocin receptor-containing neurons in the anterior cingulate cortex and amygdala when the rats acquired helping behaviour. In addition, the change in neural activation was found in the late phase of the learning. These results suggest that the oxytocin in the cingulate-amygdala pathways may play an important role in helping behaviour.

The effect of oxytocin, gender, and ovarian hormones on stress reactivity in individuals with cocaine use disorder.

RATIONALE: Cocaine use disorder (CUD) is associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which plays a critical role in the human stress response. Men and women with CUD differ in reactivity to social stressors. The hypothalamic neuropeptide oxytocin is involved in anxiolytic and natural reward processes, and has shown therapeutic potential for addictive disorders and stress reduction. OBJECTIVES: To examine the impact of oxytocin (oxytocin (OXY) vs. placebo (PBO)) and gender (female (F) vs. male (M)) on response to a social stress task in individuals with CUD. To explore whether ovarian hormones moderate this stress response. METHODS: One hundred twelve adults with CUD were randomized to receive 40 IU intranasal oxytocin (n = 56) or matching placebo (n = 56). Forty minutes after drug administration, participants were exposed to a social stressor. Generalized linear mixed models were used to examine neuroendocrine (cortisol) and subjective (craving, stress) response at pre-stressor, stressor + 0, + 10, + 30, + 60 min. RESULTS: Gender moderated the effect of oxytocin on neuroendocrine response (p = 0.048); women receiving oxytocin (F + OXY) showed blunted cortisol response compared to the other three groups (F + PBO; M + OXY; M + PBO). There was a main effect of gender on subjective stress response; women reported greater stress following the stressor compared to men (p = 0.016). Oxytocin had no significant effect on craving or stress, and gender did not moderate the effect of oxytocin on either measure. Higher endogenous progesterone was associated with lower craving response in women (p = 0.033). CONCLUSIONS: Oxytocin may have differential effects in men and women with CUD. Women may be at greater risk for relapse in response to social stressors, but ovarian hormones may attenuate this effect.

Robotically handled whole-tissue culture system for the screening of oral drug formulations.

Monolayers of cancer-derived cell lines are widely used in the modelling of the gastrointestinal (GI) absorption of drugs and in oral drug development. However, they do not generally predict drug absorption in vivo. Here, we report a robotically handled system that uses large porcine GI tissue explants that are functionally maintained for an extended period in culture for the high-throughput interrogation (several thousand samples per day) of whole segments of the GI tract. The automated culture system provided higher predictability of drug absorption in the human GI tract than a Caco-2 Transwell system (Spearman's correlation coefficients of 0.906 and 0.302, respectively). By using the culture system to analyse the intestinal absorption of 2,930 formulations of the peptide drug oxytocin, we discovered an absorption enhancer that resulted in a 11.3-fold increase in the oral bioavailability of oxytocin in pigs in the absence of cellular disruption of the intestinal tissue. The robotically handled whole-tissue culture system should help advance the development of oral drug formulations and might also be useful for drug screening applications.