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Molecules (Basel, Switzerland) Oct 2023Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological purposes, were presently...
Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological purposes, were presently tested for antiarrhythmic, and other cardiovascular effects on isolated guinea pig heart tissues in comparison to well-established reference drugs. According to their structures, the tested compounds are assembled into three subsets: (a) N-(quinolizidinyl-alkyl)-benzamides; (b) 2-(benzotriazol-2-yl)methyl-1-(quinolizidinyl)alkyl-benzimidazoles; (c) N-substituted cytisines. All compounds but two displayed antiarrhythmic activity that was potent for compounds , , , and (in ascending order). The last compound (N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC = 0.017 µM) for the increase in the threshold of ac-arrhythmia. The tested compounds shared strong negative inotropic activity; however, this does not compromise the value of their antiarrhythmic action. On the other hand, only moderate or modest negative chronotropic and vasorelaxant activities were commonly observed. Compound , which has high antiarrhythmic potency, a favorable cardiovascular profile, and is devoid of antihypertensive activity in spontaneously hypertensive rats, represents a lead worthy of further investigation.
Topics: Rats; Animals; Guinea Pigs; Quinolizidines; Anti-Arrhythmia Agents; Heart; Sparteine; Arrhythmias, Cardiac; Alkaloids
PubMed: 37836759
DOI: 10.3390/molecules28196916 -
Safety of misoprostol vs dinoprostone for induction of labor: A systematic review and meta-analysis.European Journal of Obstetrics,... Oct 2023Pharmacological agents such as prostaglandins (dinoprostone and misoprostol) are commonly used to reduce the duration of labor and promote vaginal delivery. However, key... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Pharmacological agents such as prostaglandins (dinoprostone and misoprostol) are commonly used to reduce the duration of labor and promote vaginal delivery. However, key safety considerations with its use include an increased risk of uterine rupture, tachysystole and hyperstimulation of pregnant women, which could potentially lead to a non-reassuring fetal heart rate and to fetal hypoxemia. The aim of this systematic review was to assess maternal and fetal outcomes between misoprostol group (PGE1) and dinoprostone group (PGE2) STUDY DESIGN: We search on MEDLINE (PubMed), CINHAL (EBSCOhost), EMBASE, Scopus (Ovid), CENTRAL (January 1, 1998, to December 31, 2022). Patients were eligible if they presented at greater than 36 weeks gestation with an indication for induction of labor and a single live cephalic fetus. We conducted a meta-analysis of data for both primary (cesarean section rate, instrumental deliveries rate, tachysystole, uterine rupture, post-partum haemorrage; chorionamiositis) and secondary outcomes (Apgar at 5 min <7, meconium-stained liquor, NICU admission, infant death) using odds-ratio (OR) as a measure of effect-size. Risk of bias assessment was performed with RoB-I. We performed statistical analyses using Cochrane RevMan version 5.4 software.
RESULTS
We found 39 RCTs comparing the outcomes of interest between misoprostol and dinoprostone. The pooled effect showed no statistically significant difference between the two groups in terms of cesarean section rate [OR: 0.94; 95% CI 0.84-1.05], instrumental deliveries rate [OR: 1.04; 95% CI: 0.90-1.19; p = 0.62], tachysystole [OR: 1.21; 95% CI: 0.91-1.60; p = 0.19], post-partum hemorrhage [OR: 0.85; 95% CI: 0.62-1.15p = 0.30], chorioamnionitis [OR: 0.94; 95% CI: 0.76-1.17p = 0.59], Apgar at 5 min < 7 [OR: 0.83; 95% CI: 0.61-1.12, p = 0.21], meconium-stained liquor [OR: 1.11; 95% CI: 0.97-1.27p = 0.59], NICU admission group [OR: 0.91; 95% CI: 0.77-1.09], infant death [OR: 0.57; 95% CI: 0.22-1.44]. After performing a sub-group analysis based on the type of prostaglandins administrations (oral, vaginal gel, vaginal pessary), results did not change substantially.
CONCLUSIONS
This systematic review and meta-analysis demonstrate that misoprostol and dinoprostone appear to have a similar safety profile.
Topics: Infant; Humans; Female; Pregnancy; Dinoprostone; Misoprostol; Cesarean Section; Uterine Rupture; Prostaglandins; Oxytocics; Abortifacient Agents, Nonsteroidal; Infant Death; Labor, Induced
PubMed: 37660506
DOI: 10.1016/j.ejogrb.2023.08.382 -
Peptides Jul 2024Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best... (Review)
Review
Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best known for its role in lactation and parturition, recent research has shown that it also has a significant impact on social behaviors in mammals. However, a comprehensive review of this topic is still lacking. In this paper, we systematically reviewed the effects of OXT on social behavior in mammals. These effects of OXT from the perspective of five key behavioral dimensions were summarized: parental behavior, anxiety, aggression, attachment, and empathy. To date, researchers have agreed that OXT plays a positive regulatory role in a wide range of social behaviors, but there have been controversially reported results. In this review, we have provided a detailed panorama of the role of OXT in social behavior and, for the first time, delved into the underlying regulatory mechanisms, which may help better understand the multifaceted role of OXT. Levels of OXT in previous human studies were also summarized to provide insights for diagnosis of mental disorders.
Topics: Oxytocin; Animals; Social Behavior; Humans; Neuropeptides; Mammals; Anxiety; Aggression; Empathy; Female; Maternal Behavior
PubMed: 38626843
DOI: 10.1016/j.peptides.2024.171223 -
European Journal of Obstetrics,... Aug 2023A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods... (Review)
Review
Efficacy of pharmacological and mechanical cervical priming methods for induction of labour and their applicability for outpatient management: A systematic review of randomised controlled trials.
BACKGROUND
A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods are available to achieve cervical ripening prior to induction of labour (IOL). In this systematic review, we will report the literature to date, and investigate the efficacy and safety of using the Foley catheter balloon or prostaglandins for cervical ripening, comparing both methods with each other, and discuss the implications of these findings for midwifery led units.
METHODS
English peer-reviewed journals were systematically searched in the databases PubMed, MEDLINE, EMCARE, EMBASE and CINAHL, for studies investigating cervical ripening using the FC or PGs. Additional randomised controlled trials (RCTs) and non-RCTs were identified by a manual search. Search terms included: cervix dilatation effacement, cervix ripening, outpatient, ambulatory care, obstetric patients, pharmacological preparations, and Foley catheter. Only RCTs of FC versus PG or either intervention versus placebo or intervention in the in-patient Vs. outpatient setting were included. 15 RCTs were included.
RESULTS
The results of this review show that both FC and PG analogues are equally effective cervical ripening agents. When compared to FC, PGs lead to a reduced requirement for oxytocin augmentation and a shorter intervention to delivery interval. However, PG use is also associated with an increased risk of hyperstimulation, cardiotocographic monitoring abnormalities and negative neonatal outcomes.
CONCLUSIONS
FC cervical ripening is an effective method of outpatient cervical priming, which is safe, acceptable, and cost-effective and thus has a potential role in both resource-rich and resource-poor countries. With appropriate dosing, some PG analogues also appear to offer similar outcomes.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Dinoprostone; Outpatients; Cervix Uteri; Oxytocics; Labor, Induced; Prostaglandins; Abortifacient Agents, Nonsteroidal; Cervical Ripening
PubMed: 37300982
DOI: 10.1016/j.ejogrb.2023.05.037 -
Contraception Nov 2023This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion.
STUDY DESIGN
We searched PubMed on December 18, 2022, to find published articles describing the outcomes of treatment with misoprostol-only for abortion of viable intrauterine pregnancy at ≤91 days of gestation. From each article identified, two authors independently abstracted relevant data about each group of patients treated with a distinct regimen. We assessed the risk of bias using four defined indicators. We estimated the proportion of patients with treatment failure using meta-analytic methods as well as the proportion hospitalized or transfused after treatment. We examined associations between treatment failure and selected characteristics of the groups.
RESULTS
We identified 49 papers with 66 groups that collectively included 16,354 evaluable patients, of whom 2960 (meta-analytic estimate 15%, 95% CI 12%, 19%) had treatment failures. Of 9228 patients assessed for ongoing pregnancy after treatment, 521 (meta-analytic estimate 6%, 95% CI 5%, 8%) had that condition. Failure risk was significantly associated with misoprostol dose, the total allowed number of doses, the maximum duration of dosing, and certain indicators of risk of bias. Among 11,007 patients allowed to take at least three misoprostol doses, the first consisting of misoprostol 800 mcg administered vaginally, sublingually, or buccally, the meta-analytic estimate of the failure risk was 11% (95% CI 8%, 14%). At most, 0.2% of 15,679 evaluable patients were hospitalized or received transfusions.
CONCLUSIONS
Although some studies in this updated review were adjudicated to have a high risk of bias, the results continue to support the key conclusion of our 2019 analysis: misoprostol-only is effective and safe for the termination of first-trimester intrauterine pregnancy.
IMPLICATIONS
Misoprostol-only is a safe and effective option for medication abortion in the first trimester if mifepristone is unavailable or inaccessible.
Topics: Pregnancy; Female; Humans; Misoprostol; Abortifacient Agents; Pregnancy Trimester, First; Mifepristone; Abortion, Induced; Abortifacient Agents, Nonsteroidal
PubMed: 37517447
DOI: 10.1016/j.contraception.2023.110132 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2024Prostaglandin E (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the... (Review)
Review
Prostaglandin E (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the inhibition of inflammatory PGE production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat inflammatory diseases and to relieve fever and pain symptoms. PGE mediates its functions via four different G protein-coupled receptors, named EP1-EP4. Though the limited distribution and low PGE affinity of EP1, it plays important roles in the maintenance of many physiological functions and homeostasis. Moreover, EP1 is widely involved in the inflammatory response, pain perception and multisystem pathological function regulation. In this review, we will briefly summarize the recent advances on the physiological and pathophysiological function of EP1 and its targeted drugs development.
Topics: Humans; Arachidonic Acid; Dinoprostone; Homeostasis; Pain
PubMed: 38444136
DOI: No ID Found -
American Journal of Obstetrics &... Dec 2023Pregnancies at high risk for maternal, fetal, or placental complications often necessitate induction of labor in the late preterm or early term period for delivery.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pregnancies at high risk for maternal, fetal, or placental complications often necessitate induction of labor in the late preterm or early term period for delivery. Limited data exist on the safest method of induction to use in this specific patient population.
OBJECTIVE
This study aimed to compare the combination of oxytocin plus a Cook balloon vs misoprostol plus a Cook balloon for induction of labor in high-risk pregnancies.
STUDY DESIGN
We conducted an open-label, randomized controlled trial at a single institution from July 2020 to May 2022. The study was approved by the institutional review board and registered with ClinicalTrials.gov (NCT04492072). Individuals with a high-risk pregnancy, at least ≥22 weeks' gestation, with a singleton in cephalic presentation, Bishop score ≤6, and intact membranes were offered enrollment. A high-risk pregnancy was defined as a pregnancy with any of the following complications: hypertensive disease of pregnancy, fetal growth restriction, oligohydramnios, suspected placental abruption requiring delivery, uncontrolled pregestational diabetes, or abnormal biophysical profile or nonstress test requiring delivery. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included induction to delivery interval, number of vaginal deliveries within 24 hours, rates of uterine tachysystole, intraamniotic infection, operative vaginal delivery, and postpartum hemorrhage. Secondary fetal outcomes included fetal heart rate abnormalities, stillbirth, Apgar scores <7 at 5 minutes, admission to the neonatal intensive care unit, arterial umbilical blood pH <7.1, sepsis, and neonatal death. A subgroup analysis was planned for the primary outcome to assess the different indications for cesarean delivery. An intent-to-treat analysis was performed.
RESULTS
During the 22 months of the trial, a total of 150 patients were randomized, and 73 (49%) of those were induced with oxytocin and a Cook balloon and 77 (51%) were induced with misoprostol and a Cook balloon. There was no significant difference in the overall rate of cesarean delivery between the study groups, (21.9% vs 31.1%; relative risk, 0.70; 95% confidence interval, 0.41-1.21), nor among those for which the cesarean delivery was performed for a specific indication. There were no differences in the secondary maternal and fetal or neonatal adverse outcomes.
CONCLUSION
In high-risk pregnancies, the rate of cesarean delivery and adverse maternal and fetal outcomes were similar for induction of labor with oxytocin and a Cook balloon and for induction with misoprostol and a Cook balloon.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Misoprostol; Oxytocin; Oxytocics; Pregnancy, High-Risk; Labor, Induced; Placenta; Cervical Ripening
PubMed: 37806650
DOI: 10.1016/j.ajogmf.2023.101175 -
Brain and Nerve = Shinkei Kenkyu No... Nov 2023Resilience is a term that describes the capacity of coping with and recovering from stress and adversity. In terms of the concept of allostasis, resilience is the...
Resilience is a term that describes the capacity of coping with and recovering from stress and adversity. In terms of the concept of allostasis, resilience is the ability to appropriately regulate allostasis, efficiently terminate the allostatic response, prevent the occurrence of allostatic load/overload or restore homeostasis. Recently, it has been shown that oxytocin may be involved in this series of stress adaptation systems. We aim to discuss the changes in oxytocin neuron activation, oxytocin release and its actions of stress adaptation in response to internal and external environmental changes, and the regulation of resilience by oxytocin.
Topics: Humans; Allostasis; Oxytocin; Stress, Physiological; Adaptation, Psychological; Homeostasis; Stress, Psychological
PubMed: 37936425
DOI: 10.11477/mf.1416202506 -
European Journal of Clinical... Oct 2023The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children. (Meta-Analysis)
Meta-Analysis
PURPOSE
The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children.
METHODS
A systematic literature search was conducted to identify randomized controlled trials (RCTs) of oxytocin for the treatment of core symptoms in children with ASD. The search included studies published between January 1, 1999 and March 15, 2023, that were randomized, single or double-blinded, and included a placebo control group. Standard screening rules were applied to select relevant studies, resulting in the inclusion of five RCTs involving 486 children with ASD.
RESULTS
Ultimately, a total of five RCTs, involving 486 children with ASD, were included in the review using standard screening rules.One of the included studies demonstrated a statistically significant improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale-Revised (RBS) scores when children with ASD were treated with oxytocin (24 IU/2 days for 6 weeks). The improvement in core symptoms persisted at the 6-month follow-up. The meta-analysis findings suggested that oxytocin might have a moderate effect in improving the core symptom of narrow interests and repetitive stereotyped behaviors in children with ASD.
CONCLUSION
While the therapeutic value of oxytocin in treating core symptoms of ASD in children is not fully established, the results of this meta-analysis indicate a potential moderate effect. However, further studies with larger sample sizes and more robust RCTs are needed to directly demonstrate the efficacy of oxytocin. Future research should also focus on effect size and outcome evaluation accuracy while minimizing bias in RCT experiments.
Topics: Humans; Child; Oxytocin; Autism Spectrum Disorder; Outcome Assessment, Health Care; Control Groups
PubMed: 37540265
DOI: 10.1007/s00228-023-03545-w -
Georgian Medical News Feb 2024Cervical ripening is a critical component of normal parturition. There are substantial variations in labour induction (IOL) techniques around the world. Mifepristone...
Cervical ripening is a critical component of normal parturition. There are substantial variations in labour induction (IOL) techniques around the world. Mifepristone causes the termination of unwanted pregnancies, but there is a lack of consensus on its use for labour induction. The purpose of our study was to compare the combination of Mifepristone and Misoprostol with the combination of a Foley balloon and Misoprostol for labour induction. The study included 175 pregnant women, with gestational age 37-42 weeks. In the study group - 88 pregnant aged 21-35 (28.56±3.23), a combination of Mifepristone-Misoprostol was used. A combination of Foley catheter and Misoprostol was used in the control group - 87 pregnant aged 21-35 (29.48±3.03). The outcomes were assessed. In the study group the rate of vaginal delivery was higher and the frequency of cesarean section was lower compared to the control group (75 vs. 72, and 13 vs. 15, respectively); The total duration of labour was shorter in the study group (p<0,05); There was no difference between groups in the incidences of neonatal morbidity on the first and the fifth minute of life (p>0,05); The pain level was significantly low in the study group compared to the control group (5±0,75 vs. 8±0,96) and no cervical laceration was revealed in the study group. The Mifepristone - Misoprostol combination has advantages over the Foley balloon - Misoprostol combination for induction of labour regarding reduction in pain intensity, duration of labour, and cervical laceration.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Cesarean Section; Lacerations; Mifepristone; Misoprostol; Labor, Induced; Soft Tissue Injuries
PubMed: 38609105
DOI: No ID Found