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BMC Pregnancy and Childbirth Mar 2023The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment...
Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum - a systematic review with implications for the function of the oxytocinergic system.
BACKGROUND
The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding.
AIM
To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems.
METHODS
Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables.
RESULTS
Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher. Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus.
CONCLUSIONS
Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Oxytocin; Parturition; Postpartum Period; Labor, Obstetric; Postpartum Hemorrhage
PubMed: 36864410
DOI: 10.1186/s12884-022-05221-w -
Frontiers in Neurology 2022This study aimed to construct an animal model of intracranial arterial dolichoectasia (IADE) applying the modified modeling protocol.
BACKGROUND AND PURPOSE
This study aimed to construct an animal model of intracranial arterial dolichoectasia (IADE) applying the modified modeling protocol.
MATERIALS AND METHODS
Twenty five milliunits elastase and inactivated elastase were, respectively, injected into the cerebellomedullary cistern of 60 C57/BL6 mice which were divided into experimental group (EG, = 30) and control group (CG, = 30) by using a computer-based random order generator. The modified modeling protocol clarified these aspects including brain three-dimensional parameters of mouse head fixation, angle of head inclination, fixed position of taper ear, needle holding technique, needle entry depth, prevention of liquid drug back flow, and storage conditions of elastase. And it was observed for the following parts such as mortality, inflammatory factors, craniocerebral arteries scanning, vascular tortuosity index, artery diameter, pathology of the cerebrovascular.
RESULTS
Within differently surveyed stage, the total mortality of mice in EG was 20%. ELISA illustrated that the levels of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor α (TNF-α) in peripheral blood were increased significantly after modeling. Angiography indicated that 100% of IADE in EG were observed and the diameter and tortuosity index of the basilar artery were significantly increased ( < 0.01). EVG histological processing and staining showed the disrupted internal elastic lamina, the atrophied muscle layer, and the hyalinized connective tissue of the basilar artery with the vascular wall tunica media in EG. Micro-computed tomography reported that the craniocerebral arteries of the mice in EG were outstandingly elongated, tortuous, and dilated.
CONCLUSION
The modified modeling protocol can reduce the mortality, improve the success rate, and provide a stable animal model for IADE.
PubMed: 35518204
DOI: 10.3389/fneur.2022.860541 -
American Journal of Obstetrics and... Jun 2024The principal fetal energy source is glucose provided by the placental transfer of maternal glucose. However, the placenta's glucose consumption exhibits considerable...
BACKGROUND
The principal fetal energy source is glucose provided by the placental transfer of maternal glucose. However, the placenta's glucose consumption exhibits considerable variation. Hexokinase is the first and one of the rate-limiting enzymes of glycolysis that phosphorylates glucose to glucose-6-phosphate. The role of placental hexokinase activity in human placental glucose metabolism is unknown.
OBJECTIVE
This study aimed to test the hypothesis that placental hexokinase activity is related to maternal body mass index, placental glucose uptake and consumption, and birthweight.
STUDY DESIGN
Overall, 67 healthy pregnant participants at term were included in this study at Oslo University Hospital, Oslo, Norway. Placental hexokinase activity was measured by using a colorimetric assay. The mass of glucose taken up by the uteroplacental unit and the fetus was obtained by measuring arteriovenous glucose differences combined with Doppler assessment of uterine and umbilical blood flow. Blood samples were obtained from the maternal radial artery, uterine vein, and umbilical artery and vein. The uteroplacental glucose consumption constituted the difference between uteroplacental and fetal glucose uptakes. The Spearman rank correlation was performed for statistical analyses to study the correlation of placental hexokinase activity (milliunit per milligram of protein) with prepregnancy body mass index, maternal glucose and insulin, birthweight, uteroplacental glucose uptake and consumption, and fetal glucose uptake (micromole per minute). Partial rank correlation analysis was performed when controlling for hours of fasting or placental weight.
RESULTS
Hexokinase activity was detectable in all placental tissue samples. The mean activity was 19.6 (standard deviation, 4.64) mU/mg protein. Placental hexokinase activity correlated positively with prepregnancy body mass index (Spearman rho=0.33; P=.006). On controlling for hours of fasting, hexokinase activity showed positive correlations with both maternal glucose (r=0.30; P=.01) and insulin (r=0.28; P=.02). Hexokinase activity was positively correlated with uteroplacental glucose uptake (Spearman rho=0.31; P=.01) and consumption (Spearman rho=0.28; P=.02). Hexokinase activity did not correlate with fetal glucose uptake. On controlling for placental weight, hexokinase activity showed a positive correlation with birthweight (r=0.31; P=.01).
CONCLUSION
Our findings suggest that placental hexokinase, being crucial for uteroplacental retention of glucose for disposition, is related to both maternal body mass index and birthweight independent of placental weight. Placental hexokinase may play a central role in the relationship between maternal glucose dysregulation and fetal growth. Thus, the current study supports the need to develop clinically useful tools to assess the metabolic properties of the placenta.
Topics: Humans; Female; Hexokinase; Pregnancy; Placenta; Body Mass Index; Birth Weight; Adult; Glucose; Blood Glucose; Infant, Newborn
PubMed: 37925123
DOI: 10.1016/j.ajog.2023.10.043 -
Journal of Midwifery & Women's Health Jan 2021To examine whether there is a threshold of oxytocin exposure at which the risk for primary cesarean increases among women who are nulliparous with a term, singleton,...
INTRODUCTION
To examine whether there is a threshold of oxytocin exposure at which the risk for primary cesarean increases among women who are nulliparous with a term, singleton, vertex fetus (NTSV) and how oxytocin interacts with other risk factors to contribute to this outcome.
METHODS
This was a secondary analysis of the Consortium on Safe Labor data set that used a retrospective cohort study design. Women who met the criteria for NTSV who were not admitted for a prelabor cesarean and for whom oxytocin data were available, were included in the sample. Robust logistic regression was used to examine the association of oxytocin exposure with primary cesarean birth, while controlling for demographic and clinical risk factors and clustering by provider.
RESULTS
The sample comprised 17,331 women who were exposed to oxytocin during labor. The women were predominantly white non-Hispanic (59.2%) with an average (SD) gestational age of 39.4 (1.1) weeks and an 18.5% primary cesarean rate. Exposure to greater than 11,400-milliunits (mU) of oxytocin resulted in 1.6 times increased odds of primary cesarean birth compared with less than 11,400 mU (95% CI 1.01-2.6).
DISCUSSION
Exposure to greater than 11,400 mU of oxytocin in labor was associated with an increased odds of primary cesarean birth in NTSV women.
Topics: Adolescent; Adult; Cesarean Section; Female; Humans; Labor, Induced; Labor, Obstetric; Logistic Models; Obstetric Labor Complications; Obstetrics; Oxytocics; Oxytocin; Parity; Pregnancy; Pregnancy Outcome; Retrospective Studies; Risk Factors; Young Adult
PubMed: 32930507
DOI: 10.1111/jmwh.13157 -
ACS Chemical Biology Feb 2020The enzymatic transamination of ketones into ()-amines represents an important route for accessing a range of pharmaceuticals or building blocks. Although many...
The enzymatic transamination of ketones into ()-amines represents an important route for accessing a range of pharmaceuticals or building blocks. Although many publications have dealt with enzyme discovery, protein engineering, and the application of ()-selective amine transaminases [()-ATA] in biocatalysis, little is known about the actual role and how these enzymes have evolved from the ubiquitous α-amino acid transaminases (α-AATs). Here, we show the successful introduction of an ()-transaminase activity in an α-amino acid aminotransferase with one to six amino acid substitutions in the enzyme's active site. Bioinformatic analysis combined with computational redesign of the d-amino acid aminotransferase (DATA) led to the identification of a sextuple variant having a specific activity of 326 milliunits mg in the conversion of ()-phenylethylamine and pyruvate to acetophenone and d-alanine. This value is similar to those of natural ()-ATAs, which typically are in the range of 250 milliunits mg. These results demonstrate that ()-ATAs can evolve from α-AAT as shown here for the DATA scaffold.
Topics: Bacillus subtilis; Escherichia coli; Escherichia coli Proteins; Mutagenesis, Site-Directed; Mutation; Phenethylamines; Protein Binding; Stereoisomerism; Substrate Specificity; Transaminases
PubMed: 31990173
DOI: 10.1021/acschembio.9b00888 -
EFSA Journal. European Food Safety... Apr 2021Pasteurisation of raw milk, colostrum, dairy or colostrum-based products must be achieved using at least 72°C for 15 s, at least 63°C for 30 min or any equivalent...
Pasteurisation of raw milk, colostrum, dairy or colostrum-based products must be achieved using at least 72°C for 15 s, at least 63°C for 30 min or any equivalent combination, such that the alkaline phosphatase (ALP) test immediately after such treatment gives a negative result. For cows' milk, a negative result is when the measured activity is ≤ 350 milliunits of enzyme activity per litre (mU/L) using the ISO standard 11816-1. The use and limitations of an ALP test and possible alternative methods for verifying pasteurisation of those products from other animal species (in particular sheep and goats) were evaluated. The current limitations of ALP testing of bovine products also apply. ALP activity in raw ovine milk appears to be about three times higher and in caprine milk about five times lower than in bovine milk and is highly variable between breeds. It is influenced by season, lactation stage and fat content. Assuming a similar pathogen inactivation rate to cows' milk and based on the available data, there is 95-99% probability (extremely likely) that pasteurised goat milk and pasteurised sheep milk would have an ALP activity below a limit of 300 and 500 mU/L, respectively. The main alternative methods currently used are temperature monitoring using data loggers (which cannot detect other process failures such as cracked or leaking plates) and the enumeration of Enterobacteriaceae (which is not suitable for pasteurisation verification but is relevant for hygiene monitoring). The inactivation of certain enzymes other than ALP may be more suitable for the verification of pasteurisation but requires further study. Secondary products of heat treatment are not suitable as pasteurisation markers due to the high temperatures needed for their production. More research is needed to facilitate a definitive conclusion on the applicability of changes in native whey proteins as pasteurisation markers.
PubMed: 33968255
DOI: 10.2903/j.efsa.2021.6576 -
Cureus Oct 2023Primary hypothyroidism is a commonly encountered endocrine disorder and can be associated with pericardial effusion and cardiac tamponade in severe cases. Early...
Primary hypothyroidism is a commonly encountered endocrine disorder and can be associated with pericardial effusion and cardiac tamponade in severe cases. Early detection of hypothyroidism is key since it is a potentially treatable and reversible cause of pericardial effusions. A 53-year-old female was admitted following a fall. The clinical history was remarkable, with symptoms of persistent tiredness and fatigue for six months. She had no known medical conditions and was not taking any regular medications. Vital signs were stable. Physical examination revealed bilateral pitting pedal oedema and a tense abdomen with shifting dullness. Cardiovascular and respiratory examinations were normal. Notably, the patient exhibited delayed relaxation of deep-tendon reflexes bilaterally at the patellar and ankle sites. Pertinent laboratory findings showed an elevated thyroid-stimulating hormone (TSH) level of 151.69 milliunits/L, a low free thyroxine (fT4) level of <5.4 pmol/L, a haemoglobin level of 85 g/L, and a markedly high anti-thyroid peroxidase antibody level of 957.35 IU/mL. An electrocardiogram revealed a normal sinus rhythm with a low-voltage QRS complex. Chest X-ray findings indicated cardiomegaly suggestive of left heart failure. An emergent transthoracic echocardiography (TTE) demonstrated a large pericardial effusion measuring 5.4 cm posterior to the left ventricle. The most likely aetiology in this case was severe primary hypothyroidism. She initially received intravenous liothyronine 10 micrograms every four hours, followed by oral liothyronine 5 micrograms twice a day in conjunction with levothyroxine 100 micrograms once a day. The adrenal reserve assessment was satisfactory. An urgent pericardiocentesis was performed, draining a total of 900 mL of serosanguinous fluid. Serial echocardiograms demonstrated the absence of residual effusion. Hypothyroidism is a relatively uncommon cause of pericardial effusion. By ensuring early detection and appropriate treatment, we can optimise patient outcomes and prevent potential complications associated with untreated hypothyroidism.
PubMed: 38021716
DOI: 10.7759/cureus.46947 -
SAGE Open Medical Case Reports 2022Treatment of neonates with persistent pulmonary hypertension of newborn includes optimization of ventilatory support, use of pulmonary vasodilators, and/or inotropic...
Treatment of neonates with persistent pulmonary hypertension of newborn includes optimization of ventilatory support, use of pulmonary vasodilators, and/or inotropic support. If refractory to this management, some may require extracorporeal membrane oxygenation. We describe a case series of 10 neonates with refractory persistent pulmonary hypertension of newborn treated with vasopressin in a single tertiary center. Mean initiation time of vasopressin was at 30 h of life with a dose ranging from 10 to 85 milliunits/kg/h. Oxygenation index decreased after 12 h of vasopressin exposure (25 to 11) and mean arterial pressure improved after 1 h (45 to 58 mm Hg). Extracorporeal membrane oxygenation was averted in 50% of the cases with transient hyponatremia as the only notable side effect. Although our findings are exploratory and further research is needed to establish safety and efficacy, our experience suggests that vasopressin may have rescue properties in the management of refractory persistent pulmonary hypertension of newborn.
PubMed: 35693924
DOI: 10.1177/2050313X221102289 -
Scientific Reports Feb 2021To provide novel insights into the pathogenesis of heart failure-induced renal dysfunction, we compared the effects of ACE inhibitor (ACEi) and AT receptor blocker (ARB)...
To provide novel insights into the pathogenesis of heart failure-induced renal dysfunction, we compared the effects of ACE inhibitor (ACEi) and AT receptor blocker (ARB) on systemic and kidney hemodynamics during heart failure in normotensive HanSD and hypertensive transgenic (TGR) rats. High-output heart failure was induced by creating an aorto-caval fistula (ACF). After five weeks, rats were either left untreated or treatment with ACEi or ARB was started for 15 weeks. Subsequently, echocardiographic, renal hemodynamic and biochemical measurements were assessed. Untreated ACF rats with ACF displayed significantly reduced renal blood flow (RBF) (HanSD: 8.9 ± 1.0 vs. 4.7 ± 1.6; TGR: 10.2 ± 1.9 vs. 5.9 ± 1.2 ml/min, both P < .001), ACEi had no major RBF effect, whereas ARB completely restored RBF (HanSD: 5.6 ± 1.1 vs. 9.0 ± 1.5; TGR: 7.0 ± 1.2 vs. 10.9 ± 1.9 ml/min, both P < .001). RBF reduction in untreated and ACEi-treated rats was accompanied by renal hypoxia as measured by renal lactate dehydrogenase activity, which was ameliorated with ARB treatment (HanSD: 40 ± 4 vs. 42 ± 3 vs. 29 ± 5; TGR: 88 ± 4 vs. 76 ± 4 vs. 58 ± 4 milliunits/mL, all P < .01). Unlike improvement seen in ARB-treated rats, ACE inhibition didn't affect urinary nitrates compared to untreated ACF TGR rats (50 ± 14 vs. 22 ± 13 vs. 30 ± 13 μmol/mmol Cr, both P < .05). ARB was more effective than ACEi in reducing elevated renal oxidative stress following ACF placement. A marker of ACEi efficacy, the angiotensin I/angiotensin II ratio, was more than ten times lower in renal tissue than in plasma. Our study shows that ARB treatment, in contrast to ACEi administration, prevents renal hypoperfusion and hypoxia in ACF rats with concomitant improvement in NO bioavailability and oxidative stress reduction. The inability of ACE inhibition to improve renal hypoperfusion in ACF rats may result from incomplete intrarenal RAS suppression in the face of depleted compensatory mechanisms.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Blood Pressure; Disease Models, Animal; Disease Susceptibility; Heart Failure; Hemodynamics; Hypertension; Rats; Receptor, Angiotensin, Type 1; Renal Circulation; Renal Insufficiency
PubMed: 33608612
DOI: 10.1038/s41598-021-83906-6