In Vitro Comparative Effect of Carbetocin and Oxytocin in Pregnant Human Myometrium with and without Oxytocin Pretreatment

2016 ◽  
Vol 124 (2) ◽  
pp. 378-386 ◽  
Author(s):  
Naida M. Cole ◽  
Jose C. A. Carvalho ◽  
Magda Erik-Soussi ◽  
Nivetha Ramachandran ◽  
Mrinalini Balki
Keyword(s):  
Dose Response ◽  
Salt Solution ◽  
Area Under The Curve ◽  
Primary Outcome Measure ◽  
Human Myometrium ◽  
Control Group ◽  
Organ Bath ◽  
Motility Index ◽  
Elective Cesarean

Abstract Background The purpose of this study was to compare in vitro contractile effects of oxytocin and carbetocin on human term pregnant myometrium with and without oxytocin pretreatment. Methods This laboratory investigation was conducted on myometrial samples from women undergoing elective cesarean deliveries. The samples were dissected into four strips and suspended in individual organ bath chambers containing physiologic salt solution. After equilibration, they were pretreated with oxytocin 10−5 M (experimental group) or physiologic salt solution (control group) for 2 h and then subjected to dose–response testing with increasing concentrations of oxytocin or carbetocin (10−10 to 10−5 M). The amplitude, frequency, motility index (amplitude × frequency), and area under the curve of contractions were recorded and analyzed during the equilibration and dose–response periods. Comparisons were made between oxytocin-induced and carbetocin-induced contractions in control and oxytocin-pretreated groups. Motility index was the primary outcome measure. Results Sixty-three experiments were performed (carbetocin, n = 31; oxytocin, n = 32) on samples from 18 women. The motility index of contractions (√g.contractions/10 min) produced by oxytocin was significantly higher than carbetocin in both control (regression-estimated difference, 0.857; 95% CI, 0.290 to 1.425; P = 0.003) and oxytocin-pretreated (0.813; 0.328 to 1.299; P = 0.001) groups. The motility index was significantly lower in oxytocin-pretreated groups than their respective controls for both oxytocin (−1.040; −1.998 to −0.082; P = 0.03) and carbetocin (−0.996; −1.392 to −0.560; P < 0.001). Conclusions In vitro contractions produced by oxytocin are superior to carbetocin in human myometrium with or without oxytocin pretreatment. Oxytocin pretreatment results in attenuation of contractions induced by both oxytocin and carbetocin.

Oxytocin Pretreatment Attenuates Oxytocin-induced Contractions in Human Myometrium In Vitro

2013 ◽  
Vol 119 (3) ◽  
pp. 552-561 ◽  
Author(s):  
Mrinalini Balki ◽  
Magda Erik-Soussi ◽  
John Kingdom ◽  
Jose C. A. Carvalho
Keyword(s):  
Dose Response ◽  
Area Under The Curve ◽  
Oxytocin Receptor ◽  
Control Group ◽  
Physiological Salt Solution ◽  
Dependent Manner ◽  
Receptor Desensitization ◽  
Chi Square ◽  
Motility Index

Abstract Background: Oxytocin receptor desensitization has been shown to occur in humans at biomolecular level and in isolated rat myometrium; however, its effect on human myometrial contractility has not been demonstrated. The objective of this in vitro study was to investigate the contractile response of human pregnant myometrium to oxytocin after pretreatment with different concentrations of oxytocin for variable durations. Methods: Myometrial samples were obtained from 62 women undergoing elective cesarean deliveries under regional anesthesia. The strips were pretreated with oxytocin 10−10, 10−8, 10−5M, or physiological salt solution (control) for 2, 4, 6, or 12 h, followed by a dose–response testing with oxytocin 10−10 to 10−5M. Amplitude and frequency of contractions, motility index, and area under the curve during the dose–response period were recorded, analyzed with linear regression models, and compared among groups. Results: Pretreatment with oxytocin 10−5 and 10−8M significantly reduced motility index (estimate [standard error]: −0.771 [0.270] square root units, P = 0.005 and −0.697 [0.293], P = 0.02, respectively) and area under the curve (−3.947 [1.909], P = 0.04 and −4.241 [2.189], P = 0.05, respectively) compared with control group, whereas pretreatment with oxytocin 10−10M did not significantly attenuate contractions. Increase in duration of oxytocin pretreatment from 2 to 12 h significantly decreased amplitude (type 3 generalized estimating equation analysis: chi-square = 14.0; df = 3; P = 0.003), motility index (chi-square = 9.3; df = 3; P = 0.03), and area under the curve (chi-square = 10.5; df = 3; P = 0.02), but not the frequency of oxytocin-induced contractions. Conclusion: Pretreatment with oxytocin decreases oxytocin-induced myometrial contractions in a concentration and time-dependent manner, likely as a function of the oxytocin receptor desensitization phenomenon.

A Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In Vitro

Planta Medica ◽  
2018 ◽  
Vol 85 (05) ◽  
pp. 385-393 ◽  
Author(s):  
Stefanie Santos ◽  
Christian Haslinger ◽  
Kristian Klaic ◽  
Maria Faleschini ◽  
Mónica Mennet ◽  
...  
Keyword(s):  
Cell Viability ◽  
Area Under The Curve ◽  
Progressive Increase ◽  
Human Myometrium ◽  
Organ Bath ◽  
Relaxant Effect ◽  
System Cell ◽  
Myometrial Contractility ◽  
Bryophyllum Pinnatum

Abstract Bryophyllum pinnatum has been used since the 1970s to prevent premature labour, first in anthroposophic hospitals and, more recently, also in the main Swiss perinatal centres. However, it is not known which compounds in B. pinnatum leaves contribute to the tocolytic effect. Here we studied the effects of a flavonoid-enriched fraction, the corresponding flavonoid aglycon mixture, a bufadienolide-enriched fraction, and B. pinnatum leaf press juice on human myometrial contractility in vitro. The strength (area under the curve and amplitude) and frequency of contractions were recorded using strips of human myometrium mounted in an organ bath system. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1 – 41 cell lines. Repeated addition of the flavonoid-enriched fraction, flavonoid aglycon mixture, bufadienolide-enriched fraction, or B. pinnatum leaf press juice led to a progressive decrease of contraction strength, without jeopardising the vitality of myometrium strips. The bufadienolide-enriched fraction was the most active, since 1 µg/mL of the bufadienolide-enriched fraction lowered the area under the curve to 40.1 ± 11.8% of the initial value, whereas 150 µg/mL of the flavonoid-enriched fraction, 6.2 µg/mL of the flavonoid aglycon mixture, and 10 µg/mL of the B. pinnatum leaf press juice were required to achieve comparable inhibition. A progressive increase of contraction frequency was observed, except in the case of the flavonoid aglycon mixture, which did not affect frequency. None of the test substances decreased myometrial cell viability, even at concentrations of 500 µg/mL of the flavonoid-enriched fraction, 40 µg/mL of the flavonoid aglycon mixture, 3.8 µg/mL of the bufadienolide-enriched fraction, and 75 µg/mL of the B. pinnatum leaf press juice, i.e., higher than those used in the myometrium experiments. Given the concentrations of flavonoids in the flavonoid-enriched fraction and B. pinnatum leaf press juice, and of bufadienolides in the bufadienolide-enriched fraction and B. pinnatum leaf press juice, it appears that bufadienolides may be mainly responsible for the relaxant effect.

scholarly journals Influence of oxytocin receptor single nucleotide sequence variants on contractility of human myometrium: an in vitro functional study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
F. Füeg ◽  
S. Santos ◽  
C. Haslinger ◽  
B. Stoiber ◽  
L. Schäffer ◽  
...  
Keyword(s):  
Mode Of Delivery ◽  
Oxytocin Receptor ◽  
Functional Study ◽  
Human Myometrium ◽  
Sequence Variants ◽  
Organ Bath ◽  
Single Nucleotide ◽  
Allele Distribution ◽  
Stimulation Of

Abstract Background Oxytocin receptor (OXTR) gene variants have been shown to affect the prevalence of preterm birth, mode of delivery and oxytocin (OXT) requirements for labor induction and augmentation. We hypothesized that this might be associated with different myometrium responses to oxytocin. Our aim was to investigate the influence of a selection of eight OXTR gene single nucleotide variants on oxytocin-induced stimulation of human myometrium contractility in vitro. Methods Human myometrium biopsies were collected during elective cesarean sections at term, if patients had given informed consent. Myometrial strips were submerged under tension in an organ bath and allowed to contract; the remaining material was stored at − 80 °C for further determination of relevant genetics and mRNA level. The area under the curve (AUC) of all contractions taking place in the absence of OXT and of those occurring upon OXT addition (for 30 min each) was measured. OXT stimulation, defined as the ratio between AUC measurements after OXT addition and those in the absence of OXT was calculated for each strip. TaqMan™ Assays were used to detect the allele distribution of the eight OXTR variants and to determine the relative amounts of OXTR-mRNA in the samples. For each variant, oxytocin stimulation of contractility was compared between samples homozygous for the reference allele (reference group) and samples with at least one variant allele (variant group) by linear regression. Results Sixty samples were included in the present study. For rs1042778, rs11706648, rs4686301, rs53576, rs237895, and rs237902, OXT stimulation was similar in the reference and in the variant groups. However, the values of OXT stimulation differed significantly between the reference and the variant groups for rs4686302 (3.1 vs. 4.1 times; p = 0.022) and rs237888 (3.2 vs. 5.5 times; p = 0.001). No significant differences between the levels of OXTR-mRNA in the various reference and corresponding variant groups were detected. Conclusions Patients with variant alleles of rs237888 and/or rs4686302 may be more sensitive to oxytocin stimulation, explaining why these sequence variants have been associated with lower cesarean section prevalence and premature birth, respectively.

scholarly journals In Vitro Effects of Propofol on Gravid Human Myometrium

2008 ◽  
Vol 36 (6) ◽  
pp. 802-806 ◽  
Author(s):  
A. S. Thind ◽  
R. J. Turner
Keyword(s):  
Isometric Tension ◽  
Human Myometrium ◽  
Organ Bath ◽  
Dependent Manner ◽  
Uterine Contractility ◽  
Time Curve ◽  
Lower Segment Caesarean Section ◽  
Uterine Muscle ◽  
In Vitro Effects

The aim of this study was to evaluate the direct effect of propofol (di-isopropyl phenol) on the contractile properties of gravid human uterine muscle. Six specimens of uterine muscle were obtained from term parturients undergoing elective lower segment caesarean section. Small strips (1 × 2 x 12 mm) of muscle were prepared and suspended in an organ bath containing oxygenated Kreb's solution at 36.5°C. Following preparation, spontaneous regular contractions developed at a rate of one contraction every six to 10 minutes. Force of contraction was recorded continuously using an isometric tension transducer. Following baseline measurements, propofol was introduced into the bath at concentrations corresponding to 2 /μg/ml, 5 /μg/ml and 8 /μg/ml. The specimens were also exposed to intralipid in concentrations equivalent to that found in the 8 μ/ml solution of propofol to determine whether this additive influenced uterine contractility. Contractility (defined as area under the tension/time curve) was decreased to 89 ± 6.5% of control at 2 μg/ml 53±4.3% at 5 μ/ml and 45 ± 4.1% at 8 μg/ml. This decrease in contractility was statistically significant at concentrations >2 μg/ml. Intralipid did not significantly affect uterine contractility. The results of this study show that propofol decreases isolated human uterine muscle contractility in a dose-dependent manner.

The Effects of Nitroglycerin on the Oxytocin Dose–Response Profile in Oxytocin-Desensitized and Naïve Human Myometrium: An In Vitro Study

2020 ◽  
Vol 132 (1) ◽  
pp. 231-239
Author(s):  
Gayani S. Jayasooriya ◽  
Jose C. A. Carvalho ◽  
Alice Luca ◽  
Mrinalini Balki
Keyword(s):  
Dose Response ◽  
In Vitro Study ◽  
Vitro Study ◽  
Human Myometrium ◽  
Response Profile

Chronic levothyroxine and acute T3 treatments enhance the amplitude and time course of uterine contractions in human

2013 ◽  
Vol 304 (5) ◽  
pp. E478-E485 ◽  
Author(s):  
Stéphanie Corriveau ◽  
Jean-Charles Pasquier ◽  
Simon Blouin ◽  
Diego Bellabarba ◽  
Éric Rousseau
Keyword(s):  
Pregnant Women ◽  
Time Course ◽  
Area Under The Curve ◽  
Isometric Tension ◽  
Control Group ◽  
Clinical Practices ◽  
Time To Peak ◽  
Uterine Contractions ◽  
Reduced Frequency

This study compares the functional consequences of levothyroxine (T4) treatment during pregnancy as well as the acute affects of triiodothyronine (T3) on spontaneous uterine contractile activities observed in vitro. Uterine biopsies were obtained from consenting women undergoing elective caesarean at term ( n = 28). Spontaneous contractile activities from T4-treated pregnant women ( n = 8) were compared with control patients ( n = 20) by isometric tension measurements. Effects of acute T3 and T4 on control tissues were also monitored. Area under the curve, amplitude, time to peak, duration, and frequency were quantified. In uterine strips from women treated for hypothyroidism, phasic uterine contractions of larger amplitude (+77%) were observed, with a prolonged duration at 90% relaxation (+138%) and reduced frequency (−55%) compared with values of the control group. The addition of exogenous T3 in vitro on control strips induced a significant increase in the duration of the contractions and a significant decrease in frequency ( P < 0.05), which partially mimics the results obtained in strips from T4-treated women. Significant modifications of contractile properties were observed in strips from pregnant women treated with levothyroxine, consistent with those observed with the addition of exogenous T3. Clinical practices of modern obstetrics should take into account the effect of thyroid hormones on uterine contractions' time course to ensure a tighter followup at the end of pregnancy to achieve safer delivery.

scholarly journals Effect of dual tocolysis with fenoterol and atosiban in human myometrium

2019 ◽  
Vol 47 (2) ◽  
pp. 190-194 ◽  
Author(s):  
Bernhard Stoiber ◽  
Christian Haslinger ◽  
Marie Kristin Schäffer ◽  
Roland Zimmermann ◽  
Leonhard Schäffer
Keyword(s):  
Area Under The Curve ◽  
Antagonistic Effect ◽  
Additive Effect ◽  
University Hospital ◽  
Rank Test ◽  
Human Myometrium ◽  
Tissue Samples ◽  
Significant Difference ◽  
Signed Rank Test

Abstract Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the β-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as “synergistic” or “antagonistic”, respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.

scholarly journals Glucocorticoid Resistance in Premature Adrenarche and PCOS: From Childhood to Adulthood

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Aristotle Panayiotopoulos ◽  
Amrit Bhangoo ◽  
Divya Khurana ◽  
Svetlana Ten ◽  
Josef Michl ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Control Group ◽  
Sensitivity Index ◽  
Normal Range ◽  
Glucocorticoid Sensitivity ◽  
Androgen Synthesis ◽  
Premature Adrenarche ◽  
Pcos Group ◽  
Ovarian Syndrome

Abstract Context We hypothesize that impaired glucocorticoid sensitivity (GC sensitivity) plays a role in the development of premature adrenarche (PA) and polycystic ovarian syndrome (PCOS) by increasing androgen synthesis. Objective To study glucocorticoid sensitivity in vitro in subjects with PA and PCOS. Patients and Methods Fourteen subjects (10 girls, 4 boys, 6.9 ± 0.6 years) with PA; 27 subjects with PCOS (17 ± 2.5 years) and 31 healthy controls were enrolled in the study. All subjects and controls underwent GC sensitivity analysis in vitro using a fluorescein labeled-dexamethasone (F-DEX) assay. A GC sensitivity index (GCSI) was calculated as area under the curve of the F-DEX assay results. Subjects were classified as GC resistant if the GCSI ≤ 264 and GC sensitive if the GCSI ≥ 386. Results In the PA group, 8 of 14 subjects were resistant with GCSI of 179.7 ± 39.9, 4 were within the normal range with GCSI of 299.6 ± 27.9, and 2 had increased GC sensitivity with GCSI of 423.5 ± 47.9. In the PCOS group, 18 of 27 subjects were GC-resistant with GCSI of 180.9 ± 58.2, 8 were within the normal range with GCSI of 310.7 ± 26.4, and 1 had increased GCSI of 395.4. In the PCOS GC-resistant subgroup, cortisol was higher compared with PCOS with normal GCSI (P &lt; 0.05). In the combined PCOS plus female control group, GCSI correlated negatively with cortisol and testosterone (P &lt; 0.05). Conclusion GC resistance was found in more than 50% of patients with PCOS and PA. The findings strongly suggest that GC resistance is associated with states of PA and PCOS.

scholarly journals Early intervention with a glycerol throat spray containing cold-adapted cod trypsin after self-diagnosis of the common cold: a randomised prospective, parallel group and single-blind methods trial (Glycerol-cod trypsin spray in common cold)

2021 ◽  
Author(s):  
Fredrik Lindberg ◽  
Ida Nelson ◽  
Jonas Ranstam ◽  
Donald K. Riker
Keyword(s):  
Common Cold ◽  
Area Under The Curve ◽  
Treated Group ◽  
Control Group ◽  
Symptom Scale ◽  
Cold Adapted ◽  
Parallel Group ◽  
Single Blind

Background: A glycerol throat spray containing cold-adapted cod trypsin (GCTS) deactivates common cold virus in vitro and decreases pharyngeal rhinovirus load after inoculation in humans. We relied on early self-diagnosis and evaluated two different scales to detect a treatment effect in naturally occurring common colds. Methods: Adults were enrolled in this randomised, prospective, parallel group, single-blind study to begin treatment six times daily at first sign of a common cold or were assigned to a non-treated group. Jackson′s symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 quality of life (QoL) domain were recorded daily by subjects and area under the curve over 12 days (AUC1-12) calculated. Results: Treatment resulted in reduced symptoms with an AUC1-12 of 45.1 ± 32.5 for Jackson scores compared to 53.8 ± 35.7 in the controls (p=0.023). AUC1-12 for the 9-item WURSS-21 QoL domain was likewise improved, 113.6 ± 107.7 and 152.7 ± 126.3 (p=0.006), respectively. During the first four days fewer of the treated subjects (35.3%) used rescue medication than did the control group (50.4%, p=0.014). Conclusions: Reduction in common cold symptoms was seen with treatment with a glycerol throat spray containing cold-adapted cod trypsin. This effect was best detected with the 9-item WURSS-21 QoL domain.

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