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 Pharmacological Basis of CD101 Efficacy: Exposure Shape Matters

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Elizabeth A. Lakota ◽  
Justin C. Bader ◽  
Voon Ong ◽  
Ken Bartizal ◽  
Lynn Miesel ◽  
...  
Keyword(s):  
Time Course ◽  
Fungicidal Activity ◽  
Control Group ◽  
Time Curve ◽  
Content Type ◽  
Treatment Groups ◽  
Concentration Time ◽  
Treatment Control Group ◽  
Pharmacological Basis

ABSTRACT CD101 is a novel echinocandin with concentration-dependent fungicidal activity in vitro and a long half-life (∼133 h in humans, ∼70 to 80 h in mice). Given these characteristics, it is likely that the shape of the CD101 exposure (i.e., the time course of CD101 concentrations) influences efficacy. To test this hypothesis, doses which produce the same total area under the concentration-time curve (AUC) were administered to groups of neutropenic ICR mice infected with Candida albicans R303 using three different schedules. A total CD101 dose of 2 mg/kg was administered as a single intravenous (i.v.) dose or in equal divided doses of either 1 mg/kg twice weekly or 0.29 mg/kg/day over 7 days. The studies were performed using a murine disseminated candidiasis model. Animals were euthanized at 168 h following the start of treatment. Fungi grew well in the no-treatment control group and showed variable changes in fungal density in the treatment groups. When the CD101 AUC from 0 to 168 h (AUC0–168) was administered as a single dose, a >2 log10 CFU reduction from the baseline at 168 h was observed. When twice-weekly and daily regimens with similar AUC values were administered, net fungal stasis and a >1 log10 CFU increase from the baseline were observed, respectively. These data support the hypothesis that the shape of the CD101 AUC influences efficacy. Thus, CD101 administered once per week demonstrated a greater degree of fungal killing than the same dose divided into twice-weekly or daily regimens.

Enhanced contractility during relaxation of cat papillary muscle

1975 ◽  
Vol 228 (6) ◽  
pp. 1708-1716 ◽  
Author(s):  
BG Bass
Keyword(s):  
Papillary Muscle ◽  
Time Course ◽  
Isometric Tension ◽  
Contractile Element ◽  
Cat Papillary Muscle ◽  
Postextrasystolic Potentiation ◽  
Peak Tension ◽  
Time To Peak ◽  
In Series ◽  
Antecedent Control

Contractility during relaxation of isometric tension was studied in isolated, electrically driven cat papillary muscle by interpolation of test extrasystoles, all of whichpartially fused with their antecedent (control) contractions, were separated by computer from the fused contractions and then analyzed. The time course of the restitutionof contractility during relaxation was defined by plotting maximal positive dT/dt andtime-to-peak tension of the computer-separated extrasystole versus delay preceding the extrasystole. The dT/dt and time-to-peak tension, which steadily decline with progressive prematurity between contractions, both increase again during late relaxation, become progressively greater still earlier in relaxation, peak shortly after peak isometric tension, and then again decline. This phase of an apparently enhanced contractilityduring relaxation is depressed in low Ca'++ and is transmitted into the postextrasystolic period (in which it is superimposed on the usual postextrasystolic potentiation). The possible contributions of variations in series-elastic component and contractile-element lengths, actionpotential characteristics, and other factors on contractility during relaxation are discussed. It is suggested that enhanced contractility during relaxation may also be related in part to the decay of the intracellular free Ca'++ transient.

scholarly journals Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

2020 ◽  
Vol 21 (16) ◽  
pp. 5700 ◽  
Author(s):  
Rianthong Phumsuay ◽  
Chawanphat Muangnoi ◽  
Peththa Wadu Dasuni Wasana ◽  
Hasriadi Hasriadi ◽  
Opa Vajragupta ◽  
...  
Keyword(s):  
Time Course ◽  
Area Under The Curve ◽  
Dependent Manner ◽  
Paw Edema ◽  
Inflammatory Agent ◽  
Potent Inhibition ◽  
Anti Inflammatory ◽  
Ester Prodrug

Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

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.

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 &lt; 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.

scholarly journals Thyroid function in pregnant women with mild iodine deficiency

2003 ◽  
Vol 49 (6) ◽  
pp. 23-28 ◽  
Author(s):  
V. V. Fadeev ◽  
S. V. Lesnikova ◽  
G. A. Melnichenko
Keyword(s):  
Thyroid Gland ◽  
Pregnant Women ◽  
Thyroid Function ◽  
Potassium Iodide ◽  
Iodine Deficiency ◽  
Time Course ◽  
Therapy Group ◽  
Preventive Therapy ◽  
Control Group ◽  
Additional Risk

The study whose purpose was to examine the time course of changes in the function of thyroid gland (TG) in pregnant women with mild iodine deficiency enrolled 218 females in different periods of pregnancy in accordance with the following criteria: the absence of dysfunction (of TG). In 128 patients of them, baseline TG pathology was absent; 90 patients were found to have these or those types of euthyroid goiter. Some women received iodine preventive therapy (150-200 mcg of potassium iodide daily) on an individual basis. Comparison of the levels of TTH and T4 in women receiving and no receiving iodine preventive therapy revealed that by the end of pregnancy, those receiving 150-200 pg of potassium iodide had significantly lower TTN levels and higher T4 levels. Comparing the time course of changes in the volume of TG between these groups showed that they did not increase to a significantly greater extent in the females receiving no iodine preventive therapy. Whether potassium iodide was used, there were no changes in the size of TG nodal masses during pregnancy. In the control group, active smokers were fewer than those in the goiter group (p = 0.035). Six-ten months after labor, the volume of TG further increased in the females without iodine preventive therapy group while that substantially decreased in those receiving 150-200 pg of iodine daily. It is concluded that pregnancy in the presence of mild iodine deficiency is accompanied by a higher risk of the development and progression of goiter, and by a risk for gestational hypothyroxinemia, which is prevented by an individual iodine preventive therapy with 150-200 pg of potassium iodide daily. Furthermore, pregnancy is not accompanied by a risk of increases in the size of nodal euthyroid colloid goiter that does not itself entail an additional risk for gestational hypothyroxinemia.

Substance P contracts bovine tracheal smooth muscle via activation of myosin light chain kinase

1990 ◽  
Vol 259 (2) ◽  
pp. C258-C265 ◽  
Author(s):  
M. A. Corson ◽  
J. R. Sellers ◽  
R. S. Adelstein ◽  
M. Schoenberg
Keyword(s):  
Substance P ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Time Course ◽  
Myosin Light Chain ◽  
Immunoblot Analysis ◽  
Isometric Tension ◽  
Peak Tension ◽  
Tension Response

At near-threshold substance P concentrations, the isometric tension response of bovine tracheal strips is almost completely abolished by atropine, indicating mediation of contraction via substance P-stimulated release of acetylcholine from prejunctional nerve terminals. At near-maximal concentrations, the atropine-inhibited component of the tension response is less than 25%, indicating mainly direct activation. Under conditions in which activation by substance P is direct, peak tension is reached in approximately 11 min. Immunoblot analysis of the time course of phosphorylation of the 20-kDa myosin light chain (LC20) reveals incorporation of approximately 0.5 mol phosphate/mol light chain at 10 min. Two-dimensional tryptic phosphopeptide analysis of phosphorylated light chain reveals a single major phosphopeptide. The peptide migrates identically with that produced by myosin light chain kinase phosphorylation of purified tracheal myosin in vitro. Contraction stimulated by acetylcholine is more rapid, with attainment of peak tension in 2.5 min and a peak LC20 phosphorylation of 0.65 mol/mol. These results indicate that 1) substance P mediates contraction of bovine trachea both directly and indirectly, and 2) under conditions in which activation is direct, the tension and phosphorylation responses qualitatively resemble those observed with acetylcholine.

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 Reliability and Accuracy of Peri-Interventional Stenosis Grading in Peripheral Artery Disease Using Color-Coded Quantitative Fluoroscopy: A Phantom Study Comparing a Clinical and Scientific Postprocessing Software

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Patrick Ghibes ◽  
Sasan Partovi ◽  
Gerd Grözinger ◽  
Petros Martirosian ◽  
Fritz Schick ◽  
...  
Keyword(s):  
Flow Behavior ◽  
Image Acquisition ◽  
Area Under The Curve ◽  
Vessel Diameter ◽  
Frame Rate ◽  
Low Grade ◽  
High Grade ◽  
Flat Detector ◽  
Time To Peak

Purpose. To assess quantitative stenosis grading by color-coded fluoroscopy using an in vitro pulsatile flow phantom. Methods. Three different stenotic tubes (80%, 60%, and 40% diameter restriction) and a nonstenotic reference tube were compared regarding their different flow behavior by using contrast-enhanced fluoroscopy with a flat-detector system for visualisation purposes. Time-density curves (TDC), area under the curve (AUC), time-to-peak (TTP), and different ROI sizes were analyzed in three independent measurements using two different postprocessing software solutions. In addition, exemplary TDCs of a patient with a high-grade stenosis before and after stent angioplasty were acquired. Results. Color-coded fluoroscopy enabled depiction of differences in AUC and TDC between high-grade (80%), middle (60%), low-grade (40%), and nonstenotic tubes. The best correlation between high-, middle-, and low-grade stenosis was appreciated in ROIs behind the stenosis. This effect was enhanced by using longer integration times (5s, 7s) and a maximum frame rate of image acquisition for analysis (correlation coefficient rho=0.9284 at 5s). TTP showed no significant differences between high- and low-grade stenosis. Conclusions. Various clinical studies in the literature already demonstrated reproducible and reliable stenosis grading by analyzing TDCs acquired with color-coded fluoroscopy. In contrast to TTP, AUC values derived in ROIs behind the stenosis proved to be reliable parameters for stenosis grading. However, our results also demonstrate that several factors are able to significantly impact the evaluation of AUC values. More precisely, accuracy of acquired AUC values can be improved by choosing longer integration times, a large ROI size adapted to the vessel diameter, and a higher frame rate of image acquisition.

Flow Cytometric Detection of Circulating Activated Platelets and Platelet Hyper-Responsiveness in Pre-Eclampsia and Pregnancy

1994 ◽  
Vol 86 (6) ◽  
pp. 731-739 ◽  
Author(s):  
Sarah L. Janes ◽  
Alison H. Goodall
Keyword(s):  
Pregnant Women ◽  
Ex Vivo ◽  
Antigen Expression ◽  
Normal Pregnancy ◽  
Control Group ◽  
Fibrinogen Binding ◽  
Low Concentrations ◽  
Granule Membrane ◽  
Cd63 Expression

1. Platelet activation status and response to stimulation with agonists ex vivo were studied by whole blood flow cytometry in 15 women with pre-eclampsia, 20 age- and gestational-age-matched women who completed a normal pregnancy, and 20 age-matched non-pregnant women. 2. Women with proteinuric pre-eclampsia showed evidence of activated, degranulated platelets in the circulation, with increased platelet-bound fibrinogen, increased expression of the lysosomal granule membrane antigen, CD63, and raised plasma levels of β-thromboglobulin. 3. CD63 expression and β-thromboglobulin per platelet were also significantly higher in normal pregnant women than in non-pregnant women, but in these subjects fibrinogen binding was normal. 4. There was good correlation for all subjects in degranulation, measured by CD63 antigen expression, and by plasma β-thromboglobulin levels corrected for platelet count (r = 0.65; P < 0.01). 5. Platelet responsiveness to ADP in vitro showed a heightened degranulation response (CD63 expression) in normal pregnancy compared with the non-pregnant control group, which was increased further in women with non-proteinuric and proteinuric pre-eclampsia. 6. However, this response was not accompanied by an increased binding of fibrinogen to GPIIb—IIIa. Fibrinogen binding in response to ‘weak’ agonist stimulation, by low concentrations of ADP or, in a subgroup by adrenaline, was in fact lower in the normal pregnant women than in the non-pregnant women. 7. It is postulated that women at risk of developing pre-eclampsia may have hyper-reactive platelets, primed to undergo release by passage through the abnormal placenta.

Sign in / Sign up

Export Citation Format

Share Document