Tocolytic Research Articles

Uterine Relaxation Potential of Ethanol Leaf Extract of Moringa oleifera Lam. VIA the Muscarinic Receptor Pathway

Aim: The effect of Ethanol Leaf Extract of Moringa oleifera (ELMO) on uterine smooth muscles of non- pregnant female rats was studied in vitro with a view to finding out the mechanism(s) for observed effects. Experiential Design: In vitro studies using isolated rat’s uteri. Methods: Female albino rats (140-180g) pretreated 24 hours before experiments with diethylstilbestrol were sacrificed and the uterine horns carefully harvested into a beaker of De Jalon solution bubbled with 95% oxygen and 5% carbon dioxide. Each horn was mounted in an organ bath and allowed to equilibrate for 30 minutes, then the effects of graded doses of Acetylcholine, oxytocin and ELMO were established, using a physiograph and its accessories. The drugs were re-administered in the presence of their respective antagonists (Atropine for Acetylcholine and Atosiban for Oxytocin) and also in the presence of ELMO. Results: Results obtained showed that while Acetylcholine and oxytocin induced uterine contractions, ELMO caused relaxation. ELMO significantly (P<0.05) blocked the uterine contractile effect of Acetylcholine but had no effect on Oxytocin induced uterine contractions. The experiments therefore indicate that ELMO contain active ingredients capable of inducing uterine relaxation via the muscarinic receptor pathway. Conclusion: The extract therefore, may not be a valuable tocolytic agent in cases of Oxytocin induced uterine contractions, particularly in pregnancy but its observed strong anticholinergic activity may be exploited in the treatment of diseases associated with hyper activity of the parasympathetic arm of the autonomic nervous system.

Subcutaneous Terbutaline Pump for Maintenance of Tocolysis following Arrest of Acute Preterm Labor.

Drs. Elliott and Morrison recently published a narrative review about the effectiveness of oral and subcutaneous maintenance of tocolytic agents following successful arrest of acute preterm labor [1]. The authors conclude that subcutaneous terbutaline pump is beneficial and safe for maintenance of tocolysis based on all the available evidence. While the authors have provided an exhaustive list of the 46 published studies that have examined the terbutaline pump, we would like to express some concerns about the interpretations of this evidence. The authors have formed conclusions without assessing study quality or synthesizing results. In addition, several of the studies cited are single-arm case series and we would be hesitant to draw any conclusions about the efficacy based on this weak study design. We were commissioned by the Agency for Healthcare Research and Quality to evaluate the benefits and harms of subcutaneous terbutaline pump for maintenance of tocolysis by conducting a systematic review of the literature [2, 3]. Using prespecified eligibility criteria, we included 14 unique studies [3–17]. The evidence base that we relied on to form our conclusions included all randomized and comparative observational studies. These studies have been cited by Drs. Elliott and Morrison. Of the remaining 33 studies cited by the authors, we had identified and excluded 29; primarily because these studies did not include a comparator group (i.e., they were single-arm studies). The 4 studies that were not identified by our search [18–21] would also have been excluded because there were no nonpump controls. These 14 studies were of lower quality (medium to high risk of bias) and several studies examined data from one proprietary database. Although we found that the pump was beneficial for some outcomes (i.e., neonatal death, incidence of delivery <32 weeks and <37 weeks, and prolonging pregnancy), importantly, these benefits were rated as having low strength of evidence, which means that we have low confidence that the evidence reflects the true effect [22]. The strength of evidence is a subjective—though systematic and transparent—assessment of the reviewers' confidence in the findings based on the overall risk of bias, inconsistency, indirectness, and imprecision of the body of evidence [22]. In addition, there was insufficient data on other clinically important outcomes, such as bronchopulmonary dysplasia, intraventricular hemorrhage, and neonatal and maternal harms. Our more cautious interpretation about the efficacy and safety of terbutaline pump is based on a systematic review of the evidence and scientific methods for quantitative and qualitative synthesis (i.e., meta-analysis and grading strength of evidence). While we acknowledge that the harms reported by FDA after marketing surveillance do not establish causality [23], we have shown that the evidence for efficacy has limited validity. As such, we maintain that the safety and efficacy of the pump for maintenance tocolysis are unclear. Its use should be limited to the research setting, such as further investigation in an adequately powered, randomized, controlled trial.

Strip of the Month: January 2014

Strip of the Month: January 2014

Early Intervention in Breech Presentation to Reduce of Cesarean Section and Breech Deliveries

The effect of early intervention in breech presentation is investigated by outcomes of two indices: the breech delivery rate and the breech cesarean rate. Historically-controlled retrospective study was performed from 1985 to 2012. We intervene the breech presentation with tocolysis and external cephalic version (ECV) after 32 weeks’ of pregnancy and compared two indices before introduction of ECV (1985-87) and after (1986-2012). Statistical study was carried by kaisu are test and P value less than 0.05 is significant. Utilized tocolytic agents were ritdor in hydrochloride and magnesium sulfate. ECV was performed after 24 hrs in admission. Within enrolled case of 478, one hundred and sixty two cases were office ECV was excluded due to no controls (unsuccessful cases). Adopted 316 cases of admission-controlled ECV was divided into two groups of ECV (245 cases) and no ECV (71 cases). Spontaneous version had occurred in 20 cases of ECV and in 58 cases of no ECV, so overall spontaneous version rate was 25% (78/316) and overall successful ECV rate was 66% (161/245) under low reversion rate of 2.8% (9/323). In this way, two indices of the breech delivery rate and breech cesarean section rate had reduced from 3.3 to 2.1% and from 21.3 to 12.7% respectively (p<0.01). Furthermore we have not experienced serious complications. So we considered early intervention in breech presentation with tocolysis and ECV is useful for reduction of breech delivery and breech cesarean section.

Antibiotics for preterm rupture of membranes.

Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection. To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone. We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors. We included 22 trials, involving 6872 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found antibiotics seemed to have little effect on the health of children. Routine prescription of antibiotics for women with preterm rupture of the membranes is associated with prolongation of pregnancy and improvements in a number of short-term neonatal morbidities, but no significant reduction in perinatal mortality. Despite lack of evidence of longer-term benefit in childhood, the advantages on short-term morbidities are such that we would recommend antibiotics are routinely prescribed. The antibiotic of choice is not clear but co-amoxiclav should be avoided in women due to increased risk of neonatal necrotising enterocolitis.

Tocolytic Therapy for Preterm Delivery

Objective To determine the most effective tocolytic agent at delaying delivery. Design Systematic review and network meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. Study selection Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. Data extraction At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). Results Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). Conclusions Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.

A comparison of three tocolytics for preterm labor: a randomized clinical trial

Objective: To compare the efficacy and maternal side effects of nifedipine (N), magnesium sulfate (M), and indomethacin (I) for acute tocolysis.Methods: In this single center randomized trial, women in preterm labor 24–32 weeks’ gestation received intravenous M, oral N, or I suppositories. The primary outcomes of interest were arrest of preterm labor (>48 h, ≥7 days), gestational age at delivery, and maternal side effects.Results: Over a 38-month period, 301 women were allocated to receive M (90), N (114), or I (90). Gestational age at delivery (p = 0.551) or arrest of labor >48 h, >7 days were similar between the three groups (p = 0.199, 0.654). Hypotension and tachycardia were more common in N patients compared to women receiving M or I (p = 0.003, 0.009). Patients receiving I had more fetal ductal constriction or oligohydramnios compared to M or N (p = 0.001, 0.020) but, I women were tested more often. There was one case of pulmonary edema in the M group and one with plural effusion in the N group.Conclusion: There were no differences in efficacy or in major maternal safety issues between the three tocolytic agents. Since there is no FDA approved tocolytic to treat preterm labor, clinicians should use the tocolytic that has afforded them the best results with the least maternal/neonatal side effects.

Two New Flavonol Glycosides and a Metabolite Profile of Bryophyllum pinnatum, a Phytotherapeutic Used in Obstetrics and Gynaecology

Bryophyllum pinnatum is a succulent perennial plant native to Madagascar which is used in anthroposophical medicine to treat psychiatric disorders and as a tocolytic agent to prevent premature labour. We performed a metabolite profiling study in order to obtain a comprehensive picture of the constituents in B. pinnatum leaves and to identify chromatographic markers for quality control and safety assessment of medicinal preparations. Preliminary HPLC-PDA-ESIMS analyses revealed that flavonoid glycosides were the main UV-absorbing constituents in the MeOH extract of B. pinnatum. Two phenolic glucosides, syringic acid β-D-glucopyranosyl ester (1) and 4'-O-β-D-glucopyranosyl-cis-p-coumaric acid (2), as well as nine flavonoids (3-11) including kaempferol, quercetin, myricetin, acacetin, and diosmetin glycosides were unambiguously identified by 1H and 2D NMR analysis after isolation from a MeOH extract. The flavonol glycosides quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside 7-O-β-D-glucopyranoside (3) and myricetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (4) were new natural products. With the aid of HPLC-PDA-APCIMS and authentic references isolated from the related species B. daigremontianum, the presence of four bufadienolides, bersaldegenin-1-acetate (12), bryophyllin A (13), bersaldegenin-3-acetate (14), and bersaldegenin-1,3,5-orthoacetate (15) was detected in B. pinnatum.

Non-invasive management of acute recurrent puerperal uterine inversion with Bakri postpartum balloon

Uterine inversion is a rare and alarming obstetric emergency, the accurate management of which is very challenging to inexperienced obstetricians. Recurrence of uterine inversion is not only even more challenging, but also quite rare [1]. A 22-year-old G1 Turkish woman experienced a second-degree uterine inversion (the uterine fundus was protruding through the cervical ostium) with excessive bleeding and shock. This occurred following the spontaneous vaginal delivery of the baby and removal of the placenta by umbilical cord traction. Vaginal manual reduction of the inverted uterus was unsuccessful both in the delivery room and under general anesthesia in the operating theater. No tocolytic agent was used due to the hemodynamic instability of the patient. A laparotomy ensued and the uterus was successfully reduced as described by Huntington [2]. However despite the infusion of uterotonics, the fundal portion of the uterus softened and a dimple appeared which expanded and deepened. This resulted in a tendency of the uterus to re-invert. Accordingly, an SOS Bakri tamponade balloon catheter (Cook Medical Incorporated, Bloomington, IN, USA) was transvaginally inserted into the uterus and inflated until the dimple in the flaccid uterus disappeared. Six hundred milliliters was required to achieve this and resulted in a significant decrease in uterine bleeding with no recurrence of uterine inversion. Estimated total blood loss was 2,500 ml and four units of packed red blood cells were administered. There are few reports within the literature of uterine inversion recurrence following repositioning. The earliest report described re-inversion occurring on three occasions following manual repositioning. In that case, the uterus remained flaccid and inversion recurred every time manual compression was ceased [3]. Consequently, gauze packing of the uterus was performed and removed 28 h later without any complication. Similarly, other methods such as modified uterine compression sutures have been described to prevent recurrence of uterine inversion [1, 4]. However, in one such case, involving Cho compression sutures, a hysterectomy was required due to uterine necrosis and purulent peritonitis 11 days following the procedure [5]. The Bakri postpartum balloon has been increasingly used worldwide in the conservative management of postpartum uterine bleeding since Food and Drug Administration certification in 2006. Soleymani Majd et al. [6] first described the use of the Bakri balloon in preventing uterine re-inversion in a patient who was discovered to have uterine re-inversion 2 h after the initial replacement. In the present case, we applied a Bakri balloon during the original laparotomy to correct the inverted uterus. This was done as soon as a fundal dimple was observed, which signified the tendency of the uterus to re-invert (Fig. 1). Therefore, although uterine compression sutures may be successful in the management of recurrence of uterine B. Kaya (&) Department of Obstetrics and Gynecology, Faculty of Medicine, Near East University Medical School, Nicosia-TRNC, Mersin 10, Turkey e-mail: drbariskayaizmir@gmail.com

A primigravida with single atrium and single ventricle

Patients with untreated and severe congenital heart disease (CHD) rarely survive to reproductive age. A PubMed search revealed only 1 case of single atrium and single ventricle (SA/SV) in a pregnant woman; the patient was 6 weeks pregnant when dilation and evacuation was carried out [1]. The present case involved a primigravida at 32 weeks of pregnancy with untreated SA/SV who underwent successful operative delivery. It is reported not only because of its rarity but also to draw attention to medication use and unexpected reactions to conventional drugs. Informed consent was obtained for the present report. A 20-year-old woman with a history of complicated CHD was referred to the Second Affiliated Hospital of Xi′an Jiaotong University, Xi′ an, China, following irregular uterine contractions for 12 hours. The patient’s disorder was classified as New York Heart Association functional class III. Her vital signs were recorded as follows: temperature, 36.7 °C; heart rate, 90 beats per minute; blood pressure, 130/86 mm Hg; respiratory rate, 22 breaths per minute. Oxygen saturation varied between 80% and 90%. In addition, the patient exhibited cyanosis and grade 4/6 systolic murmur. Fetal ultrasound revealed the following parameters: biparietal diameter, 7.6 cm; femur length, 5.0 cm; amniotic fluid index, 10.0 cm; and placentalmaturity, grade 1. Echocardiography showed SA/SV, transposition of large arteries, and pulmonary valve stenosis (PS) in the mother (Fig. 1). A 5-g bolus of the tocolytic agent magnesium sulfate (MgSO4) was intravenously infused for 10 minutes. However, this infusion was stopped because the patient experienced chest tightness and shortness of breath. Patellar reflex was present and a low-maintenance dosage (1.5 g per hour for 10 hours) of intravenous MgSO4 was continued, leading to a clinical response. Five days after admission, regular uterine contractions were occurring every 2 minutes and cervical changes proceeded despite MgSO4. The patient requested cesarean delivery; under continuous epidural anesthesia, a premature female was born (1-minute Apgar score of 9). Uterine atony increased after 30 minutes, so oxytocin (0.02 IU/min) was intravenously infused and the patient’s uterus was continuously massaged. The preterm neonate (birth weight 1345 g) experienced pulmonary hemorrhage 2 days later and died. The patient was discharged 4 days after delivery and was stable at 6-month follow-up. Patients with untreated SA/SV rarely survive until adulthood. A previous study showed that pulmonary hypertension is a major problem during pregnancy among women with CHD [2]. The present case was rare because SA/SV was accompanied by moderate PS. Echocardiography revealed that the pressure gradient was 80 mm Hg and the maximumvelocity across the pulmonary valve reached 4.48 m/s. Single atrium and single ventricle without PS results in significant left-to-right shunt and pulmonary congestion, thereby progressing to pulmonary hypertension in a short period. In the present case, moderate stenosis of the pulmonary valve resulted in a brief left-to-right shunt and pulmonary congestion. Medication should be selected and administered carefully to reduce the effect on hemodynamics. Dose-related cardiovascular effects of oxytocinmay compromisehigh-risk patients [3]. Themost appropriate concentration of oxytocin not associated with severe adverse effects in patients with complex CHD remains unknown. In the present case, no evident cardiovascular adverse effects were detected during the continuous intravenous administration of oxytocin (0.02 IU/min) for 4 hours. The use of MgSO4 is controversial because a bolus dose may cause discomfort. As a calcium-channel blocker, MgSO4 elicits dose-related adverse effects on vascular smooth muscle and is associated with some cardiovascular symptomatology [4]. In conclusion, pregnant women with complex CHD may experience complications, so medication should be administered with care.

Acute Postpartum Pulmonary Edema in a 32-Year-Old Woman Five Days after Cesarean Delivery

Acute dyspnea after pregnancy is a rare presentation, and a number of important conditions may accompany it. Pulmonary embolism, amniotic fluid embolism, pneumonia, aspiration and pulmonary edema are some of the potential causes that must be considered. The percentage of pregnancies that are complicated by acute pulmonary edema has been estimated 0.08%. The most common contributing factors include the administration of tocolytic agents, underlying cardiac disease, iatrogenic fluid overload and preeclampsia. Here we report a case of 32- year-old woman of 5th postpartum day following lower uterine cesarean section with acute dyspnea from her first pregnancy who was admitted in coronary care unit with history of one episode of raised blood pressure 160/90 mm Hg and cough on 1st postoperative day. Clinical examination and relevant investigations explored that it was a case of bilateral pulmonary edema. Patient was kept in ventilator and was treated with nitroglycerine (GTN), frusemide and ACE inhibitor. After diuresis, considerable improvement was observed in her respiratory status. From the 4th day, the patient became hemodynamically stable and was weaned off the ventilator. After five days, all the biochemical parameters became normal and she had no dyspnea. Journal of Enam Medical College; Vol 3 No 2 July 2013; Page 113-116 DOI: http://dx.doi.org/10.3329/jemc.v3i2.16135

Transdermal nitroglycerin for the treatment of preterm labor: a systematic review and metaanalysis

The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor. We conducted a systematic review and metaanalysis of randomized controlled trials. Thirteen studies were included (1302 women) comparing transdermal nitroglycerin vs placebo (2 studies; n = 186); β2-adrenergic receptor agonists (9 studies; n = 1024); nifedipine (1 study; n = 50); and magnesium sulfate (1 study; n = 42). There were no significant differences between transdermal nitroglycerin and placebo for delivery within 48 hours of the initiation of treatment or at <28, <34, or <37 weeks of gestation, adverse neonatal outcomes, and neurodevelopmental status at 24 months of life. Nevertheless, 1 study found a marginally significant reduction in the risk of a composite outcome of major neonatal morbidity and perinatal death (3/74 [4.1%] vs 11/79 [13.9%]; relative risk, 0.29; 95% confidence interval, 0.08-1.00). When compared with β2-adrenergic receptor agonists, transdermal nitroglycerin was associated with a significant reduction in the risk of preterm birth at <34 and <37 weeks of gestation, admission to the neonatal intensive care unit, use of mechanical ventilation, and maternal side effects. There were no significant differences between transdermal nitroglycerin and nifedipine and magnesium sulfate in delivery within 48 hours of treatment and pregnancy prolongation, respectively. Overall, women who received transdermal nitroglycerin had a higher risk of headache. Although transdermal nitroglycerin appears to be more effective than β2-adrenergic receptor agonists, the current evidence does not support its routine use as a tocolytic agent for the treatment of preterm labor. Further double-blind placebo-controlled trials are needed.

Impact of intravenous immunoglobulin on peripheral blood natural killer cells in women with recurrent spontaneous abortion

Objective To explore the impact of intravenous immunoglobulin on peripheral blood natural killer (NK) cells in women with recurrent spontaneous abortion (RSA).Methods Of 38 patients with RSA who had been hospitalized during the period of January 2011 to June 2012,18 patients received intravenous immunoglobulin (study group) while the rest 20 who refused to receive immunoglobulin were assigned to a control group.Peripheral NK cell cytotoxicity and rate of NK cells in all types of lymphocytes were detected before and after treatment by flow cytometry.Results NK cell cytotoxicity was(22.4 + 7.9)％ in the study group and (21.7 ± 8.1)％ in the control group before treatment,was (15.0 ± 4.2)％ in the study group and (25.6 ± 7.9)％ in the control group after treatment.Before treatment,the rate of NK cell was (25.1 ± 9.4) ％ in the study group and (24.0 ± 9.0) ％ in the control group,while after treatment it was (26.2 ± 8.7) ％ in the study group and (23.6 ± 6.8) ％ in the control group.NK cell c.vtotoxicity but not the rate of NK cell was significantly reduced (P＜0.05) in the study group.After treatment,NK cell cytotoxicity and the rate of NK cell did not differ significantly (P＞0.05).88.9％ of the patients in the study group but 55.0％ of the patients in the control group had pregnancy duration of longer than 24 weeks after tocolytic treatment (P＜0.05).Conclusions Intravenous immunoglobulin can reduce NK cell cytotoxicity,leading to an increase in the success rate of miscarriage prevention in patients with recurrent spontaneous abortion. Key words: Recurrent spontaneous abortion; Intravenous immunoglobulin; Natural killer cells

Transitioning labor to the ‘lean years’: the middle class and employer repression of organized labor in post-World War I Chicago

In the historiography of the American labor movement, the 1920s have long been characterized as ‘lean years’. Historians have identified many explanations for this decline, but they have not fully accounted for the role of ‘public’ or ‘middle class’ anti-labor sentiment. Opportunistic employers appealed to growing middle-class consumer discontent, set in motion by the mounting ‘high cost of living’, to build support for crippling unions during the immediate post-World War I period. Using Chicago as an example, this essay emphasizes the relationship between employers and the white-collar ‘middle class’ as an important factor in explaining the origins of the lean years.

Effect of an oxytocin receptor antagonist (atosiban) on uterine electrical activity

The purpose of this study was to investigate the effect of atosiban (Tractocile; Ferring, Limhamn, Sweden), an oxytocin receptor antagonist, on uterine electrical activity in women with preterm labor and to determine whether this information can assist in the prediction of preterm delivery. Uterine electrical activity was recorded prospectively in 21 women with preterm labor before and during treatment with Tractocile and, for purpose of comparison, in 4 pregnant women without uterine contractions to set the baseline of uterine electrical activity in a quiescent uterus. Uterine activity was recorded with a noninvasive, 9-channel recorder with an electromyography amplifier and a 3-dimensional position sensor with an automatic data analyzer. Uterine electrical activity was quantified by an electrical uterine monitor (EUM) and measured in microwatts per second (μW/s). The overall pre-Tractocile EUM index was 3.43 ± 0.58μW/s, which was significantly higher than baseline uterine activity in women without preterm contractions (2.3 ± 0.11 μW/s; P=.001). During the administration of Tractocile, the EUM index gradually decreased in a relatively constant rate from 3.43 ± 0.58μW/s to2.56± 0.88 μW/s after 330 minutes of continuous therapy (P< .001). The peak effect of Tractocile was observed 4 hours after the initiation of treatment and was followed by a relative plateau. Women with a latency of <7 days from treatment to delivery were characterized by a distinct EUM-pattern in response to Tractocile, compared with women with a latency of ≥7 days (P < .001). A similar EUM-pattern after the administration of Tractocile was also observed for women who delivered at <37 weeks of gestation compared with the women who delivered at term. Tractocile reduces uterine electrical activity in women with preterm labor. This information can provide more insight into the effects of tocolytic agents and to aid in the risk stratification of preterm delivery in women with preterm contractions.

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Dihydropyridine Ca2+ channel blockers (CCBs) are widely accepted in the treatment of premature labour. Their mechanism of action in tocolysis involves the blockade of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. In clinical practice, most experience has been gained with the use of nifedipine, whose efficacy is superior or comparable to those of β-agonists and oxytocin antagonists. Additionally, it has a favourable adverse effect profile as compared with the majority of other tocolytics. The most frequent and well-tolerated side-effects of CCBs are tachycardia, headache and hypotension. In tocolytic therapy efforts are currently being made to find combinations of tocolytic agents that yield better therapeutic action. The available human and animal studies suggest that the combination of CCBs with β-AR agonists is beneficial, although such combinations can pose risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular diseases. Preclinical data indicate the potential benefit of combinations of CCBs and oxytocin antagonists. However, the combinations of CCBs with progesterone or cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to remain one of the most important groups of drugs for the rapid inhibition of premature uterine contractions. Their significance may be magnified by further clinical studies on their combined use for tocolysis.

Sa2012 Risk Factors and Temporal Trends for Complicated Diverticulitis: A Population-Based Study

Background: Indomethacin (INDO) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of patent ductus arteriosus in preterm infants and as a tocolytic agent in pregnant women. The exposure of preterm infants to INDO is associated with an increased risk of developing enteropathies such as necrotizing enterocolitis. Despite increasing progress in establishing the pathways involved in NSAID-induced damage, understanding the pathogenesis of gastrointestinal injury by NSAIDs in neonates relies on a limited number of studies carried out in animal models. Aims: In the present study, we combined our method for maintaining the mid-gestation human intestine in serum-free organ culture with highthroughput genomic studies and bioinformatic pathway analysis to investigate the specific intestinal effects of INDO on the overall physiology of both the small and large intestine at mid-gestation. Methods: After determining the optimal concentration of INDO to be 1μM (.90% inhibition of intestinal prostaglandin E2 production), a dose that corresponds to the range of circulating levels in treated preterm babies, we used Illumina microarrays to establish global gene expression profiles in human intestinal explants (ileums and colons) in response to an INDO treatment of 48 h. Differentially expressed genes between control and INDO-treated explants were determined using the Mann-Whitney test (p , 0.05), and further analyzed with Ingenuity Pathway Analysis software (IPA 8.8) to identify biological functions and canonical pathways modulated by INDO. Results: The gene expression profiles identified revealed that a large proportion of statistically significant biological, physiological and metabolic functions were modulated by INDO in the immature intestine. As expected, a number of these significantly modulated functions were inflammation-related such as Inflammatory diseases, Inflammatory response, and Acute phase response. Noteworthily, we have identified a series of metabolic-related gene clusters that were found to be significantly modulated, namely Glycolysis/gluconeogenesis, Oxidative phosphorylation and Free radical scavenging/oxidoreductase activity. Further analysis by qPCR confirmed that the expression of representative genes involved in these metabolic functions, such as ALDOA, LDHA, NDUFA9, DUOX2, SOD2, and TFF1, was inhibited by INDO in both intestinal segments, indicating that this adverse metabolic effect could be a component of the pathogenesis of intestinal damage induced by INDO. Conclusion: This study identified several different metabolic pathways that are modulated by INDO in the immature human intestine and suggests a mechanistic basis for better understanding the contributing effects of INDO and other NSAIDs on neonatal intestinal pathologies.

Sa2011 Adverse Metabolic Effects of Indomethacin on the Immature Human Intestine

Background: Indomethacin (INDO) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of patent ductus arteriosus in preterm infants and as a tocolytic agent in pregnant women. The exposure of preterm infants to INDO is associated with an increased risk of developing enteropathies such as necrotizing enterocolitis. Despite increasing progress in establishing the pathways involved in NSAID-induced damage, understanding the pathogenesis of gastrointestinal injury by NSAIDs in neonates relies on a limited number of studies carried out in animal models. Aims: In the present study, we combined our method for maintaining the mid-gestation human intestine in serum-free organ culture with highthroughput genomic studies and bioinformatic pathway analysis to investigate the specific intestinal effects of INDO on the overall physiology of both the small and large intestine at mid-gestation. Methods: After determining the optimal concentration of INDO to be 1μM (.90% inhibition of intestinal prostaglandin E2 production), a dose that corresponds to the range of circulating levels in treated preterm babies, we used Illumina microarrays to establish global gene expression profiles in human intestinal explants (ileums and colons) in response to an INDO treatment of 48 h. Differentially expressed genes between control and INDO-treated explants were determined using the Mann-Whitney test (p , 0.05), and further analyzed with Ingenuity Pathway Analysis software (IPA 8.8) to identify biological functions and canonical pathways modulated by INDO. Results: The gene expression profiles identified revealed that a large proportion of statistically significant biological, physiological and metabolic functions were modulated by INDO in the immature intestine. As expected, a number of these significantly modulated functions were inflammation-related such as Inflammatory diseases, Inflammatory response, and Acute phase response. Noteworthily, we have identified a series of metabolic-related gene clusters that were found to be significantly modulated, namely Glycolysis/gluconeogenesis, Oxidative phosphorylation and Free radical scavenging/oxidoreductase activity. Further analysis by qPCR confirmed that the expression of representative genes involved in these metabolic functions, such as ALDOA, LDHA, NDUFA9, DUOX2, SOD2, and TFF1, was inhibited by INDO in both intestinal segments, indicating that this adverse metabolic effect could be a component of the pathogenesis of intestinal damage induced by INDO. Conclusion: This study identified several different metabolic pathways that are modulated by INDO in the immature human intestine and suggests a mechanistic basis for better understanding the contributing effects of INDO and other NSAIDs on neonatal intestinal pathologies.

Property Rights, Labor Rights and Democratization: Lessons from China and Experimental Authoritarians

This article argues that a fundamental paradox exists in efforts to promote democratization abroad that emphasize property rights to the exclusion of labor rights. Such a paradox emerges from the still tenuous connection between property rights and foreign legal development alongside the renewed emphasis on independent unionization in democratization theory. The article explores the paradox in action through the willingness of modern authoritarian regimes to experiment with rule of law reforms, and creatively so in the realm of property rights while uniformly repressive of associative labor rights. In this vein, the article further details this paradox through the example of today’s most successful experimental authoritarian, China’s Chinese Communist Party. The CCP’s approach to property rights reform is but one area where it has used formal legal regulation to improve its governance capacity and legitimacy. At the same time, the CCP has developed an expansive state-dominated corporatist labor regime while engaging in the unyielding repression of private labor organizing. The article then outlines the implications of this promotion paradox and the authoritarian experience for U.S. influence on labor rights abroad, emphasizing the troubling parallels between the emphasis on employment law and employer self-regulation favored in authoritarian regimes and current trends in U.S. labor law. Beyond questioning dominant assumptions about the role of law in democracy promotion abroad, these parallels provocatively provide a new vantage point from which to consider the classic tension between property rights and labor rights in U.S. labor law doctrine.

Ritodrine Should Be Carefully Administered during Antenatal Glucocorticoid Therapy Even in Nondiabetic Pregnancies

Aim. Antenatal glucocorticoid therapy (AGT) has been commonly used recently. However, this therapy has severe harmful effects such as maternal hyperglycemia. In Japan, ritodrine hydrochloride has been used as a tocolytic agent. In this study, we performed retrospective casecontrol study to clarify whether concomitant use of ritodrine and glucocorticoid was safe to pregnant women without diabetes mellitus. Methods. We reviewed the computerized records of pregnant women with pregestational diabetes (n = 9) and nondiabetes (n = 45) who gave birth at our hospital between 2002 and 2011. Cases and controls received AGT. Blood glucose after the therapy was analyzed, and additional volume of insulin was compared to that before the therapy. Results. From this study, 30 units of insulin were necessary when performing AGT in diabetic pregnant women. And also, an increase in blood glucose of 40 mg/dL was seen after the therapy even in nondiabetic pregnant women. Blood glucose increased significantly in the group that also received ritodrine, and it was shown that the number of pregnant women who might develop ketoacidosis might increase 11-fold. Conclusions. Ritodrine should be carefully administered during antenatal glucocorticoid therapy. It may be necessary to adequately monitor blood glucose, when performing the therapy, even in nondiabetic pregnant women.