Nicotine ameliorates inflammatory mediators in RU486 induced preterm labor model through activating cholinergic anti-inflammatory pathway.

BACKGROUND: Preterm birth is a global public health threat. Inflammatory reaction is thought to mediate preterm birth. The role of nicotine, an anti-inflammatory agent that is mediated by cholinergic anti-inflammatory pathways (CAP), remains unclear in the pathogenesis. METHODS: Pregnant rats were randomly divided into four groups (20 rats each): pregnant control group (P), RU486-treated group (PTL), RU486 and nicotine-treated group (PTL + N), RU486, nicotine and α-BGT treated group (PTL + N + A). Rats were administered RU486 (1.0 mg/kg) by subcutaneous injection on gestational day (GD) 18 to establish PTL model. Subcutaneous injection of nicotine (1 mg/kg) was administered daily from GD 16 to 18. α-BGT (1 µg/kg) was administrated subcutaneously in two sessions and each session was 30 min prior to nicotine. TNF-α, IL-1ß, IL-4, IL-6, IL-10 in myometrium and serum were detected by Luminex. Macrophage infiltration and α7nAChR were detected by IHC. RESULTS: We established a RU486-induced preterm labor rat model. Preterm labor was associated with a striking upregulation inflammatory mediators and increased macrophage infiltration. Nicotine significantly prolonged gestation (P < 0.05) and α-BGT treatment reversed the prolonged interval (P < 0.05). The cytokines all markedly elevated at 12 h, but deceased after delivery (P < 0.05). The IL-1ß and TNF-α in serum were significantly increased in PTL group vs P group (P < 0.05), and decreased after nicotine treatment (P < 0.05). The cytokines IL-1ß, IL-4, IL-6, IL-10 and TNF-α in myometrium increased as the same trend as in serum. Nicotine treatment also downregulated the expression of α7nAChR in pregnant tissue. CONCLUSION: We confirmed the increased inflammation in preterm birth. Nicotine was able to down-regulate the inflammatory mediates and prolong the pregnant duration in PTL model, which might be induced by activating α7nAChR through CAP. This study provides a novel evidence supporting the future development of therapeutic target for preterm birth.

Uterine electromyography (EMG) measurements to predict preterm caesarean section in patients with complete placenta previa.

The objective of the study was to evaluate uterine electrical activity (EA) with EMG methods in pregnant women with complete placenta previa with preterm caesarean section (CS). This prospective study included 78 patients with complete placenta previa who were recorded for uterine EA activity from 32 to 34 weeks of gestation. The clinical and the uterine EMG burst characteristics, that are responsible for contractions, were compared between a preterm CS group (case group, n = 33) and an elective control group (control group, n = 45). The uterine EA burst duration was longer in the case group compared with the control group (28.79 ± 3.75 vs 19.35 ± 2.56 s; p < .001). Also, the number of burst per 30 min was also higher in the case group compared with the control group (3.28 ± 0.18 vs 1.72 ± 0.22; p < .001), Similarly, the RMS was higher in the case group compared with the control group (0.07 ± 0.01 vs 0.04 ± 0.01 mV; p = .041). In addition, the PDS was higher in the case group compared with the control group (0.47 ± 0.03 vs 0.39 ± 0.02 Hz; p = .023). This study demonstrates that women with complete placenta previa have higher uterine EA at 32-34 weeks of gestation and this is associated with a higher risk of preterm CS due to massive vaginal bleeding.IMPACT STATEMENTWhat is already known on this subject? Antepartum massive bleeding in complete placenta previa causes maternal and foetal mortality and morbidity, currently there is no effective method to predict it.What do the results of this study add? This study showed in patients with complete placenta previa who were delivered preterm via emergent caesarean section, the uterine electrical activity measured by uterine electromyography (EMG) at 32-34 weeks of gestation had an active patternWhat are the implications of these findings for clinical practice and/or further research? Uterine EMG is a potential tool to measure uterine electrical activity and can guide clinical management of patients with complete placenta previa, further study are needed to confirm its effectiveness in a large sample size.

Measurement of Uterine and Abdominal Muscle Electromyography in Pregnant Women for Estimation of Expulsive Activities during the 2nd Stage of Labor.

BACKGROUND: The progression of labor and delivery of the fetus is dependent upon uterine contractions and the voluntary effort of abdominal muscle contractions. A good monitor of uterine contractions and pushing is necessary for obstetrical care. Electromyography (EMG) is the underlying basis for contractility of muscle including the myometrium. OBJECTIVES: The aim of this study was to determine the relationship between EMG activity of uterine and abdominal muscles and the duration of the 2nd stage of labor in pregnant women. METHODS: EMG of both uterine and abdominal muscles was simultaneously recorded from electrodes placed on the abdominal surface of 45 active 2nd stage-laboring nulliparous patients. EMG was recorded using filters to separate uterine and abdominal EMG signals, and various EMG signal parameters were analyzed. The duration of the 2nd stage of labor and other maternal and fetal characteristics were also recorded. RESULTS: Uterine EMG bursts precede abdominal bursts and are accompanied by feelings of "urge to push" by the patients. Abdominal root mean square (RMS) and power, but not uterine EMG parameters, are reduced (p< 0.005) in patients with longer labors and linear regression analysis demonstrated a negative correlation to the duration of 2nd stage of labor (p < 0.001). Multivariate linear regression analysis of clinical characteristics (fetal weight, body mass index, placental location, etc.) and parameters of EMG showed that only abdominal RMS is negatively correlated with the duration of labor. CONCLUSIONS: (1) Uterine and abdominal EMG activities reflect the expulsive involuntary (uterine) and voluntary (abdominal) muscular activities during the 2nd stage of labor. (2) RMS and power of abdominal EMG diminish with longer labor when uterine EMG intensities are similar. (3) Recording of uterine and abdominal muscle activity provides objective evaluation of the muscle activity during the 2nd stage of labor and may aid in the evaluation of any interventions.

Effects of vaginal progesterone for maintenance tocolysis on uterine electrical activity.

AIM: The effectiveness of vaginal progesterone for maintenance tocolysis after arrested preterm labor remains controversial. Myometrial contractility can be assessed objectively and non-invasively after progesterone treatment by monitoring uterine electromyography (EMG). We examined the effects of vaginal progesterone on uterine EMG after successful acute tocolysis. METHODS: This was a randomized, double-blind, single-center study performed between 2012 and 2015. Thirty women who experienced preterm labor between 24 0/7 and 33 6/7 weeks were randomly allocated to groups administered either 400 mg vaginal progesterone or a placebo 48 h after acute tocolysis. EMG measurements were taken prior to and 1 h and 2 h following treatment. Mann-Whitney U tests were used to compare EMG power density spectrum peak frequency and peak amplitude, propagation velocity of EMG signals, and duration and number of EMG bursts in 30 min recordings between the groups (P < 0.05). RESULTS: EMG propagation velocity was higher in patients receiving the placebo compared to those treated with progesterone at 1 h (27.83 ± 10.66 vs 15.60 ± 2.94 cm/s) and 2 h (26.97 ± 13.39 vs 15.12 ± 2.58 cm/s) following treatment (P = 0.001). PDS peak frequencies were higher in the placebo compared to the progesterone group at 2 h following treatment (0.54 ± 0.11 vs 0.44 ± 0.06 Hz; P = 0.003). CONCLUSIONS: Treatment of 400 mg of vaginal micronized progesterone as maintenance tocolysis significantly reduces the propagation velocity of electrical signals within the myometrium and is associated with a shift toward lower uterine electrical signal frequencies.

Uterine electromyography during active phase compared with latent phase of labor at term.

INTRODUCTION: In a prospective study in a tertiary university hospital we wanted to determine whether uterine electromyography (EMG) can differentiate between the active and latent phase of labor. MATERIAL AND METHODS: Thirty women presenting at ≥37(0/7) weeks of gestation with regular uterine contractions, intact membranes, and a Bishop score <6. EMG was recorded from the abdominal surface for 30 min. Latent phase was defined as no cervical change within at least 4 h. Student's t-test was used for statistical analysis (p ≤ 0.05 significant). Diagnostic accuracy of EMG was determined by receiver operator characteristics (ROC) analysis. The integral of the amplitudes of the power density spectrum (PDS) corresponding to the PDS energy within the "bursts" of uterine EMG activity was compared between the active and latent labor groups. RESULTS: Seventeen (57%) women were found to be in the active phase of labor and 13 (43%) were in the latent phase. The EMG PDS integral was significantly higher (p = 0.02) in the active (mean 3.40 ± 0.82 µV) compared with the latent (mean 1.17 ± 0.33 µV) phase of labor. The PDS integral had an area under the ROC curve (AUC) of 0.80 to distinguish between active and latent phases of labor, compared with number of contractions on tocodynamometry (AUC = 0.79), and Bishop score (AUC = 0.78). The combination (sum) of PDS integral, tocodynamometry, and Bishop score predicted active phase of labor with an AUC of 0.90. CONCLUSIONS: Adding uterine EMG measurements to the methods currently used in the clinics could improve the accuracy of diagnosing active labor.

Direct electrical stimulation softens the cervix in pregnant and nonpregnant rats.

OBJECTIVE: The objective of the study was to determine the effects of electrical stimulation (ES) on cervical ripening in pregnant and nonpregnant rats. STUDY DESIGN: Timed pregnant and nonpregnant Sprague-Dawley rats (n = 6-7/group) were used. Cervical ES for pregnant rats was performed in vivo on day 15 of gestation by inserting an electrical probe into the vagina in contact with the cervix. Parameters of ES varied from 0.1 to 0.2 mA, 10 pulses per second, 20 milliseconds pulse duration, and repeating pulses for 15, 30, 60, and 120 minutes for pregnant ES groups and similar times for sham control groups with electrode but without ES. Nonpregnant ES groups were stimulated with only 0.2 mA for 30 minutes. Cervical collagen was measured in controls and following ES at various times using light-induced fluorescence (LIF) of collagen. Photographs were taken following ES, and some rats were killed, the cervices were isolated, and cervical extensibility was estimated. RESULTS: LIF values of pregnant rats are significantly lower (P < .001) and extensibility greater (P < .05) in the ES treatment groups compared with the control groups on days 16 and 17 of pregnancy. Similarly LIF is lower (P < .05) and extensibility values greater (P < .05) in nonpregnant rats treated with ES. No adverse effects, including altered delivery time, pup weights, or damage to cervix, were produced by low current levels of ES needed to soften the cervix. CONCLUSION: The following conclusions were reached: (1) application of ES rapidly produces softening and ripening of the cervix in pregnant and nonpregnant rats; (2) ES treatment does not produce early delivery; (3) the exact mechanism for ES ripening is not yet known; and (4) ES might be used clinically to ripen the cervix when needed.

Nicotine treatment prolongs gestation and inhibits cervical ripening in pregnant rats.

OBJECTIVE: The aims of this study were to examine the effects of nicotine treatment on the length of gestation, on fetal outcome, on cervical ripening, and on uterine contractility during pregnancy in rats. STUDY DESIGN: Pregnant rats were treated with various concentrations of nicotine (0.25, 0.5, 1, 2 mg/kg/d, subcutaneously). Delivery times and fetal weights were obtained. Cervical collagen cross-links were assessed in vivo by collagen light-induced fluorescence (LIF), and cervical resistance to stretch was measured by in vitro extensibility tests. RESULTS: Delivery time is significantly (P = .002) prolonged after high-dose nicotine treatments. There are no significant changes in pup weights and placenta weights after nicotine treatments. Cervical collagen LIF and extensibility progressively decrease throughout pregnancy in control rats. Nicotine-treated rats showed significant (P < .001) cervical resistance to stretch and higher LIF compared with the control rats. Nicotine treatment in vitro had little effect on uterine contractility. CONCLUSION: Nicotine exposure during pregnancy prolongs gestation and inhibits cervical ripening, possibly by suppression of a cholinergic antiinflammatory response.

Nicotine, an α7 nAChR agonist, reduces lipopolysaccharide-induced inflammatory responses and protects fetuses in pregnant rats.

OBJECTIVE: The objective of the study was to examine the effects of nicotine, an α7 nicotinic acetylcholine receptor agonist, on lipopolysaccharide (LPS)-induced inflammatory responses in rats during pregnancy. STUDY DESIGN: Pregnant Sprague Dawley rats were randomly divided into groups (n = 6 rats/group): group 1 rats each received a single intraperitoneal injection of LPS (25 µg/kg) on gestation day 16; group 2 rats were first pretreated with nicotine (1 mg/kg per day, subcutaneously) on gestation days 14 and 15 and then were treated with single injections of LPS on gestational day 16; group 3 rats were treated with the vehicle (saline) used for groups 2 and 3 (controls). Maternal blood was collected at 6 hours and 24 hours after LPS and vehicle treatments and assayed for tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-10 (IL-10). In addition, the number of live pups and pup weights were obtained at the time of delivery. RESULTS: LPS treatment significantly (P < .001) elevates maternal blood levels of TNF-α and IL-6 but not IL-10 (P > .05). Nicotine treatment significantly reduces LPS-induced TNF-α and IL-6 concentrations (P < .001) but does not change (P > .05) IL-10 levels. The number of live pups in the LPS group are significantly lower (P < .001) than the vehicle treated controls, and nicotine treatment significantly (P < .011) reverses this change. Similarly, fetal weights are lower following LPS (P < .016) and higher (P < .024) in the group treated with nicotine plus LPS. CONCLUSION: Nicotine reduces the LPS-induced inflammatory responses and rescues the fetus in rats during pregnancy. Thus, nicotine exerts dramatic antiinflammatory effects. These observations have important implications for control of inflammatory responses during pregnancy.

The cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term.

Background: Cervical ripening is crucial for induction. However, its influencing factors, mechanistic understanding, and effective risk stratification are still challenging. Recent research suggested that microorganisms and their metabolites in vaginal spaces correlate to preterm birth. However, it remains unclear whether the cervicovaginal metabolome is related to the natural physiological process of cervical maturation. Objective: We aimed to analyze the cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term. Study design: Cervicovaginal swabs were collected between 40 and 41 weeks gestation from the following 2 different groups of patients: Ripe group (n = 25) which was favorable for the induction cervix and Unripe group which was unfavorable for the induction cervix (n = 25). Samples were tested using untargeted metabolomics analysis and analyzed by a bioinformatics platform. The correlation analysis between the metabolome and the previously acquired microbiome was also performed. Results: A total of 629 metabolites were identified in cervicovaginal fluid. The cervicovaginal metabolome was significantly different between the women with the ripe cervix and those with the unripe cervix, especially within each stratum of the same CST. Metabolites within the amino acid, carbohydrate, and dipeptide pathways may play a role in this distinction. Thirty-four metabolites were significantly upregulated, and the remaining fourteen were significantly downregulated in the Unripe group with an unripe cervix unfavorable for induction. Statistical modeling identified Arachidonic Acid and Nicotinate associated with the risk of cervical maturation disorder (AUC 0.87) in negative ion mode. A combination of Choline and d-Mannose identified a risk of cervical maturation disorder (AUC 0.80) in positive ion mode, improved by Lactobacillus relative abundance (AUC 0.89). Conclusion: These data suggested that the cervicovaginal space was metabolically active during pregnancy and significantly altered among the women with the mature and immature cervix. Combining the genera-level phylotypes and metabolites could build better cervix maturity prediction models. By using cervicovaginal fluid samples, we demonstrated the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to the remodeling of cervix during term pregnancy.

Costs of unnecessary admissions and treatments for "threatened preterm labor".

OBJECTIVE: Cervical length (CL) of 3 cm or greater has been shown to have a 97-99% negative predictive value for preterm delivery in women with threatened preterm labor. Consequently, hospitalization and treatment are not indicated in these patients. We analyzed how often patients with a CL of 3 cm or greater are still being admitted and treated for preterm labor and how much this contributes to the economic burden of preterm labor hospitalizations. STUDY DESIGN: Twelve month hospitalizations for preterm labor at less than 34 weeks at a single institution were reviewed and patients with a CL of 3 cm or greater were identified. We chose to use patients' hospital charges as a surrogate for health care costs, recognizing that charges are not synonymous with the final patient bill and also do not reflect additional costs such as the cost of treatment at the referring facility, transportation, physician fees, and other such costs as lost wages, need for additional child care, etc. RESULTS: Between July 2009 and June 2010, 139 patients were admitted and treated for preterm labor at our level III center. Fifty of these patients (36%) had a CL of 3 cm or greater. None of them delivered preterm. Total hospital charges for the management of these patients were $1,018 589 (mean, $20,372; median, $14,444). CONCLUSION: Unnecessary admissions and treatments for threatened preterm labor are part of clinical practice and contribute to exploding health care costs. Using currently available diagnostics, these costs could be lowered significantly without jeopardizing outcome.

Quantitative analysis for grading uterine electromyography activities during labor.

BACKGROUND: The strength of uterine contraction is one of the decisive factors for labor progression and parturition. Clinicians usually encounter difficulties in early identification of inadequate contractions and in oxytocin treatment. Electromyography-an emerging technology for uterine contraction monitoring-can quantify the intensity of myoelectric activity of uterine contraction. Therefore, grading patients with different uterine contraction intensities by electromyography is of great significance to the clinical intensive management of uterine contraction and labor process. OBJECTIVE: This study aimed to quantify and grade electromyography activity during the latent phase of the first stage of labor and explore its relationship with oxytocin treatment and length of labor. STUDY DESIGN: We performed a retrospective cohort study to identify electromyography parameters as a predictor for oxytocin treatment and length of labor among a cohort of term singleton primipara (n=508) during the latent phase who delivered in Guangzhou between August 2018 and December 2021. The electromyography parameters were graded according to the quartile method, and the significance of grading and delivery outcome was explored. Univariate and multivariate logistic regression were used to determine the predictors of oxytocin treatment. RESULTS: Maternal gestational age (adjusted risk ratio, 1.2; 95% confidence interval, 1.0-1.5), root mean square (adjusted risk ratio, 0.01; 95% confidence interval, 0.004-0.03), and power (adjusted risk ratio, 0.02; 95% confidence interval, 0.01-0.05) were significant predictors of oxytocin argumentation. The low electromyography activity group had a longer first stage labor and total labor time and were more likely to use oxytocin. CONCLUSION: Electromyography parameters root mean square and power had high predictive values for later oxytocin treatment among patients with spontaneous labor. Patients with low-grade electromyography were more likely need oxytocin treatment. Electromyography grading is very important for its clinical promotion and use, and it could lead to more reliable analyses of oxytocin treatments and eventually to more effective interventions to prevent prolonged labor.

Inhibition of uterine contractility with various tocolytics with and without progesterone: in vitro studies.

OBJECTIVE: Various tocolytics are used to suppress uterine contractility in patients in preterm labor. Progesterone (P4) is used in patients at high risk for preterm delivery. In this study, we evaluated the effects of various tocolytics with and without P4 to examine effects on uterine contractility. STUDY DESIGN: Uterine tissues (n = 280) from women undergoing cesarean at term were exposed in vitro to various agents (vehicle, magnesium sulfate [MgSO(4)], nifedipine, indomethacin, or pinacidil-all with and without P4). Contractility was measured before and after addition of the various agents. RESULTS: P4 alone at 10(-5) mol/L concentration has little effect to inhibit contractility (P ≥ .05). MgSO(4) (2-8 × 10(-3) mol/L) inhibits uterine contractility (P < .05) but there is no change when combined with P4 (P > .05). Nifedipine (10(-8) mol/L) and indomethacin (10(-5) mol/L) inhibit contractions alone (P < .05) and to a greater extent when combined with P4 (P < .05). P4 significantly (P < .05) reduced the effects of pinacidil (10(-6.5) mol/L). CONCLUSION: Combinations of P4 with nifedipine or indomethacin, but not MgSO(4), might be used to effectively suppress preterm labor.

Uterine slow wave: directionality and changes with imminent delivery.

Objective.The slow wave (SW) of the electrohysterogram (EHG) may contain relevant information on the electrophysiological condition of the uterus throughout pregnancy and labor. Our aim was to assess differences in the SW as regards the imminence of labor and the directionality of uterine myoelectrical activity.Approach. The SW of the EHG was extracted from the signals of the Icelandic 16-electrode EHG database in the bandwidth [5, 30] mHz and its power, spectral content, complexity and synchronization between the horizontal (X) and vertical (Y) directions were characterized by the root mean square (RMS), dominant frequency (domF), sample entropy (SampEn) and maximum cross-correlation (CCmax) of the signals, respectively. Significant differences between parameters at time-to-delivery (TTD) ≤7 versus >7 days and between the horizontal versus vertical directions were assessed.Main results.The SW power significantly increased in both directions as labor approached (TTD ≤ 7d versus >7d (mean±SD):RMSx = 0.12 ± 0.10 versus 0.08 ± 0.06 mV;RMSy = 0.12 ± 0.09 versus 0.08 ± 0.05 mV), as well as the dominant frequency in the horizontal direction (domFx= 9.1 ± 1.3 versus 8.5 ± 1.2mHz) and the synchronization between both directions (CCmax= 0.44 ± 0.16 versus 0.36 ± 0.14). Furthermore, its complexity decreased in the vertical direction (SampEny= 6.13·10-2 ± 8.7·10-3versus 6.50·10-2 ± 8.3·10-3), suggesting a higher cell-to-cell electrical coupling. Whereas there were no differences between the SW features in both directions in the general population, statistically significant differences were obtained between them in individuals in many cases.Significance.Our results suggest that the SW of the EHG is related to bioelectrical events in the uterus and could provide objective information to clinicians in challenging obstetric scenarios.

Changes in PGRMC1, a potential progesterone receptor, in human myometrium during pregnancy and labour at term and preterm.

This study assesses the role of progesterone receptor membrane component 1 (PGRMC1) in actions of progesterone (P4) on human myometrium during pregnancy and labour. Myometrial tissues were obtained from non-pregnant patients during hysterectomy or pregnant women undergoing C-section at term and preterm, before and during labour. PGRMC1 expression in myometrial tissues and in a human myometrial cell line (HM9) was assessed by western blots and RT-PCR. The subcellular localization of PGRMC1 in HM9 was performed by immunofluorescence staining. Isometric contractions of myometrial tissues were obtained in response to P4 with and without addition of specific antibodies against PGRMC1. Endogenous and over-expressed PGRMC1 proteins are detected by western blots in myometrial tissues, HM9 and 293 cells, respectively. PGRMC1 is localized to the plasma membrane, cytoplasm and nuclear membranes. PGRMC1 is lower in myometrium of women at term either not in labour (P = 0.004) or in labour (P = 0.005) compared with tissues from women in preterm non-labour. PGRMC1 levels are also decreased (P = 0.02) in myometrial tissues from women during preterm labour compared with preterm non-labour. P4 rapidly inhibits contractions of myometrial tissues compared with control (P < 0.05) in vitro. Pretreatment of myometrial strips with PGRMC1 antibody, suppresses the P4-induced relaxation (P < 0.05). PGRMC1 may mediate the non-genomic action of P4 and the relaxation effect on human myometrium during pregnancy. A decrease in PGRMC1 during term or preterm labour might contribute to the 'functional withdrawal' of P4 action and shift the balance to a state of heightened uterine contractility.

Noninvasive uterine electromyography for prediction of preterm delivery.

OBJECTIVE: Power spectrum (PS) of uterine electromyography (EMG) can identify true labor. EMG propagation velocity (PV) to diagnose labor has not been reported. The objective was to compare uterine EMG against current methods to predict preterm delivery. STUDY DESIGN: EMG was recorded in 116 patients (preterm labor, n = 20; preterm nonlabor, n = 68; term labor, n = 22; term nonlabor, n = 6). A Student t test was used to compare EMG values for labor vs nonlabor (P < .05, significant). Predictive values of EMG, Bishop score, contractions on tocogram, and transvaginal cervical length were calculated using receiver-operator characteristics analysis. RESULTS: PV was higher in preterm and term labor compared with nonlabor (P < .001). Combined PV and PS peak frequency predicted preterm delivery within 7 days with area under the curve (AUC) of 0.96. Bishop score, contractions, and cervical length had an AUC of 0.72, 0.67, and 0.54. CONCLUSION: Uterine EMG PV and PS peak frequency more accurately identify true preterm labor than clinical methods.

A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor.

OBJECTIVE: The purpose of this study was to determine whether optical methods can estimate cervix function during pregnancy and whether progestins modify this process. STUDY DESIGN: Photos of the external cervix of timed-pregnant rats were taken every other day from day 13 until postpartum day 5 after daily treatments with vehicle (controls) or progestin treatments (progesterone, subcutaneously or vaginally; 17-alpha-hydroxyprogesterone caproate [17P] and RU-486 subcutaneously, once on day 16). The surface area of the cervix was estimated from photos. RESULTS: The surface area of cervix increases throughout pregnancy and reverses after delivery in controls. In the progesterone subcutaneously or 17P subcutaneously groups, increases in surface area are lower (17P group until day 19 only; P < .05). Vaginal progesterone does not prevent surface area increases. Only the progesterone subcutaneously blocked delivery. RU-486 increases the surface area of the cervix (P < .05) during preterm delivery. CONCLUSION: An optical method is useful for quantitative assessment of the cervix and evaluation of agents that modify cervical function.

Progestin treatment for the prevention of preterm birth.

Progestin supplementation appears to be a promising approach to both preventing initiation of preterm labor and treating it once it is already established, given the role of progesterone in maintaining pregnancy, as well as support from basic and clinical research. Progesterone and 17α-hydroxyprogesterone acetate slow the process of cervical ripening, and this is the rationale for prophylactic long-term progestin supplementation mostly studied so far. However, progesterone (but not 17α-hydroxyprogesterone acetate) also inhibits myometrial activity even after the cervix has already ripened. Moreover, these effects depend greatly on the vehicle used and the route of administration. Understanding different mechanisms of action, as well as the importance of progestin formulation, vehicle and route of administration, is the key to finding the optimal progestin treatment for prevention of preterm birth.

Use of uterine electromyography to diagnose term and preterm labor.

Current methodologies to assess the process of labor, such as tocodynamometry or intrauterine pressure catheters, fetal fibronectin, cervical length measurement and digital cervical examination, have several major drawbacks. They only measure the onset of labor indirectly and do not detect cellular changes characteristic of true labor. Consequently, their predictive values for term or preterm delivery are poor. Uterine contractions are a result of the electrical activity within the myometrium. Measurement of uterine electromyography (EMG) has been shown to detect contractions as accurately as the currently used methods. In addition, changes in cell excitability and coupling required for effective contractions that lead to delivery are reflected in changes of several EMG parameters. Use of uterine EMG can help to identify patients in true labor better than any other method presently employed in the clinic.

A study of uterine inertia on the spontaneous of labor using uterine electromyography.

OBJECTIVE: The purpose of this study is to analyze uterine electromyography burst patterns in patients with spontaneous labor and patients with uterine inertia. MATERIALS AND METHODS: Uterine electromyography was recorded using 4 silver/silver chloride electrodes placed periumbilical. Thirty women in the spontaneous labor were enrolled. Uterine electromyography was also recorded from patients with uterine inertia before and after oxytocin treatment. EMG bursts were characterized by analysis of multiple variables including burst frequency, duration, root mean squared, amplitude, and total power. RESULTS: There were significant reductions (P < .01) in all EMG burst characteristics. In addition, uterine electromyography parameters were all increased after oxytocin treatment and were comparable (P > .05) to patients in spontaneous labor. CONCLUSIONS: Uterine electromyography can be used effectively to distinguish patients progressing with spontaneous labor from patients that develop uterine inertia. Uterine inertia is characterized by reduced EMG activity and failure of cervical dilation. Uterine electromyography is a quantitative, non-invasive assessment tool that contributes to the diagnosis, evaluation and management of patients with spontaneous labor and uterine inertia.

Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats.

Gastroparesis is a debilitating disease predominantly affecting young women. Recently, dysregulation of neuronal nitric oxide synthase (nNOS) in myenteric plexus neurons has been implicated for delayed solid gastric emptying/gastroparesis in diabetic patients. In this study, we have explored the role of tetrahydrobiopterin (BH4), a major cofactor for nNOS activity and NO synthesis in diabetic gastroparesis. Diabetes was induced with single injection of streptozotocin (55 mg/kg body wt, ip) in female rats, with experiments performed on week 3 or 9 following induction, with or without 3-wk BH4 supplementation. Gastric pyloric BH4 levels were significantly decreased in diabetic female rats compared with control (18.6 +/- 1.45 vs. 31.0 +/- 2.31 pmol/mg protein). In vitro studies showed that 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 synthesis, significantly decreased gastric NO release and nitrergic relaxation. Three-week dietary supplementation of BH4 either from day 1 or week 6 significantly attenuated diabetes-induced delayed gastric emptying for solids (3 wk: BH4, 67 +/- 6.7 vs. diabetic, 36.05 +/- 7.09; 9 wk: BH4, 57 +/- 8.45 vs. diabetic, 33 +/- 9.91) and diabetes-induced reduction in pyloric nNOS-alpha protein expression in female rats. Supplementation of BH4 significantly restored gastric nNOS-alpha dimerization in 9-wk-old diabetic female rats. In addition, BH4 treatment reversed (17.23 +/- 5.81 vs. 42.0 +/- 2.70 mmHg x s) the diabetes-induced changes in intragastric pressures (IGP) and gastric pyloric nitrergic relaxation (-0.62 +/- 0.01 vs. -0.22 +/- 0.07). BH4 deficiency plays a critical role in diabetes-induced alterations including delayed solid gastric emptying, increased IGP, reduced pyloric nitrergic relaxation, and nNOS-alpha expression in female rats. Supplementation of BH4 accelerates gastric emptying by restoring nitrergic system in diabetic female rats. Therefore, BH4 supplementation is a potential therapeutic option for female patients of diabetic gastroparesis.