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Biomedical subjects

Michael Permezel

Publications and source records attributed to Michael Permezel.

16 recordsLinked to original sources

Cesarean delivery or vaginal birth: a survey of patient and clinician thresholds.

OBJECTIVE: To estimate what level of additional fetal risk women and their caregivers in late pregnancy considered acceptable to avoid a cesarean and achieve a vaginal birth. METHODS: Six hundred women in late pregnancy and 294 obstetric consultants, registrars, midwives, and medical students were recruited to the study. With the assistance of a visual probability aid representing 10,000 births, they were asked to consider what level of fetal risk of death or serious disability they would consider acceptable to avoid cesarean and achieve vaginal birth. RESULTS: The median level of fetal risk deemed acceptable to achieve a vaginal birth for pregnant women was 10 per 10,000 births (95% confidence interval [CI] 10-13 per 10,000), although the range of responses was wide (1-5,000 per 10,000). Among staff, the median level of acceptable fetal risk was 13 per 10,000 births (95% CI 10-20 per 10,000). Women participating in lower intervention models of care, such as the birth center or team midwifery, were more tolerant of fetal risk (odds ratios [ORs] 2.1, 95% CI 1.6-2.9 and 1.5, 95% CI 1.0-2.3, for accepting a fetal risk of 20 per 10,000 or greater), whereas women with a complicated pregnancy were less tolerant of fetal risk (OR 0.7, 95% CI 0.5-0.9). CONCLUSION: Pregnant women and their caregivers have a low tolerance for fetal risk associated with vaginal birth. This study demonstrates the difficulty of minimizing obstetric intervention rates in the face of high expectations for fetal outcome. Obstetric and demographic factors were found to significantly impact the "acceptable fetal risk" threshold, which highlights the importance of individualized counseling regarding mode of birth. LEVEL OF EVIDENCE: III.

Attitude of Health Personnel↗

Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2.

Beyond their effects on central metabolic functions, leptin, resistin, and adiponectin have profound effects on a number of other physiologic processes, including immune function and inflammation. Although leptin, resistin, and adiponectin are produced in human placenta and adipose tissue, their immunoregulatory actions in these tissues are not known. Therefore, the aim of this study was to determine the effect of leptin, resistin, and adiponectin on the release of proinflammatory mediators in human placenta and sc adipose tissue. Samples were obtained from normal pregnancies at the time of cesarean section. Tissue explants (n = 5) were incubated in the absence (basal control) or presence of a leptin (1, 10, and 100 ng/ml), resistin (1, 10, and 100 ng/ml), and adiponectin (0.1 and 0.5 microg/ml). After 6 h incubation, the medium was collected, and the release of IL-1beta, IL-6, TNFalpha, prostaglandin (PG)F2alpha and PGE2 was quantified by ELISA. There was no effect of resistin on proinflammatory cytokine or prostaglandin release; however, leptin at 100 ng/ml and adiponectin at 0.1 and/or 0.5 microg/ml significantly increased the release of IL-1beta, IL-6, TNFalpha, and PGE2 from human placenta and adipose tissue. Although both leptin and adiponectin significantly increased PGF2alpha release from human placenta, there was no effect of these hormones on PGF2alpha release from adipose tissue. Furthermore, this leptin- and adiponectin-induced proinflammatory response could be abrogated by treatment with the antiinflammatory ERK1/2 MAPK inhibitor U0126, the peroxisomal proliferator-activated receptor-gamma ligand troglitazone, and the nuclear factor-kappaB inhibitor BAY 11-7082. Collectively, these data indicate that leptin and adiponectin activate proinflammatory cytokine release and phospholipid metabolism in human placenta and adipose tissue, and antiinflammatory agents can abrogate leptin- and adiponectin-induced inflammation.

Adiponectin↗

Are alterations in plasma protease concentrations during labor associated with poor obstetric outcomes?

OBJECTIVE: The purpose of this study was to assess the association between abnormal connective tissue remodeling during labor as reflected by plasma concentrations of extracellular matrix remodeling proteolytic enzymes and adverse obstetric outcomes. STUDY DESIGN: A prospective observational study of 176 nulliparous women who attended the antenatal clinics at the Mercy Hospital for Women (Melbourne, Australia) from 1999 to 2000. RESULTS: Patients with a prolonged second stage (>120 minutes) had a significantly increased plasma concentration of matrix metalloproteinase 9 after delivery compared with control subjects (P<.001); patients in labor who underwent an emergency caesarean delivery had a significantly lower concentration (P<.001). Patients with a prolonged duration of labor (>11 hours) had a significantly lower urokinase plasminogen activator plasma concentration compared with control subjects (P<.01). CONCLUSION: Altered plasma concentrations of extracellular matrix remodeling proteolytic enzymes, matrix metalloproteinase 9, and urokinase plasminogen activator were found to be associated with abnormal labor and delivery outcomes. This finding may provide a useful predictor of abnormal obstetric outcomes.

Adult↗

Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies.

The aim of this study was to determine the release and regulation of leptin, resistin and adiponectin from human placenta and fetal membranes, and maternal subcutaneous adipose tissue and skeletal muscle obtained from normal and gestational diabetes mellitus (GDM)-complicated pregnancies at the time of Cesarean section. Tissue explants were incubated in the absence (basal control) or presence of 10 mug/ml lipopolysaccharide (LPS), 10, 20 or 40 ng/ml tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, 1 microM phorbol myristate acetate, 10, 20 and 40 mM glucose, 0.1, 1 and 10 microM insulin and 0.1 1 and 10 microM dexamethasone, progesterone and estrogen. After an 18-h incubation, the medium was collected and the release of leptin, resistin and adiponectin was quantified by ELISA. Human gestational tissues and maternal tissues released immunoreactive leptin, resistin and adiponectin; however, there was no difference in the release of either resistin or adiponectin between normal pregnant women and women with gestational diabetes. The release of leptin was significantly higher in placenta, amnion and choriodecidua obtained from normal pregnant women compared with women with GDM. However, in maternal tissues, the situation was reversed, with adipose tissue and skeletal muscle obtained from women with GDM releasing significantly greater amounts of leptin. In adipose tissue and skeletal muscle the release of leptin was significantly greater in insulin-controlled GDM compared with diet-controlled GDM, and leptin release from adipose tissue was significantly correlated with maternal body mass index. In all tissues tested, there was no effect of incubation with LPS, IL-6, IL-8 or TNF-alpha on leptin, resistin or adiponectin release. PMA significantly increased the release of resistin from placenta and adipose tissue. Insulin increased placental resistin release, whereas the hormones dexamethasone, progesterone and estrogen significantly decreased placental resistin release. The data presented in this study demonstrate that dysregulation of leptin metabolism and/or function in the placenta may be implicated in the pathogenesis of GDM. Furthermore, resistin release is greatly affected by a variety of inflammatory mediators and hormones.

Adiponectin↗

Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro.

There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-kappa B (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-kappa B regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-kappa B inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm). After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA-binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-beta. The data presented in this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus.

Adiponectin↗

Metformin in obstetric and gynecologic practice: a review.

Metformin is a common treatment for women who have insulin resistance manifesting as type 2 diabetes or polycystic ovarian syndrome (PCOS). With an increasing number of these patients conceiving, it is expected that the use of metformin in and around the time of pregnancy will increase. This article reassesses the mechanisms, safety, and clinical experience of metformin use in obstetrics and gynecology. Metformin is an attractive therapeutic option because administration is simple, hypoglycemia rare, and weight loss promoted. There is a large volume of research supporting the use of metformin treatment in diabetes mellitus, androgenization, anovulation, infertility, and recurrent miscarriage. Although metformin is known to cross the placenta, there is, as yet, no evidence of teratogenicity. Metformin has an array of complex actions, accounting for the varied clinical roles, many of which are still to be fully evaluated. Much research is still needed.

Abortion, Spontaneous↗

Determination of maternal body composition in pregnancy and its relevance to perinatal outcomes.

Three models and 10 specific methods for determining maternal body composition are discussed and their perinatal relevance reviewed. English language publications (1950 to January 2004) were searched electronically and by hand. Search terms included "body composition," "human," " pregnancy," "obesity," "adiposity," "regional," "2-, 3-, 4-component," "truncal," "peripheral," "central," "visceral" along with specific techniques and outcomes listed subsequently. Three models of body composition are described: 2-component being fat and fat-free mass; 3-component being fat, water, and protein; and 4-component being fat, water, protein, and osseous mineral. Ten techniques of body composition assessment are described: 1) anthropometric techniques including skinfold thicknesses and waist-hip ratio; 2) total body water (isotopically labeled); 3) hydrodensitometry (underwater weighing); 4) air-displacement plethysmography; 5) bio-impedance analysis (BIA); 6) total body potassium (TBK); 7) dual-energy x-ray absorptiometry (DEXA); 8) computed tomography (CT); 9) magnetic resonance imaging (MRI); and 10) ultrasound (USS). Most methods estimate total adiposity. Regional fat distribution-central (truncal) compared with peripheral (limb) or visceral compared with subcutaneous-is important because of regional variation in adipocyte metabolism. Skinfolds, DEXA, CT, MRI, or USS can distinguish central from peripheral fat. CT, MRI, or USS can further subdivide central fat into visceral and subcutaneous. Perinatal outcomes examined in relation to body composition include pregnancy duration, birth weight, congenital anomalies, gestational diabetes, gestational hypertension, and the fetal origins of adult disease. A few studies suggest that central compared with peripheral fat correlates better with birth weight, gestational carbohydrate intolerance, and hypertension. Means of accurately assessing maternal body composition remain cumbersome and impractical, but may more accurately predict perinatal outcomes than traditional assessments such as maternal weight.

Absorptiometry, Photon↗

Regulation of phospholipase isozymes by nuclear factor-kappaB in human gestational tissues in vitro.

Phospholipid-derived mediators are implicated in the initiation and progression of human labor and delivery, particularly in relation to infection-induced preterm labor. We previously demonstrated that, in human intrauterine tissues, lipopolysaccharide (LPS)-stimulated nuclear factor-kappaB (NF-kappaB) DNA binding activity, and subsequent cytokine release can be suppressed by sulfasalazine (SASP) concentrations greater than 5 mM. The aim of this study was to elucidate the effect the SASP on secretory type II phospholipase A(2) (PLA(2)), cytosolic PLA(2) (cPLA(2)), cyclooxygenase (COX) isozymes, and subsequent prostaglandin F(2alpha) (PGF(2alpha)) production in human gestational tissues. Human placenta, amnion, and choriodecidua (n = 4-9 separate placentas) were incubated in the presence of SASP (0.1, 1, 5, and/or 10 mM) under either basal or LPS (10 microg/ml) conditions. After 6 h incubation, the tissues were collected and assayed for type II PLA(2) by ELISA and cPLA(2), COX-1, and COX-2 content by Western blotting. The incubation medium was collected and assayed for type II PLA(2) and 13,14-dihydro-15-keto PGF(2alpha) release by ELISA and PGF(2alpha) by RIA. Treatment of placenta, amnion, and choriodecidua with SASP concentrations greater than 5 mM significantly inhibited basal and/or LPS-stimulated type II PLA(2) content and release, 13,14-dihydro-15-keto PGF(2alpha) release, and cPLA(2) protein content (ANOVA, P < 0.05); however, no effect of SASP was observed on basal or LPS-stimulated COX-1 or COX-2 protein. Although no effect of SASP was observed on basal and LPS-stimulated PGF(2alpha) release from placenta and amnion, it significantly increased both basal and LPS-stimulated PGF(2alpha) release from choriodecidua. In addition, SASP concentrations of 5 mM or greater significantly suppressed NF-kappaB DNA binding activity. These data are consistent with the hypothesis that NF-kappaB regulates the expression and release of phospholipase isozymes.

Amnion↗

Repression of oxidant-induced nuclear factor-kappaB activity mediates placental cytokine responses in gestational diabetes.

Although oxidative stress has been implicated in the pathogenesis of type 2 diabetes, limited data are available regarding its role in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The proinflammatory cytokines TNFalpha, IL-6, and IL-8 are released from the placenta at term and have been implicated in and/or associated with various metabolic events, including decreased insulin sensitivity. Previously we reported differences in the ex situ release of proinflammatory cytokines from placental and adipose tissues obtained from women with and without GDM. We proposed that these differences reflect preexposure and/or adaptation to oxidative stress by GDM tissues. In this study, we tested the hypothesis that placental tissue from women with GDM is less responsive to oxidative stress than tissue from normal women. Under basal conditions, release of TNFalpha, IL-6, and IL-8 was similar in both control and GDM groups. However, 8-isoprostane release was 2-fold greater in the GDM group (P < 0.01). In response to oxidative stress, TNFalpha and 8-isoprostane release and nuclear factor-kappaB (NF-kappaB) DNA-binding activity were significantly increased in normal tissues (20-fold, 2-fold, and 35%, respectively, P < 0.01). In contrast, the response of GDM tissues to oxidant stress was blunted, with no change in 8-isoprostane release, a 4-fold increase in TNFalpha release, and a 40% reduction in NF-kappaB DNA-binding activity. These data support the hypothesis that placentae from women with GDM display a reduced capacity, mediated by repression of NF-kappaB activity, to respond to oxidative stress.

Adult↗

Release of proinflammatory cytokines and 8-isoprostane from placenta, adipose tissue, and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus.

The aim of this study was to 1) profile the basal release of TNF-alpha, IL-6, IL-8, and 8-isoprostane (a marker of oxidative stress); and 2) investigate the effect of stimulation on the release of cytokines from sc adipose tissue and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus (GDM). Placenta, sc adipose tissue, and skeletal muscle were incubated in the absence (control) or presence of lipopolysaccharide (LPS; 10 microg/ml), TNF-alpha (10 ng/ml), IL-6 (10 ng/ml), or IL-8 (10 ng/ml). After an 18-h incubation, the medium was collected, and the release of TNF-alpha, IL-6, IL-8, and 8-isoprostane was quantified by ELISA. In all three tissues, 8-isoprostane release was greater in women with GDM, and stimulation with LPS increased 8-isoprostane release from adipose and skeletal muscle, but not placenta, obtained from women with GDM. However, in tissues obtained from normal pregnant women, LPS stimulation increased 8-isoprostane release in placenta and had no effect in adipose tissue and skeletal muscle. Their was no difference in the release of TNF-alpha, IL-6, and IL-8 from placenta, adipose tissue, and skeletal muscle obtained from normal pregnant women and women with GDM. Stimulation of placenta, adipose tissue, and skeletal muscle with LPS and TNF-alpha resulted in greater release of IL-6 and IL-8, whereas only LPS increased TNF-alpha release from all three tissues. The data presented in this study demonstrate that there is a differential release of 8-isoprostane from fetal (placenta) and maternal (adipose tissue and skeletal muscle) tissues obtained from normal pregnant women and women with GDM. These data are consistent with the hypothesis that oxidative stress may be involved in the progression and/or pathogenesis of GDM.

Adipose Tissue↗

In utero herpes simplex encephalitis.

BACKGROUND: Transplacental intrauterine infection with herpes simplex virus is an extremely rare complication of primary herpes simplex in pregnancy. Overwhelming fetal sepsis might result in multiorgan failure, including fetal brain death. CASE: A 34-year-old multigravida presented with a healing ulcerative genital rash at 16 weeks' gestation. She subsequently reported at 28 weeks' gestation that there had been no fetal movements for 2 weeks. A cardiotocograph showed absent short- and long-term variability. At delivery, an infant was born with disseminated herpes simplex infection in poor condition. Active treatment was subsequently withdrawn, and postmortem examination confirmed disseminated herpes simplex type 2 infection. CONCLUSION: Transplacental herpes simplex is a rare and potentially lethal form of congenital herpes. Overwhelming in utero sepsis should be considered in the differential diagnosis of fetal brain death.

Adult↗

N-Acetyl-cysteine inhibits phospholipid metabolism, proinflammatory cytokine release, protease activity, and nuclear factor-kappaB deoxyribonucleic acid-binding activity in human fetal membranes in vitro.

The production of reactive oxygen species (ROS), prostaglandins (PGs), proinflammatory cytokines, and proteases has been implicated in the pathogenesis of term and preterm labor. The nuclear factor-kappaB (NF-kappaB) transcription pathway is activated by ROS and is a key regulator of PGs, proinflammatory cytokine release, and protease activity. N-Acetyl-cysteine (NAC) is an antioxidant that through its ability to scavenger ROS suppresses NF-kappaB DNA-binding activity and resultant gene expression. The aim of this study was to elucidate the effect of NAC on NF-kappaB DNA-binding activity, phospholipid metabolism, cytokine release, and protease activity from human fetal membranes. Human amnion and choriodecidua (n = 9 separate placentas) were treated with 0 (control), 5, 10, or 15 mM NAC in the presence of 10 micro g/ml lipopolysaccharide. After 6-h incubation, the tissues were collected, NF-kappaB DNA binding activity was assessed by gel shift binding assays, and matrix metalloproteinase-9 and urokinase-type plasminogen activator activity were determined by zymography. The incubation medium was collected and assayed for type II phospholipase A(2) tissue content, IL-6, IL-8, TNFalpha, and 8-isoprostane release by ELISA. The release of PGF(2alpha) was measured by RIA. Treatment of fetal membranes with NAC significantly suppressed lipopolysaccharide-stimulated type II phospholipase A(2) release and content; PGF(2alpha), IL-6, IL-8, TNFalpha, and 8-isoprostane release; and matrix metalloproteinase-9 and urokinase-type plasminogen activator enzyme activity and suppressed NF-kappaB DNA-binding activity (by ANOVA, P < 0.05). The data presented in this study demonstrate that NAC inhibits an NF-kappaB-activated pathway and subsequent phospholipid metabolism, proinflammatory cytokine release, and protease activity in human fetal membranes.

Acetylcysteine↗

Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro.

Proinflammatory cytokines are implicated in the initiation and progression of human labor and delivery, particularly in relation to infection-induced preterm labor. In nongestational tissues, the nuclear factor kappa B (NF-kappaB) transcription pathway is a key regulator of proinflammatory cytokine release. In these tissues, sulfasalazine (SASP), through its ability to inhibit NF-kappaB activation, inhibits release of interleukin (IL)-2, IL-12, and tumor necrosis factor (TNF)-alpha. Therefore, the aim of this study was to investigate whether or not NF-kappaB activation regulates the formation of proinflammatory cytokines in human gestational tissues. Human placenta, amnion, and choriodecidua (n = 9 separate placentas) were incubated with 10 microg/ml of lipopolysaccharide (LPS) in the absence (control) or presence of SASP (0.1, 1, 5, or 10 mM). After 6 h of incubation, the tissues were collected, and NF-kappaB DNA binding activity in nuclear extracts was assessed by electromobility shift binding assay. The incubation medium was collected and the release of IL-6, IL-8, and TNF-alpha was quantified by ELISA. Treatment of placenta, amnion, and choriodecidua with SASP at concentrations 5 mM or greater significantly inhibited the release of IL-6, IL-8, and TNF-alpha, and NF-kappaB activation (ANOVA, P < 0.05). The data presented in this study demonstrate that the NF-kappaB transcription pathway is a key regulator of LPS-stimulated IL-6, IL-8, and TNF-alpha release from human gestational tissues. The control of NF-kappaB activation may therefore provide an alternative therapeutic strategy for reducing the release of proinflammatory mediators in infection associated preterm labor.

Adult↗

The effect of hospitalisation on ambulatory blood pressure in pregnancy.

METHODS: Twenty-four-hour ambulatory blood pressure monitoring was performed on 40 women (20 hypertensive, 20 normotensive) on a hospitalised and non-hospitalised day. Mean blood pressure differences were calculated for the awake, sleeping and 24-hour periods on both days. RESULTS: Mean heart rate was higher at home (1.79, p = 0.04) than in hospital, but there were no significant differences in mean systolic (1.30 mmHg, p = 0.06), diastolic (0.78 mmHg, p = 0.21) or mean arterial blood pressure (0.81 mmHg, p = 0.19) between the hospitalised and non hospitalised day for the group overall. Nevertheless, the range of individual responses was wide (-8.5 mmHg to 15.4 mmHg mean arterial blood pressure). Hypertensive women receiving antihypertensive therapy had significantly greater differences in mean arterial blood pressure between the hospital and non-hospital day when compared to the rest of the group (5.8 mmHg, compared to 3.3 mm Hg, p = 0.02). CONCLUSIONS: Although hospitalisation does not significantly lower blood pressure in pregnant women as a group, women receiving antihypertensive therapy demonstrate significant differences in blood pressure between hospital and home. Based on conventional blood pressure measurements alone, these women may be at risk of either under treatment, or over treatment, of blood pressure.

Adult↗

Regulation of proinflammatory cytokines in human gestational tissues by peroxisome proliferator-activated receptor-gamma: effect of 15-deoxy-Delta(12,14)-PGJ(2) and troglitazone.

Peroxisome proliferator-activated receptor (PPAR)-gamma is a ligand-dependent nuclear receptor that is essential for murine placental development and trophoblast differentiation. In nonreproductive tissues, PPAR-gamma regulates the formation of proinflammatory cytokines. Evidence suggests that many of the observed anti-inflammatory effects of PPAR-gamma are in part caused by antagonizing the activities of the transcription factors, including nuclear factor-kappa B. The aim of this study was to elucidate whether natural [15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2))] and synthetic (troglitazone) PPAR-gamma ligands regulate the secretion of IL-6, IL-8, and TNF-alpha from human intrauterine tissues. Human placenta, amnion, and choriodecidual tissues were incubated in the presence of 10 micro g/ml lipopolysaccharide in the absence (control) or presence of 30 micro M 15d-PGJ(2) (n = 6 independent placenta) or troglitazone (n = 6 independent placentas). After a 6-h incubation, the incubation medium was collected and the release of IL-6, IL-8, and TNF-alpha was quantified by ELISA. Treatment of placental, amnion, and choriodecidual tissues with both 15d-PGJ(2) and troglitazone significantly reduced the release of lipopolysaccharide-stimulated IL-6, IL-8, and TNF-alpha (t test, P < 0.05). Gel shift analyses demonstrated that 15d-PGJ(2), but not troglitazone, suppressed nuclear factor-kappa B DNA-binding activity. The data presented in this study demonstrate that the formation of proinflammatory mediators can be modulated by currently available therapeutic agents and may therefore be of therapeutic potential in human labor.

Amnion↗