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Activin A and inhibins (A and B) are growth factors expressed during pregnancy by the human placenta, decidua and fetal membranes, and by several fetal organs. They are secreted in both the maternal and the fetal circulations, but the net contribution of the fetus to inhibins/activin A production is still unclear. In the present study we determined whether there was a difference in the serum concentration of activin A, inhibin A and inhibin B between the artery and vein of the umbilical cord. Arterial and venous umbilical cord blood was obtained immediately before elective Cesarean section of 16 term infants from uncomplicated pregnancies. Inhibins and activin A levels were assayed by specific enzyme-linked immunosorbent assays. The paired t-test and linear regression analysis were used to calculate statistical significance. Inhibin A levels did not differ between the artery and vein of the umbilical cord. In contrast, arterial inhibin B levels were significantly (p0.001) lower, and activin A concentrations significantly (p0.05) higher than the respective venous concentrations. A significant correlation between arterial and venous levels of inhibin A (r = 0.591; p0.05), inhibin B (r = 0.749; p0.0001) and activin A (r = 0.571; p0.05) was found. The present findings suggest that the human placenta is the main source of inhibin B, and the fetus of activin A, in the umbilical cord. In light of the possible roles played by inhibin and activin in erythroid differentiation, protection of neurons against brain injury and modulation of adrenal and pancreatic hormone release, the present data may be of help in evaluating their changes in the umbilical cord when gestational diseases occur.

Corticotropin-releasing factor (CRF) is produced by the placenta and intrauterine tissues and secreted in increasing amounts from early to term pregnacy. In the presecnce of labor, a more incisive increase in CRF levels has been described, and women with preterm labor or hose destined to have premature delivery have higher midpregnancy CRF levels than hose who deliver at term. Urocortin is a 40-amino acid peptide belonging to the CRF family, expressed by human trophoblast and fetal membranes, which has the same biologic effects as CRF. Acting on the same CRF receptors, urocortin stimulates myometrial contractility and ACTH and prostaglandin release from cultured human placental cells. Because no data exist about urocortin levels in the maternal circultation at parturition, we investigated whether maternal plasma urocortin and CRF levels change according to cervical dilatation in healthy pregnant women at term labor. In a cross-sectional study of labor, a single maternal blood sample was collected from healthy pregnant women at term (n = 40); in a second longitudinal sudy, plama samples were collected longitudinally in a subset of patients (n = 8) throughout labor, according to a Bishop score evaluation. Both maternal plasma CRF and urocortin levels were higher in labor than those previously reported during pregnancy, but they did not change significantly during the different stages of labor when evaluated longitudinally. Some patients showed a trend toward increasing levels, whereas others had variable concentrations. Neither CRF nor urocortin levels changed during the progression of spontaneous labor.

Human placenta produces activin A, a glycoprotein belonging to the transforming growth factor beta superfamily, which modulates several placental immune and endocrine functions. However, substances involved in controlling placental activin A production are not yet completely elucidated. The aim of the present study was to investigate the effects of placental products, corticotropin-releasing factor (CRF), urocortin, prostaglandin E(2) (PGE(2)) and endothelin-1 (ET-1) on activin A release from cultured human placental cells. Placental tissue was collected at term from normal pregnancies and a trophoblast-enriched cell preparation was cultured for 48 h. The test substances were applied (concentration from 10(-9)-10(-7)M) and the medium was harvested after 3 h incubation; vehicle-treated cells (controls) were present in each experiment. Activin A concentrations in culture medium were measured by using a specific two-site enzyme immunoassay. The addition of CRF resulted in a dose-related increase of activin A concentrations (P < 0.01). The stimulatory effect of CRF was significantly reversed by alpha-helical CRF(9-41), the CRF receptor antagonist. Urocortin showed a stimulating effect on activin A release from placental cells (P < 0.05) but not dose-related; the effect of urocortin was reversed by an equimolar dose of CRF antagonist, astressin. ET-1 significantly increased activin A concentrations in the culture medium only at the highest concentration, 10(-7)M (P < 0.05). No difference in activin A release was observed after incubating the cells with PGE(2). The evidence that CRF, urocortin and ET-1 stimulate activin A secretion from cultured placental cells suggests that these vasoactive factors may affect the changes of placental activin A secretion in pre-eclamptic woman.

Objective To assess the value of different admission tests in predicting the outcome of small-for-gestational age (SGA) fetuses with normal Doppler waveforms in the umbilical artery. Methods Criteria for admission into this retrospective study included: singleton pregnancy with a birth weight < 10th centile; absence of severe maternal complications; no evidence of fetal anomalies on the sonogram; normal umbilical artery Doppler; and availability of complete follow-up. At the first antenatal sonogram classifying the fetus as SGA, Doppler analysis of the uterine and middle cerebral arteries was performed and amniotic fluid volume was assessed. Outcome variables included adverse perinatal outcome (perinatal death, severe morbidity) and emergency Cesarean section for fetal distress. Results Two hundred and thirty-one pregnancies were included in the study. The mean ± standard deriation birth weight and gestational age at delivery were 2222 ± 502 g and 37.3 ± 2.9 weeks, respectively. In 37 cases (16%), an emergency Cesarean section was performed. There was one intrauterine death and three fetuses delivered by emergency Cesarean section developed severe morbidity. Logistic regression demonstrated that abnormal velocimetry of the uterine arteries and fetal middle cerebral artery were independently correlated with the occurrence of Cesarean section. Conclusions SGA fetuses with normal umbilical artery Doppler waveforms and abnormal uterine arteries and fetal middle cerebral artery waveforms have an increased risk of developing distress and being delivered by emergency Cesarean section. Particularly when both uterine and fetal cerebral waveforms are altered at the same time, the risk is exceedingly high (86%) and delivery as soon as fetal maturity is achieved seems advisable. On the other hand, when both vessels have normal waveforms, the chances of fetal distress are small (4%) and expectant management is the most reasonable choice.

Activin A is a dimeric protein member of the transforming growth factor-beta (TGF-beta) family: it is synthesized by a variety of organs and follistatin is an activin-binding protein. A sensitive and specific assays for bioactive dimeric activin A and follistatin have recently allowed to measure these proteins in blood and other biological fluids, giving a new insights into their possible physiological role. Since human breast is able to produce activin A, the aim of the present study was to evaluate whether it and follistatin are measurable in breast milk of women during lactation. Concentrations of activin A and follistatin were measured in milk samples collected at 3, 5 and 30 days after delivery by using specific and sensitive two-site ELISAs. For the first time the presence of immunoreactive activin A and follistatin in human milk has been shown; no significant different concentration between the third and the fifth day after delivery was found. Furthermore, no difference of activin A and follistatin concentration between the whole and the skim milk or between spontaneous delivery and cesarean section was found. Milk activin A and follistatin concentrations after 1 month of lactation were significantly decreased (P < 0.01). Activin A and follistatin are present in human milk in high concentrations in the first week of lactation, while decrease after a month suggesting a possible role as growth factors in human milk.

Calcitonin gene-related peptide (CGRP) circulates in maternal circulation throughout pregnancy, and specific receptors for CGRP (CGRPrs) are expressed by human myometrium. Because CGRP induces a dose-dependent relaxation of human myometrium, we examined a role for CGRP in modulation of myometrial smooth muscle contractility during pregnancy and labor. The aim of the present study was to evaluate the changbes of maternal serum CGRP levels during parturition, according to the mode of delivery and in relation to cervical dilatation. Circulating CGRP levels were measured in the following groups of healthy women: nonpregnant women, during the follicular phase of the menstrual cycle (n = 19); at term pregnancy (39–40 weeks; n = 24); after elective cesarrean delivery (39–40 weeks; n = 20); and at spontaneous vaginal delivery (39–40 weeks; n = 16). In a subgroup of women, blood samples were collected longitudinally throughout labor at various cervical dilatations in the progress of labor (n = 8). Pregnant women at term not in labor had significantly higher CGRP levels than nonpregnant women (P = .021). No significant difference was found between women who delivered vaginally and those who had elective cesarean, and there were no correlations between CGRP plasma levels and cervical dilatation. Parturition is characterized by no significant changes in maternal serum CGRP levels, and no significant correlation exists between plasma CGRP levels and cervical dilatation during labor.

Several findings suggest a role of placental hormones in the regulation of maternal and fetal physiology during pregnancy. The placenta and its accessory membranes, amnion and chorion, although of fetal origin, actually undertake the role of intermediary barriers and active messengers in the maternal-fetal dialogue. They synthesize, metabolize and serve as targets for numerous hormones and cytokines which control all aspects of pregnancy and parturition. Among these, corticotropin-releasing factor (CRF) has been one of the most investigated in the last decade. The secretion of placental CRF is autonomous, but increasing evidence indicates that maternal or fetal physiological and pathological conditions may influence such secretion. In the event of acute or chronic metabolic, physical or infection stress, the placenta takes part in a stress syndrome by releasing CRF, which may contribute to restore local blood flow, and to influence the timing of delivery. Placental CRF and cytokines produced in case of intrauterine infection may activate labour, thereby helping the fetus to escape from a hostile environment.On the background of maternal and/or fetal stress elicited by a number of pathological conditions, CRF appears to play a role in coordinating adaptive changes in uterine perfusion,maternal metabolism, fluid balance and possibly uterine contractility.

Our studies demonstrate significantly lower expression of relaxin and its receptor in ectopic endometriotic tissues than their expression in eutopic endometrium and in endometrium from normal controls. These data suggest that in normal and eutopic endometrium, relaxin may exert a protective effect against endometriosis.

Human placenta is a major source of corticotropin-releasing factor (CRF), and local effects of CRF in fetal membranes and placenta have been shown, i.e., adrenocorticotropic hormone (ACTH) and oxytocin release from cultured placental cells, as well as prostaglandin release from amnion, chorion and decidua. Two distinct CRF receptors (CRF-R1 and CRF-R2) have been characterized: CRF-R1 consists of two isoforms (CRF-R1alpha and CRF-R1beta) while CRF-R2 has at least three different splice variants (CRF-R2alpha, CRF-R2beta and CRF-R2gamma). To date, CRF-R1 receptor has been identified in human placenta and in pregnant myometrium, while no evidence for placental CRF-R2 receptor isoforms has been provided. The present study investigated whether the different isoforms of CRF-R1 and CRF-R2 receptor mRNA are expressed in fetal membranes and placenta. Tissues were collected after spontaneous vaginal delivery (38-40 weeks) or elective caesarean section (39-41 weeks). The gene expression of CRF receptors was first studied by reverse transcriptase-polymerase chain reaction (RT-PCR), and the presence of CRF-R1alpha, but not of CRF-R1beta, in human placental trophoblast, amnion/chorion and decidua was shown. In addition, among the three CRF-R2 splice variants, only CRF-R2beta mRNA was expressed by trophoblast and fetal membranes. By using in situ hybridization, CRF-R1 and CRF-R2 probes positively hybridized trophoblast and related membranes. CRF-R1 was localized in the syncytiotrophoblast cells, chorionic trophoblast and decidua with a small amount in the amnion. CRF-R2 probe mainly hybridized syncytiotrophoblast cells, but cytotrophoblast also contained discreet amounts of CRF-R2 mRNA signal. The CRF-R2 hybridization signal was also observed within the structure of the villi (blood vessels), chorionic trophoblast and decidual cells, but it was faint or absent in the amniotic epithelium. There was no significant difference in the distribution of CRF-R1 or CRF-R2 mRNA signal between placentas collected from vaginal delivery or caesarean section. The evidence that intrauterine tissues differently express CRF-R1alpha and CRF-R2beta supports possible different local roles of CRF and related peptides into intrauterine tissues during pregnancy.

Background: Hypoxic ischemic encephalopathy (HIE) is a major cause of permanent neurological disabilities in full-term newborns. We measured activin A in urine collected immediately after birth in asphyxiated full-term newborns, and assessed the ability of the measurements to predict the occurrence of perinatal encephalopathy.Methods: We studied 30 infants with perinatal asphyxia and 30 healthy term neonates at the same gestational age. We recorded routine laboratory variables, cranial assessments by standard cerebral ultrasound, and the presence or absence of neurological abnormalities during the first 7 days after birth. Urinary activin A concentrations were measured at first urination and 12, 24, 48, and 72 h after birth.Results: Asphyxiated infants were subdivided as follows: group A (n = 18): no or mild HIE with good prognosis and group B (n = 12): moderate or severe HIE with a greater risk of neurological handicap. Activin A concentrations in urine collected at birth (median collection time at first urination 0.08 μg/L at first urination in 10 of 12 patients with moderate or severe HIE but in none of 18 patients with no or mild HIE.Conclusions: Activin A measurements in urine soon after birth may be a promising tool to identify which asphyxiated infants are at risk of neurological sequelae.

Inhibins and activins are growth factors belonging to the transforming growth factor-beta) family and are known to influence cell proliferation and differentiation. Because transforming growth factor-beta is involved in physiological and tumoral changes of uterine tissues, the present study aimed to evaluate whether human normal and neoplastic endometrial and cervical epithelial cells express and secrete inhibin A, inhibin B, and activin A. To test this hypothesis, different approaches were used. By RT-PCR, the expression of specific messenger RNAs (mRNAs) for the inhibin alpha, activin betaA and betaB subunits, and activin receptor type II and type IIB was investigated: 1) in primary cultures of endometrial (stroma and epithelium) or cervical (epithelium) cells from healthy women; and 2) in specimens of endometrial or cervical carcinoma. To demonstrate a possible secretion of the proteins, dimeric inhibin A, inhibin B, and activin A were measured in culture medium of normal epithelial or stromal endometrial cells and in uterine washing fluid of healthy women or patients with endometrial adenocarcinoma. Levels of the proteins were also measured in serum of women with endometrial or cervical carcinoma. Cultured endometrial stromal or epithelial cells and epithelial cervical cells expressed inhibin alpha, activin betaA and betaB, and activin receptor type II and type IIB mRNAs. The same finding was obtained in specimens of endometrial or cervical carcinomas. Dimeric inhibin A, inhibin B, and activin A were measured in culture medium of both endometrial and cervical cells. In particular, resulting activin A levels were significantly higher in epithelial than in stromal cultured endometrial cells (P < 0.01). Dimeric proteins were also detected in the washing fluid of the uterine cavities of healthy women (controls) and with endometrial adenocarcinoma, in which higher activin A levels were found (P < 0.01 vs. controls). Women with endometrial carcinoma showed serum activin A levels significantly higher than healthy controls (P < 0.01), which significantly decreased after surgical removal of endometrial or cervical tumors (P < 0.01). The present study, for the first time, showed that inhibin A, inhibin B, and activin A, as well as activin receptors, are expressed in normal and neoplastic human uterine tissues. A secretion of activin A from tumoral cells into systemic circulation is suggested by the observation that the high levels in serum of patients with endometrial or cervical carcinoma decreased after the surgical removal of the tumor.

Corticotropin-releasing factor (CRF) is a 41-amino acid neurohormone involved in the neuroendocrine response to stress, also playing a role in cell-mediated immune functions and in inflammation. In the light of recent evidence showing an association between endometriosis and altered cellular immunity factors, the present study investigates immunoreactive (ir) CRF in the peritoneal fluid of healthy women, and in patients with pelvic adhesions and endometriosis. In addition, peritoneal fluid concentrations of CRF-binding protein (CRF-BP), a 37-kDA protein of 322 amino acids able to modulate central and peripheral CRF functions, were evaluated. Peritoneal fluid samples (n = 35) were collected from healthy women (n = 12), from patients with intrapelvic adhesions (n = 8), and from women with endometriosis (n = 15). In the control group a specimen of blood was collected. Peritoneal fluid and plasma CRF levels were measured by a two-site immunoradiometric assay (IRMA), and CRF-BP levels were measured by a specific radioimmunoassay (RIA). CRF and CRF-BP levels in peritoneal fluid were lower than plasma values, and independent of the phase of the menstrual cycle: in particular, in healthy women there was no significant difference between peritoneal fluid and plasma CRF-BP levels during two phases of the menstrual cycle. Peritoneal fluid levels of CRF and CRF-BP were similar in healthy patients and women with pelvic adhesions or with endometriosis, and when patients with adhesions or with endometriosis were considered as single group, no difference in CRF and CRF-BP levels was noted in comparison to the control group. In patients with endometriosis, no significant differences in peritoneal fluid CRF or CRF-BP levels were recorded, although in patients with stage 2 and stage 3 of the disease peritoneal fluid CRF-BP levels were higher than in healthy patients or in those with a lower grade of the disease. These results suggest that the peritoneal concentration of these hormones may reflect the circulating levels: the absence of any significative variations in peritoneal fluid CRF levels according to the degree of the endometriosis, suggests a limited role of CRF in the immunological changes related to the disease

This study was designed to determine whether basic fibroblast growth factor (bFGF) gene expression in human placenta varies as a function of gestational age and to evaluate whether bFGF synthesis might be altered in pathological pregnancies. Moreover, we also investigated whether human placental cells express the bFGF receptor gene. The presence of mRNA for bFGF and its receptor was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) performed on total RNA derived from human placental cells at different times of culture. Levels of bFGF mRNA were determined by competitive RT-PCR in human placental tissues collected at the beginning and at the end of pregnancy. Competitive RT-PCR was also employed to evaluate bFGF synthesis in term placentas derived from pregnancies complicated by diabetes. mRNA for both bFGF and its receptor were demonstrated in human placenta starting as early as 8 weeks of pregnancy. Values of bFGF mRNA were significantly higher in first trimester compared with term placentas. Term placentas derived from pregnancies associated with type I diabetes expressed levels of bFGF mRNA higher than those present in normal term placentas. These data demonstrate that bFGF and its receptor are synthesized in human placental cells throughout gestation. Moreover, bFGF gene expression is developmentally regulated. Finally, bFGF might also be partially responsible for the placental alterations observed in pregnancies complicated by diabetes.

Human placenta expresses subunit messenger RNAs for synthesizing inhibin A and B. Experimental studies have shown an effect of inhibins on placental hormone secretion, but an endocrine function is suggested by the high levels in maternal circulation. Although information is available on the changes of inhibin A in serum of healthy pregnant women, data on inhibin B levels are limited to early gestation. The aim of the present study was to investigate the changes of inhibin B levels in maternal circulation in healthy pregnant women throughout gestation, and to evaluate whether early pregnancy disturbances or gestational diseases are characterized by abnormal inhibin B levels. The protocol included various groups of pregnant women. A longitudinal evaluation of serum inhibin B levels was done at specific intervals (8–12, 13–18, 19–24, 25–28, 29–33, and 34–40 weeks) in the following groups: 1) healthy pregnant women (n = 13); 2) women at risk of hypertension who did not develop hypertension (n = 8); and 3) wom...

Corticotropin-releasing factor (CRF)-binding protein (CRF-BP) modulates the activity of the hypothalamus-pituitary-adrenal axis during pregnancy, counteracting the actions of circulating or locally produced CRF. The aim of the present study was to evaluate CRF and CRF-BP levels in amniotic fluid of healthy pregnant women during the last 4 weeks of gestation and during spontaneous labor at term. A cross-sectional study was conducted on amniotic fluid collected from pregnant women (n = 68), subdivided into two groups: 1) not in labor (n = 31), and 2) in labor (n = 37). CRF-BP was measurable in all specimens of amniotic fluid, but at 37 weeks of pregnancy the concentration in amniotic fluid was lower (10-fold) than that in maternal plasma (P < 0.01). Pregnant women at 39 and 40 weeks gestation had amniotic fluid CRF-BP levels significantly lower than those at 37 weeks (P < 0.01), and pregnant in women in labor had significantly lower levels than women at term but not in labor (P < 0.01). CRF levels in amniotic fluid and plasma collected in women at 40 weeks gestation not in labor or in labor were significantly higher than those at 37 weeks (P < 0.01). During the last 4 weeks of gestation, amniotic fluid CRF levels in women not in labor did not significantly differ from those obtained at term labor. During the last weeks of pregnancy, amniotic fluid CRF-BP levels decrease and are inversely correlated to CRF levels. The decrease in amniotic fluid CRF-BP at term, augmenting the amount of free CRF, supports the hypothesis that labor is associated with significant changes in local autocrine and paracrine factors that may affect PG release and myometrial contractility, contributing to the mechanism of parturition.

Aim Intraventricular haemorrhage (IVH) is the most common variety of cerebral haemorrhage and cause of neurological disabilities in preterm newborns. We evaluated the usefulness of urine Activin A concentrations for the early detection of perinatal IVH. Methods We conducted a case–control study on 100 preterm newborns (20 with IVH and 80 without IVH) in whom urine Activin A was measured at five predetermined time-points in the first 72 h after birth. IVH diagnosis and the extension of the lesion were performed by ultrasound scanning within the first 72 h and at 1 week after birth, respectively. Results Urine Activin A in infants who developed IVH was significantly higher than in controls at all monitoring time-points (p

Study Objective To show and evaluate outcomes of a modified laparoscopic hysterectomy technique (total reverse laparoscopic hysterectomy). Design Observational study (Canadian Task Force classification II-2). Setting Department of Women's and Children's Health, Obstetrics and Gynecology Clinic, University of Padova, Padova, Italy. Patients One hundred one women underwent total reverse laparoscopic hysterectomy for benign disease. Indications for surgery, patient characteristics, surgical data, complications, and patient satisfaction were recorded. Interventions Total reverse laparoscopic hysterectomy. Measurements and Main Results The modified procedure was performed starting with the incision of the vesicouterine fold and the pubocervical fascia followed by the dissection of only the anterior layer of the broad ligament, thus preserving the integrity of the posterior leaf (retrograde hysterectomy). This technique permits identification of the ureter until the cross with the uterine artery, creating a “safe triangle” for closure of the uterine vessels. The remaining surgical time did not differ from the standard technique. The average operating time was 112.1 ± 35.6 minutes, and the average intraoperative mean blood loss was 79.5 ± 138.4 mL. Ninety-one (90%) patients were very satisfied after surgery. No injuries to the ureter or bladder occurred in any patients. No other major complications were recorded. Conclusion Reverse hysterectomy is another technique for performing laparoscopic hysterectomy, and it has been proven to be safe and efficient.

Recently a new member of the corticotropin-releasing factor (CRF) family has been cloned and named urocortin. It has been localized in rat brain and to human chromosome 2. The present study investigated whether human placenta and related tissues express mRNA and immunoreactive urocortin. Using specific oligonucleotide primers, reverse transcriptase-polymerase chain reaction experiments were performed on total RNA isolated from human placenta and decidua collected both at early stage of gestation (8-11 weeks) and at term (39-40 weeks). In addition, experiments were also done on specimens of amnion and chorion collected at term. Independently from the gestational age, placental and decidual cells expressed urocortin mRNA, with a 145 bp DNA band corresponding to the expected length. The expression of urocortin mRNA was also found in amnion and chorion. Using specific antiserum and an immunoperoxidase technique, immunoreactive urocortin was then localized in syncytiotrophoblast cells and in some extent in cytotrophoblast cells of placental villi at term, as well as in fetal membranes and maternal decidua. The present findings revealed that human placenta and gestational related tissues express human urocortin gene and localize immunoreactive urocortin, supporting the concept that these tissues are capable of expressing a large number of neuroendocrine peptides.

The aim of the present study was to investigate the presence of the immunoreactive oxytocin in human placental extracts and putative factors regulating the release of immunoreactive oxytocin from cultured human placental cells. Fresh placental tissue was collected from pregnant women at term and dissected of membranes (n = 5). Presence of immunoreactive oxytocin in trophoblast tissue was evaluated by a specific radio-immunoassay after acidic extraction and high-pressure liquid chromatography. In a second set of experiments, primary cultures of placental cells were performed and, 48-72 h after dissociation, the effect of arginine vasopressin, corticotropin-releasing factor, neuropeptide Y, activin A, inhibin A, noradrenaline or prostaglandins on immunoreactive oxytocin level in culture medium was investigated. The presence of immunoreactive oxytocin was shown in the acidic extract of trophoblast at term, and in the culture medium of human placental cells, and it was identical to the native peptide. The addition of corticotropin-releasing factor or arginine vasopressin, but not of neuropeptide Y, increased the release of immunoreactive oxytocin three- to fourfold from placental cells, with a dose-dependent effect (P < 0.01). A significantly increased release of immunoreactive oxytocin was shown in presence of noradrenaline (P < 0.01), which was reversed by prazosin, an antagonist of alpha-adrenergic receptors. Recombinant human activin A (P < 0.01), but not inhibin A, stimulated the release of immunoreactive oxytocin three- to fourfold from placental cells. Prostaglandin F2 alpha was a potent secretagogue of immunoreactive oxytocin, whereas a partial or no effect was observed when prostaglandin E2 or prostaglandin I2 was added. Thus, the present findings showed that human placenta contains immunoreactive oxytocin, and that its release from cultured placental cells is regulated by neurohormones, growth factors or prostaglandins.

OBJECTIVE: The primary objective of this investigation was to evaluate whether maternal serum corticotropin-releasing factor levels during pregnancy were predictive of spontaneous preterm delivery. STUDY DESIGN: Maternal serum levels of corticotropin-releasing factor and its binding protein were measured from 20 weeks of gestation in a cross-sectional study of 396 asymptomatic women at high risk for preterm delivery. RESULTS: Gestational age–specific corticotropin-releasing factor levels were not consistently or substantially increased for preterm compared with term deliveries, whether preterm delivery was due to preterm labor or preterm premature rupture of membranes. The binding protein for corticotropin-releasing factor did not vary according to gestational age until term, when it dropped substantially. CONCLUSION: Serum corticotropin-releasing factor levels do not appear to be an important predictor of preterm birth in asymptomatic patients who subsequently have either preterm labor or preterm premature rupture of membranes. Nevertheless, the drop in the corticotropin-releasing factor binding protein level at term suggests that the bioavailability of corticotropin-releasing factor increases as parturition approaches. (AM J OBSTET GYNECOL 1996;174:1477-83.)

I. Introduction During the last 15 years our concepts of the role and functioning of intrauterine tissues during human pregnancy have been changing. While initially considered solely for their role in the exchange of gas and transfer of nutrients and waste, recent studies emphasize the contribution of placenta, decidua, and amnion-chorion to gestational development. Indeed, starting in the 1970s, evidence that human placenta is able to produce hormones, cytokines, and growth factors greatly expanded our knowledge of the functioning of intrauterine tissues and their putative roles in the physiology of pregnancy. A growing number of studies has provided strong evidence that fetal membranes (amnion, chorion) and maternal decidua are capable of hormone production and metabolism and, when containing hormonal receptors, serve as endocrine organs (Fig. 1). Intrauterine tissues are a source of brain, pituitary, gonadal, and adrenocortical peptide and steroid hormones, chemically identical to and biologically acti...

Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of alpha fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case-control study in 758 healthy women undergoing amniocentesis at mid-gestation, of whom 12 had a spontaneous intrauterine fetal death before 28 weeks, and 746 matched controls. Concentrations were corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Concentrations of S100B, but not alpha fetoprotein, were significantly higher (p0.0001) in women who later had spontaneous fetal death (median 4.431 MoM [95%CI 3.605-6.197]) than in controls (1.000 MoM [1.062-1.121]). Sensitivity, specificity, and positive and negative predictive values of S100B as a diagnostic test were 100%, suggesting that measurement of this protein at amniocentesis could be useful to identify at-risk women.

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.

Human placenta produces a large variety of bioactive substances with endocrine and neural competence: pituitary and gonadal hormones, hypothalamic-like releasing or inhibiting hormones, growth factors, cytokines and neuropeptides. The most recent findings indicate that locally produced hormones regulate the secretion of other placental hormones supporting a paracrine/autocrine regulation. In placental endocrinology, a particular relevance is played by steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been proposed as a placental internal regulatory system acting on steroids production from human placenta. In addition, activin and inhibin have been proposed as further regulatory substances of the synthesis and secretion of steroids; the addition of activin A to placental culture augments GnRH, hCG and progesterone, and this effect can be significantly reduced by the addition of inhibins. Finally, a steroid-steroid interaction is suggested by the evidence that placental estrogen has a positive role in the regulation of progesterone biosynthesis. Other steroid-protein interactions have been observed in human placenta. In fact, recent data indicate that progesterone inhibits placental corticotropin-releasing factor (CRF) and estrogens act on placental conversion of cortisol to cortisone, activating cortisol secretion by the fetal adrenal and enhancing fetal adrenal function with advancing gestation.

Background: Low cardiac output syndrome (LCOS) remains a major perioperative complications in infants subjected to open-heart surgery with cardiopulmonary bypass (CPB). The present study investigated whether perioperative blood assessment of a potent vasoactive peptide namely adrenomedullin (AM) can predict the risk of LCOS. Methods: We measured AM levels in 48 patients (LCOS: n = 9; controls: n = 39) undergone to open-heart surgery with CPB at five predetermined time points before, during and after the surgery. Clinical, laboratory and perioperative data were analyzed by a multiple logistic regression model. Results: AM significantly decreased (p

To review the treatments of the cesarean-induced isthmocele in restoring infertility, associated techniques, and the risks of complications associated with their use.Isthmocele is a reservoir-like pouch defect on the anterior wall of the uterine isthmus located at the site of a previous cesarean delivery scar. The flow of menstrual blood through the cervix may be slowed by the presence of isthmocele, as the blood may accumulate in the niche because of the presence of fibrotic tissue, causing pelvic pain in the suprapubic area. Moreover, persistence of the menstrual blood after menstruation in the cervix may negatively influence the mucus quality and sperm quality, obstruct sperm transport through the cervical canal, interfere with embryo implantation, leading to secondary infertility. The removal of the local inflamed tissue may be performed by laparoscopic, combined laparoscopic-vaginal, or vaginal surgery, and operative hysteroscopy, a minimally invasive approach to improve symptoms and restore fertility.Isthmocele occurs after cesarean section, a common method of delivery and one of the most frequent surgical procedures, so that its upward incidence appears likely to continue in the near future. Because of its minimal invasiveness, resectoscopy may be the better choice for treatment, yielding good therapeutic results.

S100B protein is a well-established marker of brain damage. Its importance in urine assessment is the convenience of a collection and sampling procedure that can be repeated without risk for the newborn. Since S100B is mainly eliminated by the kidneys and perinatal asphyxia (PA) is often associated with kidney failure we investigated whether S100B release might be kidney-mediated, thereby modifying the protein's reliability as a brain-damage marker.We examined a cohort of healthy (n=432) and asphyxiated newborns (n=32) in whom kidney function parameters (blood urea and creatinine concentrations and urine gravity) and urine S100B concentrations were assessed in the first hours after birth. Data were analyzed by multiple logistic regression analysis with S100B as independent variable among a variety of clinical and laboratory monitoring parameters.S100B urine concentrations were significantly higher (P0.01) in PA newborns than controls. No significant correlations (P0.05, for all) between total urine S100B levels and kidney function parameters such as creatinine (r=0.03), urea (r=0.04) and urine gravity (r=0.06) were found. Multiple logistic regression analysis of a series of clinical and laboratory monitoring parameters (odds ratio at sampling: 9.47) with S100B as independent variable showed a positive significant correlation only between S100B levels (P0.001) and the occurrence of PA.The present study shows that altered kidney function is not an adverse and/or confounding factor in urine S100B assessment and marks a new step towards the introduction of longitudinal monitoring of brain constituents in clinical practice.

Objective To evaluate clinical outcomes associated with the resection of both endometrioma and posterior broad ligament (PBL) among women with PBL adhesion associated with endometrioma. Methods Between January 2007 and December 2009 at the Villanova Hospital, Florence, Italy, a prospective trial was conducted on 99 consecutive patients with unilateral or bilateral endometrioma who underwent laparoscopic ovarian cystectomy by a stripping technique and homolateral PBL resection where PBL adhesion was associated with endometrioma. The prevalence of PBL adhesion and endometriosis, the association between PBL endometriosis and pain, and the recurrence of endometrioma and pain were evaluated. All data were analyzed with Prism software. Results Among 124 endometriomas treated by concomitant PBL resection, the PBL was not affected by adhesions in only 2% of patients. PBL endometriosis was superficial in 36 (29.5%) and deep in 86 (70.5%) of the histologic preparations; deep endometriosis correlated with preoperative pain. At 1-year follow-up, endometrioma had recurred in 7 patients; the main symptom reported was mid-cycle pain (24 patients, 24%; P = 0.0007). Conclusion Ovarian endometriosis was often (98%) associated with PBL endometriosis; deep endometriosis of PBL correlated with pain symptoms. Although PBL resection increased the incidence of mid-cycle pain, it was associated with low recurrence of endometrioma.

This randomized, double blind, placebo-controlled study compared the usefulness of danazol 400mg vaginally versus 600mg orally in women as a preoperative preparation for hysteroscopic surgery. Ninety-one fertile women were randomly allocated to Group A (46 patients received 400mg of danazol placed into the posterior vaginal fornix and three oral tablets of commercially available folic acid as a placebo), and Group B [45 women treated with 600mg of danazol orally (200mg three times daily) and two vaginal tablets of Lactobacillus rhamnosus as a placebo]. The patients underwent an operative hysteroscopy, transvaginal sonography, blood tests, and a histological assay. A visual analog scale (VAS) score to compute the degree of the surgeon's satisfaction was used. The outcome measures were as follows: an evaluation of the changes in the endometrial thickness, the prevalence of endometrial atrophy, changes in the blood tests, any collateral effects, the degree of difficulty and view, the duration of the surgical procedure, any complications during the operative hysteroscopy and associated side effects, and the surgeon's satisfaction with the endometrial preparation. The vaginal administration route was associated with a more pronounced effect on the endometrial thickness. Significantly more patients receiving vaginal danazol (45/46) had a hypotrophic endometrium than those receiving oral danazol (37/45, P0.01). In addition, the patients receiving danazol vaginally had a shorter operating time, lower infusion volume, fewer side effects, and a higher surgeon satisfaction. Vaginal danazol adequately prepares the endometrium for an operative hysteroscopy by thinning the endometrium effectively with few side effects and little impact on the metabolic parameters.

When endometriosis infiltrates more than 5 mm beneath the peritoneum it is called deeply infiltrating endometriosis and may involve the bladder. Only 1-2% of women with endometriosis have urinary involvement, mainly in the bladder. Resectoscopic transurethral resection alone is no longer recommended because of the surgical risks and recurrence. Usually surgeons prefer a laparotomy or laparoscopic approach depending on nodule localization and personal skill. We describe a new combined transurethral approach with Versapoint(®) and laparoscopic technique in the management of bladder endometriosis and the 12-month follow-up.We performed a prospective observational study of 12 women affected by symptomatic bladder endometriosis at the University Hospital of Padova. We utilized a transurethral approach using a 5.2-mm endoscope with a 0.6-mm-diameter bipolar electrode (Gynecare Versapoint(®)). We delimited just the edges of the lesion via cystoscopy, penetrating transmurally at 3 or 9 o'clock without trespassing into the bladder peritoneum. Then, starting from the lateral bladder hole, we excised the lesion by laparoscopy with Harmonic ACE(®). The bladder hole was repaired with a continuous 3-0 monofilament two-layer suture.Operating time ranged from 115 to 167 min and mean blood loss ranged from 10 to 200 ml. No conversion to laparotomy and no intraoperative complications occurred. No dysuria or hematuria were present at follow-up. There was one case of persistent suprapubic pelvic pain at the 12-month follow-up.A combined transurethral approach with Versapoint(®) and laparoscopic treatment is a safe and easy technique for the management of bladder endometriosis, with low risks and good resolution of symptoms.

Study Objective To estimate the efficacy and tolerability of low dose spinal anesthesia during operative hysteroscopy in a group of patients with high surgical risks. Design Case series study (Canadian Task Force Classification II-2). Setting Tertiary centers for women health care. Patients A total of 47 women affected by endometrial polyps (n = 32), myomas (n = 8), and abnormal uterine bleeding (n = 7) scheduled for inpatient operative hysteroscopy. Interventions Transvaginal ultrasonography; office diagnostic hysteroscopy; preoperative evaluation of American Society of Anesthesiologist (ASA) classification; inpatient operative hysteroscopy; low-dose spinal anesthesia with hyperbaric bupivacaine; compilation of a questionnaire. Main Outcome Measures Practicability and patients’ subjective experiences with spinal anesthesia; duration of cervical dilation and for operative hysteroscopy; infusion volume needed; incidence of surgical complications. Results Resectoscopy was performed in all patients, with the exception of 1 woman (2.1%) in which spinal anesthesia was unsuccessful. No statistically significant differences were noted among groups in terms of intra- and peri-operative findings. Sensory block induced by spinal anesthesia was suitable for surgery in all patients, and side effects occurred far less frequently than mentioned in the literature. Data reported in the questionnaire revealed that 93.5% of women would choose a spinal anesthesia again for a potential operative hysteroscopy in the future, since for 89.1% of them long lasting anesthesia is of relevance. Conclusions Low-dose spinal anesthesia is a feasible technique in the inpatient setting for operative hysteroscopy in women with high surgical risks.

Objective: Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed. Design: Multicenter randomized control trial. Setting: Three tertiary centers of neonatal intensive care units from December 2004 to December 2007. Population: Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44). Interventions: All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short-and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment. Results: High-frequency oscillatory ventilation infants showed a significant lower duration (p

In a retrospective case-control study, we compared the effectiveness of hysteroscopic correction and hormonal treatment to improve symptoms [postmestrual abnormal uterine bleeding (PAUB), pelvic pain localized in suprapubic site] associated with isthmocele. Women (n = 39; mean age ± SD, 35 ± 4.1 years) were subdivided in Group A [patients (n = 19) subjected to hysteroscopic surgery (isthmoplasty)] and, Group B [women (n = 20) undergoing hormonal treatment consisting of one oral tablet containing 0.075 mg of Gestodene and 0.030 mg of Ethynylestradiol for 21 days, followed by 7 days of suspension]. Resolution and/or improvement of menstrual disorders; patients degree of satisfaction with the treatment were measured 3 months later, by office hysteroscopy (Grop A) or phone call. PAUB and pelvic pain resolution was achieved in all patients: Group A had significant lower numbers of days of menstrual bleeding (P0.001), prevalence of pelvic pain in the suprapubic area (P = 0.04) and, higher degree of satisfaction (P0.001) compared to Group B. In conclusion, resectoscopic surgery is a valid way to treat patients with symptoms of prolonged postmenstrual uterine bleeding caused by isthmocele. Data from this study also indicate that resectoscopy may be the first choice because it is minimally invasive and yields good therapeutic results.

To evaluate the x-ray appearance of Essure microinserts 5 years after their insertion.Prospective controlled study.Tertiary referral centers for gynecologic care.Forty-five consecutive women with successful hysteroscopic bilateral placement of the Essure devices and postprocedure satisfactory hysterosalpingography confirmation test.Pelvic anteroposterior x-ray.Stability and and symmetric appearance of Essure microinsert positions; measurement of the intrauterine distance between the two devices.After 5 years from their placement, no detachment nor fracture of devices was observed. x-Ray recognition of the device after 5 years showed findings similar to those recorded at 3 months' follow-through hysterosalpingography.x-Ray evaluation of findings related to stability of position, symmetric appearance, and distance between the two Essure microinserts corroborates the irreversibility and the reliability of the fibrotic reaction that ensured tubal occlusion after devices placement.

The reproductive outcome in 41 consecutive patients with cesarean-induced isthmocele and secondary infertility was evaluated prospectively. Patients included menopausal women (mean [SD; 95% CI] age, 35 [4.1; 29-42] years), with fertility duration of 3 to 8 (4.6 [28]) years with isthmocele, postmenstrual abnormal uterine bleeding, and suprapubic pelvic pain. Transvaginal ultrasound and office hysteroscopy were used to diagnosis isthmocele. Complete fertility tests were performed to exclude other causes of infertility in both female and male participants. Operative hysteroscopy was performed to correct the cesarean scar defect, and histologic findings were evaluated. Correction of isthmocele via operative hysteroscopy was successful in all cases evaluated. Patients became pregnant spontaneously between 12 and 24 months after isthmoplasty. Thirty-seven of the 41 patients (90.2%) delivered via cesarean section, and 4 (9.8%) had a spontaneous abortion in the first trimester. Isthmoplasty resulted in resolution of postmenstrual abnormal uterine bleeding and suprapubic pelvic pain in all patients. Thus, it was concluded that surgical treatment of cesarean-induced isthmocele using a minimally-invasive approach (operative hysteroscopy) restores fertility and resolves symptoms in women with a cesarean section scar and secondary infertility.

The use of antidepressant drugs during pregnancy is rapidly increasing both in Europe and in the USA, with controversial data regarding side-effects on fetus and newborn. We investigated, in pregnant women and in fetal biological fluids whether the concentrations of a brain protein, Activin A, changed in association with the use of selective serotonin re-uptake inhibitors (SSRI).We conducted a case control study in 24 women treated with SSRIs, matched with 24 healthy pregnancies as controls. Maternal blood (during labor, T1), fetal blood (venous (T2) and arterial [T3] umbilical cord blood) and amniotic fluid (T4) were drawn for standard laboratory assessment and for Activin A measurement.Activin A concentrations in maternal and fetal biological fluids were significantly higher in SSRI users than in the control groups(P0.05, for all).Activin A in maternal and fetal biological fluids is increased after SSRI administration in the third trimester of pregnancy. The present findings open up a new cue for further studies aimed at investigating protein's key role in central nervous system protection/damage in pregnant women using these drugs.

Urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3) are neuropeptides expressed by human endometrium. This study evaluated (i) the expression of Ucn 2 and Ucn 3 mRNA in endometriotic lesions and in endometrium of women with endometriosis; (ii) the effect of Ucn 2 and Ucn 3 on cytokines secretion from cultured endometrial stromal cells. Endometriotic tissue was collected from endometrioma (n=39); endometrial specimens were obtained from women with (n=39) and without (n=41) endometriosis throughout menstrual cycle. Tissue specimens were analysed for Ucn 2 and Ucn 3 mRNA expression and peptide localization; the effects of Ucn 2 or Ucn 3 on tumour necrosis factor (TNF-α) and interleukin (IL-4) secretion from cultured endometrial stromal cells was studied. Ucn 2 and Ucn 3 mRNA expression and localization were assessed by RT-PCR and by immuohistochemistry, respectively; cytokines secretion were measured by ELISA. Results showed that endometriotic tissue expressed both Ucn 2 and Ucn 3, with Ucn 3 expression higher in ectopic than in eutopic endometrium. Endometrial Ucn 2 mRNA expression in controls showed peak values at early proliferative phase, while in endometriotic patients low expression and no significant changes throughout menstrual cycle were observed. Endometrial Ucn 3 mRNA expression was highest in late secretory phase in controls, while in endometriotic patients low levels and no menstrual-cycle-related changes were found. When added to cultured endometrial cell cultures, Ucn 2 significantly increased TNF-α (P

There is a growing evidence on the use of biomarkers in daily practice both as of markers of brain/multiorgan damage and/or trophic factors. However, among different tools, Activin A, S100B protein, and Hemeoxygenase-1 (HO-1 or Heat Shock Protein 32, HSP32) assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more noninvasive techniques to fulfill the minimal handling diagnostic and therapeutic strategy. In this regard, among different biological fluids, human milk for its unique composition can constitute a wide source of knowledge useful both in clinical daily practice and in research.Therefore, this mini-review reports recent data on the presence and the usefulness of Activin A, S100B protein, and HO-1/HSP32 assessment in human milk as brain/multiorgan development markers. Results open up a new cue on the use of these markers in perinatal medicine as a key protein for investigations focusing on fetal/neonatal development.

Activin-A is a protein over-expressed and secreted by the brain after neuronal destruction. We evaluated whether serum activin-A increases in asphyxiated full-term newborns (AFTNs) at risk of hypoxic-ischemic-encephalopathy (HIE). 105 consecutive infants (35 affected by perinatal asphyxia due to acute fetal distress; 70 healthy gestational-age matched newborns) underwent cranial assessment and neurologic examination at 12, 24 and 72 hours after birth and, on discharge from the hospital and; activin-A and monitoring laboratory variables assessment at birth. According to the occurrence of HIE within 7-days after birth, AFTNs were subdivided in Group A (n= 20; no/mild HIE with good prognosis) and Group B (n= 15; moderate/severe HIE with a greater risk of neurological handicap). Activin-A was significantly (P less than 0.0001) higher in Groups A and B than controls and highest (P less than 0.001) in Group B. At 0.66 ng/L activin-A achieved a sensitivity of 93.33 per cent and a specificity of 96.63 per cent, respectively, as HIE diagnostic test. These findings show that activin A increased in AFTNs with HIE before the appearance of related signs.

Activin A and related proteins (inhibins, follistatin [FS], follistatin-related gene [FLRG], endometrial bleeding associated factors [ebaf]) are involved in the complex mechanisms allowing the establishment and the maintenance of pregnancy. As a consequence of ovarian progesterone stimuli, activin A is expressed and secreted by the stromal endometrial cells, which locally induces the decidualization process, a prerequisite for implantation. Moreover, activin A does influence the implantation phase, also enhancing cytotrophoblast differentiation, indirectly, by increasing the expression of other molecules involved in embryo implantation, such as matrix metalloproteinases (MMPs) and leukemia inhibitory factor (LIF). The local derangement of activin A pathway in some pregnancy disorders (incomplete and complete miscarriages, recurrent abortion, and ectopic pregnancy [EP]) further sustains the hypothesis that activin A and its related proteins play a relevant role in the establishment of pregnancy.

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, S100B, activin A, neuronal specific enolase (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia.

The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, gB-endor-phin) and adrenal (Cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (V02) every 20 min) was used as physical stressor. While mean ± SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular auto-regulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present review is aimed at investigating the role of biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein, in the cascade of events leading to I-R injury in newborns complicated by perinatal asphyxia.

Objective To compare the effectiveness and safety of harmonic scalpel versus electrosurgery to reduce blood loss during laparoscopic myomectomy. Design Prospective randomized controlled study. Setting Tertiary referral centers for gynecological care. Patient(s) One hundred sixty consecutive premenopausal women with symptomatic uterine leiomyomata who were assigned to one of the two treatment groups (a total of 80 patients in each group): treatment with electrosurgery devices with a vasoconstrictive solution (50 mL of saline solution and 0.5 mL of epinephrine [1/2 vial of 1 mg/mL]; group A) or harmonic scalpel (group B). Intervention(s) Laparoscopic myomectomy. Main Outcomes Measure(s) The global operative time, the time spent for myoma enucleation and for suturing uterine wall defects, and intraoperative blood loss as well as the surgical difficulty degree and postoperative pain at 24 and 48 hours after the laparoscopic procedure. Result(s) No relevant intra- or postoperative complications were observed in either group. The degree of pain 24 hours after surgery was significantly lower in patients in whom the harmonic scalpel was used. The degree of surgical difficulty did not differ between groups, but the global operative time was significantly shorter in the harmonic scalpel group. Conclusion(s) The use of the harmonic scalpel for laparoscopic myomectomy is associated with low total operative time, low intraoperative blood loss, and low postoperative pain, with no increase in surgical difficulty.

Endometriosis is an important contributing factor to chronic pelvic pain and infertility. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) have each been implicated in the establishment of endometriotic lesions. Since relaxin regulates the expression of MMPs and VEGF in the endometrium, we tested the hypothesis that relaxin plays a role in endometriosis by comparing the expression of relaxin mRNA and its LGR7 (RXFP1) receptor mRNA in normal human endometrium to those in samples from patients with endometriosis.

Intrauterine infection is suggested to cause perinatal brain white matter injury. In the current study, we evaluated whether S100B, a brain damage marker, may be also assessed in maternal bloodstream after white matter injury induced by fetal intravenous application of lypopolisaccharide (LPS) endotoxin. Fourteen fetal sheeps were chronically catheterized at a mean gestational age of 107 days. Three days after surgery, fetuses (n = 7) received 500 ng of LPS or 2 mL 0.9% saline (n = 7) intravenously (IV). Lypopolisaccharide and placebo groups were monitored by continuous hemodynamic data recordings and at 6 predetermined time points (control value; 3, 6, 24, 48, and 72 hours after LPS/placebo administration) blood was drawn for laboratory parameters and S100B assessment. Brain damage was evaluated by light microscopy after Kluver-Barrera staining. Selected areas of the periventricular white matter were also examined by electron microscopy. White matter injury was detected in all LPS-treated fetuses, whereas no abnormalities were seen in control animals or in LPS-treated mothers. Maternal and fetal S100B protein levels were significantly higher in the LPS group than in the control group at all monitoring time points (P < .001). The highest fetal-maternal S100B levels were observed at 3-hour time-point (P < .001). We found that S100B protein is increased in the maternal district in presence of fetal periventricular brain white matter injury induced by endotoxin. The present data offer additional support for S100B assessment in the maternal circulation in pregnancies complicated by intrauterine infection at risk of white matter injury.

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents of calcium mediated effects could be responsible for reperfusion injury, which, in turns, leads to cerebral hemorrhage and damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia or cardiovascular disorders treated by risky procedures such as open heart surgery and cardiopulmonary by-pass (CPB). To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein; neuronal specific enolase (NSE), a dimeric isoenzyme; glial fibrillary acid protein (GFAP), a astroglial protein, in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia or cardiovascular disorders requiring risky therapeutic strategies such as CPB and/or extracorporeal membrane oxygenation.