ACE2: a key modulator of the renin-angiotensin system and pregnancy.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.

Clinical and in Vitro Evidence against Placenta Infection at Term by Severe Acute Respiratory Syndrome Coronavirus 2.

Despite occasional reports of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy, the question of placental infection and its consequences for the newborn remain unanswered. Herein, we analyzed the placentas of 31 coronavirus disease 2019-positive mothers by reverse transcriptase PCR, immunohistochemistry, and in situ hybridization. Only one case of placental infection was detected, which was associated with intrauterine demise of the fetus. Differentiated primary trophoblasts were then isolated from nonpathologic human placentas at term, differentiated, and exposed to SARS-CoV-2 virions. Unlike for positive control cells Vero E6, the virus inside cytotrophoblasts and syncytiotrophoblasts or in the supernatant 4 days after infection was undetectable. As a mechanism of defense, we hypothesized that trophoblasts at term do not express angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), the two main host membrane receptors for SARS-CoV-2 entry. The quantification of these proteins in the placenta during pregnancy confirmed the absence of TMPRSS2 at the surface of the syncytium. Surprisingly, a transiently induced experimental expression of TMPRSS2 did not allow the entry or replication of the virus in differentiated trophoblasts. Altogether, these results underline that trophoblasts are not likely to be infected by SARS-CoV-2 at term, but raise concern about preterm infection.

Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta.

OBJECTIVES: To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta. METHODS: Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). RESULTS: Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT_8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae. CONCLUSIONS: ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy.

Importance: The management of mother-infant dyads during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic constitutes a major issue for neonatologists. In mothers with SARS-CoV-2 infection, current recommendations suggest either to separate the dyad or encourage protected rooming-in under appropriate precautions. No data are available regarding the risk of mother-to-infant transmission of SARS-CoV-2 during rooming-in. Objective: To evaluate the risk of postnatal transmission of SARS-CoV-2 from infected mothers to their neonates following rooming-in and breastfeeding. Design, Setting, and Participants: A prospective, multicenter study enrolling mother-infant dyads from March 19 to May 2, 2020, followed up for 20 days of life (range, 18-22 days), was performed. The study was conducted at 6 coronavirus disease 2019 maternity centers in Lombardy, Northern Italy. Participants included 62 neonates born to 61 mothers with SARS-CoV-2 infection who were eligible for rooming-in practice based on the clinical condition of the mother and infants whose results of nasopharyngeal swabs were negative at birth. Exposures: Mothers with SARS-CoV-2 infection were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission. Main Outcomes and Measures: Clinical characteristics and real-time reverse transcriptase-polymerase chain reaction for SARS-CoV-2 on neonatal nasopharyngeal swabs at 0, 7, and 20 days of life. Results: Of the 62 neonates enrolled (25 boys), born to 61 mothers (median age, 32 years; interquartile range, 28-36 years), only 1 infant (1.6%; 95% CI, 0%-8.7%) was diagnosed as having SARS-CoV-2 infection at postbirth checks. In that case, rooming-in was interrupted on day 5 of life because of severe worsening of the mother's clinical condition. The neonate became positive for the virus on day 7 of life and developed transient mild dyspnea. Ninety-five percent of the neonates enrolled were breastfed. Conclusions and Relevance: The findings of this cohort study provide evidence-based information on the management of mother-infant dyads in case of SARS-CoV-2 maternal infection suggesting that rooming-in and breastfeeding can be practiced in women who are able to care for their infants.

Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling.

OBJECTIVE: Pregnant women can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet the incidence of perinatal infection is low. We hypothesized that this could be related to low expression of the membrane receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), in the fetoplacental unit. We evaluated protein expression of ACE2 at various gestational ages in both placentae and fetal organs from pregnancies not infected with SARS-CoV-2. METHODS: In May 2020, using samples from a registered biobank, we performed immunohistochemical analysis for ACE2 in tissue samples from fetal organs and placentae from five cases of second- or third-trimester medical termination of pregnancy in healthy women (performed between 15 and 38 weeks' gestation), as well as a further two placentae, one from a 7-week spontaneous miscarriage in a non-infected woman and one from a symptomatic pregnant woman positive for SARS-CoV-2 delivered by Cesarean section at 34 weeks. Samples were paraffin-embedded and organ tissues included kidney, brain, lung, intestinal tract, heart and testis. Matching tissues (kidney, intestinal tract, lung and testis) from autopsies of four 8-year-old children were tested as controls. Tissue sections were incubated with rabbit monoclonal anti-ACE2, and protein expression of ACE2 was detected by immunohistochemistry. RESULTS: ACE2 expression was detected in fetal kidney, rectum and ileum samples from 15 weeks onwards and in the pediatric controls. It was barely detectable in fetal lung samples at 15 + 5 weeks' gestation and not detectable thereafter, and, in the pediatric controls, ACE2 was detectable only in type-2 pneumocytes. No ACE2 expression was found in the cerebral ependymal or parenchymal tissues or in cardiac tissues. ACE2 was expressed in placental syncytiotrophoblast and cytotrophoblast samples, but not in the amnion, from 7 weeks onwards. The intensity and distribution of ACE2 staining in the placenta from the symptomatic SARS-CoV-2 woman was similar to that in the non-infected placentae. CONCLUSIONS: Marked placental expression of ACE2 provides a rationale for vertical transmission at the cellular level. Absence of ACE2 expression in the fetal brain and heart is reassuring regarding the risk of congenital malformation. Clinical follow-up of infected pregnant women and their children is needed to validate these observations. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Elevated transaminases in a COVID-19 positive patient at term of gestation: a case report.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome 2 virus (SARS-CoV-2) and it is spreading worldwide with an alarming high transmission rate. SARS-CoV-2 usually attacks the lungs causing a wide range of symptoms ranging from mild dyspnea to severe shortness of breath requiring intubation. Elevation of liver transaminases in the patients' sera has been described in up to 53% of the COVID-19 positive patients. The underlying pathogenic mechanisms of the virus on the liver cells are unclear and only few hypotheses are currently available. Data on COVID-19 in pregnant women are lacking and the management of COVID-19 pregnant women is challenging. An elevation of the transaminases during pregnancies infected by SARS-CoV-2 has never been described before. METHODS: Here we presented the case of a 29 years-old patient at 38 weeks of gestation COVID-19 positive with elevated transaminases. RESULTS: The patient showed a progressive decrease of transaminases after the delivery of the fetus. We provided details about the daily transaminases trend, the therapy used and the maternal/neonatal outcomes. CONCLUSIONS: We speculate that in our case the delivery of the fetus contributed to the normalization of the liver enzymes. In patients affected by COVID-19, at term of gestation, with elevated transaminases, delivery of the fetus is an appealing option. If confirmed by larger studies, our proposed management might be incorporated in the obstetrical management guidelines for COVID-19 positive patients.

Elevación de enzimas hepáticas inducida por COVID-19 en embarazada / Elevated liver enzimes induced by COVID-19 in pregnancy

INTRODUCCIÓN: Las alteraciones del perfil hepático durante el embarazo ocurren en 3-5% de las gestantes. Una nueva etiología que se ha presentado en el contexto de pandemia actual es el síndrome respiratorio agudo severo relacionado con el nuevo coronavirus (SARS-CoV-2). Éste es responsable de alteraciones hepáticas en 2 a 11% de la población general infectada por este virus, y de hasta un 30% en las embarazadas que se infectan con SARS-CoV-2. Con el objetivo de mostrar una presentación poco frecuente del SARS-CoV-2 se expone un caso clínico de elevación de transaminasas en embarazada inducida por este nuevo virus. CASO CLÍNICO: Paciente de 36 años, cursando embarazo de 20+6 semanas, consulta por dolor abdominal asociado a ictericia y coluria. Se solicita estudio donde destaca elevación de transaminasas. Ecografía abdominal con vía biliar fina. Se descartan diferentes etiologías de hepatitis aguda y crónica (dada la falta de antecedentes). Finalmente se solicita PCR para COVID-19 que resulta positiva. CONCLUSIÓN: Luego de un estudio exhaustivo de diferentes etiologías de elevación de transaminasas, se atribuye esta alteración enzimática a SARS-CoV-2. Se decide seguimiento ambulatorio estricto con pruebas hepáticas cada dos semanas. La paciente evoluciona estable con exámenes normales luego de un mes desde que se indica el alta hospitalaria. Después de descartar etiologías frecuentes de elevación de transaminasas durante el embarazo, sugerimos solicitar el estudio de este virus con PCR para COVID-19, ya que podría ser una presentación poco frecuente de SARS-CoV-2.

INTRODUCTION: Approximately 3-5% of women present alterations of hepatic enzymes during pregnancy. Under the new circumstances that the world is facing with the SARS-COV2 pandemic, a new etiology for hepatic enzyme alterations has risen. The severe acute respiratory syndrome that the novel coronavirus causes is responsible for hepatic enzyme alterations in 2 to 11% of the sick population that did not have a previous underlying hepatic condition. Furthermore, hepatic enzyme alterations in pregnant women infected with SARS-COV2 presents in up to 30% of the cases. An infrequent presentation of SARS-COV2 is presented as our clinical case. CLINICAL CASE: A 36-year-old patient with a 20+6 week pregnancy presents abdominal pain, jaundice and choluria. General blood workup shows elevated transaminases. The abdominal ultrasound revealed a thin bile duct. Acute and chronic hepatitis etiologies were discarded. Finally, a PCR of COVID-19 was solicited, which turned out to be positive. CONCLUSIÓN: After an exhaustive study to determine the etiology of the elevated transaminases, the hepatic alterations were attributed to SARS-COV2 infection. A conservative management was adopted, with outpatient follow-up with liver testing every two weeks. The patient progresses with a stable steady decline in hepatic enzyme levels, and one-month post hospital discharge, her transaminases had reached normal values. Based on this clinical case, after ruling out frequent etiologies for elevated transaminases during pregnancy, it seems reasonable to request a PCR for COVID-19, since it could be a rare presentation of SARS-CoV-2.

Liver Enzyme Elevation in Pregnant Women Receiving Antiretroviral Therapy in the ANRS-French Perinatal Cohort.

BACKGROUND: High rates of liver enzyme elevation (LEE) in women receiving antiretroviral treatment (ART) during pregnancy have been reported, but causes remain unclear. We estimated the prevalence and risk factors of LEE in a national prospective multicenter cohort. METHODS: We studied 5748 pregnant women living with HIV enrolled in the French Perinatal Cohort 2005-2014, treated with ART, with no active hepatitis B or C coinfection. Adjusted hazard ratio (aHR) was estimated using Cox models with ART as time-dependent variable, separately for women on ART at conception and those initiating ART during pregnancy. RESULTS: LEE (grade ≥ 1) was observed in 16.7%, grade 3-4 in 2%. Among women with LEE, 6.7% had pre-eclampsia, 9.8% intrahepatic cholestasis of pregnancy, and 1.4% other identified medical causes. Most LEEs (82.2%) were unexplained. In women with unexplained LEE, LEE was the reason for hospitalization in 51 (6%) women, cesarean section in 13 (2%), induction of labor in 3 (0.4%), and change in ART regimen in 49 (6%) women. Unexplained LEE was associated with higher risk of preterm births, P < 0.001. Among women on ART at conception, the risk of unexplained LEE was lower with NNRTI-based regimens than with PI-based regimens: aHR = 0.5 (0.3-0.7), with no difference among the PI drugs. Most women initiating ART during pregnancy were on a PI-based regimen (89%). Among them, LEE was less frequent for women on nelfinavir vs. lopinavir/r [aHR = 0.4 (0.2-0.8)]. CONCLUSIONS: Rates of LEE among pregnant women living with HIV are high and impact obstetrical care management. The possible role of PIs needs further investigation.

Mast cell chymase decreases the severity of group B Streptococcus infections.

BACKGROUND: Group B Streptococcus (GBS) or Streptococcus agalactiae are ß-hemolytic gram-positive bacteria that colonize the lower genital tracts of women and are frequently associated with infections during pregnancy. Innate immune defenses are critical for controlling GBS dissemination and systemic infection. Mast cells are resident sentinel cells that come into contact with pathogens early during colonization and infection. OBJECTIVE: We aimed to investigate the contribution of chymase to systemic GBS infection and rates of preterm birth. METHODS: Pharmacologic and genetic approaches using mice deficient in mast cell protease (MCPT) 4, the mouse functional homologue of human chymase, were used. RESULTS: Our studies show that mast cells release a protease with chymotrypsin-like cleavage specificity in response to GBS. Additionally, increased GBS systemic infection and preterm births were observed in MCPT4-deficient mice versus MCPT4-sufficient mice. Furthermore, we observed that proteolytic cleavage of the host extracellular matrix protein fibronectin by peritoneal cell-derived mast cell lysates diminished GBS adherence. Consistent with this observation, the increase in GBS dissemination and preterm births observed in MCPT4-deficient mice was abolished when GBS was deficient in expression of the fibronectin-binding protein SfbA. CONCLUSIONS: Taken together, our results suggest that the protective effect of MCPT4 against GBS dissemination and preterm labor can be attributed in part to MCPT4-mediated proteolysis of fibronectin. Our studies reveal a novel role of mast cells in defense against bacterial infections.

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

BACKGROUND: It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. METHODS: We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. RESULTS: HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels. CONCLUSIONS: Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.

Extended-spectrum ß-lactamase infections during pregnancy: a growing threat.

Extended-spectrum ß-lactamases (ESBLs) are rapidly evolving plasmid transferrable enzymes that confer unique patterns of antibiotic resistance on various bacterial species. Such organisms pose special challenges to laboratory identification, as well as antibiotic selection, administration, and follow-up. Although such infections are increasingly common in the obstetric population, issues surrounding ESBLs are not widely recognized by practicing obstetricians, and controversies exist regarding diagnosis and management. This article provides the practitioner with a summary of clinically pertinent information that will assist in the proper care of pregnant patients with ESBL infection.

Alteration in cytochrome P450 3A4 activity as measured by a urine cortisol assay in HIV-1-infected pregnant women and relationship to antiretroviral pharmacokinetics.

OBJECTIVES: Pregnancy results in physiological changes altering the pharmacokinetics of drugs metabolized by cytochrome P450 3A4 (CYP3A4). The urinary ratio of 6-ß hydroxycortisol to cortisol (6ßHF : F) is a marker of CYP3A4 induction. We sought to evaluate its change in antiretroviral (ARV)-treated HIV-1-infected women and to relate this change to ARV pharmacokinetics. METHODS: Women receiving various ARVs had pharmacokinetic evaluations during the third trimester of pregnancy (>30 weeks) and postpartum with determination of 6ßHF : F carried out on the same days. The Wilcoxon signed rank test was used to compare the ratio antepartum to postpartum. The relationship between the change in ratio and the change in pharmacokinetics was analysed using Kendall's tau. RESULTS: 6ßHF : F ratios were available for 107 women antepartum, with 54 having postpartum values. The ratio was higher antepartum (P=0.033) (median comparison 1.35; 95% confidence interval 1.01, 1.81). For 71 women taking a protease inhibitor (PI), the antepartum vs. postpartum 6ßHF : F comparison was marginally significant (P=0.058). When the change in the 6ßHF : F ratio was related to the change in the dose-adjusted ARV area under the plasma concentration vs. time curve (AUC) between antepartum and postpartum, the 35 subjects in the lopinavir/ritonavir (LPV/r) arms demonstrated an inverse relationship (P=0.125), albeit this correlation did not reach statistical significance. CONCLUSIONS: A 35% increase in the urinary 6ßHF : F ratio was measured during late pregnancy compared with postpartum, indicating that CYP3A induction occurs during pregnancy. The trend towards an inverse relationship between the change in the 6ßHF : F ratio and the change in the LPV AUC antepartum vs. postpartum suggests that CYP3A induction may be one mechanism behind altered LPV exposure during pregnancy.

Prevention of Chlamydia-induced infertility by inhibition of local caspase activity.

Tubal factor infertility (TFI) represents 36% of female infertility and genital infection by Chlamydia trachomatis (C. trachomatis) is a major cause. Although TFI is associated with host inflammatory responses to bacterial components, the molecular pathogenesis of Chlamydia-induced infertility remains poorly understood. We investigated the hypothesis that activation of specific cysteine proteases, the caspases, during C. trachomatis genital infection causes the disruption of key fertility-promoting molecules required for embryo development and implantation. We analyzed the effect of caspase inhibition on infertility and the integrity of Dicer, a caspase-sensitive, fertility-promoting ribonuclease III enzyme, and key micro-RNAs in the reproductive system. Genital infection with the inflammation- and caspase-inducing, wild-type C. trachomatis serovar L2 led to infertility, but the noninflammation-inducing, plasmid-free strain did not. We confirmed that caspase-mediated apoptotic tissue destruction may contribute to chlamydial pathogenesis. Caspase-1 or -3 deficiency, or local administration of the pan caspase inhibitor, Z-VAD-FMK into normal mice protected against Chlamydia-induced infertility. Finally, the oviducts of infected infertile mice showed evidence of caspase-mediated cleavage inactivation of Dicer and alteration in critical miRNAs that regulate growth, differentiation, and development, including mir-21. These results provide new insight into the molecular pathogenesis of TFI with significant implications for new strategies for treatment and prevention of chlamydial complications.

Lipopolysaccharide-induced murine embryonic resorption involves nitric oxide-mediated inhibition of the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase.

The initial inactivation of prostaglandins (PGs) is mediated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). PGs are potent mediators of several biological processes, including inflammation and reproduction. In uterus, PGs play a key role in infection-induced pregnancy loss, in which concentration of this mediator increased. This process is accompanied with the induction of nitric oxide synthase expression and a marked increase in uterine levels of nitric oxide. There is no information concerning nitric oxide contribution to potential changes in PG catabolism, but experimental evidence suggests that nitric oxide modulates PG pathways. The specific objectives of the study were to evaluate the protein expression of HPGD (15-PGDH) and to characterize the nitric oxide-dependent regulation of this enzyme in a model of lipopolysaccharide (LPS)-induced embryonic resorption. Results show that LPS decreased HPGD protein expression and augmented PGE synthase activity; therefore, PGE2 levels increased in uterus in this inflammatory condition. Just as LPS, the treatment with a nitric oxide donor diminished HPGD protein expression in uterine tissue. In contrast, the inhibition of nitric oxide synthesis both in control and in LPS-treated mice increased 15-PGDH levels. Also, we have found that this enzyme and PGE2 levels are not modulated by peroxynitrite, an oxidant agent derived from nitric oxide. This study suggests that LPS and nitric oxide promote a decrease in the ability of the uterus for PG catabolism during bacterially triggered pregnancy loss in mice.

Bacterial vaginosis and biomarkers of oxidative stress in amniotic fluid.

OBJECTIVE: In this study we tried to determine if the activities of the primary antioxidant enzymes are detectable in amniotic fluid and if they can be used as early biomarkers of complications in pregnancy connected with bacterial vaginosis. METHODS: This was a prospective study in which amniotic fluid was taken between 16 and 19 weeks of gestation. 161 pregnant women were divided into two groups: study group--patients with the treated local infection and control group--healthy pregnant women. Levels of reduced glutathione, and the activities of glutathione peroxidase, glutathione reductase, glutathione S-transferase, xanthine oxidase, superoxide dismutase and lipid peroxidation were determined spectrophotometrically in amniotic fluid samples. RESULTS: Concentration of malonyldialdehide (product of lipid peroxidation) varied greatly between investigated groups. Xanthine oxidase and superoxide dismutase activities, though very low, were present in amniotic fluid samples. Also, enzymes of glutathione cycle and reduced glutathione concentrations were detectable and showed certain variations. CONCLUSION: Although, biomarkers of antioxidant activity are present in the amniotic fluid, they are not different between women with and without bacterial vaginosis.

Protective role of heme oxygenase-1 in Listeria monocytogenes-induced abortion.

It is well-known fact that various pathogens, including bacteria, virus, and protozoa, induce abortion in humans and animals. However the mechanisms of infectious abortion are little known. In this study, we demonstrated that Listeria monocytogenes infection in trophoblast giant cells decreased heme oxygenase (HO)-1 and B-cell lymphoma-extra large (Bcl-XL) expression, and that their overexpression inhibited cell death induced by the infection. Furthermore, HO-1 and Bcl-XL expression levels were also decreased by L. monocytogenes in pregnant mice. Treatment with cobalt protoporphyrin, which is known to induce HO-1, inhibited infectious abortion. Taken together, our study indicates that L. monocytogenes infection decreases HO-1 and Bcl-XL expression and induces cell death in placenta, leading to infectious abortion.

Pancreatic adenocarcinoma presenting as acute pancreatitis during pregnancy: clinical and radiologic manifestations.

Only seven cases of pancreatic adenocarcinoma diagnosed during pregnancy have been reported. In this article, we describe a case of pancreatic adenocarcinoma presenting clinically as acute pancreatitis in a pregnant patient. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) revealed a pancreatic mass with an inflammatory component and multiple hyperintense metastatic lesions in the liver. The patient was initially treated for biliary pancreatitis, and pancreatic cancer was not suspected given her young age and absence of risk factors. A diagnosis of pancreatic cancer in a pregnant patient requires a high index of suspicion, and pancreatitis can be a mode of presentation.

Asymptomatic bacteriuria in pregnancy: evaluation of reagent strips in comparison to microbiological culture.

Screening for asymptomatic bacteriuria during pregnancy, the major risk factor for symptomatic urinary tract infection during pregnancy have been recommended. This cross sectional study was conducted to determine prevalence of asymptomatic bacteriuria in Ibadan and evaluate the diagnostic accuracy and relative cost effectiveness of dipstick tests for nitrite and leucocyte esterase in comparison to laboratory culture. Two hundred and five patients, presenting for their first antenatal visit at the University College Hospital, Ibadan, participated in the study. Urine samples obtained from the participants were subjected to two tests; reagent dipstick test for nitrite and leucocyte esterase and routine laboratory culture, which is the gold standard for diagnosis. Main outcome measures were sensitivity, specificity, positive and negative predictive values of the reagent dipstick tests as well as likelihood ratios. The prevalence of asymptomatic bacteriuria in pregnancy with routine laboratory culture and using combined leucocyte esterase and nitrite strip tests were 10.7% and 11.7% respectively. Compared with laboratory culture, combined strip tests had sensitivity, specificity and negative predictive values of 50%, 92.9% and 93.9% respectively, indicating a statistically significant lower level of accuracy (P < 0.05). The corresponding likelihood ratios for positive and negative strip tests (LR+ and LR-) were 7 and 0.5 respectively. The study concludes that combined Leucocyte esterase-nitrite dipstick test is not sufficiently sensitive and specific to be used for routine screening of bacteriuria in pregnancy in place of laboratory culture, though may be more cost effective in low resource settings.

Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights.

Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube.