The role of various transporters in the placental uptake of ofloxacin in an in vitro model of human villous trophoblasts.

Introduction: Six years after the US Food and Drug Administration approval of the broad-spectrum antibiotic ofloxacin (OFLX), the chiral switching of this racemic mixture resulted in a drug composed of the L-optical isomer levofloxacin (LVFX). Since both fluoroquinolones (FQs) were introduced to the pharmaceutical market, they have been widely prescribed by physicians, with careful administration during pregnancy and breastfeeding. Therefore, the role of the influx and efflux placental transporters in the concentrations of these drugs that permeate through human placental barrier model was investigated in this study.

The effects of pravastatin on the normal human placenta: Lessons from ex-vivo models.

Introduction: Research in animal models and preliminary clinical studies in humans support the use of pravastatin for the prevention of preeclampsia. However, its use during pregnancy is still controversial due to limited data about its effect on the human placenta and fetus.

Methods: In the present study, human placental cotyledons were perfused in the absence or presence of pravastatin in the maternal reservoir (PraM).

In first-time mothers, post-partum depressive symptom prospectively predict symptoms of post-traumatic stress.

Background: Symptoms of both depression and Post-Traumatic Stress Disorder (PTSD) are prevalent among first-time mothers following birth. However, the direction of the association between the two types of symptoms is unclear.

Methods: Ninety six first-time mothers giving birth via vaginal delivery (N=38), emergency C-Section (N=27) and planned C-Section (N=21) were assessed for depression and PTSD twice: Six weeks post-partum and six-weeks later.

The physiologic anticoagulant and anti-inflammatory role of heparins and their utility in the prevention of pregnancy complications.

Accumulating evidence supports the concept of increased thrombin generation, placental vascular lesions, and inflammation as crucial points in the development of the great obstetrical syndromes [preeclampsia, intrauterine growth restriction (IUGR), preterm labor (PTL), preterm prelabor rupture of membranes (PROM), fetal demise and recurrent abortions]. In light of this, the role of heparins for primary or secondary prevention of these syndromes is becoming more and more apparent, mainly due to the antithrombotic and anti-inflammatory effects of heparins. There is agreement regarding the use of heparin in the prevention of gestational complications in patients with antiphospholipid syndrome, while its use for other obstetrical complications is under debate.

The physiologic and therapeutic role of heparin in implantation and placentation.

Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications.

Recurrent pregnancy loss: a risk factor for long-term maternal atherosclerotic morbidity?

Objective: We sought to investigate whether patients with a history of recurrent pregnancy loss (RPL) have an increased risk for future maternal atherosclerotic morbidity.

Study Design: A population-based study compared the incidence of long-term atherosclerotic morbidity (renal and cardiovascular) in a cohort of women with and without a diagnosis of RPL. Patients had a mean follow-up duration of more than a decade.

Detection of S100B in maternal blood before and after fetal death.

Background: S100B is a brain damage biomarker. When measured immediately after birth, it reflects neonatal brain damage following asphyxia. In this study, we used feticide as a novel model of fetal brain damage.

Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines.

Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus.

Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: an ex vivo study.

Objective: Drugs of abuse affect pregnancy outcomes, however, the mechanisms in which cannabis exerts its effects are not well understood. The aim of this study was to examine the influence of short-term (1-2 hours) exposure to cannabidiol, a major phytocannabinoid, on human placental breast cancer resistance protein function.

Study Design: The in vitro effect of short-term exposure to cannabidoil on breast cancer resistance protein in BeWo and Jar cells (MCF7/P-gp cells were used for comparison) was tested with mitoxantrone uptake, and nicardipine was used as positive control.

An association between preterm delivery and long-term maternal cardiovascular morbidity.

Objective: The purpose of this study was to investigate whether a history of preterm delivery (PTD) poses a risk for subsequent maternal long-term cardiovascular morbidity.

Study Design: A population-based study compared the incidence of cardiovascular morbidity in a cohort of women who delivered preterm (<37 weeks' gestation) and those who gave birth at term at the same period. Deliveries occurred during the years 1988-1999 with follow up until 2010.

The effects of magnesium sulfate on placental vascular endothelial growth factor expression in preeclampsia.

Objective: To evaluate the effect of magnesium sulfate (MgSO(4)) on placental expression levels of vascular endothelial growth factor (VEGF).

Materials And Methods: Cotyledons of term normotensive and preeclamptic placentas were dually perfused for 6 h, with MgSO(4) (6-7 mg%) in the maternal reservoir [normotensive (n = 3); preeclamptic (n = 4)] and with the control medium (without MgSO(4)) [normotensive (n = 3); preeclamptic (n = 6)]. After perfusion, placental tissue samples were collected from four different placental compartments (amnion, chorion, placental villous and decidua).

Low levels of circulating alpha-1 antitrypsin are associated with spontaneous abortions.

Objective: Alpha-1 antitrypsin (AAT), a circulating anti-inflammatory molecule, rises four- to sixfold during acute phase responses and during pregnancy. AAT deficiency is linked with various pregnancy complications. The aim of this study is to determine plasma concentrations and activity of AAT and serum cytokine levels in blood samples from women undergoing spontaneous abortions as compared with elective abortions.

Perfusion with magnesium sulfate increases sFlt-1 secretion only in the fetal side of placenta of women with preeclampsia.

Objective: To examine the effect of magnesium sulfate (MgSO(4)) on sFlt (soluble fms-like tyrosine kinase)-1 in the fetal and maternal compartments of normotensive and preeclamptic placentas.

Methods: Cotyledons of term normotensive and preeclamptic placentas were dually perfused for six hours, with control medium and MgSO(4) (6-7 mg %) in the maternal reservoir. Perfusate sFlt-1 concentrations were measured.

Placental secretion of interleukin-1 and interleukin-1 receptor antagonist in preeclampsia: effect of magnesium sulfate.

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and systemic endothelial dysfunction. Interleukin (IL)-1β is a possible mediator of maternal endothelial dysfunction in preeclampsia. Serum IL-1β as well as its natural inhibitor IL-1 receptor antagonist (IL-1Ra) were reported to be increased in women with preeclampsia.

Lower circulation levels and activity of α-1 antitrypsin in pregnant women with severe preeclampsia.

Objective: α-1 antitrypsin (AAT) is an anti-protease, anti-inflammatory and tissue-protective molecule. Normal circulating levels are <3.5 mg/dl and rise during pregnancy.

Passive fetal monitoring by adaptive wavelet denoising method.

Fetal Heart Rate (FHR) monitoring is one of the most important fetal well being tests. Existing FHR monitoring methods are based on Doppler ultrasound technique, which has several disadvantages. Passive fetal monitoring by phonocardiography is an appropriate alternative; however, its implementation is a challenging task due to low energy of fetal heart sounds and multiple interference signals presence.

An initial miscarriage is associated with adverse pregnancy outcomes in the following pregnancy.

Objective: The objective of the study was to determine whether 1 previous miscarriage is associated with an increased rate of adverse pregnancy outcomes in the following pregnancy.

Study Design: Second pregnancies of women with and without a miscarriage in their initial pregnancy were compared. Multivariable logistic regression models were constructed to control for confounders.

α1-antitrypsin insufficiency is a possible contributor to preterm premature rupture of membranes.

Objective: α1-antitrypsin (AAT) is protective of tissue damage induced by enzymes of inflammatory cell source. Inflammatory cells are involved in preterm labor, preterm premature rupture of membrane (PPROM) and term premature rupture of membrane (PROM). The purpose of this research was to examine whether plasma concentration and activity of AAT differ between these manifestations.

Drug transport across the placenta.

It has become clear that almost any drug or chemical substance administered to the mother is able to cross the placenta to some extent, unless it is metabolized or altered during passage, or else its molecular size and low lipid solubility do not allow transplacental transfer. A number of transport systems have been identified in the placenta, which recognizes a wide variety of pharmacological active drugs as substrates. In recent years, research on human placental transporters has been developing due to the increase of knowledge technology in pharmacology.

Risk factors for intrauterine fetal death (1988-2009).

Objective: To determine risk factors for intrauterine fetal death (IUFD).

Study Design: A retrospective population-based study, of all singleton deliveries between the years 1988-2009 was conducted. Intrapartum deaths, postpartum death, and multiple gestations were excluded.

Placental abruption: critical analysis of risk factors and perinatal outcomes.

Objective: To investigate risk factors and pregnancy outcome of patients with placental abruption.

Methods: A population-based study comparing all pregnancies of women with and without placental abruption was conducted. Stratified analysis using multiple logistic regression models was performed to control for confounders.

Magnesium sulfate normalizes placental interleukin-6 secretion in preeclampsia.

Interleukin-6 (IL-6) is one of the main proinflammatory mediators of hypertension and endothelial dysfunction in preeclampsia. In this study, we investigated the capacity of the preeclamptic placenta to secrete IL-6 and the effect of magnesium sulfate (MgSO(4)) on it. Placentas from normotensive (37-40 weeks) and preeclamptic (36-40 weeks) pregnancies were dually perfused for 6 h in the absence [normotensive (n = 3); preeclamptic (n = 4)] and presence [normotensive (n = 3); preeclamptic (n = 4)] of MgSO(4).

Peripartum cesarean hysterectomy: critical analysis of risk factors and trends over the years.

Objective: To investigate time trends and risk factors for peripartum cesarean hysterectomy.

Methods: A population-based study comparing all deliveries that were complicated with peripartum hysterectomy to deliveries without this complication was conducted. Deliveries occurred during the years 1988-2007 at a tertiary medical center.

Perinatal outcomes in condyloma acuminata pregnancies.

Objective: To investigate pregnancy outcome in patients with condyloma acuminata.

Methods: A retrospective cohort study comparing pregnancy outcome of women with and without condyloma acuminata was performed. A sub-group analysis was performed between patients with localized disease (n = 40), extended disease (n = 25) and no condyloma acuminata (n = 227,202).

Pregnancy complication and outcome in women with history of allergy to medicinal agents.

Problem: Pregnancy outcome in women with a previous history of drug allergy and the role of drug allergies in adverse pregnancy outcomes is unclear.

Method Of Study: A retrospective cohort study comparing pregnancies of women with and without history of drug allergy was conducted. Data were collected from the computerized perinatal database.