Up-regulation of miR-203 expression induces endothelial inflammatory response: Potential role in preeclampsia.

Problem: To determine whether miR-203 mediates endothelial inflammatory response in preeclampsia.

Method Of Study: Maternal vessel miR-203 expression was assessed by in situ hybridization. Suppressor of cytokine signaling-3 (SOCS-3) and ICAM expression was determined by immunostaining.

1,25(OH)2D3 Induces Placental Vascular Smooth Muscle Cell Relaxation by Phosphorylation of Myosin Phosphatase Target Subunit 1Ser507: Potential Beneficial Effects of Vitamin D on Placental Vasculature in Humans.

Placental vascular dysfunction has been linked to insufficiency/deficiency of maternal vitamin D levels during pregnancy. In contrast, sufficient maternal vitamin D levels have shown beneficial effects on pregnancy outcomes. To study the role of vitamin D in pregnancy, we tested our hypothesis that vitamin D exerts beneficial effects on placental vasculature.

Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia.

To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated.

Management of Persistent Postpartum Hemorrhage Caused by Inner Myometrial Lacerations.

Background: Postpartum hemorrhage management must involve rapid recognition of the source of bleeding. Inner myometrial laceration is an uncommonly recognized cause; most cases are demonstrated only by evaluation of peripartum hysterectomy specimens. The exact cause of this laceration is unknown; however, it can be identified by uterine cavity exploration and managed with conservative surgery that preserves fertility.

Down-regulation of TIMP3 leads to increase in TACE expression and TNFα production by placental trophoblast cells.

Problem: To determine whether down-regulation of TIMP3 expression promotes TACE expression and increases in TNFα production by placental trophoblast cells.

Method Of Study: Placental expression of TIMP3 and TACE was examined by immunostaining and Western blot. Effects of TIMP3 on TACE expression and TNFα production were assessed by transfection of TIMP3 siRNA into trophoblasts isolated from normal placentas.

Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells.

Endothelial dysfunction associated with vitamin D deficiency has been linked to many chronic vascular diseases. Vitamin D elicits its bioactive actions by binding to its receptor, vitamin D receptor (VDR), on target cells and organs. In the present study, we investigated the role of VDR in response to 1,25(OH)₂D₃ stimulation and oxidative stress challenge in endothelial cells.

Differential miRNA expression profiles between the first and third trimester human placentas.

To determine placental microRNA (miRNA) expression at different gestational age, total RNA from six first and six third trimester placentas was isolated. miRNA expression was analyzed by Affymetrix miRNA microarray, and miRNA clusters were identified by web-based programs MirClust and miRGen Cluster. qRT-PCR was carried out to validate miRNA expression, and in situ hybridization (ISH) was performed to determine compartmental localization of miRNAs within villous tissue.

Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies.

Vitamin D insufficiency/deficiency during pregnancy has been linked to increased risk of preeclampsia. Placenta dysfunction plays an important role in the pathogenesis of this pregnancy disorder. In this study, we tested the hypothesis that disturbed vitamin D metabolism takes place in preeclamptic placentas.

Elevated acetoacetate and monocyte chemotactic protein-1 levels in cord blood of infants of diabetic mothers.

Background: Infants of diabetic mothers (IDMs) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of the ketone bodies acetoacetate (AA) and β-hydroxybutyrate (BHB).

Objective: The aim of this study was to examine how hyperketonemia in diabetic mothers affects markers of inflammation and oxidative stress in their offspring.

Dynamics of pregnancy-associated polyomavirus urinary excretion: a prospective longitudinal study.

Asymptomatic polyomaviruria of pregnancy has been documented in point prevalence studies, but little attention has been given to the dynamics of polyomavirus excretion during pregnancy because of its benign course. We tested the hypothesis that the frequency and/or magnitude of polyomavirus excretion would increase as pregnancy progresses. Urine specimens were obtained prospectively from 179 healthy women during uncomplicated pregnancies and 37 healthy non-pregnant women.

Increased urinary excretion of nephrin, podocalyxin, and βig-h3 in women with preeclampsia.

Emerging evidence has shown that podocyte injury and reduced specific podocyte protein expressions contribute to proteinuria in preeclampsia. We collected urine specimens from women with preeclampsia to study whether podocyte-specific protein shedding is associated with renal barrier dysfunction. Urine specimens from women with normal pregnancies and from pregnant women complicated by chronic hypertension were used for comparison.

Use of a visual aid to improve counseling at the threshold of viability.

Objectives: To pilot-test a visual aid developed to help counsel pregnant women.

Methods: After agreeing to participate, pregnant women at >28 weeks of gestation were assigned randomly to counseling with or without a visual aid. The visual aid contained pictures, graphics, and short messages about delivery room resuscitation, chances of survival, anticipated neonatal course, and long-term neurodevelopmental disabilities.

Altered nephrin and podoplanin distribution is associated with disturbed polarity protein PARD-3 and PARD-6 expressions in podocytes from preeclampsia.

This study was undertaken to test the hypothesis that altered podocyte slit protein nephrin distribution is associated with disturbed polarity protein expressions in podocytes from preeclampsia (PE). We examined expressions and distributions of nephrin, podoplanin, polarity protein partitioning defective-3 (PARD-3), and PARD-6 in podocytes from PE. Podocyte cell line (AB 8/13 cells) was used as control.

Elevated maternal soluble Gp130 and IL-6 levels and reduced Gp130 and SOCS-3 expressions in women complicated with preeclampsia.

Increased inflammatory response plays a significant role in the vascular pathophysiology in preeclampsia. However, the mechanism for increased inflammatory response in preeclampsia is largely unknown. Interleukin (IL)-6 levels are elevated in women with preeclampsia.

Factors derived from preeclamptic placentas perturb polarity protein PARD-3 expression and distribution in endothelial cells.

Objective: This study aimed to examine (1) whether polarity protein partitioning defective-3 (PARD-3) was expressed in endothelial cells (ECs) and contributed to endothelial barrier integrity and (2) whether altered PARD-3 expression and distribution were associated with disturbed endothelial junction protein VE-cadherin expression induced by factors derived from preeclamptic (PE) placentas.

Methods: PARD-3 and VE-cadherin expressions were examined by immunofluorescent staining and Western blot in confluent ECs and in ECs treated with normal and PE placental conditioned medium (CM). Protein-protein interactions between PARD-3/VE-cadherin, PARD-3/ atypical protein kinase C (aPKCλ), and VE-cadherin/aPKCλ were examined by immuno-precipitation and immunobloting.

Decreasing extremes in patient waiting time.

Introduction: We present a conceptual framework for approaching reducing excessive patient wait time in an outpatient setting. We hypothesized that statistical process control techniques can be used to identify extremes in waiting time; root cause analysis can be used to identify specific delay causes; and minimizing the contribution of the root causes will lead to an improvement in system performance.

Subject And Method: We conducted a prospective study of waiting times in a private outpatient clinic providing high-risk obstetrical care.

Bundling unbundled charges: a case study in an academic obstetrical practice.

In the practice of obstetrics, the non-stress test (NST) and the biophysical profile (BPP) are used to assess fetal well-being. Failure to bundle the NST with the ultrasound BPP will result in a rejected claim if both procedures are performed at the same visit. We implemented a quality improvement program to reduce the number of charge tickets that were coded incorrectly because same-day NST and ultrasound BPP were not bundled.

Decreased nephrin and GLEPP-1, but increased VEGF, Flt-1, and nitrotyrosine, expressions in kidney tissue sections from women with preeclampsia.

Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood.

Chymotrypsin-like protease (chymase) mediates endothelial activation by factors derived from preeclamptic placentas.

Endothelial cells (EC) activation is an important inflammatory phenotypic change in the vascular system in women with preeclampsia (PE). In PE, maternal vessel chymotrypsin-like protease (CLP)/chymase expression was increased. Chymase is an inflammatory protease.

Increased neutrophil numbers account for leukocytosis in women with preeclampsia.

We evaluated the leukocyte differentials in women with normal pregnancies and in pregnancies complicated by preeclampsia (PE). A retrospective study was performed in 240 women who were delivered at Louisiana State University Health Sciences Center-Shreveport, Louisiana, from January 1, 2002, to July 31, 2003. A total of 80 patients were studied in each group: normal pregnancy, mild PE, or severe PE.

Elevated maternal IL-16 levels, enhanced IL-16 expressions in endothelium and leukocytes, and increased IL-16 production by placental trophoblasts in women with preeclampsia.

Cytokine IL-16 plays an important role in innate immune responses. However, little information is available about IL-16 function in human pregnancy. In this study, we collected maternal blood samples from 125 pregnant women between 26 and 41 wk of gestation, 63 from normal pregnant women and 62 from women with preeclampsia (PE).

Increased superoxide generation and decreased stress protein Hsp90 expression in human umbilical cord vein endothelial cells (HUVECs) from pregnancies complicated by preeclampsia.

Objective: Endothelial dysfunction is associated with increased oxidative stress in the vascular system in women with preeclampsia (PE), a hypertensive disorder occurring during human pregnancy. However, due to the nature of the disease, direct evidence of increased endothelial oxidative stress in the maternal vascular system at an in vivo situation is still lacking. We previously reported that primary cultured endothelial cells (ECs) from umbilical cords (HUVECs) from pregnancies complicated by PE exhibit phenotypic changes compared to those from normal pregnancies such as reduced eNOs expression associated with disorganized endothelial junction protein distribution and increased endothelial permeability.

A prospective randomized trial of magnesium sulfate in severe preeclampsia: use of diuresis as a clinical parameter to determine the duration of postpartum therapy.

Objective: The purpose of this study was to assess the use of the onset of diuresis in the determination of the duration of postpartum magnesium sulfate therapy among patients with severe preeclampsia.

Study Design: A prospective randomized trial of postpartum therapy with magnesium sulfate was conducted. The control group received 24 hours of therapy, and the study group received therapy until the onset of diuresis (urine output >100 mL/hr for 2 consecutive hours).