Association of Argatroban Dose With Coagulation Laboratory Test in Patients on Extracorporeal Membrane Oxygenation: Activated Clotting Time vs Activated Partial Thromboplastin Time.

BACKGROUND: Only some studies have directly compared and analyzed the roles of activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in coagulation monitoring during argatroban administration. OBJECTIVES: This study aims to assess the correlation of argatroban dose with ACT and aPTT values and to identify the optimal coagulation test for argatroban dose adjustment. METHODS: We evaluated 55 patients on extracorporeal membrane oxygenation (ECMO) who received argatroban for more than 72 hours. The correlation between argatroban dose and aPTT and ACT values was evaluated. To compare argatroban dose and bleeding events according to liver dysfunction, the patients were divided into 2 groups based on alanine aminotransferase and total bilirubin. RESULTS: Among the 55 patients, a total of 459 doses and coagulation tests were evaluated. The aPTT and ACT values showed a weak correlation with argatroban dose, with the Pearson correlation coefficients of 0.261 (P < 0.001) and 0.194 (P = 0.001), respectively. The agreement between the target 150 to 180 seconds for ACT and 55 to 75 seconds for aPTT was observed in 140 patients (46.1%). Twenty-four patients (43.6%) had liver dysfunction when they started argatroban. The median argatroban dose was lower in the liver dysfunction group than in the control group (0.094 mcg/kg/min vs 0.169 mcg/kg/min, P = 0.020). Difference was not observed between the 2 groups in the amount of red blood cell (0.47 vs 0.43 pack, P = 0.909) and platelet (0.60 vs 0.08 pack, P = 0.079) transfusion per day. CONCLUSION AND RELEVANCE: A weak correlation was observed between argatroban dose and the aPTT and ACT values. However, the agreement between aPTT and ACT was only 46.1% regarding the scope of target range. Further research is necessary to determine how to assess the optimal argatroban dose for patients administered argatroban while undergoing ECMO at the intensive care unit.

Prenatal diagnosis and in utero treatment of congenital adrenal hyperplasia: An up-to-date comprehensive review.

Congenital adrenal hyperplasia (CAH) is a term that encompasses a wide range of conditions that affect the adrenals. Diagnosis and treatment before birth are important as irreparable birth defects can be avoided, decreasing the need for surgical intervention later in life, especially regarding genitalia anomalies. Although early implementation of dexamethasone in the prenatal treatment of CAH has been controversial, there is recent evidence that this treatment can reduce long-term complications.

Peroxidasin is essential for endothelial cell survival and growth signaling by sulfilimine crosslink-dependent matrix assembly.

Peroxidasin (PXDN) has been reported to crosslink the C-terminal non-collagenous domains of collagen IV (Col IV) by forming covalent sulfilimine bond. Here, we explored the physiological role of PXDN and its mechanism of action in endothelial cell survival and growth. Silencing of PXDN using siRNAs decreased cell proliferation without increase of the number of detached cells and decreased cell viability under serum-starved condition with increased fragmented nuclei and caspase 3/7 activity. Conditioned medium (CM) containing wild-type PXDN restored the proliferation of PXDN-depleted cells, but CM containing mutant PXDN with deletion of either N-terminal extracellular matrix (ECM) motifs or peroxidase domain failed to restore PXDN function. Accordingly, anti-PXDN antibody [raised against IgC2 (3-4) subdomain within ECM motifs] and peroxidase inhibitor phloroglucinol prevented the rescue of the PXDN-depleted cells by PXDN-containing CM. PXDN depletion resulted in loss of sulfilimine crosslinks, and decreased dense fibrillar network assembly of not only Col IV, but also fibronectin and laminin like in Col IV knockdown. Exogenous PXDN-containing CM restored ECM assembly as well as proliferation of PXDN-depleted cells. Accordingly, purified recombinant PXDN protein restored the proliferation and ECM assembly, and prevented cell death of the PXDN-depleted cells. PXDN depletion also showed reduced growth factors-induced phosphorylation of FAK and ERK1/2. In addition, siPXDN-transfected cell-derived matrix failed to provide full ECM-mediated activation of FAK and ERK1/2. These results indicate that both the ECM motifs and peroxidase activity are essential for the cellular function of PXDN and that PXDN is crucial for ECM assembly for survival and growth signaling.

Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone.

Preterm labor commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. Most research has focused on establishing a causal link between innate immune activation and pathological inflammation leading to preterm labor and birth. However, the role of maternal effector/activated T cells in the pathogenesis of preterm labor/birth is poorly understood. In this study, we first demonstrated that effector memory and activated maternal T cells expressing granzyme B and perforin are enriched at the maternal-fetal interface (decidua) of women with spontaneous preterm labor. Next, using a murine model, we reported that prior to inducing preterm birth, in vivo T cell activation caused maternal hypothermia, bradycardia, systemic inflammation, cervical dilation, intra-amniotic inflammation, and fetal growth restriction, all of which are clinical signs associated with preterm labor. In vivo T cell activation also induced B cell cytokine responses, a proinflammatory macrophage polarization, and other inflammatory responses at the maternal-fetal interface and myometrium in the absence of an increased influx of neutrophils. Finally, we showed that treatment with progesterone can serve as a strategy to prevent preterm labor/birth and adverse neonatal outcomes by attenuating the proinflammatory responses at the maternal-fetal interface and cervix induced by T cell activation. Collectively, these findings provide mechanistic evidence showing that effector and activated T cells cause pathological inflammation at the maternal-fetal interface, in the mother, and in the fetus, inducing preterm labor and birth and adverse neonatal outcomes. Such adverse effects can be prevented by treatment with progesterone, a clinically approved strategy.

A Low Cerebroplacental Ratio at 20-24 Weeks of Gestation Can Predict Reduced Fetal Size Later in Pregnancy or at Birth.

AIM: To determine whether Doppler evaluation at 20-24 weeks of gestation can predict reduced fetal size later in pregnancy or at birth. METHODS: Fetal biometry and Doppler velocimetry were performed in 2,986 women with a singleton pregnancy at 20-24 weeks of gestation. Predictive performances of the umbilical artery pulsatility index (UA-PI) or the mean uterine artery pulsatility index (UtA-PI) >95th percentile, middle cerebral artery pulsatility index, or cerebroplacental ratio (CPR) <5th percentile for early small for gestational age (SGA; <34 weeks of gestation), late SGA (≥34 weeks of gestation), or SGA at birth (birthweight <10th percentile) were analyzed. RESULTS: The prevalence of early SGA, late SGA, and SGA at birth was 1.1, 9.6, and 14.7%, respectively. A CPR <5th percentile had a positive likelihood ratio (LR+) of 8.2 (95% confidence interval [CI] 5.7-12.0) for early SGA, a LR+ of 1.6 (95% CI 1.1-1.2) for late SGA, and a LR+ of 1.9 (95% CI 1.4-2.6) for SGA at birth. A UtA-PI >95th percentile was associated with late SGA and SGA at birth, while an UA-PI >95th percentile was associated with early SGA. Associations were higher in fetuses with an estimated fetal weight <10th percentile. CONCLUSION: Fetal biometry and Doppler evaluation at 20-24 weeks of gestation can predict early and late SGA as well as SGA at birth.

Intermediate Diastolic Velocity as a Parameter of Cardiac Dysfunction in Growth-Restricted Fetuses.

OBJECTIVE: To evaluate the intermediate intracardiac diastolic velocities in fetuses with growth restriction. METHODS: Doppler waveforms of the two atrioventricular valves were obtained. Peak velocities of the E (early) and A (atrial) components, and the lowest intermediate velocity (IDV) between them, were measured in 400 normally grown and in 100 growth-restricted fetuses. The prevalence of abnormal IDV, E/IDV, and A/IDV ratios in fetuses presenting with perinatal death or acidemia at birth (pH ≤7.1) was estimated. RESULTS: IDV was significantly lower and E/IDV ratios significantly higher in the two ventricles of growth-restricted fetuses with reduced diastolic velocities in the umbilical artery (p < 0.05). In 13 fetuses presenting with perinatal death or acidemia at birth, 11 (85%) had either an E/IDV or A/IDV ratio >95th percentile, whereas 5 (38%) showed absent or reversed atrial velocities in the ductus venosus (DV-ARAV; p < 0.04). Fetuses without DV-ARAV but with elevated E/IDV ratios in either ventricle were nearly 7-fold more likely to have perinatal demise or acidemia at birth (OR 6.9, 95% CI 1.4-34) than those with E/IDV ratios <95th percentile. CONCLUSION: The E/IDV and A/IDV ratios in the two cardiac ventricles might provide information about the risk of perinatal demise or acidemia in growth-restricted fetuses.

Priming Wharton's jelly-derived mesenchymal stromal/stem cells with ROCK inhibitor improves recovery in an intracerebral hemorrhage model.

Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and to secrete paracrine factors for neuroprotection and regeneration. Previously, Rho-kinase inhibitors have been reported to potentiate differentiation of rodent bone marrow MSCs into neuron-like cells induced by CoCl2 (HIF-1α activation-mimicking agent). Here, a strategy of priming MSCs with fasudil, a Rho-kinase inhibitor, was investigated using Wharton's jelly-derived MSCs (WJ-MSCs) to improve recovery in a rat model of intracranial hemorrhage (ICH). In vitro culture of WJ-MSCs by co-treatment with fasudil (30 µM) and CoCl2 provoked morphological changes of WJ-MSCs into neuron-like cells and increased the expression of neuronal markers. Assessment of the secretion profiles showed that fasudil (30 µM) specifically increased glial cell line-derived neurotrophic factor (GDNF) among the secreted proteins at the transcription and secretion levels. For in vivo experiments, WJ-MSCs primed with fasudil (10 µM, exposure for 6 h) were transplanted into ICH rats with HIF-1α upregulation 1 week after injury, and neurological function was assessed via rotarod and limb placement tests for 7 weeks after transplantation. The group with WJ-MSCs primed with fasudil showed improved functional performance compared with the non-primed group. Accordingly, the primed group showed stronger expression of GDNF and higher levels of microtubule-associated protein 2 and neurofilament-H positive-grafted cells in the ICH lesion 3 weeks after transplantation compared with the non-primed group. Therefore, this work suggests that priming WJ-MSCs with fasudil is a possible application for enhanced cell therapy in stroke, with additional beneficial effect of up-regulation of GDNF.

Strain at the internal cervical os assessed with quasi-static elastography is associated with the risk of spontaneous preterm delivery at ≤34 weeks of gestation.

AIM: To evaluate the association between cervical strain assessed with quasi-static elastography and spontaneous preterm delivery. METHODS: Quasi-static elastography was used to estimate cervical strain in 545 pregnant women with singleton pregnancies from 11 weeks to 28 weeks of gestation. Cervical strain was evaluated in one sagittal plane and in the cross-sectional planes of the internal cervical os and external cervical os. The distribution of strain values was categorized into quartiles for each studied region and their association with spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation was evaluated using logistic regression. RESULTS: The prevalence of spontaneous preterm delivery at <37 weeks of gestation was 8.2% (n=45), and that at ≤34 weeks of gestation was 3.8% (n=21). Strain in the internal cervical os was the only elastography value associated with spontaneous preterm delivery. Women with strain values in the 3rd and 4th quartiles had a significantly higher risk of spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation when compared to women with strain values in the lowest quartile. When adjusting for a short cervix (<25 mm) and gestational age at examination, women with strain values in the 3rd quartile maintained a significant association with spontaneous preterm delivery at ≤34 weeks (OR 9.0; 95% CI, 1.1-74.0; P=0.02), whereas women with strain values in the highest quartile were marginally more likely than women with lowest quartile strain values to deliver spontaneously at ≤37 weeks of gestation (OR 95% CI: 2.8; [0.9-9.0]; P=0.08). CONCLUSION: Increased strain in the internal cervical os is associated with higher risk of spontaneous preterm delivery both at ≤34 and <37 weeks of gestation.

Dynamic Changes in the Myometrium during the Third Stage of Labor, Evaluated Using Two-Dimensional Ultrasound, in Women with Normal and Abnormal Third Stage of Labor and in Women with Obstetric Complications.

OBJECTIVE: To investigate dynamic changes in myometrial thickness during the third stage of labor. METHODS: Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the mid-region of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n = 30), postpartum hemorrhage (n = 4), preterm delivery (n = 7) and clinical chorioamnionitis (n = 4). Differences between myometrial thickness of the uterine segments and as a function of time were evaluated. RESULTS: There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p < 0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p < 0.0001). In women with postpartum hemorrhage, preterm delivery, and clinical chorioamnionitis, an uncoordinated pattern among the uterine segments was observed. CONCLUSION: A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk of postpartum hemorrhage.

Cervical strain determined by ultrasound elastography and its association with spontaneous preterm delivery.

OBJECTIVE: To determine if there is an association between cervical strain, evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD) <37 weeks of gestation. METHODS: One hundred and eighty nine (189) women at 16-24 weeks of gestation were evaluated. Ultrasound elastography was used to estimate cervical strain in three anatomical planes: one mid-sagittal in the same plane used for cervical length measurement, and two cross sectional images: one at the level of the internal cervical os, and the other at the level of the external cervical os. In each plane, two regions of interest (endocervix and entire cervix) were examined; a total of six regions of interest were evaluated. RESULTS: The prevalence of sPTD was 11% (21/189). Strain values from each of the six cervical regions correlated weakly with cervical length (from r=-0.24, P<0.001 to r=-0.03, P=0.69). Strain measurements obtained in a cross sectional view of the internal cervical os were significantly associated with sPTD. Women with strain values ≤25th centile in the endocervical canal (0.19) and in the entire cervix (0.14) were 80% less likely to have a sPTD than women with strain values >25th centile [endocervical: odds ratio (OR) 0.2; 95% confidence interval (CI), 0.03-0.96; entire cervix: OR 0.17; 95% CI, 0.03-0.9]. Additional adjustment for gestational age, race, smoking status, parity, maternal age, pre-pregnancy body mass index, and previous preterm delivery did not appreciably alter the magnitude or statistical significance of these associations. Strain values obtained from the external cervical os and from the sagittal view were not associated with sPTD. CONCLUSION: Low strain values in the internal cervical os were associated with a significantly lower risk of spontaneous preterm delivery <37 weeks of gestation.

Effect of depth on shear-wave elastography estimated in the internal and external cervical os during pregnancy.

AIM: To investigate the effect of depth on cervical shear-wave elastography. METHODS: Shear-wave elastography was applied to estimate the velocity of propagation of the acoustic force impulse (shear wave) in the cervix of 154 pregnant women at 11-36 weeks of gestation. Shear-wave speed (SWS) was evaluated in cross-sectional views of the internal and external cervical os in five regions of interest: anterior, posterior, lateral right, lateral left, and endocervix. Distance from the center of the ultrasound (US) transducer to the center of each region of interest was registered. RESULTS: In all regions, SWS decreased significantly with gestational age (P=0.006). In the internal os, SWS was similar among the anterior, posterior, and lateral regions and lower in the endocervix. In the external os, the endocervix and anterior regions showed similar SWS values, lower than those from the posterior and lateral regions. In the endocervix, these differences remained significant after adjustment for depth, gestational age, and cervical length. SWS estimations in all regions of the internal os were higher than those of the external os, suggesting denser tissue. CONCLUSION: Depth from the US probe to different regions in the cervix did not significantly affect the SWS estimations.

Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation.

The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma.

Presence of an umbilical artery notch in monochorionic/monoamniotic twins.

OBJECTIVE: To examine the association between an umbilical artery notch and fetal deterioration in monochorionic/monoamniotic (MC/MA) twins. METHODS: Six MC/MA twin pregnancies were admitted at 24-28 weeks of gestation for close fetal surveillance until elective delivery at 32 weeks or earlier in the presence of signs of fetal deterioration. Ultrasound (US) examinations were performed twice weekly. The presence of cord entanglement, umbilical artery notch, abnormal Doppler parameters, a non-reassuring fetal heart rate pattern, or an abnormal fetal biophysical profile were evaluated. RESULTS: Umbilical cord entanglement was observed on US in all pregnancies. The presence of an umbilical artery notch was noted in four out of six pregnancies and in two of them an umbilical artery notch was seen in both twins. The umbilical artery pulsatility index was normal in all fetuses. Doppler parameters of the middle cerebral artery and ductus venosus, fetal biophysical profile and fetal heart rate monitoring remained normal until delivery in all pregnancies. All neonates experienced morbidity related to prematurity; however, all were discharged home in good condition. CONCLUSION: The presence of an umbilical artery notch and cord entanglement, without other signs of fetal deterioration, are not indicative of an adverse perinatal outcome.

Mirror artifacts in obstetric ultrasound: case presentation of a ghost twin during the second-trimester ultrasound scan.

Mirror artifacts are produced by the reflection of ultrasound waves after they propagate through a structure and encounter a strong and smooth interface capable of acting as a mirror. Ultrasound waves bounce back and forth between the mirroring interface and the reflective object and then eventually return to the transducer. The typical display of the mirror artifact consists of two similar structures separated and at similar distances from the reflective interface. We report a mirror artifact in a patient with a singleton gestation at 18 weeks. The image was interpreted as consistent with a twin gestation using transabdominal and transvaginal ultrasound. The differential diagnosis consisted of an abdominal heterotopic pregnancy. The presence of synchronized but opposite movements of both fetuses, and the blurred image of the second fetus, suggested a mirror artifact. The reflective surface was created by the interface located between a distended rectosigmoid filled with gas and the posterior uterine wall. Mirror artifacts can lead to diagnostic errors. This case illustrates how a distended rectosigmoid colon can generate an image that simulates either a twin gestation or an abdominal heterotopic pregnancy.

Efficient nonadhesive ex vivo expansion of early endothelial progenitor cells derived from CD34+ human cord blood fraction for effective therapeutic vascularization.

Endothelial progenitor cells (EPCs) have been shown to have therapeutic potential in ischemic disease. However, the number of EPCs for cell therapy is limited. In this study, instead of the typical adherent culture method, we investigated a more efficient, clinically applicable nonadhesive expansion method for early EPCs using cord blood-derived cells to overcome rapid cellular senescence. After a suspension culture of isolated CD34(+) cells in serum-free medium containing each cytokine combination was maintained for 9 d, the number of expanded functional EPCs was assessed by an adherent culture assay. Compared to mononuclear cells, the CD34(+) fraction was superior in its expansion of functional EPCs that could differentiate into acLDL/UEA-1(+) cells without significant cellular senescence, whereas the CD34(-) fraction showed no EPC expansion. Among the cytokine combinations tested for the CD34(+) fraction, a combination (SFIb) consisting of stem cell factor (SCF), FMS-like tyrosine kinase 3 ligand, interleukin-3, and basic fibroblast growth factor resulted in a reproducible 64- to 1468-fold EPC expansion from various cord blood origins. Interestingly, the SFIb combination displayed markedly increased EPC expansion (2.43-fold), with a higher percentage of CD34(+) cells (2.17-fold), undifferentiated blasts (2.38-fold) and CXCR4(+) cells (1.68-fold) compared to another cytokine combination (SCF, thrombopoietin, and granulocyte colony-stimulating factor), although the two cytokine combinations had a similar level of total mononucleated cell expansion (∼ 10% difference). Accordingly, the cells expanded in the SFIb combination were more effective in recovery of blood flow and neovascularization in hind-limb ischemia in vivo. Taken together, these results suggest that the nonadhesive serum-free culture conditions of the CD34(+) fraction provide an effective EPC expansion method for cell therapy, and an expansion condition leading to high percentages of CD34(+) cells and blasts is likely important in EPC expansion.

Enhancement of endothelial progenitor cell numbers and migration by H1152, a Rho kinase specific inhibitor.

Endothelial progenitor cells (EPCs) are applied in the treatment of ischemic diseases. In ex vivo culture of human cord-blood derived EPCs, H1152, (S)-(+)-2-methyl-1-[(4-methyl-5-iso-quinolinyl) sulfonyl]-homopiperazine, markedly increased the number of EPCs. It also induced EPC migration, stimulated the phosphorylation of AKT, and reduced the expression of p27 in the EPCs. Thus H1152 can be used effectively in ex vivo expansion of EPCs.

Variation in the uterine arteries Doppler parameters when obtained transvaginally or transabdominally at different sampling locations.

INTRODUCTION: To evaluate differences in Doppler velocimetry parameters when the uterine arteries (UtA) are evaluated transabdominally (TA) at different sampling locations and transvaginally (TV). MATERIALS AND METHODS: Five hundred and fifty-seven pregnant women were evaluated between 11 and 39 weeks of gestation. The mean UtA pulsatility index (PI) and prevalence of bilateral notching were obtained at four different locations: (1) TA just above the crossing with the iliac artery; (2) TA just below the crossing with the iliac artery; (3) TA well above approximately 3 cm away from the crossing with the iliac artery; and (4) TV at the point closest to the internal cervical os. Measurements obtained just above the external iliac artery were considered the standard for comparison. Differences among different locations per gestational week were calculated. RESULTS: The mean UtA-PI and prevalence of bilateral notching were similar when the uterine arteries were sampled TA just above or just below the crossing with the external iliac artery. The mean UtA-PI values and prevalence of bilateral notching were significantly higher (p < .0001) when obtained TV and significantly lower when obtained 3 cm above the crossing with the external iliac artery (p = .004), as compared to the standard plane just above the crossing. CONCLUSION: The mean UtA-PI and prevalence of bilateral notching vary significantly when the uterine arteries are sampled far above the crossing with the external iliac artery or when obtained transvaginally.Key MessageThe predictive performance of the uterine arteries during pregnancy can significantly vary in relation to the approach selected for evaluation and to the location of the Doppler sampling gate.

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney.

Oxidative stress occurs when there is an imbalance between reactive oxygen species/reactive nitrogen species and antioxidant systems. The interplay between these complex processes is crucial for normal pregnancy and fetal development; however, when oxidative stress predominates, pregnancy related complications and adverse fetal programming such as preterm birth ensues. Understanding how oxidative stress negatively impacts outcomes for the maternal-fetal dyad has allowed for the exploration of antioxidant therapies to prevent and/or mitigate disease progression. In the developing kidney, the negative impact of oxidative stress has also been noted as it relates to the development of hypertension and kidney injury mostly in animal models. Clinical research addressing the implications of oxidative stress in the developing kidney is less developed than that of the neurodevelopmental and respiratory conditions of preterm infants and other vulnerable neonatal groups. Efforts to study the oxidative stress pathway along the continuum of the perinatal period using a team science approach can help to understand the multi-organ dysfunction that the maternal-fetal dyad sustains and guide the investigation of antioxidant therapies to ameliorate the global toxicity. This educational review will provide a comprehensive and multidisciplinary perspective on the impact of oxidative stress during the perinatal period in the development of maternal and fetal/neonatal complications, and implications on developmental programming of accelerated aging and cardiovascular and renal disease for a lifetime.

Outgrowing endothelial progenitor-derived cells display high sensitivity to angiogenesis modulators and delayed senescence.

Outgrowing endothelial progenitor-derived cells (EPDCs) originate from a novel hierarchy of endothelial progenitor cells. In this study, EPDCs isolated from human cord blood were examined for phenotype and functional features upon aging. Young or aged EPDCs were similar to human umbilical vein endothelial cells (HUVECs), in exhibiting typical endothelial phenotypes. However, EPDCs were more sensitive to angiogenesis inducers or inhibitors in proliferation and migration. In addition, EPDCs underwent senescence markedly slowly with sustained endothelial NO synthase expression and activation, and their ability to undergo capillary morphogenesis was retained throughout longterm culture. Thus, these results suggest that a homogenous population of EPDCs derived from clonogenic expansion may provide an effective vasculogenesis tool.

In vivo T-cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth.

PROBLEM: Activated/effector T cells seem to play a role in the pathological inflammation associated with preterm labor. The aim of this study was to determine whether in vivo T-cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth. METHOD OF STUDY: Pregnant B6 mice were intraperitoneally injected with a monoclonal αCD3ε antibody or its isotype control. The gestational age, the rates of preterm birth and pup mortality at birth as well as the fetal heart rate and umbilical artery pulsatility index were determined. RESULTS: Injection of a monoclonal αCD3ε antibody led to preterm labor/birth (αCD3ε 83 ± 16.97% [10/12] vs isotype 0% [0/8]) and increased the rate of pup mortality at birth (αCD3ε 87.30 ± 8.95% [77/85] vs isotype 4.91 ± 4.34% [3/59]). In addition, injection of a monoclonal αCD3ε antibody decreased the fetal heart rate and increased the umbilical artery pulsatility index when compared to the isotype control. CONCLUSION: In vivo T-cell activation by a monoclonal αCD3ε antibody in late gestation induces preterm labor and birth.