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Introduction: Maternal glucocorticoid exposure increases the risk of preterm delivery; however, the association between glucocorticoids and preterm premature rupture of membranes (pPROM)-a direct cause of preterm delivery-has rarely been investigated.Methods: To examine this association, we evaluated the clinical data of patients with systemic lupus erythematosus (SLE). Mechanism analysis was performed in both human amnion-derived mesenchymal cells (as a model for fetal membranes) and the amnion from SLE patients. We characterized the effects of glucocorticoids on the amnion in both models through comprehensive gene expression profiling and by electric cell-substrate impedance sensing in the mesenchymal cells.Results: The average glucocorticoid dose in cases with pPROM (13.3 mg/day, n = 10) was significantly higher than in those without pPROM (8.5 mg/day, n = 65; P < 0.01) among pregnant patients with well-controlled SLE (SLEDAI <4, n = 75); however, we did not observe a statistically significant difference in it between cases with or without chorioamnionitis. Glucocorticoid-treated human amnion mesenchymal cells showed decreased electric resistance between cells, indicating increased permeability. Differentially expressed genes upon glucocorticoid treatment were significantly enriched with cell adhesion-related genes. Among them, ITGA8 was strikingly induced in both the amnion mesenchymal cells and in amnion derived from patients with SLE.Discussion: We observed an association between glucocorticoids and pPROM with non-infectious etiology. Our findings indicate that glucocorticoids increase amnion permeability and modulate cell-adhesion related genes. ITGA8 represents a primary molecule that triggers pPROM through fibrotic remodeling and preventing resealing of the rupture site in fetal amnion. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies. Methods: This was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n =51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n =81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann–Whitney U test. Results: Compared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P =0.049) and those not requiring valproic acid (77% vs. 56%, P =0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P =0.018) and changes in antiepileptic drugs (24% vs. 41%, P =0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations. Conclusion: For women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs. [Copyright &y& Elsevier]

To compare the prevalence of enlarged ovarian and intrapelvic parasitic arteries to the gravid uterus between cases of placenta accreta spectrum (PAS) and those with normal placentation using unenhanced magnetic resonance (MR) angiography. Unenhanced time-of-flight MR angiography was performed in 12 consecutive women with PAS (mean age, 34 years; range, 23–42 years) and 24 women with normal placentation (mean age, 31 years; range, 24–42 years) in their third trimester and reviewed by two independent observers. The consensus reading served as the reference standard. Findings of pelvic arteriography performed at cesarean hysterectomy were reviewed in all cases of PAS. The prevalence of enlarged ovarian and intrapelvic parasitic arteries was compared using Fisher's exact test. The interobserver agreement was assessed with Kappa statistics. The prevalence of enlarged ovarian arteries was not significantly different between cases of PAS and normal placentation (17% [4/24 pelvic sides] vs. 4% [2/48 pelvic sides], P =.091). The prevalence of intrapelvic parasitic arteries was significantly higher in cases of PAS than in those with normal placentation (67% [16/24 pelvic sides] vs. 0% [0/48 pelvic sides], P <.0001). On a patient-by-patient basis, the intrapelvic parasitic artery was frequently present in women with PAS (92% [11/12 patients]). The Kappa values were 0.915 and 0.852 for detecting enlarged ovarian and intrapelvic parasitic arteries, respectively, indicating excellent interobserver agreement. The development of intrapelvic parasitic arteries was an anomalous phenomenon observed on unenhanced MR angiography in the majority of women with PAS but was not observed in those with normal placentation. • MR angiography showed enlarged ovarian and intrapelvic parasitic arteries to the gravid uterus. • Enlarged ovarian arteries were rarely seen with or without placenta accreta spectrum. • Intrapelvic parasitic arteries were seen in the majority of cases with placenta accreta spectrum. • Intrapelvic parasitic arteries were not observed in cases with normal placentation. [ABSTRACT FROM AUTHOR]

Objective: To clarify the impact of a mild form of gestational diabetes mellitus (GDM) on neonatal birth size, and on insulin-related hormones and adiponectin (AdipoQ) in cord blood.Methods: Two hundred and sixteen Japanese pregnant women diagnosed as having normal glucose tolerance according to the JSOG criteria were enrolled. Of the 216 women, 38 women were reclassified into a mild GDM (mGDM) group according to the IADPSG criteria. Of the remaining 178 women, 135 women with normal 50-g glucose challenge test were reclassified into a normal glucose tolerance (NGT) group. Cord blood insulin-like growth factor (IGF)-1, IGF-binding proteins (IGFBPs) and AdipoQ were measured in the offspring of the two groups.Results: Birth weight and its SD scores were larger in the mGDM group than in the NGT group. The incidence of large-for-gestational age (LGA) newborns was higher in the mGDM than in the NGT group. No differences in cord blood free IGF-1, IGFBP-1, IGFBP-2 or AdipoQ levels were observed between the mGDM and NGT groups.Conclusions: Our study suggests that mild GDM reclassified according to the IADPSG criteria influences neonatal birth size, but neither the IGF-IGFBP axis nor AdipoQ can account for the changes of birth size in offspring of women with mild GDM. [ABSTRACT FROM AUTHOR]

Monoacylglycerol acyltransferase 2 (MGAT2) plays an important role in intestinal fat absorption. We discovered the novel MGAT2 inhibitor, JTP-103237, and evaluated its pharmacological profile. JTP-103237 selectively inhibited MGAT2 without remarkable species differences and reduced absorbed lipids in circulation. After lipid administration, JTP-103237 slightly but significantly decreased triglyceride content in proximal small intestine and significantly increased the lipids content in the distal small intestine. In addition, JTP-103237 significantly increased MGAT substrate (monoacylglycerol and fatty acid) content in the small intestine. JTP-103237 increased plasma peptide YY levels after lipid loading and reduced food intake in a dietary fat-dependent manner. After chronic treatment, JTP-103237 significantly decreased body weight and increased O 2 consumption in the early dark phase in high fat diet induced obese (DIO) mice. Moreover, JTP-103237 improved glucose tolerance and decreased fat weight and hepatic triglyceride content in DIO mice. Our findings indicate that JTP-103237 prevents diet-induced obesity by inhibiting intestinal MGAT2 and has unique properties as a drug for the treatment of obesity. [ABSTRACT FROM AUTHOR]

Objective: Transcription factor GATA1 plays a critical role in erythropoiesis through the integrated regulation of cell proliferation, differentiation, and apoptosis. In Gata1.05 gene knockdown mice, Gata1 expression deteriorates to 5% of wild-type allelic expression, a level insufficient for supporting normal erythropoiesis and one that leads to accumulation of erythroid progenitors that are readily transformed into erythroblastic leukemia. Serial engraftment of leukemic cells into primary or subsequent nude mice reconstituted complete leukemic phenotype in recipient. To delineate characteristics of leukemic stem cells (LSCs), we analyzed LSCs of Gata1.05 leukemia, which have a potential to reestablish leukemia in mice. Materials and Methods: Leukemic cells isolated from the first recipient mice of Gata1.05 leukemia cells were divided into two fractions using Hoechst dye. Fractionated cells were transplanted into second recipient, or analyzed gene expression profiles and cell-cycle status. Consequences of 5-fluorouracil (5-FU) treatment on leukemic cells in vivo were studied. Results: LSCs were enriched in the Hoechst dye-excluded side population (SP), and leukemic cells in the SP population (LSP cells) were morphologically and immunophenotypically indistinguishable from other leukemic cells. However, expression of hematopoietic stem cell (HSC)−related genes was upregulated in the LSP cells. In cell-cycle analyses, LSP cells were quiescent like HSCs, but reentry into the cell cycle was stimulated by 5-FU treatment. Nonetheless, 5-FU treatment established a point of newly adjusted equilibrium in the LSP cells and the cells never recovered to their previous quiescent state. Conclusion: Based on this observation, distinct self-renewal regulatory mechanisms in LSCs may be considered as one of the causes of worsening of the features of leukemia after injury and relapse. [Copyright &y& Elsevier]

An abstract of the article "AAV Vector-Mediated Neonatal Gene Transfer: Efficient Transgene Expression in Muscles after Intraperitoneal Cavity Vector Injection," by Tsuyoshi Ogura, Hiroaki Mizukami, Jun Mimuro, Takashi Okada, Hiromi Hamada, Akihiro Kume and Hiroyuki Yoshikawa is presented.