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  1. Article ; Online: Potential treatment option of rivaroxaban for breastfeeding women: A case series.

    Yamashita, Yugo / Hira, Daiki / Morita, Makiko / Katsube, Yurie / Takakura, Masahito / Tomotaki, Hiroko / Tomotaki, Seiichi / Xiong, Wei / Shiomi, Hiroki / Horie, Takahiro / Ueshima, Satoshi / Mizuno, Tomoyuki / Terada, Tomohiro / Ono, Koh

    Thrombosis research

    2024  Volume 237, Page(s) 141–144

    Abstract: The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 ... ...

    Abstract The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration). The milk-to-plasma (M:P) ratios were 0.27 in Case 1 and 0.32 in Case 2. The estimated relative infant dose (RID) was 0.82 % in Case 1 Children 1 and 2, and 1.27 % in Case 2. The rivaroxaban concentration in the infant plasma was below the lower limit of quantification in all infants. In addition, even in the high-exposure case simulation based on 5 days of breastfeeding in Case 2, the infant plasma concentration level was below the lower limit of quantification. At 3 months of follow-up, breastfeeding was continued, and all infants grew and developed without any health problems including bleeding events. The current case series showed that there were no pharmacokinetic or clinical concerns for breastfeeding women or breastfed infants, and provides support for rivaroxaban as a safe treatment option for these patients.
    MeSH term(s) Humans ; Rivaroxaban/therapeutic use ; Rivaroxaban/pharmacokinetics ; Female ; Breast Feeding ; Adult ; Factor Xa Inhibitors/therapeutic use ; Factor Xa Inhibitors/pharmacokinetics ; Milk, Human/chemistry ; Milk, Human/metabolism ; Infant ; Venous Thromboembolism/drug therapy ; Infant, Newborn ; Pregnancy
    Chemical Substances Rivaroxaban (9NDF7JZ4M3) ; Factor Xa Inhibitors
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Case Reports ; Journal Article ; Letter
    ZDB-ID 121852-9
    ISSN 1879-2472 ; 0049-3848
    ISSN (online) 1879-2472
    ISSN 0049-3848
    DOI 10.1016/j.thromres.2024.04.003
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 863: Show issues Location:
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  2. Article ; Online: Hyposecretion of cervical MUC5B is related to preterm birth in pregnant women after cervical excisional surgery.

    Ueda, Yusuke / Mogami, Haruta / Chigusa, Yoshitsugu / Kawamura, Yosuke / Inohaya, Asako / Takakura, Masahito / Yasuda, Eriko / Matsuzaka, Yu / Shimada, Miho / Ito, Shinji / Morita, Satoshi / Mandai, Masaki / Kondoh, Eiji

    American journal of reproductive immunology (New York, N.Y. : 1989)

    2024  Volume 91, Issue 3, Page(s) e13832

    Abstract: Problem: Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin ... ...

    Abstract Problem: Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy. We thus hypothesized that hyposecretion of cervical MUC5B is associated with preterm birth after cervical excisional surgery.
    Method of study: This prospective nested case-control study (Study 1) included pregnant women who had previously undergone cervical excisional surgery across 11 hospitals. We used proteomics to compare cervicovaginal fluid at 18-22 weeks of gestation between the preterm and term birth groups. In another case-control analysis (Study 2), we compared MUC5B expression in nonpregnant uterine tissues between 15 women with a history of cervical excisional surgery and 26 women without a history of cervical surgery.
    Results: The abundance of MUC5B in cervicovaginal fluid was significantly decreased in the preterm birth group (fold change = 0.41, p = .035). Among the 480 quantified proteins, MUC5B had the second highest positive correlation with gestational age at delivery in the combined preterm and term groups. The cervicovaginal microbiome composition was not significantly different between the two groups. Cervical length was not correlated with gestational age at delivery (r = 0.18, p = .079). Histologically, the MUC5B-positive area in the nonpregnant cervix was significantly decreased in women with a history of cervical excisional surgery (0.85-fold, p = .048). The distribution of MUC5B-positive areas in the cervical tissues of 26 women without a history of cervical excisional surgery differed across individuals.
    Conclusions: This study suggests that the primary mechanism by which cervical excisional surgery causes preterm birth is the hyposecretion of MUC5B due to loss of the cervical glands.
    MeSH term(s) Female ; Pregnancy ; Infant, Newborn ; Humans ; Cervix Uteri/surgery ; Premature Birth ; Pregnant Women ; Case-Control Studies ; Prospective Studies ; Retrospective Studies ; Mucin-5B
    Chemical Substances MUC5B protein, human ; Mucin-5B
    Language English
    Publishing date 2024-03-11
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 604542-x
    ISSN 1600-0897 ; 0271-7352 ; 8755-8920 ; 1046-7408
    ISSN (online) 1600-0897
    ISSN 0271-7352 ; 8755-8920 ; 1046-7408
    DOI 10.1111/aji.13832
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    Zs.A 1653: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  3. Article ; Online: Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts†.

    Inohaya, Asako / Chigusa, Yoshitsugu / Takakura, Masahito / Io, Shingo / Kim, Min-A / Matsuzaka, Yu / Yasuda, Eriko / Ueda, Yusuke / Kawamura, Yosuke / Takamatsu, Shiro / Mogami, Haruta / Takashima, Yasuhiro / Mandai, Masaki / Kondoh, Eiji

    Biology of reproduction

    2023  Volume 110, Issue 2, Page(s) 300–309

    Abstract: The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of ... ...

    Abstract The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.
    MeSH term(s) Female ; Pregnancy ; Humans ; Placenta/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Placenta Growth Factor/metabolism ; Trophoblasts/metabolism ; Chorionic Gonadotropin/pharmacology ; Chorionic Gonadotropin/metabolism ; Cell Differentiation
    Chemical Substances Placenta Growth Factor (144589-93-5) ; Chorionic Gonadotropin
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1118-6
    ISSN 1529-7268 ; 0006-3363
    ISSN (online) 1529-7268
    ISSN 0006-3363
    DOI 10.1093/biolre/ioad143
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 551: Show issues Location:
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  4. Article ; Online: Fetal macrophages assist in the repair of ruptured amnion through the induction of epithelial-mesenchymal transition.

    Kawamura, Yosuke / Mogami, Haruta / Yasuda, Eriko / Takakura, Masahito / Matsuzaka, Yu / Ueda, Yusuke / Inohaya, Asako / Kawasaki, Kaoru / Chigusa, Yoshitsugu / Mandai, Masaki / Kondoh, Eiji

    Science signaling

    2022  Volume 15, Issue 751, Page(s) eabi5453

    Abstract: The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair ... ...

    Abstract The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the embryo. Macrophages migrated to and resided at rupture sites in both human and mouse amnion. A process called epithelial-mesenchymal transition (EMT), in which epithelial cells acquire a mesenchymal phenotype and which is implicated in tissue repair, was observed at rupture sites. In dams bearing macrophage-depleted fetuses, the repair of amnion ruptures was compromised, and EMT was rarely detected at rupture sites. The migration of cultured amnion epithelial cells in wound healing assays was mediated by EMT through transforming growth factor-β (TGF-β)-Smad signaling. These findings suggest that fetal macrophages are crucial in amnion repair because of their ability to induce EMT in amnion epithelial cells.
    MeSH term(s) Amnion ; Animals ; Epithelial-Mesenchymal Transition ; Female ; Fetal Membranes, Premature Rupture ; Fetus ; Humans ; Infant, Newborn ; Macrophages ; Mice ; Premature Birth
    Language English
    Publishing date 2022-09-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417226-1
    ISSN 1937-9145 ; 1945-0877
    ISSN (online) 1937-9145
    ISSN 1945-0877
    DOI 10.1126/scisignal.abi5453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cervical MUC5B and MUC5AC are Barriers to Ascending Pathogens During Pregnancy.

    Ueda, Yusuke / Mogami, Haruta / Kawamura, Yosuke / Takakura, Masahito / Inohaya, Asako / Yasuda, Eriko / Matsuzaka, Yu / Chigusa, Yoshitsugu / Ito, Shinji / Mandai, Masaki / Kondoh, Eiji

    The Journal of clinical endocrinology and metabolism

    2022  Volume 107, Issue 11, Page(s) 3010–3021

    Abstract: Context: Cervical excision is a risk factor for preterm birth. This suggests that the cervix plays an essential role in the maintenance of pregnancy.: Objective: We investigated the role of the cervix through proteomic analysis of cervicovaginal ... ...

    Abstract Context: Cervical excision is a risk factor for preterm birth. This suggests that the cervix plays an essential role in the maintenance of pregnancy.
    Objective: We investigated the role of the cervix through proteomic analysis of cervicovaginal fluid (CVF) from pregnant women after trachelectomy surgery, the natural model of a lack of cervix.
    Methods: The proteome compositions of CVF in pregnant women after trachelectomy were compared with those in control pregnant women by liquid chromatography-tandem mass spectrometry and label-free relative quantification. MUC5B/AC expression in the human and murine cervices was analyzed by immunohistochemistry. Regulation of MUC5B/AC expression by sex steroids was assessed in primary human cervical epithelial cells. In a pregnant mouse model of ascending infection, Escherichia coli or phosphate-buffered saline was inoculated into the vagina at 16.5 dpc, and the cervices were collected at 17.5 dpc.
    Results: The expression of MUC5B/5AC in cervicovaginal fluid was decreased in pregnant women after trachelectomy concomitant with the anatomical loss of cervical glands. Post-trachelectomy women delivered at term when MUC5B/AC abundance was greater than the mean normalized abundance of the control. MUC5B levels in the cervix were increased during pregnancy in both humans and mice. MUC5B mRNA was increased by addition of estradiol in human cervical epithelial cells, whereas MUC5AC was not. In a pregnant mouse model of ascending infection, E. coli was trapped in the MUC5B/AC-expressing mucin of the cervix, and neutrophils were colocalized there.
    Conclusion: Endocervical MUC5B and MUC5AC may be barriers to ascending pathogens during pregnancy.
    MeSH term(s) Female ; Infant, Newborn ; Humans ; Mice ; Pregnancy ; Animals ; Cervix Uteri/surgery ; Cervix Uteri/metabolism ; Proteomics ; Escherichia coli ; Premature Birth/metabolism ; Vagina/surgery ; Mucin-5B/metabolism ; Mucin 5AC/metabolism
    Chemical Substances MUC5B protein, human ; Mucin-5B ; MUC5AC protein, human ; Mucin 5AC ; Muc5ac protein, mouse ; Muc5b protein, mouse
    Language English
    Publishing date 2022-09-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/clinem/dgac545
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.134: Show issues Location:
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