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1.
Membranes (Basel) ; 11(1)2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33466331

ABSTRACT

Hexagonal tungsten oxide (h-WO3) membrane is a novel candidate for dehydration of acetic acid (CH3COOH)/water mixtures owing to its molecular sieving property and acidic resistance. Meanwhile, c-plane orientation is an important factor for h-WO3 membranes because the pores of h-WO3 run along its c-axis. However, so far, high c-plane orientation has not been successful on tubular substrates. Here, the effect of synthesis conditions of h-WO3 membranes on tubular substrates against c-plane orientation and CH3COOH/water separation performance are investigated. The h-WO3 membranes were prepared by hydrothermal synthesis from a precursor sol containing various amounts of sodium tungstate (Na2WO4) in the presence of tubular substrates with seeds embedded on their outside surface. The seeding method and the amount of Na2WO4 in the precursor sol significantly affected both crystal orientation and densification of the membrane. A precursor sol with appropriate amounts of Na2WO4 was essential to simultaneously satisfy high c-plane orientation and densification of the membrane while excess Na2WO4 drastically decreased the degree of c-plane orientation. A highly c-plane oriented h-WO3 membrane was successfully obtained under the optimized condition, which exhibited a maximum separation factor of 40.0 and a water permeance of 1.53 × 10-7 mol·m-2·s-1·Pa-1 in a 90:10 wt % CH3COOH/water mixture. The water permeance approximately doubled compared to the previous report, possibly owing to the significantly higher degree of c-plane orientation. Furthermore, it was found that its separation ability can be maintained while stored in 90:10 wt % CH3COOH/water mixture with pH < 0 for more than 500 h.

2.
Taiwan J Obstet Gynecol ; 59(3): 356-360, 2020 May.
Article in English | MEDLINE | ID: mdl-32416879

ABSTRACT

OBJECTIVE: This study aimed to evaluate whether the Edinburgh Postnatal Depression Scale (EPDS) score predicts the occurrence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) after delivery. MATERIALS AND METHODS: The women in this study were registered at 35-36 weeks of pregnancy at Mie University Hospital from 2013 to 2015. We prospectively divided the puerperants into those with an EPDS score ≥9 (the high-EPDS group) and those with an EPDS score <9 (the low-EPDS group) at 1 month postpartum. We compared the incidence rate of severe PMS and PMDD between both groups at 1 year after delivery. RESULTS: Of 200 registered cases, 178 (89.0%) did not experience severe PMS or PMDD before pregnancy. Among them, 21 were in the high-EPDS group, and 89 in the low-EPDS group. Four of the 21 women (19.0%) in the high-EPDS group and five of the 89 (5.6%) in the low-EPDS group had severe PMS or PMDD at 1 year after delivery. The incidence rate of severe PMS or PMDD in the high-EPDS group was higher than that in the low-EPDS group (p = 0.07). CONCLUSIONS: The novel finding of this study is that the EPDS may predict the occurrence of severe PMS/PMDD after delivery. The EPDS will contribute to the early detection of these diseases and to improving the quality of life of the patients by allowing treatment initiation at an early stage.


Subject(s)
Postpartum Period/psychology , Pregnant Women/psychology , Premenstrual Dysphoric Disorder/diagnosis , Premenstrual Syndrome/diagnosis , Psychiatric Status Rating Scales/statistics & numerical data , Adult , Female , Humans , Incidence , Predictive Value of Tests , Pregnancy , Premenstrual Dysphoric Disorder/epidemiology , Premenstrual Syndrome/epidemiology , Prospective Studies , Severity of Illness Index
3.
J Matern Fetal Neonatal Med ; 33(23): 3894-3899, 2020 Dec.
Article in English | MEDLINE | ID: mdl-30829091

ABSTRACT

Background: We aimed to retrospectively review data of pregnant women with the α-fibrinogen Thr331Ala polymorphism; evaluate the relationship between this polymorphism and spontaneous abortion (SA), fetal growth restriction (FGR), and intrauterine fetal death (IUFD); and assess the effects of aspirin and/or heparin.Materials and methods: We examined the outcomes of 29 pregnancies (nine women) in women with the α-fibrinogen Thr331Ala polymorphism. Of these, 16 were untreated, whereas 13 were treated with heparin and/or aspirin.Results: The live birth rate was significantly higher in the treated group than in the nontreated group (69.2 versus 6.2%; p = .0004). In addition, the prophylactic use of a low dose of aspirin and/or heparin during early pregnancy in women with Thr331Ala may be an effective method for reducing fetal loss in these patients.Conclusions: This polymorphism interacts with pregnancy to result in poor obstetrical outcomes, but these effects can be mitigated with medical intervention. This study is the first to report outcomes of pregnancies complicated by the Thr331Ala polymorphism, which we believe may cause thrombophilia, SA, and IUFD. This study highlights the need for further research on this polymorphism in pregnancy.

4.
J Matern Fetal Neonatal Med ; 33(1): 167-170, 2020 Jan.
Article in English | MEDLINE | ID: mdl-29886797

ABSTRACT

Purpose: The aim of this study is to evaluate the safety of clinical usage of tadalafil in women with preeclampsia.Materials and methods: Maternal, fetal, and neonatal adverse events were closely examined in eight preeclampsia patients receiving tadalafil treatment.Results: There were no maternal adverse events associated with 10 mg/day of tadalafil. Even at 20 mg/day, only grade 1 headaches in two cases and grade 1 palpitation in one case were observed, which resolved spontaneously within 3 days. At a dose of 40 mg/day, there was only one case of grade 1 headache. All these adverse events were grade 1 and spontaneously resolved within 3 days. There were no fetal adverse events. All observed neonatal adverse events were thought to be caused by prematurity and not related to tadalafil.Conclusion: This study shows that tadalafil treatment for preeclampsia is deemed sufficiently tolerable. Although there was a dose-dependent increase in maternal adverse events, all the adverse events were mild and deemed to be safe for the mother and fetus at all dosages.


Subject(s)
Pre-Eclampsia/drug therapy , Tadalafil/administration & dosage , Tadalafil/adverse effects , Adult , Arrhythmias, Cardiac/chemically induced , Birth Weight/drug effects , Cesarean Section/statistics & numerical data , Dose-Response Relationship, Drug , Female , Headache/chemically induced , Humans , Pregnancy , Pregnancy Outcome , Treatment Outcome
5.
Biomed Res Int ; 2019: 3261279, 2019.
Article in English | MEDLINE | ID: mdl-31781611

ABSTRACT

AIM: To determine whether the area of the foveal avascular zone (FAZ), as a morphological indicator of the microcirculation of the perifoveal capillary network, changes in the carbohydrate metabolism disorders during pregnancy (the gestational age of patients with gestational diabetes mellitus (GDM) and preexisting diabetes (PexD)). METHODS: Ten normal individuals and 41 eyes of 41 patients, 28 with GDM and 13 with PexD, were studied. A 3 × 3 mm area of the FAZ of the superficial capillary plexus layer (SCP) and the deep capillary plexus layer (DCP) was determined by optical coherence tomography angiography (OCTA; RS-3000 Advance, NIDEK). The significance of the correlation between the size of the FAZ and the weeks of pregnancy was determined. RESULTS: The area of the FAZ of the SCP was 0.38 ± 0.11 mm2 (normal eyes), 0.41 ± 0.16 mm2 (GDM), and 0.43 ± 0.10 mm2 (PexD). The area of the FAZ of the DCP was 0.78 ± 0.23 mm2 (normal eyes), 0.69 ± 0.16 mm2 (GDM), and 0.79 ± 0.25 mm2 (PexD). No significant difference in the FAZ sizes was observed between the groups. The average number of weeks of pregnancy was 24.1 ± 8.2 weeks in the eyes with GDM and 23.3 ± 11.4 weeks in the eyes with PexD (P > 0.05). Significant correlations were found between the size of the FAZ of the SCP and the number of weeks (r = 0.37, P=0.04 for GDM, and r = 0.49, P=0.04 for PexD, Spearman's rank-order correlation coefficient). CONCLUSIONS: For GDM and PexD under established glycemic control, the area of the FAZ is not affected, but vascular changes occurred at the early phase of pregnancy.


Subject(s)
Carbohydrate Metabolism, Inborn Errors/metabolism , Fovea Centralis/metabolism , Macula Lutea/metabolism , Pregnancy Complications/metabolism , Adult , Carbohydrate Metabolism/genetics , Carbohydrate Metabolism, Inborn Errors/diagnostic imaging , Carbohydrate Metabolism, Inborn Errors/pathology , Diabetes Mellitus/diagnostic imaging , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Diabetes, Gestational/diagnostic imaging , Diabetes, Gestational/metabolism , Diabetes, Gestational/pathology , Female , Fovea Centralis/blood supply , Fovea Centralis/diagnostic imaging , Fovea Centralis/pathology , Humans , Macula Lutea/blood supply , Macula Lutea/diagnostic imaging , Macula Lutea/pathology , Male , Pregnancy , Pregnancy Complications/pathology , Tomography, Optical Coherence
6.
PLoS One ; 14(8): e0220650, 2019.
Article in English | MEDLINE | ID: mdl-31415573

ABSTRACT

The aim of this study was to determine the action of molecules in carbohydrate metabolism disorders during pregnancy. The concentration of different types of cytokines and vascular endothelial growth factor (VEGF) in the plasma were measured in 4 groups of women: Group I, normal pregnancy (n = 10); Group II, patients with gestational DM (n = 12); Group III, pregnant patients with preexisting DM (n = 16); and Group IV, diabetic non-pregnant women (n = 22). The plasma VEGF concentration was significantly higher in the women in Group IV than in other groups (P <0.01). The concentration of the soluble form of the VEGF receptor-1 (sVEGFR-1) was significantly higher in Group I than in other groups (P <0.01). The concentration of soluble form of the VEGF receptor-2 (sVEGFR-2) was significantly lower in Groups I than in other groups (P <0.05). The concentrations of monocyte chemotactic protein-1 (MCP-1) and eotaxin were significantly lower in Group I than in Groups III and IV. The levels of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were significantly higher in Group I than in Group IV. Both the VEGF-related molecules and the Inflammatory cytokines are altered in pregnant women with the carbohydrate metabolism disorders.


Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetes, Gestational/blood , Inflammation/blood , Pregnancy in Diabetics/blood , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Carbohydrate Metabolism , Female , Humans , Interleukin-6/blood , Interleukin-8/blood , Pregnancy , Tumor Necrosis Factor-alpha/metabolism
7.
J Nanosci Nanotechnol ; 19(10): 6841-6848, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31027039

ABSTRACT

MOR zeolite is an effective adsorbent for separating organic molecules from various solutions owing to its large windows of 0)65 × 0)70 nm and its relatively high silica-alumina ratio which provides higher hydrophobicity. Fine powdery MOR zeolite is desirable for adsorption of organic molecules considering its larger surface area; however, fine particles are difficult to remove from solutions after treatment. Intensification of magnetic susceptibility through combination with magnetic particles ensure quick and easy removal of fine adsorbents by magnetic force. Meanwhile, seed assisted method is a powerful technique to direct and accelerate zeolite synthesis by adding seed crystals into the precursor sol prior to hydrothermal synthesis. In this work, we selected magnetite as the magnetic particle and propose the hydrothermal synthesis of MOR zeolite/magnetite composite via seed assisted method for the first time. MOR zeolite/magnetite composite with high MOR zeolite crystallinity was obtained by synthesizing for only 6 hours at 463 K when adding seed crystals, while no sign of crystallization was observed even after 24 hours in their absence. In addition, pre-milling of seed crystals together with magnetite was found to be effective to incorporate magnetite into MOR zeolite during crystallization and to decrease the primary crystal size of the crystallized MOR zeolite.

8.
Sci Rep ; 9(1): 234, 2019 01 18.
Article in English | MEDLINE | ID: mdl-30659198

ABSTRACT

We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.


Subject(s)
Fetal Growth Retardation/prevention & control , Hypoxia/prevention & control , Pre-Eclampsia/drug therapy , Tadalafil/administration & dosage , Vasodilator Agents/administration & dosage , Animals , Basic Helix-Loop-Helix Transcription Factors/analysis , Brain/pathology , Disease Models, Animal , Female , Mice , Placenta/pathology , Pregnancy , Treatment Outcome
9.
J Matern Fetal Neonatal Med ; 32(15): 2460-2462, 2019 Aug.
Article in English | MEDLINE | ID: mdl-29415591

ABSTRACT

BACKGROUND: The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. MATERIALS AND METHODS: We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. RESULTS: Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. CONCLUSIONS: Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.


Subject(s)
Fetal Growth Retardation/drug therapy , Heart/drug effects , Tadalafil/adverse effects , Vasodilator Agents/adverse effects , Adult , Female , Humans , Pregnancy
10.
J Matern Fetal Neonatal Med ; 32(19): 3221-3225, 2019 Oct.
Article in English | MEDLINE | ID: mdl-29614894

ABSTRACT

Purpose: Fetal growth restriction (FGR) is a concerning health issue. However, studies on FGR management are limited due to its rarity. We aimed to evaluate the efficacy of the contraction stress test (CST) for FGR management. Materials and methods: A case-control retrospective study design. Our institute innovated CST in FGR management in 2017. We included women in their 33rd-40th week of pregnancy with a diagnosis of FGR and retrospectively divided them into groups: the CST group (FGR management with CST) and no CST group (FGR management without CST) before and after CST development. Neonatal outcome, pH, and pO2 of umbilical artery (UA) were compared between the two groups. Results: No significant differences in the rate of birth weight, Apgar score <7 (5 minutes), neonatal death, hospitalization to newborn childhood intensive care unit (NICU), and UA pH were found between groups. Average UA pH was 7.29 ± 0.05 and 7.29 ± 0.04 in the CST and no CST groups, respectively (p = .864). Average UA pO2 values were 21.1 ± 8.6 and 15.7 ± 5.0 mmHg in the CST and no CST groups, respectively (p = .016), showing significant differences. Conclusions: Neonatal outcomes and UA pH were slightly different between the groups managed with and without CST. However, UA pO2 values significantly differed between the groups. For FGR management, the use of a CST may allow for early intervention before fetal acidemia and acidosis. For establishing the effects of a CST for FGR management, analysis including several cases and investigation of long-term outcomes of newborn infants is necessary.


Subject(s)
Exercise Test/methods , Fetal Growth Retardation/therapy , Uterine Contraction/physiology , Adult , Apgar Score , Birth Weight/physiology , Case-Control Studies , Female , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/metabolism , Humans , Infant, Newborn , Male , Nipples/physiology , Oxytocin/metabolism , Perinatal Death , Physical Stimulation/methods , Pregnancy , Pregnancy Outcome/epidemiology , Retrospective Studies , Treatment Outcome
11.
J Matern Fetal Neonatal Med ; 32(17): 2879-2882, 2019 Sep.
Article in English | MEDLINE | ID: mdl-29580120

ABSTRACT

Purpose: We recently demonstrated the efficacy of tadalafil treatment for fetal growth restriction (FGR). This study aimed to evaluate the utility of serum placental growth factor (PlGF) level for predicting the efficacy of tadalafil for the treatment of FGR. Materials and methods: The correlations between serum level of PlGF and fetal growth velocity were retrospectively assessed in nine pregnant women receiving tadalafil for FGR before 30 weeks' gestation. Results: Median gestational age was 26 weeks (range 26-28 weeks), and median deviation of estimated fetal weight from standard weight was -2.1 standard deviations (SD) (-2.2 to -1.9 SD) at the beginning of tadalafil treatment. The median serum PlGF level was 227 pg/ml (40.2-427.0 pg/ml) before tadalafil treatment and 278 pg/ml (66.2-729.5 pg/ml) more than 2 weeks after initiation of tadalafil treatment (median gestational week at measurement of PlGF after treatment, 33 weeks [28-33 weeks]). The median fetal growth velocity from enrollment to birth was 17.5 g/day (12.1-20.3 g/day). Maternal serum PlGF levels were increased after tadalafil treatment in all nine cases (median increase in PlGF, 73.1 pg/ml [26.0-281.5 pg/ml]). Notably, maternal serum PlGF level before tadalafil treatment significantly correlated with fetal growth velocity (R2 = 0.63, p < .01). Conclusions: Tadalafil treatment may increase maternal serum PlGF levels. Our results suggest that maternal serum PlGF levels can be used as a predictor of the efficacy of tadalafil treatment for FGR.


Subject(s)
Fetal Growth Retardation/drug therapy , Phosphodiesterase 5 Inhibitors/pharmacology , Placenta Growth Factor/blood , Tadalafil/pharmacology , Administration, Oral , Adult , Female , Fetal Development/drug effects , Fetal Growth Retardation/blood , Gestational Age , Humans , Phosphodiesterase 5 Inhibitors/therapeutic use , Placenta Growth Factor/drug effects , Pregnancy , Retrospective Studies , Tadalafil/therapeutic use
12.
BMJ Open ; 8(10): e020948, 2018 10 30.
Article in English | MEDLINE | ID: mdl-30381311

ABSTRACT

INTRODUCTION: There is no proven therapy to reverse or ameliorate fetal growth restriction (FGR). Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has been reported to potentially play a therapeutic role in FGR, but this has not been established. Tadalafil is also a selective PDE5 inhibitor. We have demonstrated the efficacy of tadalafil against FGR along with short-term outcomes and the feasibility of tadalafil treatment. Based on the hypothesis that tadalafil will safely increase the likelihood of increased fetal growth in FGR, we designed this phase II study to prospectively evaluate the efficacy and safety of tadalafil against FGR. METHODS AND ANALYSIS: This study is a multicentre, randomised controlled phase II trial. A total of 140 fetuses with FGR will be enrolled from medical centres in Japan. Fetuses will be randomised to receive either the conventional management for FGR or a once-daily treatment with 20 mg of tadalafil along with the conventional management until delivery. The primary endpoint is fetal growth velocity from the first day of the protocol-defined treatment to birth (g/day). To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery was established in this study. The investigator will evaluate fetal baseline conditions at enrolment and will decide the timing of delivery based on this fetal indication. Infants will be followed up for development until 1.5 years of age. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Mie University Hospital and each participating institution. Our findings will be widely disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: UMIN000023778.


Subject(s)
Fetal Growth Retardation/drug therapy , Phosphodiesterase 5 Inhibitors/administration & dosage , Tadalafil/administration & dosage , Clinical Trials, Phase II as Topic , Female , Gestational Age , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Japan , Multicenter Studies as Topic , Perinatal Mortality , Phosphodiesterase 5 Inhibitors/adverse effects , Pregnancy , Prenatal Care/methods , Prospective Studies , Randomized Controlled Trials as Topic , Tadalafil/adverse effects , Ultrasonography, Doppler
13.
J Obstet Gynaecol Res ; 44(7): 1318-1321, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29673009

ABSTRACT

Posterior urethral valve (PUV) rarely causes bladder rupture. We experienced hydronephrosis due to ureteral obstruction after the natural repair of a ruptured bladder in a fetus with PUV. Fetal ascites and oligohydramnios were diagnosed at 26 weeks' gestational age. While we followed up with ultrasonography, we regularly removed the fetal ascites via abdominal puncture, injecting warm saline instead of amniotic fluid. At 35 weeks' gestational age, the infant was diagnosed with severe bilateral hydronephrosis, absent of ascites and oligohydramnios. Therefore, a Caesarean section was performed. After birth, the infant was diagnosed with hydronephrosis due to ureteral obstruction after the natural repair of a ruptured bladder associated with PUV. Thus, a ruptured bladder in a fetus with PUV that has naturally repaired should be closely monitored via ultrasonography for hydronephrosis due to ureteral obstruction.


Subject(s)
Fetal Diseases/diagnosis , Hydronephrosis/diagnostic imaging , Infant, Newborn, Diseases/diagnosis , Oligohydramnios/diagnosis , Rupture, Spontaneous/diagnosis , Urethra/abnormalities , Urinary Bladder Diseases/diagnosis , Urogenital Abnormalities/diagnostic imaging , Adult , Female , Fetal Diseases/diagnostic imaging , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnostic imaging , Male , Oligohydramnios/diagnostic imaging , Pregnancy , Rupture, Spontaneous/diagnostic imaging , Ultrasonography, Prenatal , Urinary Bladder Diseases/diagnostic imaging
14.
Am J Hypertens ; 31(1): 89-96, 2017 Dec 08.
Article in English | MEDLINE | ID: mdl-28992178

ABSTRACT

BACKGROUND: We investigated the efficacy and mechanisms of tadalafil, a selective phosphodiesterase 5 inhibitor, in treating preeclampsia (PE) with fetal growth restriction (FGR) using L-NG-nitroarginine methyl ester (L-NAME)-induced PE with FGR in pregnant mice as our experimental model. METHODS: C57BL/6 mice were divided into 2 groups 11 days postcoitum (d.p.c.). A control group of dams (C dam) received 0.5% carboxymethylcellulose (CMC). A L-NAME-treated group received 1 mg/ml L-NAME dissolved in CMC. The L-NAME-treated dams were divided into 2 subgroups 13 d.p.c. One subgroup continued to receive L-NAME (L dams). The other subgroup received L-NAME with 0.08 mg/ml tadalafil suspended in CMC (TL dams). Maternal systolic blood pressure (SBP) and proteinuria were assessed 16 d.p.c. Fetal weight was recorded, and placentas and maternal kidneys were collected 17 d.p.c. RESULTS: Maternal SBP, proteinuria, and fetal weight were improved for TL dams compared to L dams. The placental concentration of placental growth factor (PlGF) was higher for TL dams than for the C and L dams. The placental maternal blood sinuses of L dams were narrower than those of C dams, but those of TL dams improved to a similar width as C dams. Glomerular oxidative stress was ameliorated in TL dams compared to L dams. CONCLUSIONS: Tadalafil dilates the placental maternal blood sinuses, which leads to increase PlGF production, and contributes to facilitate fetal growth and improve maternal SBP. Moreover, tadalafil ameliorates glomerular damage by reducing oxidative stress. These results suggest that tadalafil is a candidate for treatment of PE with FGR.


Subject(s)
Enzyme Inhibitors , Fetal Growth Retardation/chemically induced , Fetal Growth Retardation/prevention & control , NG-Nitroarginine Methyl Ester , Phosphodiesterase 5 Inhibitors/therapeutic use , Pre-Eclampsia/chemically induced , Pre-Eclampsia/prevention & control , Tadalafil/therapeutic use , Animals , Blood Pressure/drug effects , Cyclic GMP/urine , Female , Fetal Development/drug effects , Fetal Growth Retardation/pathology , Kidney/pathology , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Placenta/pathology , Pre-Eclampsia/pathology , Pregnancy , Proteinuria/chemically induced
15.
J Obstet Gynaecol Res ; 43(7): 1159-1168, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28718213

ABSTRACT

AIM: We designed a safety and dose-finding trial of tadalafil administered for fetal growth restriction (FGR). METHODS: Three cases were initially commenced on 10 mg/day and monitored for major adverse events. Should a major adverse event be observed in one or more of the three cases, an examination into its relation with tadalafil would be conducted by a safety evaluation committee. If one or more of these new cases exhibited the same adverse event, the trial would be stopped completely. If there were no harmful side-effects, the trial would be extended to three cases at 20 mg/day, and the protocol would continue as in the 10-mg/day dose. The 40-mg/day dosage was tried in six cases as the dosage was considered to be high. RESULTS: The study population consisted of pregnant women with FGR. Maternal adverse events in all doses were recorded as least one grade 1 adverse events, as tadalafil was considered acceptable from the viewpoint of the mothers. However, a dose of 40 mg/day increased the number of grade 1 adverse events. The only fetal adverse event was a case of intrauterine fetal death related to the velamentous insertion of the umbilical cord. Neonatal adverse events showed no correlation to tadalafil dose, but were found more frequently in preterm births and, therefore, were correlated to infant prematurity. CONCLUSION: This safety and dose-finding trial showed that tadalafil had a favorable safety profile for pregnant women and fetuses with FGR.


Subject(s)
Fetal Death , Fetal Growth Retardation/drug therapy , Phosphodiesterase 5 Inhibitors/administration & dosage , Phosphodiesterase 5 Inhibitors/adverse effects , Premature Birth , Tadalafil/administration & dosage , Tadalafil/adverse effects , Adult , Female , Humans , Pregnancy , Premature Birth/etiology
16.
Clin Appl Thromb Hemost ; 23(6): 622-630, 2017 Sep.
Article in English | MEDLINE | ID: mdl-26759371

ABSTRACT

Thrombotic thrombocytopenic purpura (TTP) frequently develops in patients with connective tissue diseases (CTDs). ADAMTS13 and von Willebrand factor (VWF) are closely related to the onset of TTP. We investigated the roles of ADAMTS13 and VWF in thrombotic events of patients with CTD. ADAMTS13 activity and VWF and VWF propeptide (VWFpp) levels in CTD, primary antiphospholipid antibody syndrome (pAPS), and controls were measured to examine their relationship with thrombosis. ADAMTS13 activity levels were significantly low in the patients with CTD but not in the patients with pAPS. No significant difference in the ADAMTS13 activity levels among the various CTD subgroups was found. The levels of VWF and VWFpp were significantly elevated in the patients with pAPS and CTD compared with that of control groups. Eleven patients with CTD developed TTP, and their ADAMTS13 activity levels were significantly lower than patients having CTD without TTP. However, the ADAMTS13 activity levels showed no difference between the patients having CTD with and without thrombotic events. The VWF antigen levels were significantly high in the patients having CTD with TTP. There were no significant differences in the VWF levels of the patients having CTD with TTP and thrombosis. The VWFpp levels were significantly high in the patients having CTD with TTP and thrombosis. The VWF and VWFpp levels were significantly high in the patients with pAPS. Decreased ADAMTS13 activity and elevated VWF and VWFpp levels were observed in patients with CTD. These abnormalities in patients with CTD may represent the increased risk of thrombosis in CTD.


Subject(s)
ADAMTS13 Protein/blood , Antiphospholipid Syndrome/complications , Connective Tissue Diseases/complications , von Willebrand Factor/analysis , Adult , Aged , Aged, 80 and over , Antiphospholipid Syndrome/blood , Case-Control Studies , Connective Tissue Diseases/blood , Female , Humans , Male , Middle Aged , Purpura, Thrombotic Thrombocytopenic , Thrombosis/etiology , Young Adult
18.
Clin Appl Thromb Hemost ; 23(1): 52-57, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26139837

ABSTRACT

We analyzed a cohort of 36 females with pregnancy loss. In addition to 11 patients with antiphospholipid antibody syndrome and 2 patients with congenital antithrombin (AT) or protein C deficiency, we identified 5 patients with low fibrinogen levels (median 110 mg/dL) prior to 10 weeks of gestation. Four of these 5 patients underwent a fibrinogen gene analysis, and all 4 were found to be heterozygotes for the α-fibrinogen (FGA) Thr321Ala polymorphism. One female without hypofibrinogenemia with a history of 8 pregnancy losses was found to be homozygous for the same polymorphism, and she also showed hypercoagulability without thrombosis. In conclusion, there was a relatively high frequency of pregnancy loss in the setting of hypofibrinogenemia and/or the FGA Thr312Ala polymorphism, and this may be an important risk factor for pregnancy loss and a hypercoagulable state in later pregnancy.


Subject(s)
Abortion, Habitual/etiology , Afibrinogenemia/complications , Antiphospholipid Syndrome/complications , Fibrinogen/genetics , Abortion, Habitual/epidemiology , Abortion, Habitual/genetics , Adult , Afibrinogenemia/genetics , Cohort Studies , Female , Fibrinogen/metabolism , Humans , Polymorphism, Genetic , Pregnancy , Protein C Deficiency/complications , Risk Factors
19.
J Obstet Gynaecol Res ; 43(2): 291-297, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27987345

ABSTRACT

AIM: The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes. METHODS: We retrospectively analyzed 11 Japanese singleton pregnant women with FGR who received tadalafil along with conventional management for FGR at Mie University Hospital from July 2015 to February 2016 (tadalafil group). These women were matched for maternal age, parity, gestational age, and estimated fetal weight at enrollment with 14 singleton pregnant women who received only the conventional management for FGR in 2014 (conventional management group). The conventional management for FGR was performed according to guidelines for obstetric practice in Japan. RESULTS: Both birthweight and fetal growth velocity from enrollment to birth were significantly higher in the tadalafil group than in the conventional management group. The cesarean delivery rate was approximately twofold higher in the conventional management group than in the tadalafil group. Importantly, cesarean section due to non-reassuring fetal status was performed in seven pregnant women in the conventional management group (58.3%) but in none in the tadalafil group (P < 0.05, chi-squared test). CONCLUSIONS: Tadalafil may improve perinatal outcome in FGR by modulating fetal growth through maintenance or improvement of fetal well-being.


Subject(s)
Birth Weight/drug effects , Delivery, Obstetric , Fetal Growth Retardation/drug therapy , Outcome Assessment, Health Care , Phosphodiesterase 5 Inhibitors/pharmacology , Tadalafil/pharmacology , Adult , Female , Humans , Phosphodiesterase 5 Inhibitors/administration & dosage , Pregnancy , Retrospective Studies , Tadalafil/administration & dosage
20.
Int J Hematol ; 105(3): 272-279, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27766527

ABSTRACT

Congenital thrombophilia which is characterized by deficiencies in proteins such as antithrombin (AT), protein C (PC) and protein S (PS), is a major cause of venous thromboembolism (VTE). A total of 130 patients with VTE were evaluated for congenital thrombophilia based on the activity of AT, PC, or PS. Fifteen VTE patients with congenital AT deficiency (11.5 %), 16 with congenital PC deficiency (12.3 %) and eight with congenital PS deficiency (6.2 %) were diagnosed using DNA analysis. The frequency of congenital AT deficiency was significantly higher in subjects with pregnancy-related and idiopathic VTE than in those with VTE due to other causes, and congenital PC and PS deficiency were frequently associated with idiopathic VTE. Among the groups examined, the plasma levels of AT were the lowest in subjects with pregnancy-related VTE. Although our findings may have been influenced by some unintentional bias, congenital thrombophilia is nevertheless a major cause of VTE in pregnant patients as well as in young or middle-aged patients without any underlying diseases.


Subject(s)
Pregnancy Complications, Hematologic/etiology , Thrombophilia/congenital , Thrombophilia/complications , Venous Thromboembolism/etiology , Adolescent , Adult , Aged , Antithrombin Proteins/deficiency , Female , Humans , Male , Middle Aged , Pregnancy , Prevalence , Protein C Deficiency/diagnosis , Protein S Deficiency/diagnosis , Pulmonary Embolism/etiology , Sequence Analysis, DNA
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