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1.
Sci Rep ; 14(1): 15055, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38956291

RESUMEN

The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents' decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents' decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89-0.99; Model 2: 0.95 0.90-0.997). Critical disease (5.25; 1.09-25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21-14.53; Model 2: 5.47, 1.50-19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14-2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility.


Asunto(s)
Aborto Inducido , Toma de Decisiones , Padres , Diagnóstico Prenatal , Humanos , Femenino , Embarazo , Aborto Inducido/psicología , Adulto , Padres/psicología , Edad Gestacional , Cardiopatías Congénitas , Cardiopatías , Factores de Riesgo , Enfermedades Fetales , Masculino , Índice de Severidad de la Enfermedad
2.
J Obstet Gynaecol ; 44(1): 2362968, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38885134

RESUMEN

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, caesarean section (CS) has been the preferred deliver method for pregnant women with COVID-19 in order to limit the use of hospital beds and prevent morbidity among healthcare workers. METHODS: To evaluate delivery methods used during the COVID-19 pandemic as well as the rates of adverse events and healthcare worker morbidity associated with caesarean deliveries. METHODS: We investigated maternal and neonatal backgrounds, delivery methods, indications and complication rates among pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture, Japan. The predominant mutation period was classified as the pre-Delta, Delta and Omicron epoch. RESULTS: Of the 1291 pregnant women with COVID-19, 59 delivered; 23 had a vaginal delivery and 36 underwent CS. Thirteen underwent CS with no medical indications other than mild COVID-19, all during the Omicron epoch. Neonatal complications occurred significantly more often in CS than in vaginal delivery. COVID-19 in healthcare workers was not attributable to the delivery process. CONCLUSION: The number of CS with no medical indications and neonatal complications related to CS increased during the COVID-19 pandemic. Although this study included centres that performed vaginal deliveries during COVID-19, there were no cases of COVID-19 in healthcare workers. It is possible that the number of CS and neonatal complications could have been reduced by establishing a system for vaginal delivery in pregnant women with recent-onset COVID-19, given that there were no cases of COVID-19 among the healthcare workers included in the study.


We evaluated the incidence of adverse events associated with caesarean section (CS) deliveries and the morbidity of health care workers, which increased during the coronavirus infection pandemic. Maternal and neonatal background, delivery methods, indications and complication rates of pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture were investigated by time of onset. Of the 1291 pregnant women with COVID-19, 59 delivered while affected; 23 underwent vaginal delivery and 36 CS. Of these, 13 who underwent CS in the omicron epoch had no medical indication other than mild COVID-19. Neonatal complications were significantly more common with CS than with vaginal delivery, and there was no occurrence of COVID-19 in healthcare workers. In this study, there were no cases of COVID-19 among health care workers; establishing a system to perform vaginal delivery for pregnant women with COVID-19 could have reduced the number of CS and neonatal complications.


Asunto(s)
COVID-19 , Cesárea , Parto Obstétrico , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Humanos , Femenino , Embarazo , COVID-19/epidemiología , Japón/epidemiología , Adulto , Complicaciones Infecciosas del Embarazo/epidemiología , Cesárea/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Parto Obstétrico/métodos , Recién Nacido
3.
Int J Infect Dis ; 146: 107154, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38936654

RESUMEN

OBJECTIVES: To clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). METHODS: A retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. RESULTS: Among the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. CONCLUSION: Most antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.


Asunto(s)
Complicaciones Infecciosas del Embarazo , Choque Séptico , Infecciones Estreptocócicas , Streptococcus pyogenes , Humanos , Femenino , Japón/epidemiología , Infecciones Estreptocócicas/mortalidad , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Choque Séptico/mortalidad , Choque Séptico/microbiología , Estudios Retrospectivos , Embarazo , Streptococcus pyogenes/aislamiento & purificación , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/mortalidad , Adulto , Mortalidad Materna , COVID-19/mortalidad , COVID-19/epidemiología , Muerte Materna/estadística & datos numéricos , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/epidemiología
4.
Viruses ; 16(6)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38932183

RESUMEN

Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , ADN Viral , Feto , Carga Viral , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/diagnóstico , Humanos , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , ADN Viral/genética , Masculino , Femenino , Feto/virología , Embarazo , Adulto , Autopsia , Complicaciones Infecciosas del Embarazo/virología
5.
Reprod Med Biol ; 23(1): e12585, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38807753

RESUMEN

Purpose: Sperm DNA fragmentation (SDF) has recently received attention as a cause of male infertility. However, SDF cannot be fully assessed using conventional semen parameter evaluations alone. Therefore, the authors aimed to elucidate the relationship between SDF and sperm parameters via computer-assisted sperm analysis (CASA) to improve treatment strategies in reproductive medicine. Methods: This retrospective observational study analyzed the relationship between sperm parameters assessed by CASA and SDF values determined by the TUNEL assay in 359 patients who visited the Mie University Hospital for infertility treatment. The methodology involved semen analyses covering concentration, motility, and morphology, followed by SDF quantification using the flow cytometry. Results: Statistical analysis revealed significant correlations between SDF and various factors, including age, sexual abstinence period, and specific CASA-measured parameters. Notably, lower sperm motility rates and abnormal head dimensions were associated with higher SDF values, indicating that these parameters were predictive of SDF. Conclusions: This study highlights the importance of sperm motility and head morphology as indicators of SDF, suggesting their usefulness in assessing male fertility. These findings demonstrate the efficacy of detailed sperm analysis, potentially increasing the success rate of assisted reproductive technologies by improving sperm selection criteria.

6.
J Obstet Gynaecol Res ; 50(7): 1111-1117, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38627884

RESUMEN

AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.


Asunto(s)
Mortalidad Materna , Ritodrina , Tocolíticos , Humanos , Ritodrina/administración & dosificación , Ritodrina/efectos adversos , Tocolíticos/administración & dosificación , Tocolíticos/efectos adversos , Femenino , Embarazo , Japón/epidemiología , Estudios Retrospectivos , Adulto , Trabajo de Parto Prematuro/tratamiento farmacológico , Edema Pulmonar/mortalidad , Edema Pulmonar/inducido químicamente
7.
Biomedicines ; 12(4)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38672159

RESUMEN

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

8.
J Cardiol Cases ; 29(2): 55-58, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38362581

RESUMEN

Prompt termination of pregnancy in patients with decompensated pulmonary arterial hypertension (PAH) is imperative for improvement of maternal hemodynamics, but such termination may also result in maternal death due to further deterioration of PAH immediately after delivery. However, there have been limited reports on whether implementation of PAH therapy with continuation of pregnancy improves the maternal outcome, especially in treatment-naïve patients with PAH. A 24-year-old woman was admitted to our hospital with a chief complaint of dyspnea (WHO functional class IV) at 22 weeks and 3 days of gestation. She was diagnosed with PAH accompanied by right heart failure and low cardiac output. Intensive treatment was initiated with inotropic agents, oxygen therapy, and PAH therapy, resulting in improvement of her hemodynamics. A caesarean section was performed at 23 weeks and 3 days. Although her pulmonary arterial pressure transiently increased with oxygenation deteriorating immediately after delivery, worsening PAH improved without mechanical circulatory support. She continued receiving pulmonary vasodilators without relapse of pulmonary hypertension for three years. The improvement of pulmonary hemodynamics prior to delivery with PAH therapy led to a favorable outcome after delivery. Learning objective: Pulmonary hemodynamics in pregnant patients with pulmonary arterial hypertension (PAH) can deteriorate with the continuation of pregnancy, while termination can also cause PAH surge immediately after delivery. In treatment-naïve patients with PAH, who are most likely to benefit from PAH therapy, implementation of PAH therapy with continuation, even with a decompensated status, may improve the hemodynamics prior to delivery, resulting in a favorable outcome after delivery.

9.
J Obstet Gynaecol Res ; 50(4): 604-610, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38308457

RESUMEN

AIM: Reduced Lactobacillus occupancy in the uterine microflora has been associated with implantation failure. This study aimed to evaluate a treatment for improving the uterine microflora. METHODS: This study included patients diagnosed with repeated implantation failure-defined as failure to achieve pregnancy after two or more transfers of viable embryos-who were classified as non-Lactobacillus dominant. Treatment A comprised oral administration of antibiotics for 1 week, followed by oral probiotic butyrate tablets (3 g/day) for approximately 30 days. Treatment B comprised a 1-week course of oral (750 mg/day) and vaginal (250 mg/day) metronidazole, followed by a 1-week intravaginal administration of probiotic capsules (1 capsule/day) and continued oral administration of probiotics (1 capsule/day). Both treatments were compared in terms of efficacy in improving vaginal flora. Improvement was defined as Lactobacillus occupancy >90% or an increase in Lactobacillus occupancy >20%. RESULTS: Seven (41.2%) of 17 patients in the Treatment A group improved in response to the treatment. Contrastingly, 9 (90.0%) of 10 patients improved in the Treatment B group (p = 0.0127). Following treatment, Lactobacillus occupancy in the Treatment B group (62.9% ± 12.7%) was significantly higher than that in the Treatment A group (5.7% ± 9.8%) (p = 0.0242). CONCLUSIONS: This study demonstrates the effectiveness of combining antibiotics and probiotics in vaginal formulations for treating abnormal uterine microflora. However, its potential impact on in vitro fertilization outcomes remains unclear and warrants further investigation through larger, more comprehensive studies.


Asunto(s)
Microbiota , Vaginosis Bacteriana , Femenino , Embarazo , Humanos , Administración Intravaginal , Lactobacillus , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/diagnóstico , Estudios de Casos y Controles , Vagina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Resultado del Tratamiento
10.
EMBO J ; 43(5): 868-885, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38351385

RESUMEN

Lymphatic vessel development studies in mice and zebrafish models have demonstrated that lymphatic endothelial cells (LECs) predominantly differentiate from venous endothelial cells via the expression of the transcription factor Prox1. However, LECs can also be generated from undifferentiated mesoderm, suggesting potential diversity in their precursor cell origins depending on the organ or anatomical location. Despite these advances, recapitulating human lymphatic malformations in animal models has been difficult, and considering lymphatic vasculature function varies widely between species, analysis of development directly in humans is needed. Here, we examined early lymphatic development in humans by analyzing the histology of 31 embryos and three 9-week-old fetuses. We found that human embryonic cardinal veins, which converged to form initial lymph sacs, produce Prox1-expressing LECs. Furthermore, we describe the lymphatic vessel development in various organs and observe organ-specific differences. These characterizations of the early development of human lymphatic vessels should help to better understand the evolution and phylogenetic relationships of lymphatic systems, and their roles in human disease.


Asunto(s)
Estructuras Embrionarias , Células Endoteliales , Vasos Linfáticos , Sistema Porta/embriología , Humanos , Animales , Ratones , Filogenia , Pez Cebra , Factores de Transcripción
11.
J Minim Invasive Gynecol ; 31(5): 445-452, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38417674

RESUMEN

STUDY OBJECTIVE: To assess the impact visceral adipose tissue percentage (VAT%) on surgical outcomes during minimally invasive surgery in obese women with endometrial cancer. DESIGN: Retrospective observational cohort study. SETTING: Mie University Hospital, Japan. PATIENTS: Of the 73 women (body mass index [BMI] >30 kg/m2) with obesity and primary endometrial cancer, 52 underwent robotic surgery, while 21 underwent laparoscopic surgery between April 2014 and December 2022. INTERVENTIONS: We investigated the correlation between surgical outcomes (operative time and blood loss) and obesity (BMI and visceral adipose tissue percentage [VAT%]). MEASUREMENTS AND MAIN RESULTS: Abdominal fat-related parameters were measured at the level of the umbilicus using preoperative computed tomography. A weak negative correlation was found between BMI and VAT% (CC = -0.313, p = .001). Multivariate analysis showed that VAT% had a stronger correlation to total and practical operative time than BMI (ß = 0.338 vs 0.267, ß = 0.311 vs 0.209, respectively) and was an independent predictor of blood loss. VAT% was an independent predictive marker prolonged for operative time and increased blood loss during lymphadenectomy. CONCLUSION: VAT% could be an indicator of surgical outcomes for patients with obesity and endometrial cancer.


Asunto(s)
Índice de Masa Corporal , Neoplasias Endometriales , Grasa Intraabdominal , Laparoscopía , Obesidad , Tempo Operativo , Humanos , Femenino , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Neoplasias Endometriales/complicaciones , Grasa Intraabdominal/diagnóstico por imagen , Estudios Retrospectivos , Persona de Mediana Edad , Obesidad/complicaciones , Anciano , Laparoscopía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Pérdida de Sangre Quirúrgica , Resultado del Tratamiento , Japón/epidemiología , Escisión del Ganglio Linfático/métodos
12.
J Obstet Gynaecol Res ; 50(3): 403-423, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38163757

RESUMEN

AIM: This study aimed to determine the weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy body mass index (BMI) and make recommendations for optimal weight gain in Japan. METHODS: The Japan Society of Obstetrics and Gynecology perinatal database for 2015-2017 was used. From the 719 723 deliveries included in this database, parturients with underlying diseases or missing data were excluded, and 419 114 deliveries were analyzed. A questionnaire survey was also conducted to weigh each perinatal adverse event. For each of the nine outcomes, a restricted cubic spline model was made to estimate the association between the "expected gestational weight gain at 40 weeks" and the outcome risk. RESULTS: Since the classes of medical facilities were generally the same, weights were assigned according to the mean of the questionnaires rather than by the class of the facility. For each pre-pregnancy BMI, the weight gains during pregnancy that minimized the predicted probability of various adverse perinatal events were 12-15, 10-13, 7-10, and upper limit of 5 kg for the underweight, normal-weight, obese 1, and obese ≥2 groups, respectively. CONCLUSIONS: The weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy BMI was established.


Asunto(s)
Obesidad , Aumento de Peso , Femenino , Embarazo , Humanos , Japón/epidemiología , Estudios Retrospectivos , Obesidad/epidemiología , Sistema de Registros
13.
J Obstet Gynaecol Res ; 50(3): 448-455, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38165071

RESUMEN

AIM: This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic-ischemic encephalopathy. METHODS: The study used a three-case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil-associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery. RESULTS: A total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms-like tyrosine kinase-1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration. CONCLUSIONS: The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.


Asunto(s)
Feto , Trabajo de Parto , Recién Nacido , Embarazo , Humanos , Femenino , Tadalafilo/efectos adversos , Factor de Crecimiento Placentario , Atención Prenatal
14.
J Pharm Sci ; 113(2): 486-492, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37981232

RESUMEN

Tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, is a candidate therapeutic agent for fetal growth restriction and hypertensive disorders of pregnancy. In this study, we elucidated the fetal transfer of tadalafil in comparison with that of sildenafil, the first PDE5 inhibitor to be approved. We also examined the contributions of multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) to fetal transfer. Tadalafil or sildenafil was administered to wild-type, Mdr1a/b-double-knockout or Bcrp-knockout pregnant mice by continuous infusion from gestational day (GD) 14.5 to 17.5, and the fetal-to-maternal plasma concentration ratio of unbound drug (unbound F/M ratio) was evaluated at GD 17.5. The values of unbound F/M ratio of tadalafil and sildenafil in wild-type mice were 0.80 and 1.6, respectively. The unbound F/M ratio of tadalafil was increased to 1.1 and 1.7 in Mdr1a/b-knockout and Bcrp-knockout mice, respectively, while the corresponding values for sildenafil were equal to or less than that in wild-type mice, respectively. A transcellular transport study revealed that basal-to-apical transport of both tadalafil and sildenafil was significantly higher than transport in the opposite direction in MDCKII-BCRP cells. Our research reveals that tadalafil is a newly identified substrate of human and mouse BCRP, and it appears that the fetal transfer of tadalafil is, at least in part, attributed to the involvement of BCRP within the placental processes in mice. The transfer of sildenafil to the fetus was not significantly constrained by BCRP, even though sildenafil was indeed a substantial substrate for BCRP.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Intercambio Materno-Fetal , Inhibidores de Fosfodiesterasa 5 , Placenta , Citrato de Sildenafil , Tadalafilo , Animales , Femenino , Humanos , Ratones , Embarazo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Ratones Noqueados , Inhibidores de Fosfodiesterasa 5/farmacocinética , Placenta/metabolismo , Citrato de Sildenafil/farmacocinética , Tadalafilo/farmacocinética
15.
J Adolesc Young Adult Oncol ; 13(1): 197-202, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37535825

RESUMEN

Purpose: Although fertility preservation for pediatric cancer patients is becoming more widespread in Japan, some facilities do not provide sufficient information regarding fertility. This study aimed to elucidate the problems pertaining to the lack of information about fertility among patients. Methods: Based on a 2020 survey, seminars addressing fertility preservation were held from the Designated Pediatric Cancer Care Hospitals in each of the seven blocks in Japan to their partner hospital (pediatric cancer hospitals). The seminar consisted of lectures and group discussions, and a questionnaire was also administered after each seminar. Results: In the group discussions, a lack of explanations to patients and explanatory materials for children were cited as issues by many facilities. The survey results revealed a lack of material explaining fertility preservation and a lack of knowledge among health care providers. There were also many requests to use the patient explanation videos presented at the seminar. Conclusion: The results indicate that further education for health care providers by seminar and other sources and enhancement of explanatory materials are important for fertility preservation in pediatric cancer hospitals in Japan.


Asunto(s)
Preservación de la Fertilidad , Neoplasias , Humanos , Niño , Preservación de la Fertilidad/métodos , Japón , Neoplasias/terapia , Fertilidad , Servicios de Salud , Encuestas y Cuestionarios
16.
Placenta ; 146: 1-8, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38157651

RESUMEN

INTRODUCTION: We aimed to examine the effect of uterine arterial (UtA) blood flow changes after tadalafil treatment for fetal growth restriction (FGR) using two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI). METHODS: We recruited 14 pregnant women with FGR aged 20-44 years, at ≥20 weeks' gestation, between May 2019 and July 2020. They underwent 2D PC-MRI for UtA blood flow measurement 3 days (interquartile range: 2-4) after diagnosis. This group (FGR group) was compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received treatment with tadalafil administered at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI a week later. RESULTS: The median total UtA blood/body surface area was 420 mL/min/m2 (290-494) in the FGR group and 547 mL/min/m2 (433-681) in the control group (p = 0.01). Percent increase in blood flow were significantly different between the FGR cases treated with tadalafil and control at 15.8 % (14.3-21.3) and 4.2 % (3.6-8.7), respectively (p = 0.03). DISCUSSION: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil is expected to improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.


Asunto(s)
Retardo del Crecimiento Fetal , Mujeres Embarazadas , Femenino , Embarazo , Humanos , Tadalafilo/farmacología , Tadalafilo/uso terapéutico , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/tratamiento farmacológico , Placenta , Arterias , Ultrasonografía Prenatal
18.
Sci Rep ; 13(1): 20945, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-38016993

RESUMEN

Although digital examination of the cervix is the standard method used worldwide for evaluating the progress of delivery, it is subjective. Transperineal ultrasound (TPU) is combined with digital evaluation for accurate assessment of fetal descent and rotation of the advanced part of the fetus. This retrospective study aimed to clarify the impact of introducing TPU on perinatal outcomes at Mie University Hospital. We analyzed singleton pregnant women who underwent delivery management at our hospital between April 2020 and March 2021. Perinatal outcomes were compared between patients who used TPU (TPU+ group) and those who did not (TPU- group). The angle of progression and head direction were measured. The rate of vaginal delivery was significantly increased (90.9% vs. 71.6%; P = 0.0017), and the second stage of labor was significantly prolonged in the TPU+ group (148.1 vs. 75.8 min; P < 0.0001). A significant difference was observed in termination in the latent phase between the TPU+ group [3/8 (37.5%) cases] and TPU- group [20/25 (80.0%) cases] (P = 0.036). The rate of vaginal delivery can be increased through accurate evaluation of the progress of delivery with TPU.


Asunto(s)
Parto Obstétrico , Trabajo de Parto , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Estudios Prospectivos , Parto Obstétrico/métodos , Ultrasonografía/métodos , Ultrasonografía Prenatal/métodos
20.
Cells ; 12(22)2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37998320

RESUMEN

Sperm DNA fragmentation (SDF) that occurs during the freezing-thawing of sperm may negatively impact the treatment outcomes of assisted reproductive technologies (ART). In a previous study, we developed a human sperm cryopreservation reagent containing carboxylated poly-L-lysine (CPLL) that reduced SDF after freeze-thawing compared with clinically popular cryopreservation reagents containing human serum albumin. However, it is unclear whether CPLL reduces SDF, as it differed from the constituents of the commercial cryopreservation reagents used for comparison. Therefore, here, we examined whether CPLL reduces the SDF of human sperm and evaluated reactive oxygen species (ROS) levels and lipid peroxidation (LPO), which are the causes of SDF; mitochondrial injury, ROS production; and impaired sperm motility. Furthermore, optimal antioxidants and their concentrations that could further enhance the reduction in SDF were determined for future clinical application in ART and underwent the same functional evaluations. CPLL can reduce SDF via inhibition of intracytoplasmic ROS and LPO. Furthermore, the addition of 0.1 mM resveratrol avoided the enhancement of SDF, which potentially affects mitochondrial and cytoplasmic ROS and LPO. This novel human sperm cryopreservation reagent containing CPLL and resveratrol has the potential to improve treatment outcomes in ART using frozen sperm.


Asunto(s)
Polilisina , Preservación de Semen , Humanos , Masculino , Congelación , Resveratrol/farmacología , Polilisina/farmacología , Especies Reactivas de Oxígeno , Fragmentación del ADN , Crioprotectores/farmacología , Motilidad Espermática/fisiología , Semen , Espermatozoides/fisiología , Criopreservación
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