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1.
J Obstet Gynaecol Res ; 50(7): 1111-1117, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38627884

RESUMO

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.


Assuntos
Mortalidade Materna , Ritodrina , Tocolíticos , Humanos , Ritodrina/administração & dosagem , Ritodrina/efeitos adversos , Tocolíticos/administração & dosagem , Tocolíticos/efeitos adversos , Feminino , Gravidez , Japão/epidemiologia , Estudos Retrospectivos , Adulto , Trabalho de Parto Prematuro/tratamento farmacológico , Edema Pulmonar/mortalidade , Edema Pulmonar/induzido quimicamente
2.
BMC Pregnancy Childbirth ; 24(1): 318, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664622

RESUMO

BACKGROUND: Some studies have compared the efficacy of nifedipine with that of other tocolytic drugs in the treatment of preterm labor, but the reported results are conflicting. OBJECTIVE: To compare the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor. METHODS: In this systematic review and meta-analysis, PubMed/MEDLINE, Scopus, Clarivate Analytics Web of Science, and Google Scholar were searched until April 3,2024 using predefined keywords. Randomized controlled trials (RCTs) and clinical trials that compared the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor were included. Two authors independently reviewed the articles, assessed their quality and extracted the data. The quality of the included RCTs based on the Cochrane Risk of Bias Tool 1 for clinical trial studies. The risk difference (RD) with the associated 95% confidence interval (CI) was calculated. A forest plot diagram was used to show the comparative point estimates of nifedipine and other tocolytic drugs on the prevention of preterm labor and their associated 95% confidence intervals based on the duration of pregnancy prolongation. Study heterogeneity was evaluated by the I2 index, and publication bias was evaluated by Egger's test. RESULTS: Forty studies enrolling 4336 women were included. According to our meta-analysis, there was a significant difference in the prolongation of preterm labor within the first 48 h between the nifedipine group and the nitroglycerine group (RD, -0.04; 95% CI, -0.08 to -0.00; I2: 32.3%). Additionally, there were significant differences between nifedipine and ritodrine (RD, 0.11; 95% CI, 0.02 to 0.21; I2, 51.2%) for more than one week RD, 0.10; 95% CI, 0.03 to 0.19; I2, 33.2%) and for 34 weeks and more. The difference between nifedipine and magnesium sulfate was not significant in any of the four time points. CONCLUSIONS: Considering the superiority of nifedipine over ritodrine and nitroglycerine and its similar efficacy to magnesium sulfate for tocolysis, it seems that the side effects of these options determine the first drug line.


Assuntos
Sulfato de Magnésio , Nifedipino , Nitroglicerina , Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Humanos , Nifedipino/uso terapêutico , Feminino , Gravidez , Trabalho de Parto Prematuro/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Ritodrina/uso terapêutico , Tocolíticos/uso terapêutico , Nitroglicerina/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
BMC Pregnancy Childbirth ; 24(1): 213, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509456

RESUMO

BACKGROUND: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. CASE PRESENTATION: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. CONCLUSION: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.


Assuntos
Hemangioma , Trabalho de Parto Prematuro , Ritodrina , Recém-Nascido , Gravidez , Feminino , Humanos , Adulto , Ritodrina/efeitos adversos , Hidropisia Fetal/induzido quimicamente , Cesárea/efeitos adversos , Placenta , Trabalho de Parto Prematuro/tratamento farmacológico , Hemangioma/complicações , Hemangioma/tratamento farmacológico , Síndrome
4.
Basic Clin Pharmacol Toxicol ; 134(2): 241-249, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37987176

RESUMO

In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with an intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (Ctrough ) was 22.6 ± 17.3 ng/mL, the maximum plasma concentration (Cmax ) was 30.9 ± 15.3 ng/mL and the time to maximum concentration (Tmax ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUCtau ) was 152.3 ± 91.8 mg/L・h, and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUCtau of nifedipine can predict term delivery. The AUCtau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.


Assuntos
Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Feminino , Humanos , Recém-Nascido , Gravidez , Nifedipino , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/prevenção & controle , Ritodrina/uso terapêutico , Tocólise/métodos , Tocolíticos/efeitos adversos , Estudos Prospectivos
5.
Taiwan J Obstet Gynecol ; 62(5): 682-686, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37678995

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of atosiban and ritodrine in pregnant women who were hospitalized for threatened preterm labor (TPL). MATERIALS AND METHODS: Diagnosis records of preterm labor and subsequent pregnancy-related records and medical records of newborns were extracted from the Clinical Data Warehouse of the Catholic Medical Center's affiliated hospital. Since 2009, cases of preterm labor diagnosed before 34 weeks of pregnancy for first-time mothers who delivered at any one of three hospitals and who received drug treatment for more than 2 days to delay delivery were included in the dataset. Based on characteristics of Korea's national health insurance system, the drug treatment after diagnosis of preterm labor could be classified into cases using only ritodrine (571 women), cases using only atosiban (244 women), and cases where ritodrine treatment was started and then changed to atosiban (275 women). Demographic factors, obstetric outcomes, neonatal outcomes of the two groups were analyzed. RESULTS: The duration and maintenance of pregnancy were found to be similar between the two groups, although the initial cervical length was significantly shorter in the atosiban cohort (AC). Only in multifetal pregnancies, the maintenance of pregnancy was significantly longer in the AC. The total duration of pregnancy did not show any significant difference between the two groups regardless of singleton or multiple pregnancy. However, the distribution graph showed non-responders in the ritodrine cohort (RC). Our study showed a difference in neonatal birth weight of singleton between the two groups. The length of hospitalization and the NICU admission rate were also significantly higher in the RC for singleton. Although not significant, the proportion of numbers with an Apgar score less than 7 was higher in the RC. Neonatal death was more common in the RG (8 cases in AC and 18 cases in RC). CONCLUSIONS: Using atosiban for TPL is more effective than using ritodrine for maintaining pregnancy in the case of a multifetal pregnancy. In singleton pregnancies, neonatal outcomes of the atosiban group were superior to those of the ritodrine group. There seems to be a non-responder group when using ritodrine for TPL. Further studies are needed to determine causes of non-responders of ritodrine and effects of ritodrine on the fetus.


Assuntos
Trabalho de Parto Prematuro , Ritodrina , Recém-Nascido , Gravidez , Feminino , Humanos , Ritodrina/uso terapêutico , Mães , Resultado da Gravidez , Estudos Retrospectivos , Gravidez Múltipla , Trabalho de Parto Prematuro/tratamento farmacológico
6.
Pediatr Int ; 65(1): e15604, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37551666

RESUMO

BACKGROUND: We recently reported on a late preterm infant born at 36 weeks' gestation with serious arrhythmia due to hyperkalemia associated with long-term maternal ritodrine administration. It is unknown whether ritodrine alone increases the risk of neonatal hyperkalemia in infants born at 34-36 weeks' gestation. METHODS: This single-center, retrospective, cohort study enrolled late preterm infants (34-36 gestational weeks) born between 2004 and 2018. Cases with maternal magnesium sulfate use were not sufficient for statistical analysis and so were excluded from the study. Risk factors for the occurrence of hyperkalemia were determined based on clinical relevance and previous reports. RESULTS: In all, 212 late preterm infants with maternal ritodrine use and 400 infants without tocolysis were included in the study. Neonatal hyperkalemia occurred in 5.7% (12/212) in the ritodrine group and 1.8% (7/400) in the control group. The risk of neonatal hyperkalemia was significantly increased by maternal ritodrine administration with a crude odds ratio (OR) of 3.37 (95% confidence interval [CI]: 1.30-8.69; p < 0.01) and an adjusted OR of 3.71 (95% CI: 1.41-9.74; p < 0.01) on multivariable analysis. Long-term tocolysis (≥28 days) with ritodrine increased the risk of neonatal hyperkalemia with 9.3% (11/118) of infants developing hyperkalemia (adjusted OR 4.86; 95% CI: 1.59-14.83; p < 0.01). Neonatal hyperkalemia was not found within 2 weeks of ritodrine administration. CONCLUSION: This research suggests that late preterm infants born after long-term ritodrine administration are at risk of neonatal hyperkalemia and require special attention.


Assuntos
Hiperpotassemia , Trabalho de Parto Prematuro , Ritodrina , Gravidez , Lactente , Feminino , Recém-Nascido , Humanos , Ritodrina/efeitos adversos , Trabalho de Parto Prematuro/induzido quimicamente , Estudos Retrospectivos , Estudos de Coortes , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Recém-Nascido Prematuro
7.
Front Endocrinol (Lausanne) ; 14: 1199628, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529595

RESUMO

Background: It's challenging for healthcare workers to detect neonatal hypoglycemia due to its rapid progression and lack of aura symptoms. This may lead to brain function impairment for the newborn, placing a significant care burden on the family and creating an economic burden for society. Tools for early diagnosis of neonatal hypoglycemia are lacking. This study aimed to identify newborns at high risk of developing neonatal hypoglycemia early by developing a risk prediction model. Methods: Using a retrospective design, pairs (470) of women and their newborns in a tertiary hospital from December 2021 to September 2022 were included in this study. Socio-demographic data and clinical data of mothers and newborns were collected. Univariate and multivariate logistic regression were used to screen optimized factors. A neonatal hypoglycemia risk nomogram was constructed using R software, and the calibration curve and receiver operator characteristic curve (ROC) was utilized to evaluate model performance. Results: Factors integrated into the prediction risk nomogram were maternal age (odds ratio [OR] =1.10, 95% CI: 1.04, 1.17), fasting period (OR=1.07, 95% CI: 1.03, 1.12), ritodrine use (OR=2.00, 95% CI: 1.05, 3.88), gestational diabetes mellitus (OR=2.13, 95% CI: 1.30, 3.50), gestational week (OR=0.80, 95% CI: 0.66, 0.96), fetal distress (OR=1.76, 95% CI: 1.11, 2.79) and neonatal body mass index (OR=1.50, 95% CI: 1.24, 1.84). The area under the curve (AUC) was 0.79 (95% confidence interval [CI]: 0.75, 0.82), specificity was 0.82, and sensitivity was 0.62. Conclusion: The prediction model of this study demonstrated good predictive performance. The development of the model identifies advancing maternal age, an extended fasting period before delivery, ritodrine use, gestational diabetes mellitus diagnosis, fetal distress diagnosis and an increase in neonatal body mass index increase the probability of developing neonatal hypoglycemia, while an extended gestational week reduces the probability of developing neonatal hypoglycemia.


Assuntos
Diabetes Gestacional , Doenças Fetais , Hipoglicemia , Doenças do Recém-Nascido , Ritodrina , Gravidez , Humanos , Recém-Nascido , Feminino , Estudos Retrospectivos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Idade Materna , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia
8.
Eur J Obstet Gynecol Reprod Biol ; 282: 77-82, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36682208

RESUMO

OBJECTIVE: To investigate whether the short-term tocolysis protocol is as effective as the traditional long-term tocolysis protocol with intravenous ritodrine hydrochloride for preterm labour. STUDY DESIGN: This single-centre, retrospective, observational study was conducted at Kitano Hospital, Osaka, Japan between April 2016 and July 2021. At the study hospital, the management protocol for preterm labour after 26 weeks of gestation was changed from the long-term tocolysis protocol to the short-term tocolysis protocol in November 2019. This study compared patients managed with the two protocols, using propensity score analysis to overcome the potential weaknesses of a retrospective study. The primary outcome was the frequency of preterm birth before 34 weeks of gestation before and after the protocol was revised. The secondary outcomes were frequency of neonatal intensive care unit admission and frequency of neonatal chronic lung disease. RESULTS: The study population consisted of 82 patients managed by the long-term tocolysis protocol and 56 patients managed by the short-term tocolysis protocol. After propensity score-weighted adjustment, the median durations of intravenous ritodrine administration in the long-term and short-term protocols were 18 days and 3 days, respectively. Differences were not detected between the long-term and short-term protocols in terms of the frequency of preterm delivery before 34 weeks of gestation [23.7 % vs 21.6 %, risk ratio (RR) 0.91, 95 % confidence interval (CI) 0.47-1.77], frequency of neonatal intensive care unit admission due to preterm birth (49.5 % vs 39.3 %, RR 0.79, 95 % CI 0.53-1.19) and frequency of neonatal chronic lung disease (4.4 % vs 9.2 %, RR 2.07, 95 % CI 0.51-8.48). CONCLUSION: Using propensity score analysis, changing from the long-term tocolysis protocol to the short-term tocolysis protocol for the management of preterm labour after 26 weeks of gestation did not have a negative effect on the frequency of preterm birth or neonatal prognosis.


Assuntos
Pneumopatias , Trabalho de Parto Prematuro , Nascimento Prematuro , Ritodrina , Tocolíticos , Gravidez , Feminino , Humanos , Recém-Nascido , Ritodrina/uso terapêutico , Nascimento Prematuro/prevenção & controle , Tocolíticos/uso terapêutico , Estudos Retrospectivos , Tocólise/métodos , Pontuação de Propensão , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/prevenção & controle
9.
BMC Pregnancy Childbirth ; 23(1): 11, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611175

RESUMO

BACKGROUND: Ritodrine hydrochloride, a ß2-adrenergic agonist, has been widely used in Asia and Europe to treat preterm labor in pregnant women. It has some typical side effects, such as palpitations, pulmonary edema, and hypokalemia. Here, we report a case of rhabdomyolysis and psychiatric symptoms might be associated with intravenous ritodrine. CASE PRESENTATION: A 32-year-old Chinese primigravida woman who was pregnant with twins by in vitro fertilization-embryo transfer was diagnosed with placenta previa and threatened abortion at 21 gestational weeks (GW). The patient was then treated with ritodrine hydrochloride. The initial dose of ritodrine was 150 µg/min, gradually increasing to 360 µg/min at 235/7 GW and 400 µg/min at 271/7 GW. Magnesium sulfate was added to the ritodrine regimen at 215/7 GW in dosage of 1-2 g/h. Psychiatric symptoms appeared at 245/7, 265/7, and 273/7 GW, manifesting as depression, anxiety, and suicidal tendencies. Severe muscle pain in her limbs and general weakness appeared after six weeks of ritodrine administration, which might have been a sign of rhabdomyolysis resulting from ritodrine administration. After ceasing the administration of ritodrine, the muscle pain and relevant data from laboratory tests on the patient were significantly improved, and her mood was stable. It is worth noting that this is the first time to report psychiatric symptoms may associated with the administration of ritodrine. In addition, we reviewed and analyzed six reported cases of rhabdomyolysis caused by ritodrine. CONCLUSION: Our results suggest that we should pay more attention to the risk of rhabdomyolysis and psychiatric symptoms induced by intravenous ritodrine hydrochloride, especially in patients with a history of neuromuscular disorder, or concomitant use of magnesium sulfate.


Assuntos
Rabdomiólise , Ritodrina , Tocolíticos , Recém-Nascido , Gravidez , Humanos , Feminino , Adulto , Tocolíticos/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Mialgia/induzido quimicamente , Mialgia/tratamento farmacológico , Rabdomiólise/induzido quimicamente
10.
J Obstet Gynaecol Res ; 49(2): 606-613, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36443932

RESUMO

AIM: To investigate the effect of ritodrine hydrochloride infusion on fetal movement. METHOD: We gathered 20 pregnant women who received ritodrine hydrochloride infusion as the treated group, and 147 pregnant women who did not as the control group. All women recorded gross fetal movement with the fetal movement acceleration measurement recorder after 28 gestational weeks. The record was divided into epochs of 10 s, and the ratio of movement-positive epochs to all epochs was calculated as the fetal movement index. Furthermore, the mean duration and the mean number per hour of no-fetal movement period, where the fetus did not move for 5 min or more, were calculated as the indexes of no-fetal movement. All indexes were compared between the two groups at 28-31 and 32-35 gestational weeks. RESULTS: The fetal movement indexes (%) were 17.29 ± 7.46 (mean ± SD) in the control group and 13.65 ± 7.13 in the treated group at 28-31 weeks (p = 0.139). At 32-35 weeks, they were 14.55 ± 6.43 and 18.50 ± 5.33, respectively (p = 0.03). Similarly, the no-fetal movement indexes (min, times/h) were 15.03 ± 10.99 and 1.61 ± 0.88, and 18.70 ± 15.80 and 1.75 ± 0.96 (p = 0.824, and 0.673) at 28-31 weeks. At 32-35 weeks, they were 18.13 ± 10.88 and 1.95 ± 0.97, and 9.20 ± 5.51 and 1.14 ± 0.71, respectively (p = 0.003, and 0.003). CONCLUSION: Ritodrine hydrochloride infusion increased the fetal movement and decreased the no-fetal movement period at 32-35 weeks.


Assuntos
Ritodrina , Gravidez , Feminino , Humanos , Ritodrina/farmacologia , Feto , Cuidado Pré-Natal , Infusões Parenterais , Aceleração
11.
Pediatr Int ; 64(1): e15315, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36331237

RESUMO

BACKGROUND: Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. METHODS: This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. RESULTS: The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. CONCLUSION: The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.


Assuntos
Ritodrina , Lactente , Recém-Nascido , Feminino , Gravidez , Humanos , Ritodrina/uso terapêutico , Recém-Nascido Prematuro , Sulfato de Magnésio/uso terapêutico , Sulfatos , Estudos de Coortes , Estudos Prospectivos , Potássio
12.
Hum Exp Toxicol ; 41: 9603271221120650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36000350

RESUMO

Endometriosis (EMS) is often observed in women of childbearing age and significantly impacts patients' quality of life. Ritodrine is a ß2 receptor agonist applied for relaxing the uterine smooth muscle. Its inhibitory effects on inflammation have recently been noted. The present study explored the protective impact of Ritodrine on hypoxia/reoxygenation (H/R)- induced injury in endometrial stromal cells (ESCs). Human ESCs (HESCs) were treated with Ritodrine (0.1, 0.5 µM) for 24 h, followed by exposure to H/R for 6 h. Ritodrine ameliorated H/R-induced higher reactive oxygen species (ROS), declined glutathione (GSH) concentration and increased production of tumor necrosis factor-α (TNF-α), interleukin- 6 (IL-6), and monocyte chemotactic protein 1 (MCP-1) in HESCs. Furthermore, Ritodrine ameliorated the H/R-induced higher nuclear level of nuclear factor κ-B (NF-κB) p65 expression and increased luciferase activity of the NF-κB promoter. In addition, we show that Ritodrine mitigated H/R-induced higher estrogen receptor α (ER-α) expression in HESCs. Interestingly, overexpressing ER-α abolished the regulatory effects of Ritodrine on oxidative stress and the NF-κB pathway-mediated inflammation. Collectively, our data reveal that Ritodrine alleviated H/R-induced injury in ESCs by inhibiting the ER-α/NF-κB pathway.


Assuntos
NF-kappa B , Ritodrina , Feminino , Humanos , Hipóxia/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Oxirredução , Qualidade de Vida , Ritodrina/metabolismo , Ritodrina/farmacologia , Células Estromais , Fator de Necrose Tumoral alfa/metabolismo
13.
Endocrinology ; 163(8)2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35695766

RESUMO

Regulatory mechanisms of iodothyronine deiodinases (DIOs) require further elucidation, and conventional methods for evaluating DIOs are unsuitable for high-throughput screening (HTS). Here we explored factors of transcriptional regulation of 3 types of DIOs (DIO1, DIO2, and DIO3) from a chemical library using our designed HTS. We constructed HTS based on a promoter assay and performed a screen of 2480 bioactive compounds. For compounds that were clinically approved, we validated hit compounds through a retrospective cohort study in our department that evaluated changes in thyroid function in patients using the compounds as drug therapy. Furthermore, we verified the involvement of DIOs using mice treated with the compounds. Of the hit compounds, 6 and 7 compounds transcriptionally up- and downregulated DIO1, respectively; 34 transcriptionally upregulated DIO2; and 5 and 2 compounds transcriptionally up- and downregulated DIO3, respectively. The cohort study clarified the clinical effects of some hit compounds: ritodrine increased free triiodothyronine (fT3)/free thyroxine (fT4) ratio and decreased serum thyroid-stimulating hormone (TSH) levels, tadalafil increased serum fT3 levels, and tyrosine kinase inhibitors (TKIs) decreased serum fT3 and fT4 levels and increased serum TSH levels. Following in vivo experiments using treated mice, consistent results were observed in ritodrine, which upregulated DIO2 in the thyroid gland. In conclusion, we completed HTS for DIOs and obtained attractive hit compounds. Our cohort study revealed the clinical significance of ritodrine, sildenafil, and TKIs. We hope our unique method will contribute to analyzing various targets and lists of hit compounds will promote understanding of DIOs.


Assuntos
Iodeto Peroxidase , Ritodrina , Animais , Estudos de Coortes , Ensaios de Triagem em Larga Escala , Humanos , Iodeto Peroxidase/genética , Camundongos , Estudos Retrospectivos , Tireotropina , Tiroxina , Tri-Iodotironina
14.
PLoS One ; 17(3): e0265872, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358222

RESUMO

Ritodrine hydrochloride is used for pregnancy prolongation and intrauterine fetal resuscitation. However, its clinical significance in intraamniotic inflammation during preterm labor and intrauterine fetal distress is unclear. We investigated the effects of maternal ritodrine hydrochloride administration (MRA; 200 µg/min for 2 h, followed by 800 µg/min for 2 h after 24 h) on fetal physiological parameters. For this purpose, we used chronically instrumented pregnant sheep at 113-119 d (term = 145 d) of gestation without (Group 1, n = 5) and with (Group 2, n = 5) intraamniotic inflammation induced by lipopolysaccharide injection into the amniotic cavity. The changes in fetal heart rate (FHR) and short-term variability (STV) and long-term variability (LTV) in FHR, fetal blood pressure, and fetal arterial blood gas (FABG) values were measured before and at 1 and 2 h after initiating MRA. Before MRA, all parameters were similar between Groups 1 and 2; however, there was significantly higher STV in Group 2 than in Group 1 before MRA at 800 µg/min, significantly higher partial arterial pressure of carbon dioxide in FABG in Group 2 than in Group 1 before MRA at 200 µg/min, and significantly lower blood glucose (BG) in Group 2 than in Group 1 before MRA at 800 µg/min. One hour after MRA, the FHR, STV, and LTV were significantly higher at 800 µg/min than those at the baseline in Group 1, as determined by the Friedman test; however, no significant difference was observed in Group 2. Additionally, the FABG pH significantly decreased 1 h after MRA at 800 µg/min in Group 2, whereas FABG lactate and BG significantly increased 2 h after MRA at 800 µg/min in Groups 1 and 2. Thus, short-term MRA at 800 µg/min increased the FHR, STV, and LTV significantly; these values were further modified under intraamniotic inflammation.


Assuntos
Ritodrina , Animais , Gasometria , Feminino , Feto , Frequência Cardíaca , Frequência Cardíaca Fetal , Inflamação , Gravidez , Ovinos
15.
Minerva Obstet Gynecol ; 74(4): 337-342, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35107244

RESUMO

BACKGROUND: Treatment with beta-agonist tocolytics preceding external cephalic version (ECV) attempt increases success rates. Most studies have focused on intravenously and orally administered beta-agonists, while other administration routes including intramuscularly (IM) and subcutaneously (SC) are understudied. The aim of this study was to compare the efficacy of IM ritodrine to SC salbutamol given prior to ECV. METHODS: A retrospective study of patients who underwent ECV between 1/2012 and 12/2019 at two medical centers. We compared patients undergoing ECV following IM ritodrine versus SC salbutamol. We matched the two groups by parity and placental location. Maternal, pregnancy, ECV procedure and neonatal characteristics were compared. RESULTS: Overall, 601 women were included in each group. Median maternal age and amniotic fluid index (AFI) were lower in the Ritodrine group (27 vs. 32 years, P<0.001, 11 vs. 15 AFI cm, P<0.001, respectively). The median gestational age at ECV was higher in the Ritodrine group (380/7 vs. 370/7 weeks gestation). Success rate was higher in the Ritodrine group (71.7% vs. 63.8%, P=0.003). Vaginal delivery rate was higher in the Ritodrine group (70.7% vs. 60.1%, P<0.001). The number needed to treat to benefit was 10. In a multivariate analysis, Ritodrine was independently associated with higher ECV success rates as compared with Salbutamol (aOR 2.1, 95%CI 1.52-2.89). CONCLUSIONS: Intramuscular ritodrine significantly improved the success rate of ECV compared to SC salbutamol, and both drugs were safe and acceptable before ECV.


Assuntos
Apresentação Pélvica , Ritodrina , Versão Fetal , Albuterol/uso terapêutico , Apresentação Pélvica/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Placenta , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Ritodrina/uso terapêutico , Versão Fetal/métodos
16.
J Obstet Gynaecol ; 42(4): 563-568, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34396888

RESUMO

No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses.Impact statementWhat is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors.What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses.What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.


Assuntos
Ressuscitação , Ritodrina , Tocolíticos , Cesárea/efeitos adversos , Feminino , Feto , Frequência Cardíaca Fetal , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Ritodrina/uso terapêutico , Tocólise/métodos , Tocolíticos/efeitos adversos
17.
J Matern Fetal Neonatal Med ; 35(1): 80-85, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931641

RESUMO

OBJECTIVE: To assess the efficacy of atosiban versus ritodrine as tocolytics in external cephalic version (ECV). MATERIALS AND METHODS: A prospective comparative trial was carried out in a tertiary hospital. 430 women with singleton breech pregnancies ≥36 weeks were recruited for ECV, 215 with ritodrine and 215 with atosiban as tocolytic agents. The efficacy, complications and perinatal outcomes were compared between both groups. The associations between variables were analyzed using the chi-square test (χ2) (qualitative), Student's t test (quantitative, parametric) or Mann-Whitney test (nonparametric). Statistical significance was established as p < .05. RESULTS: The overall ECV success rate was 47.9% (206/430), 46.0% in the atosiban group (99/215) and 49.8% in the ritodrine group (107/215). This difference showed no statistical significance (p = .440). A higher rate of uterine contractions after the maneuver was observed in the atosiban group (34.4 versus 22.8%; p = .008), but without clinical relevance. Perinatal outcomes were similar in both groups, with no significant differences. CONCLUSION: Atosiban and ritodrine showed similar efficacy as tocolytic agents in ECV, with no differences in complications and perinatal outcomes between these two agents.


Assuntos
Apresentação Pélvica , Ritodrina , Tocolíticos , Versão Fetal , Feminino , Humanos , Gravidez , Estudos Prospectivos , Vasotocina/análogos & derivados
18.
BMC Pediatr ; 21(1): 370, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465290

RESUMO

BACKGROUND: Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature. CASE PRESENTATION: A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K+, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 µg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified. CONCLUSIONS: This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration.


Assuntos
Hiperpotassemia , Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Cesárea , Feminino , Humanos , Hiperpotassemia/induzido quimicamente , Lactente , Recém-Nascido , Masculino , Gravidez , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos
19.
Pediatr Allergy Immunol ; 32(7): 1455-1463, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34013624

RESUMO

BACKGROUND: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. METHODS: This study analyzed the data of the participants enrolled in the Japan Environment and Children's Study, a nationwide prospective birth cohort study, between 2011 and 2014. Data of women with singleton live births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, including smoking environment and childhood viral infections, a logistic regression model was used to calculate odds ratios for "wheezing ever," diagnosis of asthma in the last 12 months, and "asthma ever" in women with MRA, with women who did not receive MRA as the reference. Additionally, participants were stratified by term births, and odds ratios for outcomes were calculated using a logistic regression model. RESULTS: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing was 1.17 (95% confidence interval, 1.12-1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. CONCLUSION: MRA was associated with a slightly increased incidence of childhood wheezing up to three years, irrespective of term or preterm birth status. It is important that perinatal physicians consider the potential effects of MRA on the offspring's childhood health.


Assuntos
Nascimento Prematuro , Ritodrina , Criança , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Sons Respiratórios , Ritodrina/efeitos adversos
20.
Kobe J Med Sci ; 66(5): E166-E169, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-34001683

RESUMO

OBJECTIVE: Acute pulmonary edema associated with ritodrine hydrochloride is a rare, life-threatening complication, and dose and duration of ritodrine use are closely associated with this pathology. We report a case of acute pulmonary edema associated with short-duration infusion of ritodrine hydrochloride in a patient with pectus excavatum as an underlying factor. CASE REPORT: A 30-year-old healthy pregnant woman was treated with oral ritodrine for tocolysis between 31 and 35 weeks of pregnancy. At 36 weeks of gestation, she went into preterm labor, with premature rupture of the membrane and breech presentation, and received an infusion of ritodrine hydrochloride for a few hours. Although she was normotensive until labor onset, mild hypertension and proteinuria were recognized. Intraoperatively, a funnel-chest deformity was observed, and she developed postoperative pulmonary edema associated with dyspnea and wet cough and confirmed on chest radiography and arterial gas analysis, and recovered with supportive care. CONCLUSION: Small-dose infusion of ritodrine hydrochloride might cause pulmonary edema in patients with underlying medical problems, including pectus excavatum.


Assuntos
Pulmão/efeitos dos fármacos , Trabalho de Parto Prematuro/prevenção & controle , Edema Pulmonar/induzido quimicamente , Ritodrina/administração & dosagem , Tocolíticos/administração & dosagem , Contração Uterina/efeitos dos fármacos , Adulto , Cesárea , Feminino , Humanos , Infusões Parenterais , Gravidez , Edema Pulmonar/tratamento farmacológico , Ritodrina/efeitos adversos , Ritodrina/uso terapêutico , Tocolíticos/efeitos adversos , Tocolíticos/uso terapêutico , Resultado do Tratamento
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