Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.872
Filtrar
1.
Medicina (Kaunas) ; 58(4)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35454354

RESUMO

The coronaviruses belong to the Coronaviridae family, and one such member, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is causing significant destruction around the world in the form of a global pandemic. Although vaccines have been developed, their effectiveness and level of protection is still a major concern, even after emergency approval from the World Health Organisation (WHO). At the community level, no natural medicine is currently available as a cure. In this study, we screened the vast library from Drug Bank and identified Hemi-Babim and Fenoterol as agents that can work against SARS-CoV-2. Furthermore, we performed molecular dynamics (MD) simulation for both compounds with their respective proteins, providing evidence that the said drugs can work against the MPro and papain-like protease, which are the main drug targets. Inhibiting the action of these targets may lead to retaining the virus. Fenoterol is a beta-2 adrenergic agonist used for the symptomatic treatment of asthma as a bronchodilator and tocolytic. In this study, Hemi-Babim and Fenoterol showed good docking scores of -7.09 and -7.14, respectively, and performed well in molecular dynamics simulation studies. Re-purposing the above medications has huge potential, as their effects are already well-proven and under public utilisation for asthma-related problems. Hence, after the comprehensive pipeline of molecular docking, MMGBSA, and MD simulation studies, these drugs can be tested in-vivo for further human utilisation.


Assuntos
Asma , COVID-19 , COVID-19/tratamento farmacológico , Fenoterol/farmacologia , Fenoterol/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Papaína , Peptídeo Hidrolases , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , SARS-CoV-2
2.
Sci Rep ; 12(1): 3618, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256673

RESUMO

Metabolic reprogramming contributes to oncogenesis, tumor growth, and treatment resistance in pancreatic ductal adenocarcinoma (PDAC). Here we report the effects of (R,S')-4'-methoxy-1-naphthylfenoterol (MNF), a GPR55 antagonist and biased ß2-adrenergic receptor (ß2-AR) agonist on cellular signaling implicated in proliferation and metabolism in PDAC cells. The relative contribution of GPR55 and ß2-AR in (R,S')-MNF signaling was explored further in PANC-1 cells. Moreover, the effect of (R,S')-MNF on tumor growth was determined in a PANC-1 mouse xenograft model. PANC-1 cells treated with (R,S')-MNF showed marked attenuation in GPR55 signal transduction and function combined with increased ß2-AR/Gαs/adenylyl cyclase/PKA signaling, both of which contributing to lower MEK/ERK, PI3K/AKT and YAP/TAZ signaling. (R,S')-MNF administration significantly reduced PANC-1 tumor growth and circulating L-lactate concentrations. Global metabolic profiling of (R,S')-MNF-treated tumor tissues revealed decreased glycolytic metabolism, with a shift towards normoxic processes, attenuated glutamate metabolism, and increased levels of ophthalmic acid and its precursor, 2-aminobutyric acid, indicative of elevated oxidative stress. Transcriptomics and immunoblot analyses indicated the downregulation of gene and protein expression of HIF-1α and c-Myc, key initiators of metabolic reprogramming in PDAC. (R,S')-MNF treatment decreased HIF-1α and c-Myc expression, attenuated glycolysis, shifted fatty acid metabolism towards ß-oxidation, and suppressed de novo pyrimidine biosynthesis in PANC-1 tumors. The results indicate a potential benefit of combined GPR55 antagonism and biased ß2-AR agonism in PDAC therapy associated with the deprogramming of altered cellular metabolism.


Assuntos
Neoplasias Pancreáticas , Fosfatidilinositol 3-Quinases , Agonistas Adrenérgicos/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Fenoterol/farmacologia , Humanos , Camundongos , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Canabinoides/metabolismo , Transdução de Sinais
3.
Pharmacology ; 107(1-2): 116-121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34781292

RESUMO

Fenoterol is a ß2-adrenoceptor (AR)-selective agonist that is commonly used to investigate relaxation responses mediated by ß2-AR in smooth muscle preparations. Some data have questioned this because fenoterol had low potency in the rat urinary bladder when a muscarinic agonist was used as a pre-contraction agent and because some investigators proposed that fenoterol may act in part via ß3-AR. We designed the present study to investigate whether fenoterol is a proper pharmacological tool to study ß2-AR-mediated relaxation responses in the rat urinary bladder. Firstly, we have compared the effect of pre-contraction agents on fenoterol potency and found that fenoterol potency was about 1.5 log units greater against KCl than carbachol (pEC50 7.19 ± 0.66 and 5.62 ± 1.09 of KCl and of carbachol, respectively). To test the selectivity of fenoterol, we have determined the effects of the ß2-AR antagonist ICI 118,551 and the ß3-AR antagonist L 748,337 on relaxation responses to fenoterol. While 300 nM L 748,337 had little effect on the potency of fenoterol (pEC50 6.56 ± 0.25 and 6.33 ± 0.61 in the absence and presence of L 748,337, respectively), the relaxation curve for fenoterol was right-shifted in the presence 300 nM ICI 118,551 (pEC50 5.03 ± 0.18). Thus, we conclude that fenoterol is a proper pharmacological tool to assess ß2-AR-mediated responses in the rat urinary bladder and most likely in other smooth-muscle preparations containing multiple subtypes of the ß-AR.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Fenoterol/farmacologia , Bexiga Urinária/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Aminofenóis/farmacologia , Aminofenóis/uso terapêutico , Animais , Carbacol/farmacologia , Carbacol/uso terapêutico , Feminino , Fenoterol/uso terapêutico , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Cloreto de Potássio/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Ratos Sprague-Dawley , Ratos Wistar , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
4.
Biochem Pharmacol ; 197: 114871, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34902340

RESUMO

Stereoselectivity is important in many pharmacological processes but its impact on drug membrane transport is scarcely understood. Recent studies showed strong stereoselective effects in the cellular uptake of fenoterol by the organic cation transporters OCT1 and OCT2. To provide possible molecular explanations, homology models were developed and the putative interactions between fenoterol enantiomers and key residues explored in silico through computational docking, molecular dynamics simulations, and binding free energy calculations as well as in vitro by site-directed mutagenesis and cellular uptake assays. Our results suggest that the observed 1.9-fold higher maximum transport velocity (vmax) for (R,R)- over (S,S)-fenoterol in OCT1 is because the enantiomers bind to two distinct binding sites. Mutating PHE355 and ILE442, predicted to interact with (R,R)-fenoterol, reduced the vmax ratio to 1.5 and 1.3, respectively, and to 1.2 in combination. Mutating THR272, predicted to interact with (S,S)-fenoterol, slightly increased stereoselectivity (vmax ratio of 2.2), while F244A resulted in a 35-fold increase in vmax and a lower affinity (29-fold higher Km) for (S,S)-fenoterol. Both enantiomers of salbutamol, for which almost no stereoselectivity was observed, were predicted to occupy the same binding pocket as (R,R)-fenoterol. Unlike for OCT1, both fenoterol enantiomers bind in the same region in OCT2 but in different conformations. Mutating THR246, predicted to interact with (S,S)-fenoterol in OCT2, led to an 11-fold decreased vmax. Altogether, our mutagenesis results correlate relatively well with our computational predictions and thereby provide an experimentally-corroborated hypothesis for the strong and contrasting enantiopreference in fenoterol uptake by OCT1 and OCT2.


Assuntos
Fenoterol/química , Fenoterol/metabolismo , Fator 1 de Transcrição de Octâmero/química , Fator 1 de Transcrição de Octâmero/metabolismo , Transportador 2 de Cátion Orgânico/química , Transportador 2 de Cátion Orgânico/metabolismo , Agonistas de Receptores Adrenérgicos beta 2/química , Agonistas de Receptores Adrenérgicos beta 2/metabolismo , Transporte Biológico/fisiologia , Células HEK293 , Humanos , Simulação de Acoplamento Molecular/métodos , Mutagênese Sítio-Dirigida/métodos , Fator 1 de Transcrição de Octâmero/genética , Transportador 2 de Cátion Orgânico/genética , Mutação Puntual/genética , Estrutura Secundária de Proteína , Estereoisomerismo
5.
Circ Res ; 128(2): 262-277, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33208036

RESUMO

RATIONALE: The ß2-adrenoceptor (ß2-AR), a prototypical GPCR (G protein-coupled receptor), couples to both Gs and Gi proteins. Stimulation of the ß2-AR is beneficial to humans and animals with heart failure presumably because it activates the downstream Gi-PI3K-Akt cell survival pathway. Cardiac ß2-AR signaling can be regulated by crosstalk or heterodimerization with other GPCRs, but the physiological and pathophysiological significance of this type of regulation has not been sufficiently demonstrated. OBJECTIVE: Here, we aim to investigate the potential cardioprotective effect of ß2-adrenergic stimulation with a subtype-selective agonist, (R,R')-4-methoxy-1-naphthylfenoterol (MNF), and to decipher the underlying mechanism with a particular emphasis on the role of heterodimerization of ß2-ARs with another GPCR, 5-hydroxytryptamine receptors 2B (5-HT2BRs). METHODS AND RESULTS: Using pharmacological, genetic and biophysical protein-protein interaction approaches, we studied the cardioprotective effect of the ß2-agonist, MNF, and explored the underlying mechanism in both in vivo in mice and cultured rodent cardiomyocytes insulted with doxorubicin, hydrogen peroxide (H2O2) or ischemia/reperfusion. In doxorubicin (Dox)-treated mice, MNF reduced mortality and body weight loss, while improving cardiac function and cardiomyocyte viability. MNF also alleviated myocardial ischemia/reperfusion injury. In cultured rodent cardiomyocytes, MNF inhibited DNA damage and cell death caused by Dox, H2O2 or hypoxia/reoxygenation. Mechanistically, we found that MNF or another ß2-agonist zinterol markedly promoted heterodimerization of ß2-ARs with 5-HT2BRs. Upregulation of the heterodimerized 5-HT2BRs and ß2-ARs enhanced ß2-AR-stimulated Gi-Akt signaling and cardioprotection while knockdown or pharmacological inhibition of the 5-HT2BR attenuated ß2-AR-stimulated Gi signaling and cardioprotection. CONCLUSIONS: These data demonstrate that the ß2-AR-stimulated cardioprotective Gi signaling depends on the heterodimerization of ß2-ARs and 5-HT2BRs.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Cardiomiopatias/prevenção & controle , Fenoterol/análogos & derivados , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Receptor 5-HT2B de Serotonina/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Cardiotoxicidade , Morte Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Doxorrubicina , Etanolaminas/farmacologia , Fenoterol/farmacologia , Fibrose , Peróxido de Hidrogênio , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Multimerização Proteica , Ratos Sprague-Dawley , Receptor 5-HT2B de Serotonina/genética , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais
6.
PLoS One ; 15(5): e0226539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413046

RESUMO

A murine model to study the effect of cold-induced stress (CIS) on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Previous results in the lab show that CIS increases the intensity of chlamydia genital infection, but little is known about the effects and mechanisms of CIS on the differentiation and activities of CD4+ T cell subpopulations and bone marrow-derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines are not well defined. In this study, we examined whether CIS modulates the expressions of beta-adrenergic receptor (ß-AR), transcription factors, hallmark cytokines of Th1 and Th2, and differentiation of BMDCs during C. muridarum genital infection in the murine model. Our results show that the mRNA level of the beta2-adrenergic receptor (ß2-AR) compared to ß1-AR and ß3-AR was high in the mixed populations of CD4+ T cells and BMDCs. Furthermore, we observed decreased expression of T-bet, low level of Interferon-gamma (IFN-γ) production, increased expression of GATA-3, and Interleukin-4 (IL-4) production in CD4+ T cells of stressed mice. Exposure of BMDCs to Fenoterol, ß2-AR agonist, or ICI118,551, ß2-AR antagonist, revealed significant ß2-AR stimulation or inhibition, respectively, in stressed mice. Moreover, co-culturing of mature BMDCs and naïve CD4+ T cells increased the production of IL-4, IL-10, L-17, and IL-23 cytokines, suggesting that stimulation of ß2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that CIS promotes the switching from a Th1 to Th2 cytokine environment. This was evidenced in the murine stress model by the overexpression of GATA-3 concurrent with elevated IL-4 production, reduced T-bet expression, and IFN-γ secretion.


Assuntos
Infecções por Chlamydia/imunologia , Resposta ao Choque Frio , Células Th1/imunologia , Células Th2/imunologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Células Cultivadas , Chlamydia muridarum , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Fenoterol/farmacologia , Interferon gama/genética , Interferon gama/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Propanolaminas/farmacologia , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
7.
Arch Gynecol Obstet ; 301(3): 687-692, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32112180

RESUMO

PURPOSE: Despite safety concerns, ß2-sympathomimetics are still widely used as tocolytic agents. ß-Blockers in turn are used to treat vasculo-proliferative diseases of the newborn such as retinopathy of prematurity (ROP), which may lead to visual impairment and blindness. The scope of this study was to investigate whether antenatal exposure to the ß2-sympathomimetic fenoterol contributes to the development of ROP. METHODS: For this single-center retrospective case-control study of prospectively collected clinical data, all infants born before 32 weeks of gestation between 2001 and 2012 were included. The association of prenatal exposure to fenoterol and the development of ROP were analyzed by multivariate logistic regression. RESULTS: n = 1134 infants < 32 weeks of gestation were screened for eligibility, out of which n = 722 met the inclusion criteria. Exposure to fenoterol (n = 505) was not associated with a higher rate of ROP (OR 0.721, 95% CI 0.463-1.122). Further, duration of exposure (days) did not alter the incidence of ROP (OR 1.001, 95% CI 0.986-1.016). Frequency distribution of different ROP stages and the need for therapeutic intervention was also not affected by prenatal exposure to fenoterol. Risk factors for the development of ROP like low birth weight, low gestational age, prolonged respiratory support and multiple gestation were confirmed in our large study cohort. CONCLUSION: ß2-Sympathomimetic tocolysis does not increase the rate of ROP in premature infants born < 32 weeks of gestation. Our results render fenoterol a safe tocolytic agent regarding neonatal ROP development.


Assuntos
Broncodilatadores/efeitos adversos , Fenoterol/efeitos adversos , Retinopatia da Prematuridade/induzido quimicamente , Adulto , Broncodilatadores/farmacologia , Estudos de Casos e Controles , Feminino , Fenoterol/farmacologia , Humanos , Masculino , Gravidez , Estudos Prospectivos , Estudos Retrospectivos
8.
Res Vet Sci ; 128: 43-48, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710963

RESUMO

ß2-adrenoceptor agonists are considered the most effective drugs to counteract bronchoconstriction in horses with asthma, but only clenbuterol is commonly employed in clinical practice. We evaluated the effects of different selective ß2 agonists: clenbuterol, ritodrine, salbutamol, and fenoterol on the contractions of isolated bronchial muscle of horses induced by electrical field stimulation (EFS), carbachol, histamine, and KCl. All ß2 agonists reduced the amplitude of contraction induced by the different stimuli but with variable efficacy and potency. Fenoterol and salbutamol were more effective than clenbuterol in relaxing the bronchial contractions induced by EFS and histamine, and were able to completely abolish carbachol-induced contractions, unlike clenbuterol and ritodrine. The respective potency values (pEC50) of clenbuterol, ritodrine, salbutamol, and fenoterol were 7.74 ±â€¯0.20, 7.77 ±â€¯0.17, 7.30 ±â€¯0.23, 8.01 ±â€¯0.13, for EFS-induced contractions; 8.39 ±â€¯0.26, 5.49 ±â€¯0.28, 6.63 ±â€¯0.14, 7.68 ±â€¯0.11, for carbachol-induced contraction; 7.39 ±â€¯0.27, 7.04 ±â€¯0.28, 6.45 ±â€¯0.34, 7.34 ±â€¯0.22, for histamine-induced contraction; 7.15 ±â€¯0.06, 6.07 ±â€¯0.20, 6.48 ±â€¯0.14, 6.70 ±â€¯0.18, for KCl-induced contraction. Salbutamol and fenoterol showed a higher efficacy than clenbuterol in relaxing horse bronchial muscle pre-contracted by most stimuli. Clenbuterol displayed a good potency but a rather low efficacy, and this may be due to its partial agonist nature; ritodrine showed lower or not significantly different efficacy and potency compared to the other agonists. An evaluation of the clinical efficacy by fenoterol and salbutamol in horses with asthma could be of great interest to assess if they could represent more effective bronchodilators compared to clenbuterol.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Brônquios/efeitos dos fármacos , Broncodilatadores/farmacologia , Cavalos/fisiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Albuterol/farmacologia , Animais , Brônquios/fisiologia , Clembuterol/farmacologia , Fenoterol/farmacologia , Masculino , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Ritodrina/farmacologia
9.
Biochem Pharmacol ; 171: 113731, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783011

RESUMO

Stereoselectivity is well described for receptor binding and enzyme catalysis, but so far has only been scarcely investigated in carrier-mediated membrane transport. We thus studied transport kinetics of racemic (anti)adrenergic drugs by the organic cation transporters OCT1 (wild-type and allelic variants), OCT2, OCT3, MATE1, and MATE2-K with a focus on stereospecificity. OCT1 showed stereoselective uptake with up to 2-fold higher vmax over their corresponding counterpart enantiomers for (R,R)-fenoterol, (R,R)-formoterol, (S)-salbutamol, (S)-acebutolol, and (S)-atenolol. Orciprenaline and etilefrine were also transported stereoselectively. The Km was 2.1-fold and 1.5-fold lower for the (S,S)-enantiomers of fenoterol and formoterol, while no significant difference in Km was seen for the other aforementioned drugs. Common OCT1 variants showed similar enantiopreference to wild-type OCT1, with a few notable exceptions (e.g. a switch in enantiospecificity for fenoterol in OCT1*2 compared to the wild-type). Other cation transporters showed strong differences to OCT1 in stereoselectivity and transport activity: The closely related OCT2 displayed a 20-fold higher vmax for (S,S)-fenoterol compared to (R,R)-fenoterol and OCT2 and OCT3 showed 3.5-fold and 4.6-fold higher vmax for the pharmacologically active (R)-salbutamol over (S)-salbutamol. MATE1 and MATE2-K generally mediated transport with a higher capacity but lower affinity compared to OCT1, with moderate stereoselectivity. Our kinetic studies showed that significant stereoselectivity exists in solute carrier-mediated membrane transport of racemic beta-adrenergic drugs with surprising, and in some instances even opposing, preferences between closely related organic cation transporters. This may be relevant for drug therapy, given the strong involvement of these transporters in hepatic and renal drug elimination.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/farmacologia , Proteínas de Transporte de Cátions Orgânicos/agonistas , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Acebutolol/química , Acebutolol/metabolismo , Acebutolol/farmacologia , Agonistas Adrenérgicos/química , Agonistas Adrenérgicos/metabolismo , Antagonistas Adrenérgicos/química , Antagonistas Adrenérgicos/metabolismo , Atenolol/química , Atenolol/farmacologia , Transporte Biológico , Fenoterol/química , Fenoterol/metabolismo , Fenoterol/farmacologia , Fumarato de Formoterol/química , Fumarato de Formoterol/metabolismo , Fumarato de Formoterol/farmacologia , Células HEK293 , Humanos , Cinética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 1 de Cátions Orgânicos/agonistas , Transportador 1 de Cátions Orgânicos/antagonistas & inibidores , Transportador 1 de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/agonistas , Transportador 2 de Cátion Orgânico/antagonistas & inibidores , Transportador 2 de Cátion Orgânico/metabolismo , Estereoisomerismo
10.
Nat Commun ; 10(1): 4836, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645561

RESUMO

Despite the crowded nature of the cellular milieu, ligand-GPCR-G protein interactions are traditionally viewed as spatially and temporally isolated events. In contrast, recent reports suggest the spatial and temporal coupling of receptor-effector interactions, with the potential to diversify downstream responses. In this study, we combine protein engineering of GPCR-G protein interactions with affinity sequestration and photo-manipulation of the crucial Gα C terminus, to demonstrate the temporal coupling of cognate and non-cognate G protein interactions through priming of the GPCR conformation. We find that interactions of the Gαs and Gαq C termini with the ß2-adrenergic receptor (ß2-AR), targeted at the G-protein-binding site, enhance Gs activation and cyclic AMP levels. ß2-AR-Gα C termini interactions alter receptor conformation, which persists for ~90 s following Gα C terminus dissociation. Non-cognate G-protein expression levels impact cognate signaling in cells. Our study demonstrates temporal allostery in GPCRs, with implications for the modulation of downstream responses through the canonical G-protein-binding interface.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Agonistas Adrenérgicos beta , Regulação Alostérica , Animais , Sítios de Ligação , AMP Cíclico/metabolismo , Epinefrina/metabolismo , Fenoterol/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Isoproterenol/metabolismo , Cinética , Ligantes , Camundongos , Modelos Moleculares , Ligação Proteica , Engenharia de Proteínas , Estrutura Terciária de Proteína , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Vasopressinas/metabolismo , Transdução de Sinais
11.
Adv Ther ; 36(9): 2487-2492, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31317391

RESUMO

INTRODUCTION: Pressurised metered-dose inhalers (pMDIs) are associated with global warming potential values as they contain a hydrofluoroalkane (HFA) propellant, whereas the Respimat® Soft Mist™ inhaler is propellant-free. The original disposable Respimat has recently been updated to provide a reusable device that is similar in performance and use but is more convenient to patients and reduces environmental impact. This study compared the product carbon footprint (PCF) of Respimat (both disposable and reusable) and pMDIs to understand life cycle hotspots, and also to determine the potential quantitative environmental benefits of a reusable Respimat product. METHODS: PCFs of four inhalation products-tiotropium bromide (Spiriva®) Respimat, ipratropium bromide/fenoterol hydrobromide (Berodual®) Respimat, Berodual HFA pMDI and ipratropium bromide (Atrovent®) HFA pMDI-were assessed across their whole life cycle. RESULTS: Data show that Respimat inhalers have a lower PCF (carbon dioxide equivalent per kilogram) than HFA pMDIs: pMDI Atrovent 14.59; pMDI Berodual 16.48; disposable Spiriva Respimat 0.78; disposable Berodual Respimat 0.78. Approximately 98% of the pMDI life cycle total is due to HFA propellant emissions during use and end-of-life phases. The impact of the material used for the Respimat product outweighs the impact of the material used to make the empty cartridge. Furthermore, compared with the single-use device over 1 month, the PCF of Spiriva Respimat was further reduced by 57% and 71% using the device with refill cartridges over 3 and 6 months, respectively. CONCLUSION: Together, these data suggest that Respimat inhalers, and in particular the new reusable inhaler, can reduce the environmental impact associated with inhaler use. FUNDING: Boehringer Ingelheim.


Assuntos
Broncodilatadores/administração & dosagem , Fenoterol/administração & dosagem , Ipratrópio/administração & dosagem , Inaladores Dosimetrados , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Adulto , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Hidrocarbonetos Fluorados/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Testes de Função Respiratória
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 217: 182-189, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933783

RESUMO

A simple selective luminescent dependent approach was established for quantitation of two selective ß2 agonists namely; Fenoterol hydrobromide (FEN) and Salmeterol xinafoate (SAL). This approach utilizes the capability of the cited drugs to undergo a complexation reaction with Europium ion (Eu3+) in the presence of 1,10-phenanthroline as a co-ligand. The resultant complex leads to a hypersensitive transition and enhancement of the Eu3+ emission peak at 615nm (279nm excitation). Under the optimized conditions, the rectilinear concentration plots of both drugs were (70-1500ngmL-1) and (100-2000ngmL-1) with limit of quantitation 51.3 and 84.4ngmL-1 for FEN and SAL, respectively. The luminescence properties of the complex and its optimum formation conditions were carefully investigated according to the regulations of ICH and the method was successfully applied in plasma. The good accuracy and selectivity of the suggested method allowed extending the proposed protocol into stability study of the cited drugs.


Assuntos
Európio/química , Fenoterol/sangue , Fenoterol/química , Xinafoato de Salmeterol/sangue , Xinafoato de Salmeterol/química , Estabilidade de Medicamentos , Humanos
13.
Cytokine ; 116: 97-105, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30703694

RESUMO

Despite considerable progress in the field of perinatal care, infectious diseases, especially when caused by gram negative bacteria, remain a major reason for neonatal morbidity and mortality. Notably infants born prematurely and those with very low birth weight are at risk due to their immature and deficient immune system and their prolonged hospitalization which promotes nosocomial infections. In case of impending preterm birth, betamethasone is given to induce lung maturation and tocolytic agents like indomethacin or fenoterol are administered to suppress premature labor. The aim of this study was to analyze the effects of these drugs on the immune system of mothers and neonates. Therefore, mononuclear cells from cord blood and peripheral maternal blood were stimulated with Escherichia coli and incubated with betamethasone, indomethacin and fenoterol. Subsequently the effect of the treatment on cytokine production was determined. Betamethasone alone and in combination with tocolytic agents inhibited the production of pro- and anti-inflammatory cytokines. Not only does betamethasone dampen the immune response by reducing the production of cytokines, it also has a variety of other detrimental short- and long-term effects on the neonate. In conclusion we would recommend using biological markers to determine if premature labor actually leads to preterm birth and subsequently administer betamethasone only to mothers giving birth prematurely.


Assuntos
Anti-Inflamatórios/farmacologia , Betametasona/farmacologia , Citocinas/sangue , Fenoterol/farmacologia , Indometacina/farmacologia , Tocolíticos/farmacologia , Adulto , Escherichia coli/imunologia , Feminino , Humanos , Recém-Nascido , Leucócitos Mononucleares/imunologia , Trabalho de Parto Prematuro/tratamento farmacológico , Gravidez , Adulto Jovem
14.
J Perinat Med ; 47(2): 190-194, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30218606

RESUMO

Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the ß-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as "synergistic" or "antagonistic", respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.


Assuntos
Interações Medicamentosas/fisiologia , Fenoterol/farmacologia , Miométrio , Contração Uterina/efeitos dos fármacos , Vasotocina/análogos & derivados , Adulto , Área Sob a Curva , Biópsia , Feminino , Humanos , Miométrio/efeitos dos fármacos , Miométrio/patologia , Miométrio/fisiopatologia , Gravidez , Tocólise/métodos , Tocolíticos/farmacologia , Vasotocina/farmacologia
15.
Rev. colomb. obstet. ginecol ; 69(4): 270-302, Oct.-Dec. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-985512

RESUMO

ABSTRACT Objective: To assess the efficacy and safety of atosiban in pregnant women with risk of preterm delivery as compared to nifedipine, indomethacin, terbutaline, fenoterol and placebo. Materials and methods: A systematic literature review was carried out in eight electronic databases, including Medline, Central, and Embase, using free and standardized search terms. Outcomes assessment included time delay until delivery, neonatal mortality, ratio of adverse maternal events, and ratio of neonatal complications. The quality of the evidence was evaluated per study and for the body of evidence and, whenever feasible, the information was synthesized into a meta-analysis. Alternatively, a narrative summary was presented. Results: Eleven studies were included. Atosiban did not show any statistically significant differences in terms of delaying delivery versus other uterine contraction inhibitors. The neonatal mortality was lower compared to indomethacin (RR = 0.21; 95% CI: 0.05 to 0.92), and the percentage of total maternal adverse events was lower compared to fenoterol (RR = 0.16; 95% CI: 0.08 to 0.31), nifedipine (RR = 0.48; 95% CI: 0.3 to 0.78), and terbutaline (RR = 0.44; 95% CI: 0.28 to 0.71). Conclusions: Atosiban has similar efficacy for delivery delay in patients with risk of preterm delivery as compared to other agents (moderate certainty), showing some advantages regarding neonatal mortality (low certainty) versus indomethacin, and compared to fenoterol, nifedipine and terbutaline in terms of maternal adverse events (moderate certainty).


RESUMEN Objetivo: evaluar la eficacia y seguridad de atosiban en gestantes con amenaza de parto pretérmino comparado con nifedipino, indometacina, terbutalina, fenoterol y placebo. Materiales y métodos: se realizó una revisión sistemática de la literatura en ocho bases de datos electrónicas (Medline, Central, Embase, entre otras), mediante términos de búsqueda libres y estandarizados. Los desenlaces evaluados incluyeron tiempo de retardo del parto, mortalidad neonatal, proporción de eventos adversos maternos y proporción de complicaciones neonatales. Se evaluó la calidad de la evidencia por estudio y para el cuerpo de evidencia, y se sintetizó la información mediante metaanálisis, cuando fue posible; de lo contrario, se resumió de forma narrativa. Resultados: se incluyeron once estudios. Atosiban no mostró diferencias estadísticamente significativas en retardo del parto contra otros uteroinhibidores. Mostró menor mortalidad neonatal que la indometacina (RR = 0,21; IC 95 %: 0,05 a 0,92), y menor proporción de eventos adversos maternos totales que el fenoterol (RR = 0,16; IC 95 %: 0,08 a 0,31), el nifedipino (RR = 0,48; IC 95 %: 0,3 a 0,78) y la terbutalina (RR = 0,44; IC 95 %: 0,28 a 0,71). Conclusiones: atosiban tiene una eficacia similar para retardar el parto ante la amenaza de un parto pretérmino con otros comparadores (certeza moderada), con ventajas frente a indometacina en mortalidad neonatal (certeza baja) y frente a fenoterol, nifedipino y terbutalina en eventos adversos maternos (certeza moderada).


Assuntos
Humanos , Trabalho de Parto Prematuro , Placebos , Terbutalina , Nifedipino , Indometacina , Metanálise , Fenoterol
16.
Biomedica ; 38(3): 303-307, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30335235

RESUMO

Salbutamol is a ß2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the ß2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Albuterol/efeitos adversos , Mioclonia/induzido quimicamente , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Albuterol/uso terapêutico , Terapia Combinada , Sinergismo Farmacológico , Quimioterapia Combinada , Emergências , Evolução Fatal , Fenoterol/efeitos adversos , Fenoterol/uso terapêutico , Humanos , Ipratrópio/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/terapia , Transtornos Relacionados ao Uso de Substâncias/complicações
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 204: 702-707, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29982162

RESUMO

A new, specific, precise and very sensitive spectrofluorimetric methodology has been established and approved for determination of Fenoterol hydrobromide (FEN) in its pharmaceutical forms and spiked plasma. The strategy utilized the phenolic nature of FEN and its capacity to undergo Von Pechman synthesis of coumarin. In this study, Fenoterol hydrobromide reacts with ethyl acetoacetate in presence of concentrated sulfuric acid to form an extremely fluorescent coumarin derivative measured at 480 nm (λex: 420 nm). Different reaction variables affecting development and stability of the formed coumarin derivative were precisely examined and enhanced to guarantee greatest sensitivity of the strategy. The recommended procedure was found to obey Beer's law in concentration range of (300-2000) pg mL-1 with quantitation limit 130 pg mL-1, revealing high sensitivity of the suggested method. The proposed procedure was completely examined and approved through the ICH guidelines and was efficiently applied for the determination of the cited drug in spiked plasma and its dosage forms.


Assuntos
Cumarínicos/química , Fenoterol/análise , Fenoterol/química , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Fenoterol/sangue , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Ácidos Sulfúricos
18.
Cochrane Database Syst Rev ; 7: CD009770, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29971813

RESUMO

BACKGROUND: Uterine tachysystole (more than 5 contractions per 10 minutes in 2 consecutive intervals) is common during labour, particularly with use of labour-stimulating agents. Tachysystole may reduce fetal oxygenation by interrupting maternal blood flow to the placenta during contractions. Reducing uterine contractions may improve placental blood flow, improving fetal oxygenation. This review aimed to evaluate the use of tocolytics to reduce or stop uterine contractions for improvement of the condition of the fetus in utero. This new review supersedes an earlier Cochrane Review on the same topic. OBJECTIVES: To assess the effects of the use of acute tocolysis during labour for uterine tachysystole or suspected fetal distress, or both, on fetal, maternal and neonatal outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (2 February 2018), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating acute tocolysis for uterine tachysystole, intrapartum fetal distress, or both. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We included eight studies (734 women), conducted in hospital settings, predominantly in high-income countries (USA, Austria, Uruguay). Two trials were conducted in upper and lower middle-income countries (South Africa, Sri Lanka). The hospital facilities all had the capacity to perform caesarean section. Overall, the studies had a low risk of bias, except for methods to maintain blinding. All of the trials used a selective beta2 (ß2)-adrenergic agonist in one arm, however the drug used varied, as did the comparator. Limited information was available on maternal outcomes.Selective ß2-adrenergic agonist versus no tocolytic agent, whilst awaiting emergency deliveryThere were two stillbirths, both in the no tocolytic control group (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.01 to 4.55; 2 studies, 57 women; low-quality evidence). One had gross hydrocephalus and the second occurred with vaginal delivery after waiting 55 minutes for caesarean section. The decision for caesarean section delivery was an inclusion criterion in both studies so we could not assess this as an outcome under this comparison. Abnormal fetal heart trace is probably lower with tocolytic treatment (RR 0.28, 95% CI 0.08 to 0.95; 2 studies, 43 women; moderate-quality evidence). The effects on the number of babies with Apgar score below seven were uncertain (low-quality evidence).Intravenous (IV) atosiban versus IV hexoprenaline (1 study, 26 women) One infant in the hexoprenaline group required > 24 hours in the neonatal intensive care unit (NICU) following a forceps delivery (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence). There were no fetal or neonatal mortalities and no Apgar scores below seven. There was one caesarean delivery in the IV hexoprenaline group (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence), and one case of abnormal fetal heart score in the atosiban group (RR 3.00, 95% CI 0.13 to 67.51; very low-quality evidence).IV fenoterol bromhydrate versus emergency delivery (1 study, 390 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. IV fenoterol probably increases the risk of caesarean delivery (RR 1.12, 95% CI 1.04 to 1.22; moderate-quality evidence). Fenoterol may have little or no effect on the risk of Apgar scores below seven (RR 1.28, 95% CI 0.35 to 4.68; low-quality evidence).IV hexoprenaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 37 women) No data were reported for perinatal death or severe morbidity. There were two fetal deaths in the no tocolytic control group (RR 0.23, 95% CI 0.01 to 4.55; low-quality evidence). The rate of caesarean delivery was not reported. There were two babies with Apgar scores below seven in the control group and none in the hexoprenaline group (RR 0.24, 95% CI 0.01 to 4.57; 35 women; low-quality evidence).Subcutaneous terbutaline versus IV magnesium sulphate (1 study, 46 women)No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. The decision for caesarean section was an inclusion criterion, so we could not assess this. The effects on abnormal fetal heart trace are uncertain (very low-quality evidence).Subcutaneous terbutaline with continuation of oxytocic infusion versus cessation of oxytocic infusion without tocolytic agent (1 study, 28 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery in the subcutaneous terbutaline (8/15) and control groups (4/13) (RR 1.73, 95% CI 0.68 to 4.45; low-quality evidence). There were no cases of Apgar scores below seven or abnormal fetal heart trace.Subcutaneous terbutaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 20 women) No data were reported for perinatal death or severe morbidity. There were no fetal or neonatal mortalities. The decision for caesarean section was an inclusion criterion, so we could not assess this. There were two babies with Apgar scores below seven in the control group and none in the terbutaline group (RR 0.17, 95% CI 0.01 to 3.08; low-quality evidence).IV terbutaline versus IV nitroglycerin (1 study, 110 women)No data were reported for perinatal death or severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery between the IV terbutaline (30/57) and control groups (29/53) (RR 0.96, 95% CI 0.68 to 1.36; low-quality evidence). There were no cases of Apgar scores below seven. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effects of tocolytics for uterine tachysystole or suspected fetal distress during labour. The clinical significance for some of the improvements in measures of fetal well-being with tocolytics is unclear. The sample sizes were too small to detect effects on neonatal morbidity, mortality or serious adverse effects. The majority of studies are from high-income countries in facilities with access to caesarean section, which may limit the generalisability of the results to lower-resource settings, or settings where caesarean section is not available.Further well-designed and adequately powered RCTs are required to evaluate clinically relevant indicators of maternal and neonatal morbidity and mortality.


Assuntos
Sofrimento Fetal/tratamento farmacológico , Tocólise/métodos , Tocolíticos/uso terapêutico , Contração Uterina/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Cesárea/estatística & dados numéricos , Feminino , Fenoterol/uso terapêutico , Hexoprenalina/uso terapêutico , Humanos , Nitroglicerina/uso terapêutico , Morte Perinatal , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Terbutalina/uso terapêutico , Vasotocina/análogos & derivados , Vasotocina/uso terapêutico
19.
Arch Gynecol Obstet ; 298(3): 521-527, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29938346

RESUMO

PURPOSE: ß2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the ß2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other ß2-mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different ß2-sympathomimetic tocolytic drugs.


Assuntos
Fenoterol/uso terapêutico , Hemangioma/epidemiologia , Simpatomiméticos/uso terapêutico , Tocolíticos/uso terapêutico , Peso ao Nascer , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Gravidez , Estudos Retrospectivos , Tocólise
20.
Eur J Obstet Gynecol Reprod Biol ; 228: 137-142, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29940417

RESUMO

OBJECTIVE: To develop a prediction model for the chance of successful external cephalic version (ECV). STUDY DESIGN: This is a secondary analysis of a multicenter, open-label randomized controlled trial that assessed the effectiveness of atosiban compared to fenoterol as uterine relaxant during ECV in women with a singleton fetus in breech presentation with a gestational age of 36 weeks or more. Potential predictors included maternal, pregnancy, fetal, and treatment characteristics and were recorded in all participants. Multivariable logistic regression analysis with a stepwise backward selection procedure was used to construct a prediction model for the occurrence of successful ECV. Model performance was assessed using calibration and discrimination. RESULTS: We included a total of 818 women with an overall ECV success rate of 37%. Ten predictive factors were identified with the stepwise selection procedure to be associated with a successful ECV: fenoterol as uterine relaxant, nulliparity, Caucasian ethnicity, gestational age at ECV, Amniotic Fluid Index, type of breech presentation, placental location, breech engagement, possibility to palpate the head and relaxation of the uterus. Our model showed good calibration and a good discriminative ability with a c-statistic of 0.78 (95% CI 0.75 to 0.81). CONCLUSION: Prediction of success of ECV seems feasible with a model showing good performance. This can be used in clinical practice after external validation.


Assuntos
Modelos Estatísticos , Versão Fetal/estatística & dados numéricos , Adulto , Apresentação Pélvica/terapia , Feminino , Fenoterol/uso terapêutico , Humanos , Gravidez , Tocolíticos/uso terapêutico , Vasotocina/análogos & derivados , Vasotocina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...