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1.
Viruses ; 12(5)2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32466302

RESUMO

Influenza A virus, one of the major human respiratory pathogens, is responsible for annual seasonal endemics and unpredictable periodic pandemics. Despite the clinical availability of vaccines and antivirals, the antigenic diversity and drug resistance of this virus makes it a persistent threat to public health, underlying the need for the development of novel antivirals. In a cell culture-based high-throughput screen, a ß2-adrenergic receptor agonist, nylidrin, was identified as an antiviral compound against influenza A virus. The molecule was effective against multiple isolates of subtype H1N1, but had limited activity against subtype H3N2, depending on the strain. By examining the antiviral activity of its chemical analogues, we found that ifenprodil and clenbuterol also had reliable inhibitory effects against A/H1N1 strains. Field-based pharmacophore modeling with comparisons of active and inactive compounds revealed the importance of positive and negative electrostatic patterns of phenyl aminoethanol derivatives. Time-of-addition experiments and visualization of the intracellular localization of nucleoprotein NP demonstrated that an early step of the virus life cycle was suppressed by nylidrin. Ultimately, we discovered that nylidrin targets hemagglutinin 2 (HA2)-mediated membrane fusion by blocking conformational change of HA at acidic pH. In a mouse model, preincubation of a mouse-adapted influenza A virus (H1N1) with nylidrin completely blocked intranasal viral infection. The present study suggests that nylidrin could provide a core chemical skeleton for the development of a direct-acting inhibitor of influenza A virus entry.


Assuntos
Antivirais/farmacologia , Hemaglutininas/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Fusão de Membrana/efeitos dos fármacos , Nilidrina/farmacologia , Células A549 , Animais , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Nucleoproteínas/metabolismo , Nilidrina/análogos & derivados , Internalização do Vírus/efeitos dos fármacos
2.
Rev Invest Clin ; 63(4): 335-43, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-22364032

RESUMO

INTRODUCTION: Acute respiratory infections are the second leading cause of morbidity in children under 18 years. Several drugs have been used with variable efficacy and safety, trying to reduce the associated symptoms and improve quality of life. OBJECTIVE: To evaluate the efficacy and safety of buphenine, aminophenazone and diphenylpyraline hydrochloride when compared with placebo for the control of symptoms associated with common cold in children 6-24 months of age. MATERIAL AND METHODS: Randomized clinical trial, double blind, placebo controlled, in 100 children < 24 months of any gender, with symptoms associated to common cold. They received the drug under study vs. placebo for seven days. Both groups received acetaminophen. The change on common cold related symptoms were evaluated. Statistic analysis was made with STATA 11.0 for Mac. RESULTS: Fifty-three children were randomized to study drug and forty-seven to placebo. Age of children in each group was similar (12.2 +/- 5.8 months vs. 12.7 +/- 5.8 months, p NS). There were significant differences between groups in relation to rhinorrea and sneezing resolution, with better results in Flumil group and no adverse events observed. CONCLUSIONS: The results in this study indicates that Flumil is a safe and effective drug for control of symptoms present in the common cold in children aged 6-24 months.


Assuntos
Aminopirina/uso terapêutico , Resfriado Comum/tratamento farmacológico , Nilidrina/uso terapêutico , Piperidinas/uso terapêutico , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Aminopirina/administração & dosagem , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Mucosa Nasal/metabolismo , Nilidrina/administração & dosagem , Piperidinas/administração & dosagem , Espirro/efeitos dos fármacos
3.
Ophthalmic Physiol Opt ; 23(5): 383-99, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12950886

RESUMO

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in the developed world. The lack of effective treatment modalities, coupled with evidence supporting an oxidative pathogenesis, has increased interest in the potential preventative role of nutritional supplementation. This article reviews seven randomised controlled trials (RCTs) that have investigated the role of nutritional supplementation in AMD. Three of these trials reported a positive effect of nutritional supplementation on AMD; the Age-related eye study (AREDS), the Lutein Antioxidant Supplementation Trial (LAST), and the oral zinc trial by Newsome et al. (1988). However, the oral zinc trial by Newsome et al. (1988) was unlikely to detect any difference between treatments smaller than 72%, and the AREDS results were based on a subgroup of their study population. Lutein was considered for the AREDS formulation, but was not commercially available at that time. The findings of the LAST support a possible therapeutic role of lutein in AMD.


Assuntos
Suplementos Nutricionais , Degeneração Macular/dietoterapia , Vitamina E/análogos & derivados , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Carotenoides/metabolismo , Combinação de Medicamentos , Humanos , Luteína/administração & dosagem , Degeneração Macular/etiologia , Nilidrina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina E/administração & dosagem , Vitaminas/metabolismo , Zinco/administração & dosagem , alfa-Tocoferol/administração & dosagem , beta Caroteno/administração & dosagem
4.
J Med Chem ; 41(18): 3499-506, 1998 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-9719603

RESUMO

A series of bis(phenylalkyl)amines, structural analogues of ifenprodil and nylidrin, were synthesized and tested for antagonism of N-methyl-D-aspartate (NMDA) receptors. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The bis(phenylalkyl)amines were selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, the most potent of these, N-[2-(4-hydroxyphenyl)ethyl]-5-phenylpentylamine hydrochloride (20), has an IC50 value of 8 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. The structure-activity relationship of the bis(phenylalkyl)amine series indicates that the piperidine ring and alkyl chain substitutions common to NR2B-selective antagonists such as ifenprodil, CP 101,606, and Ro 25-6981 are not necessary to generate potent and selective ligands. The primary determinants of potency are the phenolic OH group, acting as a hydrogen bond donor, the distance between the two rings, and an electrostatic interaction between the receptor and the basic nitrogen atom. This study provides a framework for designing structurally novel NR2B-selective antagonists which may be useful for treatment of a variety of neurological disorders.


Assuntos
Butilaminas , Antagonistas de Aminoácidos Excitatórios , Fenóis , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Butilaminas/síntese química , Butilaminas/química , Butilaminas/farmacologia , Antagonistas de Aminoácidos Excitatórios/síntese química , Antagonistas de Aminoácidos Excitatórios/química , Antagonistas de Aminoácidos Excitatórios/farmacologia , Nilidrina/farmacologia , Oócitos , Fenóis/síntese química , Fenóis/química , Fenóis/farmacologia , Ratos , Receptores de N-Metil-D-Aspartato/biossíntese , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/biossíntese , Relação Estrutura-Atividade , Xenopus laevis
5.
Neurosci Lett ; 225(1): 29-32, 1997 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-9143010

RESUMO

Ifenprodil is an atypical N-methyl-D-aspartate (NMDA) receptor antagonist that selectively blocks receptors containing the NR2B subunit. It has been proposed that ifenprodil may act at a stimulatory polyamine site on NMDA receptors, although interactions between ifenprodil and polyamines are non-competitive. NMDA receptors are also inhibited by extracellular protons, and an interaction between protons and polyamine stimulation has been described. Using voltage-clamp recording of recombinant NR1/NR2B receptors expressed in oocytes, ifenprodil inhibition was found to be pH sensitive with a smaller inhibition at alkaline pH. Similar effects of pH were seen on inhibition by nylidrin, eliprodil, and haloperidol, which are thought to act at the ifenprodil binding site. The pH sensitivity of ifenprodil block occurs at NR1B/NR2B as well as NR1A/NR2B receptors, suggesting that it is not influenced by the exon-5 insert that is present in NR1B but absent in NR1A. Protons may directly affect the ifenprodil binding site or may alter the coupling of ifenprodil binding to inhibition of channel gating.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Fármacos Neuroprotetores/farmacologia , Oócitos/efeitos dos fármacos , Piperidinas/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Haloperidol/farmacologia , Concentração de Íons de Hidrogênio , Nilidrina/farmacologia , Técnicas de Patch-Clamp , Xenopus laevis
6.
Eur J Pharmacol ; 337(2-3): 197-208, 1997 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-9430414

RESUMO

The 1,4-di-substituted piperidines ifenprodil, eliprodil, CP 101,606 ((1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol ) and Ro 25-6981 ((R-(R*,S*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenyl-methyl)-1- piperidinepropanol) are allosteric antagonists of NMDA receptors. Inhibition of diheteromeric NMDA receptors by this class of antagonist is characterized by pronounced selectivity for NR1/2B subunit combinations. In the current study, we assayed effects of nylidrin, a structurally-related non-piperidine, on recombinant and neuronal NMDA receptors. Nylidrin was a potent (IC50 = 0.18 microM) antagonist of NR1A/2B receptors expressed in Xenopus oocytes and was at least 150-fold weaker against NR1A/2A and NR1A/2C receptors. The blockade of NR1A/2B responses by nylidrin was not surmounted by increasing the concentrations of glutamate or glycine and was not voltage-dependent. Potency of inhibition increased approximately 3-fold upon lowering extracellular pH from 8 to 6.8. Nylidrin inhibited NMDA responses in cultured rat cortical neurons with similar potency and apparent mechanism of action as the NR1A/2B receptors. Our results suggest that nylidrin interacts with the same allosteric inhibitory site previously described for the related piperidine antagonists, and should serve as a structural lead for designing novel subtype-selective inhibitors of NMDA receptors.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Nilidrina/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Sinergismo Farmacológico , Agonistas de Aminoácidos Excitatórios/farmacologia , Concentração de Íons de Hidrogênio , Potenciais da Membrana/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oócitos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Xenopus
7.
Neuropediatrics ; 27(4): 174-7, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8892364

RESUMO

Indomethacin, a prostaglandin synthesis inhibitor, is a more efficient tocolytic than the beta-sympathomimetic nylidrin, but causes more frequent unwanted effects in the neonatal period. In order to elucidate the effects on neurodevelopment, infants randomly exposed in utero to either compound were followed up to 18 months. A total of 93 children (40 exposed to nylidrin and 53 exposed to indomethacin) were examined at the age of 12 months. A detailed neurological examination was carried out in 44 of these infants at the age of 18 months. At the age of 12 months the children in the indomethacin group showed poor outcome (death or severe BPD and/or CP and/or severe ROP) in 23% and the children in the nylidrin group in 5% (p = 0.039, Fisher Exact Test). Concerning the children born during tocolysis the corresponding figures were 73% and 13% respectively (p = 0.002, Fisher Exact Test). The growth of the children did not differ significantly between the two treatment groups. Neurological assessment at the age of 18 months revealed more subnormally scoring children in the indomethacin group, but the differences were not significant. It was concluded that the higher incidence of poor outcome and a lest favourable neurological development in the indomethacin group do not support indomethacin's position as the drug of choice for tocolysis.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Indometacina/efeitos adversos , Nilidrina/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Tocolíticos/efeitos adversos , Feminino , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido Prematuro/fisiologia , Gravidez , Distribuição por Sexo , Resultado do Tratamento , Trigêmeos , Gêmeos
8.
Ophthalmologica ; 209(6): 302-5, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8751336

RESUMO

Age-related macular degeneration (AMD) is the main cause of a reduction in visual acuity in patients over the age of 65 years. A positive influence of medical treatment (i.e. with vitamins and trace minerals) has been suggested but remains unproven. In this randomized, double-blind study, 20 patients in an early stage of AMD were included. Over a period of 6 months, 9 patients were treated with Visaline and 11 with a placebo. The effect of the treatment was not statistically different between the two groups, admittedly small in number, in terms of visual and retinal acuity, color vision, and contrast sensitivity. Despite the lack of such measureable differences, the patients' own subjective assessments, however, were much better in the Visaline-treated group. Due to the short duration of the observation time, we can not comment on a possible long-term effect.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Antioxidantes/uso terapêutico , Degeneração Macular/tratamento farmacológico , alfa-Tocoferol/análogos & derivados , Idoso , Ácido Ascórbico/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Pressão Intraocular , Degeneração Macular/fisiopatologia , Masculino , Nilidrina/uso terapêutico , Projetos Piloto , Comprimidos , Tocoferóis , Visão Ocular/fisiologia , Acuidade Visual , Vitamina E/análogos & derivados , Vitamina E/uso terapêutico , beta Caroteno/uso terapêutico
9.
J Pediatr ; 124(5 Pt 1): 782-8, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8176569

RESUMO

The aim of this randomized study was to compare the neonatal outcome in infants who have been exposed in utero to indomethacin with that in infants exposed to a beta-adrenergic agonist, nylidrin hydrochloride. Eighty pregnant women threatened with preterm labor between 24 and 34 weeks of gestation were enrolled in the study. An intravenous infusion of nylidrin or enterally administered indomethacin was given for a maximum of 72 hours. If preterm labor recurred, all parturient patients were treated with nylidrin. Indomethacin prolonged gestation significantly more than the beta-adrenergic agonist (6.6 weeks vs 4.5 weeks; p = 0.04). Ten of the forty-two infants exposed to indomethacin and 2 of the 45 infants exposed to nylidrin had bronchopulmonary dysplasia (24% vs 5%; p = 0.02). Among the 28 infants delivered within 120 hours after the start of treatment, the incidences of respiratory distress syndrome (82% vs 29%; p = 0.02), bronchopulmonary dysplasia (73% vs 6%; p = 0.0006), and necrotizing enterocolitis or focal intestinal perforation (27% vs 0%; p = 0.03) were higher among those exposed to indomethacin than among those exposed to nylidrin. We infer that administration of indomethacin to pregnant women threatened with premature labor is associated with an increased risk of bronchopulmonary dysplasia in their infants if delivery occurs early.


Assuntos
Displasia Broncopulmonar/induzido quimicamente , Indometacina/uso terapêutico , Nilidrina/uso terapêutico , Trabalho de Parto Prematuro/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal , Tocolíticos/efeitos adversos , Adulto , Feminino , Humanos , Indometacina/efeitos adversos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Tocólise/métodos
10.
Pediatr Res ; 33(6): 615-9, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8378121

RESUMO

To study the effect of antenatal indomethacin or nylidrin hydrochloride treatment on the fetal and neonatal ductus arteriosus and tricuspid valve function, 84 pregnant women with threatened premature birth between 22.9 and 34.0 wk gestation and 94 of their offspring born at 24.7 to 41.6 wk of gestation were studied by Doppler echocardiography. Forty-six women were treated with indomethacin and 38 with nylidrin. Both peak systolic and peak diastolic velocities in the ductus increased after administration of indomethacin and exceeded the corresponding velocities in the fetuses of the nylidrin group (p = 0.0001). Ductal constriction occurred in 42 of 49 fetuses treated with indomethacin (86%). Tricuspid valve regurgitation (TR) was evident in 11 of 49 fetuses treated with indomethacin (22%). The mean gestational age of the fetuses with TR (30.0 wk) tended to be higher than those without TR (28.3 wk, p = 0.056). In the nylidrin group, no fetus had ductal constriction or TR. A significant increase in peak systolic velocity (r = 0.54, p = 0.0001) and in peak diastolic velocity (r = 0.46, p = 0.0001) in the ductus with advancing gestational age was demonstrated in the indomethacin group; however, in the nylidrin group, there was a less remarkable increase in peak systolic velocity (r = 0.35, p = 0.04) and no increase in peak diastolic velocity (r = 0.02, p = 0.93). In infants born at or before 35 wk gestation, incidences of both spontaneous closure and indomethacin-induced closure of ductus were similar in both study groups (p > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Permeabilidade do Canal Arterial/tratamento farmacológico , Feto/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Indometacina/farmacologia , Nilidrina/farmacologia , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Permeabilidade do Canal Arterial/fisiopatologia , Permeabilidade do Canal Arterial/prevenção & controle , Feminino , Doenças Fetais/tratamento farmacológico , Feto/fisiologia , Idade Gestacional , Humanos , Indometacina/administração & dosagem , Recém-Nascido , Masculino , Troca Materno-Fetal , Nilidrina/administração & dosagem , Gravidez
11.
Am J Obstet Gynecol ; 166(1 Pt 1): 150-4, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1733190

RESUMO

OBJECTIVE: We studied the role of smooth muscle-relaxing prostacyclin and its endogenous antagonist, thromboxane A2, in preterm labor by assessing the urinary output of the breakdown products of prostacyclin (6-keto-prostaglandin F1 alpha and 2,3-dinor-6-keto-prostaglandin F1 alpha) and those of thromboxane A2 (thromboxane B2, 2,3-dinor-thromboxane B2). STUDY DESIGN: Thirty-three women in preterm labor between 25 and 34 weeks of gestation were studied before, during, and after treatment with indomethacin (n = 16) or nylidrin (n = 17). Urinary prostanoid levels were determined by high-performance liquid chromatography followed by radioimmunoassay, and the excretion was expressed as nanograms of prostanoids per millimole of creatinine. Statistical analyses were done by paired and unpaired Student t test, by Spearman's correlation, and by Wilcoxon signed-rank test. RESULTS: Preterm labor was accompanied by a median 32% higher output of prostacyclin and thromboxane A2 metabolites as compared with those in 25 controls. At 8 hours after the start of treatment indomethacin induced maximal drops in 6-keto-prostaglandin F1 alpha (70%), in dinor-6-keto-prostaglandin F1 alpha (60%), in thromboxane B2 (85%), and in dinor-thromboxane B2 (95%) excretion. Within 1 week after the cessation of indomethacin, output of prostacyclin metabolites had recovered to pretreatment values, whereas output of thromboxane A2 metabolites was yet lower than the pretreatment value. Nylidrin induced no change in the output of prostacyclin and thromboxane A2 metabolites. CONCLUSION: Threatened preterm labor is associated with a rise in prostacyclin and thromboxane A2 synthesis. Indomethacin inhibits more thromboxane A2 than does prostacyclin synthesis. These findings may explain the fetal vascular changes during maternal indomethacin treatment.


Assuntos
Epoprostenol/urina , Indometacina/uso terapêutico , Nilidrina/uso terapêutico , Trabalho de Parto Prematuro/urina , Tromboxano B2/urina , 6-Cetoprostaglandina F1 alfa/análogos & derivados , 6-Cetoprostaglandina F1 alfa/urina , Adulto , Feminino , Humanos , Cinética , Trabalho de Parto Prematuro/tratamento farmacológico , Gravidez , Tromboxano B2/análogos & derivados , Tocólise
13.
Obstet Gynecol ; 78(6): 1093-7, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1945214

RESUMO

We compared the tocolytic effect of indomethacin and nylidrin in a prospective double-blind trial in which the appearance of the tocolytic treatment (always intravenous infusion and rectal suppositories/oral capsules) was identical to the subjects. Sixty healthy women in imminent preterm labor between 25-34 weeks of singleton gestation were included. Thirty of these women received indomethacin (concomitantly with placebo infusion), with doses as follows: day 1, 100-mg rectal suppository followed by two oral capsules (50 mg) at 8-hour intervals; days 2 and 3, three 50-mg oral capsules each day. Thirty women received intravenous nylidrin (concomitantly with rectal/oral placebo), initiated with the dose of 50 micrograms/minute and continued at the dose of 100-150 micrograms/minute for a maximum of 3 days. Preterm labor was arrested for 24, 48, and 72 hours in 100, 96, and 90%, respectively, of subjects in the indomethacin group, compared with 100, 76, and 73% of women in the nylidrin group; the difference was significant (P less than .05) at 48 hours. Women progressed beyond 37 gestational weeks more commonly (P less than .05) with indomethacin (21 of 30, 70%) than with nylidrin (13 of 30, 43%). Indomethacin treatment was accompanied by maternal side effects 20% of the time, significantly less commonly (P less than .001) than with nylidrin (83%). The neonatal outcome was similar in the two study groups. We conclude from this double-dummy technique trial that indomethacin is more effective and better tolerated than nylidrin in arresting imminent preterm labor.


Assuntos
Indometacina/uso terapêutico , Nilidrina/uso terapêutico , Trabalho de Parto Prematuro/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Humanos , Gravidez , Estudos Prospectivos
14.
Br J Obstet Gynaecol ; 98(7): 685-91, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1883793

RESUMO

The role of corticotrophin-releasing hormone (CRH) in preterm labour was studied in 23 women in preterm labour at between 26 and 33 weeks gestation who were randomly allocated to receive treatment with indomethacin (n = 11) or with nylidrin a beta-sympathomimetic agent (n = 12). Maternal plasma CRH in the preterm group (median 70, range 9-597 pmol/l) before therapy was higher (P less than 0.05) than that in 23 control pregnancies, without uterine contractions, matched for gestational age (median 51, range 4-127 pmol/l). CHR levels determined after 3 and 24 h of treatment showed a 10% decrease in the indomethacin group and 10-20% decrease in the nylidrin group, but these changes were not statistically significant. After cessation of uterine contractions during tocolysis, 12 women proceeded to give birth preterm (less than 37 weeks) and their pretreatment CRH levels (median 195, range 9-597 pmol/l) were higher (P less than 0.05) than those in women whose pregnancy proceeded to term (median 52, range 16-207 pmol/l). In another group of women, full-term labour was not accompanied by any changes in maternal CRH levels. Umbilical plasma CRH levels were 1.1-9.8% of the paired maternal levels and did not rise with advancing gestational age. Nor had the type of delivery (elective caesarean section before labour, or preterm or term vaginal delivery) any effect on fetal CRH levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Hormônio Liberador da Corticotropina/sangue , Indometacina/uso terapêutico , Nilidrina/uso terapêutico , Trabalho de Parto Prematuro/sangue , Adulto , Feminino , Humanos , Hidrocortisona/sangue , Trabalho de Parto Prematuro/tratamento farmacológico , Gravidez , Distribuição Aleatória , Contração Uterina/efeitos dos fármacos
16.
Am J Obstet Gynecol ; 164(1 Pt 1): 141-6, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1986601

RESUMO

To study the effect of maternal indomethacin or nylidrine hydrochloride treatment on the fetus ductus arteriosus and the pulmonary artery, 27 women with threatened preterm labor between 24 and 34 weeks' gestation were studied by echocardiography. Fourteen women were treated with indomethacin and 13 with nylidrin. Both systolic and diastolic velocities in the ductus increased after administration of indomethacin indicating constriction in nine fetuses, and exceeded the corresponding velocities in the fetuses of the nylidrin group (p = 0.001). However, there were no changes in pulmonary artery flow velocities (p greater than 0.5). In the indomethacin group, there was a significant linear positive relationship between the gestational age and the change in ductal flow velocity. Three of the nine patients with ductal constriction also had tricuspid regurgitation. These findings indicate that indomethacin, not nylidrin, causes transient constriction of the ductus arteriosus and the constrictive response increases with the gestational age. We recommend echocardiographic surveillance of fetal hemodynamics when prostaglandin synthesis inhibitors are used in the treatment of spontaneous preterm labor.


Assuntos
Canal Arterial/efeitos dos fármacos , Feto/efeitos dos fármacos , Indometacina/uso terapêutico , Nilidrina/uso terapêutico , Trabalho de Parto Prematuro/tratamento farmacológico , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Baixo Débito Cardíaco/induzido quimicamente , Parto Obstétrico , Método Duplo-Cego , Ecocardiografia , Feminino , Idade Gestacional , Humanos , Indometacina/efeitos adversos , Nilidrina/efeitos adversos , Gravidez , Sístole
17.
Acta Obstet Gynecol Scand ; 70(3): 187-91, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1927294

RESUMO

Catecholamines that are released in excess during human labor are inactivated mainly by catechol-O-methyltransferase (COMT). To ascertain whether uterine contractions are associated with changes in COMT activity in red blood cells (RBCs), we studied 25 women with established threat of preterm labor between 25 and 33 weeks of gestation, 25 gestational age-matched control women not experiencing uterine contractions, 25 women who were in term labor, and 25 non-pregnant healthy women. COMT activity in pregnant women without uterine contractions (median 0.3, range 0.1-0.8 pmol/mg/min) was lower (p less than 0.05) than that in non-pregnant control series (median 0.5, range 0.3-0.7 pmol/mg/min). RBCs' COMT activity in women with preterm labor (median 0.6, range 0.2-1.1 pmol/mg/min) was greater (p less than 0.05) than that in pregnant and non-pregnant control women, but similar to that during term labor (median 0.5, range 0.2-1.7 pmol/mg/min). Women with preterm labor were treated with indomethacin (12 women) or nylidrin (13 women). Nylidrin treatment was accompanied by a 35% rise in COMT activity 3 h later, whereas indomethacin caused no significant change. Apart from cessation of uterine contractions during tocolysis, 13 women went into labor before the 37th gestational week, but their pretreatment COMT activity (median 0.7, range 0.2-1.1 pmol/mg/min) did not differ from COMT activity in women whose pregnancy proceeded to term (median 0.5, range 0.3-1.0 pmol/mg/min).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Catecol O-Metiltransferase/sangue , Eritrócitos/enzimologia , Indometacina/uso terapêutico , Nilidrina/uso terapêutico , Trabalho de Parto Prematuro/enzimologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Trabalho de Parto Prematuro/sangue , Trabalho de Parto Prematuro/prevenção & controle , Gravidez , Contração Uterina/efeitos dos fármacos
18.
Acta Obstet Gynecol Scand ; 69(1): 17-21, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-1971738

RESUMO

Intravenous infusion of buphenine hydrochloride was administered on 4 successive days to 8 pregnant women with imminent preterm labor. Serial blood samples taken before and throughout the study were assayed for lymphocyte beta 2-adrenoceptor density and cyclic adenosine-3',5'-monophosphate (cAMP). The lymphocyte beta 2-adrenoceptor density declined significantly (p less than 0.01) during the treatment. The plasma cAMP concentration was highest 4 h after commencement of infusion and decreased thereafter. Despite the decrease in lymphocyte beta 2-adrenoceptor density, the clinical response remained good and the parturients did not go into labor until several days after infusion was started.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Linfócitos/metabolismo , Nilidrina/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacos , Adulto , AMP Cíclico/sangue , Feminino , Humanos , Trabalho de Parto Prematuro/tratamento farmacológico , Gravidez
19.
Zentralbl Gynakol ; 111(19): 1308-13, 1989.
Artigo em Alemão | MEDLINE | ID: mdl-2588861

RESUMO

Inhibitory effects of Partusisten, Dilatol, Papaverin and Magnesium-sulfat on the activity of smooth muscle were tested in vitro on 18 isolated stripes of rats uteri, exhibiting both a high sensitivity against oxytocin and a distinct spontaneous activity. Minimal inhibitory concentrations of all drugs tested were determined, and their influence on the frequency and amplitude of contraction as well as on lag phase between inhibition and onset of spontaneous activity were registered. Basing on these experimental data conclusions were drawn concerning their clinical relevance.


Assuntos
Fenoterol/farmacologia , Sulfato de Magnésio/farmacologia , Músculo Liso/efeitos dos fármacos , Nilidrina/farmacologia , Papaverina/farmacologia , Útero/efeitos dos fármacos , Animais , Feminino , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Ocitocina/metabolismo , Ratos , Ratos Endogâmicos , Tempo de Reação/efeitos dos fármacos
20.
Doc Ophthalmol ; 70(1): 77-87, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3229296

RESUMO

The effects of the beta-adrenergic agonist nylidrin and the beta 2-adrenergic agonist clenbuterol on electroretinogram and optic nerve response were studied in the isolated and arterially perfused, light-adapted cat eye. Two cone mechanisms, short wavelength-sensitive and long wavelength-sensitive, were functionally separated by means of intense yellow adaptation. A reversible increase in b-wave amplitude in response to nylidrin or clenbuterol was observed for the cone systems. Both drugs also caused a reversible alteration in configuration of the optic nerve response, mainly a depression of the late components related in time to the changes in the electroretinogram. These observations suggest that beta-adrenergic mechanisms are involved in cone systems. The greater increase in b-wave amplitude on 558-nm stimulation and preliminary evidence for greater increase in sensitivity observed in the V-log I function compared with 439 nm further suggest that the short and long wavelength cone systems are affected differently by beta-adrenergic agonists.


Assuntos
Clembuterol/farmacologia , Etanolaminas/farmacologia , Nilidrina/farmacologia , Células Fotorreceptoras/efeitos dos fármacos , Animais , Gatos , Eletrorretinografia , Nervo Óptico/efeitos dos fármacos , Perfusão , Retina/efeitos dos fármacos
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