RESUMEN
OBJECTIVE: To analyze outcomes of singleton pregnancies with idiopathic polyhydramnios through a systematic review and meta-analysis. METHODS: Electronic databases, including MEDLINE, OVID, EBSCO, Cochrane collection and Science Citation Index, were searched from 1946 to 2019. Gray literature and tables of contents of relevant journals were also screened. Prospective and retrospective studies with a control group were included. Two authors independently reviewed the abstracts retrieved from the literature search. Inclusion criteria were: studies documented in English, singleton pregnancy and idiopathic polyhydramnios determined by amniotic fluid volume assessment on ultrasound. Exclusion criteria were: maternal diabetes, fetal structural or chromosomal anomaly, alloimmunization and intrauterine fetal infection. RESULTS: Twelve studies met the inclusion criteria, giving a total of 2392 patients with idiopathic polyhydramnios and 160 135 patients with normal amniotic fluid volume. Pregnancies complicated by idiopathic polyhydramnios were at a higher risk of neonatal death (odds ratio (OR), 8.68 (95% CI, 2.91-25.87)), intrauterine fetal demise (OR, 7.64 (95% CI, 2.50-23.38)), neonatal intensive care unit admission (OR, 1.94 (95% CI, 1.45-2.59)), 5-min Apgar score < 7 (OR, 2.21 (95% CI, 1.34-3.62)), macrosomia (OR, 2.93 (95% CI, 2.39-3.59)), malpresentation (OR, 2.73 (95% CI, 2.06-3.61)) and Cesarean delivery (OR, 2.31 (95% CI, 1.79-2.99)). CONCLUSIONS: This study suggests that pregnancies complicated by idiopathic polyhydramnios are at increased risk of adverse outcome. Future investigations should aim to determine an amniotic fluid volume threshold above which antenatal fetal surveillance is appropriate in the management of these pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Polihidramnios , Recién Nacido , Embarazo , Humanos , Femenino , Polihidramnios/diagnóstico por imagen , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Estudios Prospectivos , Líquido Amniótico/diagnóstico por imagenRESUMEN
OBJECTIVE: To evaluate adverse pregnancy outcomes in singleton pregnancies diagnosed with oligohydramnios through a systematic review and meta-analysis of controlled trials. METHODS: We searched electronic databases via OVID, EBSCO, Web of Science, Google Scholar and others from 1980 to 2015. Prospective and retrospective studies with a control group were included. Two authors independently reviewed the abstracts from the literature search. Inclusion criteria were: studies in English, singleton pregnancy, normal fetal anatomy, intact membranes and oligohydramnios determined by the amniotic fluid index (AFI) technique. We stratified the meta-analysis into two groups according to risk: high risk including studies of oligohydramnios with comorbid conditions (e.g. hypertension) and low risk including studies of isolated oligohydramnios. RESULTS: Fifteen trials met the inclusion criteria. Nine were high-risk and six were low-risk studies, including 8067 and 27 526 women, respectively. Compared with women with normal AFI, those with isolated oligohydramnios had significantly higher rates of an infant with meconium aspiration syndrome (relative risk (RR), 2.83; 95% CI, 1.38-5.77), Cesarean delivery for fetal distress (RR, 2.16; 95% CI, 1.64-2.85) and admission to the neonatal intensive care unit (NICU) (RR, 1.71; 95% CI, 1.20-2.42). Patients with oligohydramnios and comorbidities were more likely to have an infant with low birth weight (RR, 2.35; 95% CI, 1.27-4.34). However, rates of 5-min Apgar score < 7 (RR, 1.85; 95% CI, 0.69-4.96), NICU admission (RR, 2.09; 95% CI, 0.80-5.45), meconium-stained amniotic fluid (RR, 1.32; 95% CI, 0.62-2.81) and Cesarean delivery for fetal distress (RR, 1.65; 95% CI, 0.81-3.36) were similar to those for women with normal AFI. Stillbirth rates were too low to analyze in the meta-analysis. CONCLUSIONS: This review helps to delineate which adverse outcomes are increased with oligohydramnios in low-risk pregnancy (NICU admission, Cesarean delivery for fetal distress and meconium aspiration syndrome), but does not provide enough data to determine the optimal timing of delivery in such cases. Oligohydramnios in complicated pregnancy is associated with an increased risk of delivery of an infant with low birth weight, but this may be confounded by the comorbid condition. Therefore, in high-risk pregnancy, management should be dictated by the comorbid condition and not the presence of oligohydramnios. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Oligohidramnios/epidemiología , Complicaciones del Embarazo/clasificación , Peso al Nacer , Ensayos Clínicos como Asunto , Femenino , Humanos , Recién Nacido , Embarazo , Complicaciones del Embarazo/epidemiología , Resultado del EmbarazoRESUMEN
Energy is an essential nutrient for all horses, and it is especially important in performance horses, pregnant and lactating mares, and young growing horses. A negative energy balance in horses such as these may result in unsatisfactory performance, decreased fertility, or slow growth. Therefore, ensuring adequate energy intake is an important aspect of the nutritional management of the equine. This study was undertaken to investigate the effects of feeding large, carbohydrate-rich, concentrate meals on the satiety-inducing hormone, leptin. Three groups of yearling horses were rotated through 3 feeding schedules in a replicated 3x3 Latin square design. Horses were fed 2, 3, or 4 times per day (2x, 3x, and 4xfeeding schedules, respectively), each for a period of 11 d, with the total amount of daily feed held constant. Horses were weighed and BCS was determined on the first day of each period. Blood samples were collected before the morning meal on d 1, 4, and 7 of each period. Additionally, blood was sampled for the last 24 h of the 2xand 4xdietary periods. Neither weight nor BCS changed during the study (P = 0.99 and P = 0.28, respectively). Both mean and peak plasma glucose were greatest in 2xhorses (P < 0.05), as were mean areas under the curve. Serum leptin concentration increased in 2xhorses (P < 0.05), but not in horses fed 3 or 4 times daily. Leptin was elevated in horses with greater BCS (P < 0.05) and increased steadily throughout the study (P < 0.05). Data from the 24-h collection indicated that 2xhorses had fluctuations in leptin production throughout the day (P < 0.05), whereas horses fed 4 times daily did not. Overall, this study indicates that feeding horses 2 large concentrate meals daily can increase mean serum leptin concentrations and may cause fluctuations in leptin production over a 24-h period. This departure from baseline leptin concentration has the potential to affect appetite, along with numerous other physiological processes.
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Crianza de Animales Domésticos , Dieta/veterinaria , Caballos/sangre , Caballos/fisiología , Leptina/sangre , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Metabolismo Energético , Femenino , Masculino , Caracteres Sexuales , Factores de TiempoRESUMEN
HOX proteins and some orphan homeodomain proteins form complexes with either PBX or MEIS subclasses of homeodomain proteins. This interaction can increase the binding specificity and transcriptional effectiveness of the HOX partner. Here we show that specific members of both PBX and MEIS subclasses form a multimeric complex with the pancreatic homeodomain protein PDX1 and switch the nature of its transcriptional activity. The two activities of PDX1 are exhibited through the 10-bp B element of the transcriptional enhancer of the pancreatic elastase I gene (ELA1). In pancreatic acinar cells the activity of the B element requires other elements of the ELA1 enhancer; in beta-cells the B element can activate a promoter in the absence of other enhancer elements. In acinar cell lines the activity is mediated by a complex comprising PDX1, PBX1b, and MRG1 (MEIS2). In contrast, beta-cell lines are devoid of PBX1b and MRG1, so that a trimeric complex does not form, and the beta-cell-type activity is mediated by PDX1 without PBX1b and MRG1. The presence of specific nuclear isoforms of PBX and MEIS is precisely regulated in a cell-type-specific manner. The beta-cell-type activity can be detected in acinar cells if the B element is altered to retain binding of PDX1 but prevent binding of the PDX1-PBX1b-MRG1 complex. These observations suggest that association with PBX and MEIS partners controls the nature of the transcriptional activity of the organ-specific PDX1 transcription factor in exocrine versus endocrine cells.
Asunto(s)
Proteínas de Homeodominio/metabolismo , Islotes Pancreáticos/metabolismo , Páncreas/metabolismo , Elastasa Pancreática/biosíntesis , Elastasa Pancreática/genética , Proteínas Represoras , Transactivadores/metabolismo , Animales , Línea Celular , Células Cultivadas , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/aislamiento & purificación , Proteínas de Unión al ADN/metabolismo , Elementos de Facilitación Genéticos , Regulación de la Expresión Génica , Biblioteca de Genes , Globinas/biosíntesis , Células HeLa , Proteínas de Homeodominio/biosíntesis , Hormona de Crecimiento Humana/biosíntesis , Humanos , Islotes Pancreáticos/citología , Ratones , Páncreas/citología , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Ratas , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/metabolismo , Transactivadores/biosíntesis , Transactivadores/química , Transactivadores/aislamiento & purificación , Transcripción Genética , Transfección , Xenopus laevisRESUMEN
Meis1 locus was isolated as a common site of viral integration involved in myeloid leukemia in BXH-2 mice. Meis1 encodes a novel homeobox protein belonging to the TALE (three amino acid loop extension) family of homeodomain-containing proteins. The homeodomain of Meis1 is the only known motif within the entire 390-amino-acid protein. Southern blot analyses using the Meis1 homeodomain as a probe revealed the existence family of Meis1-related genes (Mrgs) in several diverged species. In addition, the 3' untranslated region (UTR) Meis1 was remarkably conserved in evolution. To gain a further understanding of the role Meis1 plays in leukemia and development, as well as to identify conserved regions of the protein that might reveal function, we cloned and characterized Mrgs from the mouse and human genomes. We report the sequence of Mrg1 and MRG2 as well as their chromosomal locations in murine and human genomes. Both Mrgs share a high degree of sequence identity with the protein coding region of Meis1. We have also cloned the Xenopus laevis ortholog of (XMeis1). Sequence comparison of the murine and Xenopus clones reveals that Meis1 is highly conserved throughout its coding sequence as well as the 3' UTR. Finally, comparison of Meis1 and the closely related Mrgs to known homeoproteins suggests that Meis1 represents a new subfamily of TALE homeobox genes.
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Genes Homeobox , Proteínas de Homeodominio/genética , Leucemia Mieloide/genética , Familia de Multigenes , Proteínas de Neoplasias/genética , Proteínas Represoras , Animales , Evolución Biológica , Northern Blotting , Southern Blotting , Quimera/genética , Mapeo Cromosómico , Clonación Molecular , ADN Complementario/genética , Regulación de la Expresión Génica , Humanos , Ratones , Datos de Secuencia Molecular , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide , Filogenia , Polimorfismo de Longitud del Fragmento de Restricción , ARN/análisis , ARN/aislamiento & purificación , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico , Transcripción Genética , XenopusRESUMEN
The amino terminus of the E2F1 transcription factor is a protein-protein interaction domain since it associates with cyclin A/cdk2. Here, the two-hybrid yeast screen was used to clone genes whose products associate with the amino terminus of E2F1. The amino-terminal 121 amino acids of E2F1 were fused to the Lex A binding domain while a partial length cDNA library from the embryo of a 12 day old mouse was fused to the VP16 activation domain. Following coexpression of these fusions in yeast, two novel genes were cloned that code for proteins that associate with E2F1. In an in vitro assay, these E2F1 Binding Proteins (EBP1 and EBP2) associate with residues 1-121 of E2F1 or with the full-length protein; however, they do not associate with its carboxy terminus (residues 88-437). When EBP1 or EBP2 were expressed in COS cells along with E2F1 and the target promoter DNA polymerase alpha, repression of transcription was observed. However, no repression of DNA polymerase alpha was seen if the cells expressed a nonassociating mutant E2F1 (residues 88-437), along with EBP1 or EBP2. Finally, expression of the EBP2 gene is up-regulated in growing NIH3T3 fibroblasts, relative to serum-starved cells. However, this up-regulation of EBP2 expression is not seen in fibroblasts constitutively expressing E2F1.
Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , ADN Complementario/aislamiento & purificación , Proteínas de Unión al ADN , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , Northern Blotting , Células COS , Proteínas Portadoras/química , Proteínas Portadoras/genética , División Celular , Línea Celular , Cromatografía de Afinidad , Ciclinas/química , Ciclinas/metabolismo , ADN Complementario/química , Factores de Transcripción E2F , Factor de Transcripción E2F1 , Electroforesis en Gel de Poliacrilamida , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Datos de Secuencia Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Proteínas de Unión al ARN , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteína 1 de Unión a Retinoblastoma , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae , Factor de Transcripción DP1 , Factores de Transcripción/química , Factores de Transcripción/genéticaRESUMEN
STUDY OBJECTIVES: To determine the utility of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in predicting intra-abdominal injury in blunt trauma patients. DESIGN: Descriptive review of 309 blunt trauma admissions during study period. SETTING: A 1,000-bed Level I trauma center in a major metropolitan area. TYPE OF PARTICIPANTS: Consecutive adult blunt trauma admissions to the trauma service. INTERVENTIONS: Serum levels of study enzymes were measured at initial evaluation and subsequent hospitalization. Results of all intra-abdominal evaluations were recorded. MAIN RESULTS: Significantly greater numbers of patients with SGOT and/or SGPT elevated to more than 130 IU/L had associated intra-abdominal injuries as compared with patients with enzyme elevations of less than 130 IU/L (52% versus 8%). All 18 patients with liver injuries had one or both enzymes elevated to more than 130 IU/L. Higher enzyme levels were more frequently associated with liver injury. CONCLUSIONS: Elevation of serum levels of the study enzymes is a marker for intra-abdominal injury. Levels in excess of 130 IU/L are relative indicators of abdominal computed tomography scan. Levels of less than 130 IU/L are unlikely to be associated with liver injury.
Asunto(s)
Traumatismos Abdominales/diagnóstico , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Heridas no Penetrantes/diagnóstico , Traumatismos Abdominales/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Evaluación como Asunto , Femenino , Humanos , Hígado/lesiones , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Índices de Gravedad del Trauma , Heridas no Penetrantes/sangreRESUMEN
Mouse fibroblast cell lines which secrete bovine (b) GH have been generated. This was accomplished by cotransforming mouse L cells (thymidine kinase-negative [TK-] and adenine phosphoribosyl transferase-negative [APRT-]) with DNA molecules encoding the Rous sarcoma virus-long-terminal repeat and bGH genes along with the herpes viral TK gene and the hamster APRT gene. One stable cell line, Pd lambda-pbGH 4-13, was found to secrete approximately 75 micrograms bGH per 24 h/5.0 X 10(6) cells. Media from this cell line were collected for purification of recombinant bGH (rbGH). Purification involved (NH4)2SO4 fractionation, ion-exchange chromatography, and gel filtration on Sephacryl S-200. The rbGH was characterized by bioassay, RIA, radioreceptor assay, and sodium dodecyl sulfate gel electrophoresis. Results of these analyses were compared with those obtained with a highly purified pituitary bGH. In the rat tibia bioassay, rbGH was found to be as potent as pituitary bGH. Results from the RIA, radioreceptor assay, and sodium dodecyl sulfate gel electrophoresis and Western blot analysis also suggested that the rbGH was similar to that of pituitary origin. Amino acid composition, partial (amino-terminal) sequence, and tryptic peptide maps were also found to be similar between the rbGH and pituitary bGH preparations. The amino terminus of the rbGH showed similar heterogeneity to that of the bGH of pituitary origin. We conclude that rbGH which was synthesized, processed, and secreted from transformed mouse fibroblasts possessed almost exactly the same physiochemical properties as pituitary bGH.
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Fibroblastos/metabolismo , Hormona del Crecimiento/biosíntesis , Proteínas Recombinantes/biosíntesis , Aminoácidos/análisis , Animales , Bioensayo , Desarrollo Óseo , Bovinos , Línea Celular , Fenómenos Químicos , Química Física , Hormona del Crecimiento/aislamiento & purificación , Ratones , Fragmentos de Péptidos , Radioinmunoensayo , Ensayo de Unión Radioligante , RatasRESUMEN
Based upon the clinical finding that a Merck somatostatin-14 (S-14) analog induced steatorrhea in man, we sought to develop animal models to study the effects of S-14 and a series of synthetic analogs on absorption. Rats were trained to eat a diet (preweighed) containing 15% fat. Following the feeding period, the remaining diet was removed and the amount consumed recorded. This food conditioning of the rats was continued until the rats consumed approximately 15 g of the diet per day. Feces were collected and weighed prior to feeding periods. On test days, S-14 or analogs were administered sc to rats immediately prior to feeding. For each compound tested, fat absorption decreased in dose-dependent fashion. For example, S-14 at 0.5 mg/kg did not increase % of dietary fat in feces (% DFF). At 1.0 mg/kg, S-14 increased % DFF from 7.9 to 10.2 (p less than 0.01, pretest day vs test day), and at 10 mg/kg S-14, % DFF increased from 9.1 to 12.8 (p less than 0.001). For each analog, the subcutaneous dose required to decrease fat absorption in rats was several orders of magnitude higher than the intravenous dose required to inhibit insulin and glucagon. Moreover, the threshold for production of statistically significant increases in fecal fat differed among analogs when compared to their endocrine potencies. One analog administered in the model for 14 days was shown to produce consistent fat malabsorption throughout the entire test period; however, this lipid malabsorption was substantially more pronounced on the first three days of the treatment period. When the compound was not administered on day 15, the % DFF significantly decreased. In an attempt to develop a system more suitable for rapid screening, pancreatic secretagogues such as secretin or cholecystokinin, were administered intravenously to anesthetized rats whose duodena had been cannulated and perfused to enable collection of pancreatic secretions. Total amylase, lipase, and protein were determined in single animals in response to a secretagogue, both before and after iv pretreatment by S-14 or an analog. Pancreatic enzyme secretion in response to sequential secretagogue-stimulation was found to be reproducible for up to three injections and behaved in a dose-dependent fashion. In general, secretagogue-induced increases in amylase, lipase, and total protein were comparable. Pretreatment with the S-14 analogs substantially inhibited secretagogue-induced pancreatic exocrine secretion and was dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Grasas de la Dieta/metabolismo , Absorción Intestinal/efectos de los fármacos , Somatostatina/farmacología , Animales , Heces/metabolismo , Humanos , Masculino , Jugo Pancreático/metabolismo , Ratas , Ratas Endogámicas , Tasa de Secreción/efectos de los fármacos , Somatostatina/análogos & derivados , Relación Estructura-ActividadRESUMEN
Highly purified growth hormone (GH) has been isolated from pituitary glands of chicken (Gallus domesticus), and a specific homologous radioimmunoassay (RIA) has also been developed. The purified chicken GH was active in the rat tibia bioassay and it gave a dose-dependent response which paralleled that of the bovine GH standard. High pressure liquid chromatography revealed that the purified chicken GH was homogenous. Chicken GH had an Rf value of 0.2 in disc electrophoresis, and a MW of 26,000 from sodium dodecyl sulfate-gel electrophoresis. The isoelectric point was estimated to be 7.6 by gel isoelectric focusing. The amino acid composition of chicken GH was found to be similar to that of mammalian GH, and the NH2-terminal amino acid was threonine. Partial sequencing (114 amino acids) of the chicken GH showed 79% homology with bovine GH. An antiserum was developed to the purified chicken GH in a rabbit, and it was used to develop a homologous RIA using 125I-labeled chicken GH as the ligand. The purified chicken GH was iodinated via the lactoperoxidase method to a specific activity of approximately 100 microCi/micrograms. Plasma from chickens, medium from incubation of pituitary glands, and homogenates of pituitary glands gave parallel dilution-response curves with the chicken GH standard. Mammalian GH, prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) showed no cross-reaction with the 125I-labeled chicken GH. Purified turkey GH showed parallel dose response with the chicken GH, but purified turkey PRL did not cross-react. Chicken FSH and LH also showed no inhibition of binding. The minimum detectable concentration of the assay was 0.93 ng/tube, and the intraassay and interassay coefficients of variation were 9 and 16%, respectively. The specific binding of 125I-labeled chicken GH to a microsomal fraction isolated from chicken liver was identified, and the specific binding was generally low (1-4%). Turkey PRL, and chicken LH and FSH showed no inhibition of the 125I-labeled chicken GH hepatic binding and the ontogeny of the hepatic GH receptor binding sites in male and female chickens was examined.
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Hormona del Crecimiento/análisis , Hipófisis/análisis , Envejecimiento , Secuencia de Aminoácidos , Animales , Bioensayo , Bovinos , Pollos , Cromatografía Líquida de Alta Presión , Femenino , Hormona del Crecimiento/metabolismo , Hormona del Crecimiento/farmacología , Humanos , Masculino , Microsomas Hepáticos/metabolismo , Peso Molecular , Radioinmunoensayo , Ratas , Receptores de Superficie Celular/metabolismo , Receptores de Somatotropina , Especificidad de la Especie , Hormona Liberadora de Tirotropina/farmacología , Tibia/efectos de los fármacosRESUMEN
The cerebral uptake of subcutaneously injected [3H] 2-deoxyglucose (2DG) was used to determine regional changes of cerebral glucose uptake associated with peptide-induced behaviors in mice. Evidence is presented that the use of [3H] 2DG (s.c.) gives results qualitatively similar to those obtained using intravenous [14C] 2DG. Lysine vasopressin, 1 microgram intracerebroventricularly (i.c.v.) induced the characteristic hyperactivity previously described, and significantly decreased [3H] 2DG uptake in frontal cortex. ACTH1-24 (1 microgram i.c.v.) induced excessive grooming and concomitant decreases in [3H] 2DG uptake in the olfactory bulb, pyriform cortex, and amygdala, and an increase in cerebellum. These results are only partly consistent with previous results on the cerebral sites of action of ACTH and vasopressin. These patterns of 2DG uptake are distinct from those observed following footshock, indicating that the peptide hormones mediate the effects of footshock on [3H] 2DG uptake only partially if at all.
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Hormona Adrenocorticotrópica/análogos & derivados , Glucemia/metabolismo , Corteza Cerebral/efectos de los fármacos , Cosintropina/farmacología , Lipresina/farmacología , Animales , Autorradiografía , Conducta Animal/efectos de los fármacos , Desoxiglucosa/metabolismo , Masculino , Ratones , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/metabolismoRESUMEN
Intermittent and concomitant acetylsalicylic acid (ASA) therapy was superimposed onto a 21-day regimen with diflunisal 250 mg b.i.d. Low doses of ASA (600 mg single dose or 300 mg q.i.d.) did not influence signficantly diflunisal blood levels whereas a 600 mg q.i.d. dosing caused a small significant drop, especially at trough level. This drop is not expected to be clinically significant. No ototoxicity could be demonstrated with any treatment of diflunisal though four of fourteen subjects reported mild tinnitus during concomitant therapy at the higher doses of ASA. Diflunisal at 375 mg b.i.d. failed to alter the metabolism of a single dose of labelled ASA (600 mg) as judged by plasma levels, urinary excretion and plasma binding. Daily urinary excretion of prostaglandins E1 and E2 major metabolite was decreased by about 70% by diflunisal.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Salicilatos/farmacología , Adulto , Antiinflamatorios no Esteroideos/metabolismo , Aspirina/efectos adversos , Aspirina/metabolismo , Interacciones Farmacológicas , Hemostasis/efectos de los fármacos , Humanos , Masculino , Prostaglandinas E/biosíntesis , Salicilatos/metabolismo , Acúfeno/inducido químicamenteRESUMEN
Fecal blood loss was evaluated in normal subjects with 51Cr-labeled red cells. In a double-blind parallel study in 10 subjects, 250 mg diflunisal twice daily did not significantly increase blood loss in two consecutive treatment periods, while 750 mg acetylsalicylic acid (ASA) 4 times daily did so. In a double-blind crossover study in 2 subjects, diflunisal, 250 mg twice daily again did not significantly affect fecal blood loss during a 4-day treatment period, and there also was no significant effth diflunisal during two additional treatment days. ASA, 600 mg 4 times daily, induced an increase in blood loss and this effect was significantly enhanced by the addition of alcohol. The difference between treatments in the way they interact with alcohol was also statistically significant.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Etanol/efectos adversos , Hemorragia Gastrointestinal/inducido químicamente , Salicilatos/efectos adversos , Adulto , Ensayos Clínicos como Asunto , Método Doble Ciego , Interacciones Farmacológicas , Humanos , MasculinoRESUMEN
Faecal blood loss was measured in normal male volunteers using 51Cr-labelled red cells. In a double-blind parallel study in 10 subjects, the effect of 250 mg diflunisal twice daily was compared with 750 mg aspirin 4-times daily. Drugs were taken during two 7-day periods separated by a 1-week control period. Mean daily faecal blood loss during the two treatment periods was 0.32 ml and 0.53 ml in the diflunisal group versus 6.87 ml and 3.20 ml in the aspirin group. Diflunisal did not significantly increase blood loss, while aspirin had a significant effect. In a double-blind crossover study in 12 subjects, the effect of 250 mg diflunisal twice daily was compared with 600 mg aspirin 4-times daily. Alcohol (120 ml, 40%) was added during the last 2 days of each 6-day treatment period. Faecal blood loss was not significantly affected by diflunisal and there was also no significant effect on blood loss when alcohol was co-administered. Aspirin significantly increased faecal blood loss and this effect was significantly enhanced by the addition of alcohol.
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Analgésicos/efectos adversos , Aspirina/efectos adversos , Compuestos de Bifenilo/efectos adversos , Etanol/efectos adversos , Sangre Oculta , Adulto , Radioisótopos de Cromo , Método Doble Ciego , Interacciones Farmacológicas , HumanosRESUMEN
Studies are reviewed on diflunisal, a new analgesic agent with an improved therapeutic index, compared with acetylsalicylic acid, in animals and humans. Pharmacokinetic data indicate that a twice-daily dosage regimen of diflunisal is adequate for therapeutic purposes. Diflunisal inhibits prostaglandin E synthesis, but in humans at clinically effective doses it does not alter bleeding time or platelet aggregation. Diflunisal is uricosuric at clinically effective doses. No clinically important drug interactions with diflunisal have been found to date, although some slight alterations in blood and urine drug levels have been noted. The slight increase in prothrombin time seen when diflunisal and acenocoumarol were co-administered is not considered to be of major clinical importance.
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Antiinflamatorios no Esteroideos/farmacología , Salicilatos/farmacología , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Fenómenos Químicos , Química , Perros , Interacciones Farmacológicas , Femenino , Alimentos , Humanos , Cinética , Masculino , Ratas , Salicilatos/efectos adversos , Salicilatos/metabolismo , Salicilatos/uso terapéuticoRESUMEN
Bioassays were conducted to determine various endocrinological properties of two spirolactone derivatives, 4',5'-dihydrospiro-[estr-4-ene-17,2'(3'H)-furan]-3-one (Compound I) and dispiro[cyclopropane-1,6'-estr-4'-ene-17',2"(3"h)-furan]-3'-one (Compound II). They proved to be very potent estrogen antagonists in immature mice and castrate ewes and neither exhibited inherent estrogenicity. They were moderately active as progestins and gonadotropin inhibitors. Compound II possessed slight androgenic activity and was more active orally than I. Compound I underwent a limited amount of testing in normally cycling rhesus monkeys. It was found to increase viscosity of the cervical mucus and, in oral doses of 0.5 or 2.0 mg/day, prevented pregnancy. One animal given 0.5 mg/day did become pregnant in her first treatment cycle, probably before a drug effect had been established. The results obtained indicate both compounds have potential utility as low-dose oral contraceptives.
Asunto(s)
Espironolactona/análogos & derivados , Andrógenos , Animales , Castración , Anticonceptivos Sintéticos Orales , Relación Dosis-Respuesta a Droga , Implantación del Embrión/efectos de los fármacos , Antagonistas de Estrógenos , Femenino , Haplorrinos , Ratones , Ovulación/efectos de los fármacos , Embarazo , Congéneres de la Progesterona , Ratas , Espironolactona/farmacologíaAsunto(s)
Antiinflamatorios no Esteroideos/farmacología , Salicilatos/farmacología , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/metabolismo , Anticoagulantes/farmacología , Benzotiadiazinas , Glucemia/metabolismo , Plaquetas/efectos de los fármacos , Diuréticos , Interacciones Farmacológicas , Fluorobencenos/efectos adversos , Fluorobencenos/metabolismo , Fluorobencenos/farmacología , Hemorragia Gastrointestinal/inducido químicamente , Trastornos de la Audición/inducido químicamente , Humanos , Hipoglucemiantes/farmacología , Cinética , Masculino , Prostaglandinas/orina , Salicilatos/efectos adversos , Salicilatos/metabolismo , Inhibidores de los Simportadores del Cloruro de Sodio/farmacología , Factores de Tiempo , Ácido Úrico/orinaRESUMEN
5-(2'4'-Difluorophenyl) [carboxy-14C]salicyclic acid (MK-647) was quickly and completely absorbed in rats, dogs, and man. Peak levels of plasma radioactivity occurred in 1-2 hr after oral administration. The dose was 10 mg/kg in rats and dogs, and 50 or 500 mg in man. Most of the drug in plasma was intact MK-647 which was extensively bound to plasma protein. In man the peak concentration following the 500-mg dose was approximately 10 times that after the lower dose, which suggests that absorption rates of both doses were similar. Elimination of drug from plasma was dose-dependent. The area under the curve for MK-647-14C in plasma was 18 times higher following the 500-mg dose than the 50-mg dose. Dogs given 10 mg/kg orally or intravenously excreted 44% of the dose in the urine and 42% in the feces in 72 hr. Rats given the same dose level by either route of administration excreted 80% in the urine and 11% in the feces. In man approximately 95% of a 50- or 500-mg oral dose was excreted in the urine and 3% in the feces, in 96 hr. MK-647 and two metabolites were present in the urine of three species. The ether and ester glucuronides were identified in human urine. The latter metabolite was also identified in rat and dog urine. The glycine conjugate of MK-647 was not observed in the urine of the three species. No interaction was observed between MK-647 and bishydroxycoumarin in the prothrombin time test nor with tolbutamide in the glucose tolerance test. A significant lowering of hexobarbital sleeping time was observed in female, but not male rats after four consecutive daily doses of MK-647. After repeated daily administration of MK-647 (12.5-100 mg/kg), the diurnal plasma level in dogs was not significantly altered, indicating that no saturation, induction, or inhibition of its own metabolism took place.