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Comparison of methods for prediction of nephrotoxicity during development. 发育期间肾毒性预测方法的比较。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000457468
J Klein, G Koren, S M MacLeod
{"title":"Comparison of methods for prediction of nephrotoxicity during development.","authors":"J Klein,&nbsp;G Koren,&nbsp;S M MacLeod","doi":"10.1159/000457468","DOIUrl":"https://doi.org/10.1159/000457468","url":null,"abstract":"<p><p>Drugs with nephrotoxic potential are continuously introduced into perinatal and pediatric medicine, and assessment of their relative toxicity is important. We compared different methods of assessment of renal damage during development in an attempt to establish their relative sensitivity, age and dose dependence. Newborn, 6- to 8-day-old and adult rats were treated for 7 days with intramuscular gentamicin (5, 10 or 20 mg/kg/day) or amikacin (5, 20 or 40 mg/kg/day). Renal damage was assessed by serum and urine creatinine, urine N-acetyl beta-glucosaminidase and beta 2-microglobulin, cortical sphingomyelinase in vivo and in vitro and morphologic changes in light and electron microscopy. As expected, there was a dose-dependent damage, with gentamicin being more nephrotoxic than amikacin, and with newborn rats more resistant. The light- and electron-microscopic assessment were more sensitive than all other methods, followed by urinary N-acetyl glucosaminidase and then by beta 2-microglobulin. Sphingomyelinase changes occurred only at the highest doses of gentamicin.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12513592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Acute effects of amiodarone on sodium currents in isolated neonatal ventricular myocytes: comparison with procainamide. 胺碘酮对分离新生儿心室肌细胞钠电流的急性影响:与普鲁卡因胺的比较。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000457473
F Chen, G T Wetzel, T S Klitzner
{"title":"Acute effects of amiodarone on sodium currents in isolated neonatal ventricular myocytes: comparison with procainamide.","authors":"F Chen,&nbsp;G T Wetzel,&nbsp;T S Klitzner","doi":"10.1159/000457473","DOIUrl":"https://doi.org/10.1159/000457473","url":null,"abstract":"<p><p>Recent studies suggest that amiodarone's acute clinical effects in infants and children are related predominantly to its class I antiarrhythmic activity. However, the effects of amiodarone on Na+ currents have not been investigated directly in immature cardiac cells. Accordingly, the tight seal whole cell voltage clamp technique was used to measure time- and voltage-dependent Na+ currents in acutely isolated neonatal ventricular myocytes from 2- to 5-day-old rabbits, before and after addition of amiodarone (0.1-10 microM). To evaluate the class I antiarrhythmic activity of amiodarone in this age group, the effects of amiodarone on Na+ currents were compared with those of procainamide. Similar to procainamide, amiodarone significantly decreased peak inward Na+ current in neonatal ventricular myocytes. Moreover, both amiodarone and procainamide shifted the steady-state inactivation curve to more negative membrane potentials and delayed recovery of the Na+ current from inactivation. Thus, the effects of amiodarone on the Na+ current in immature myocardium are qualitatively similar to those of procainamide, suggesting that amiodarone may act acutely as a class I antiarrhythmic agent in the newborn heart.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12514419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Hypoxic-ischemic damage in the neonatal brain: excitatory amino acids. 新生儿脑缺氧缺血性损伤:兴奋性氨基酸。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000480613
H. Hagberg
{"title":"Hypoxic-ischemic damage in the neonatal brain: excitatory amino acids.","authors":"H. Hagberg","doi":"10.1159/000480613","DOIUrl":"https://doi.org/10.1159/000480613","url":null,"abstract":"Perinatal brain damage is a major clinical problem. Recent studies suggest that excitatory amino acids (EAAs) may be important for the development of hypoxic-ischemic brain injury in the newborn. Experimental work demonstrates that the immature brain is hypersensitive to the toxic effects EAA ('excitotoxicity'), hypoxic-ischemia is accompanied by an extracellular overflow of EAAs and hypoxic-ischemic brain damage is reduced by EAA receptor antagonists. Clinical investigations demonstrate the presence of EAA receptors in vulnerable areas of the newborn human brain and the concentrations of EAAs in the cerebrospinal fluid are higher in asphyxiated than in control infants. Clinical studies are warranted to evaluate the importance of excitotoxicity for development of brain lesions after severe asphyxia.","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76731627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 40
Placental transport of dioxins from mother to fetus. II. PCBs, dioxins and furans and vitamin K metabolism. 二恶英从母体到胎儿的胎盘运输。2多氯联苯，二恶英，呋喃和维生素K代谢。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000480592
Janna G. Koppe, K. Olie, J. V. Wijnen
{"title":"Placental transport of dioxins from mother to fetus. II. PCBs, dioxins and furans and vitamin K metabolism.","authors":"Janna G. Koppe, K. Olie, J. V. Wijnen","doi":"10.1159/000480592","DOIUrl":"https://doi.org/10.1159/000480592","url":null,"abstract":"Placental transport of dioxins and furans from mother to fetus takes place. It is probably related to the fatty acid transport. Between 10 and 20% of fatty acids in a full-term baby are of maternal origin. In adipose tissue of children that died in the early neonatal period concentrations of +/- 25% were found of three dioxin and furan congeners 12378 P5CDD, 123678 H6CDD, and 23478 P5CDF in relation to a mean concentration of these congeners in the fat of 14 breastmilk samples. Data of concentrations are given as measured in liver and adipose tissue. In the placenta of a Dutch woman an accumulation of dioxins and furans is found in relation to blood. Animal studies support the hypothesis that polychlorobifenyls play a role in the cause of the late hemorrhagic disease in the newborn, in particular the 2, 4, 5, 2, 4, 5-hexachlorobifenyl that is present in relatively high concentrations in breastmilk.","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78909762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 26
Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies. 右美沙芬细胞色素p450依赖性代谢:胎儿和成人研究。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000480616
Evelyne Jacqz-Aigrain, Thierry Cresteil
{"title":"Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies.","authors":"Evelyne Jacqz-Aigrain, Thierry Cresteil","doi":"10.1159/000480616","DOIUrl":"https://doi.org/10.1159/000480616","url":null,"abstract":"Dextromethorphan undergoes O-demethylation to dextrorphan and N-demethylation to 3-methoxymorphinan. 3-Hydroxymorphinan, a didemethylated compound, is secondarily formed. The O-demethylation pathway to dextrorphan is polymorphic and under CYP2D6 genetic control. Adult and fetal studies were performed to characterize the cytochrome P450 families involved in dextromethorphan metabolism and their ontogeny. In adult volunteers in vivo and in vitro studies demonstrate that the O-demethylation pathway to dextrorphan is dependent on CYP2D6 and is predominant in extensive metabolizers and defective in poor metabolizers of the drug. The N-demethylation pathway to 3-methoxymorphinan is accessory and is dependent on the CYP3A subfamily. In human fetal microsomes, CYP2D6 protein and activity are not detectable until birth, while CYP2D6 RNA is present in significant amounts before birth. CYP3A activity is detectable in large amounts as early as the 17th week of gestation. Fetal and adult members of the CYP3A subfamily have close, although different, properties, as demonstrated by immunoinhibition studies.","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84832970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 47
Expression and release of neuroregulators during development: monoamines and neuropeptides. 发育过程中神经调节因子的表达和释放:单胺和神经肽。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01
H Lagercrantz, H Holgert, J M Pequignot, M Srinivasan
{"title":"Expression and release of neuroregulators during development: monoamines and neuropeptides.","authors":"H Lagercrantz,&nbsp;H Holgert,&nbsp;J M Pequignot,&nbsp;M Srinivasan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The turnover of catecholamines (CA) was determined in the adrenal medulla and brain of rat fetuses and pups. In general we found a considerable increase soon after birth. The expression of mRNA for CA-synthesizing enzymes was also considerably enhanced in the adrenals shortly after birth. Furthermore, we demonstrated increased expression of neuropeptides after birth, increased synthesis of mRNA encoding for neuropeptide Y in the adrenals 24 h after birth; and considerable activation of the substance P gene in a respiratory nuclei of rabbit pups which had been breathing for 2 h as compared with fetuses at term.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12480982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activated charcoal for theophylline toxicity in a premature infant on the second day of life. 活性炭对茶碱毒性的早产儿在生命的第二天。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000457471
R Jain, D A Tholl
{"title":"Activated charcoal for theophylline toxicity in a premature infant on the second day of life.","authors":"R Jain,&nbsp;D A Tholl","doi":"10.1159/000457471","DOIUrl":"https://doi.org/10.1159/000457471","url":null,"abstract":"<p><p>A premature infant received an overdose of aminophylline on the 2nd day of life and was successfully treated with activated charcoal. The use of activated charcoal this early postnatally has never been reported.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12514417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug? 水合氯醛对新生儿的镇静/催眠作用:三氯乙醇还是母体药物?
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000457475
D J Mayers, K W Hindmarsh, D K Gorecki, K Sankaran
{"title":"Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug?","authors":"D J Mayers,&nbsp;K W Hindmarsh,&nbsp;D K Gorecki,&nbsp;K Sankaran","doi":"10.1159/000457475","DOIUrl":"https://doi.org/10.1159/000457475","url":null,"abstract":"<p><p>Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been reported, there have been no attempts to correlate CH or its metabolite, trichloroethanol (TCE) with the sedative or hypnotic effects. In order to determine whether plasma concentrations of CH or TCE reflect the sedative/hypnotic effects, a sedation/agitation scale was developed. Based on the results of the present study, the sedative/hypnotic effects of TCE cannot be ruled out completely. However, in the neonate, the parent drug CH seems to have a more important role than has been previously suggested from human research.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12514420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Prostacyclin synthesis and stimulation of cyclic AMP production in ovine fetal vasculature: heterogeneity in pulmonary and systemic arteries. 前列环素合成和刺激羊胎儿血管循环AMP的产生:肺动脉和全身动脉的异质性。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01
P W Shaul, M A Farrar, R R Magness
{"title":"Prostacyclin synthesis and stimulation of cyclic AMP production in ovine fetal vasculature: heterogeneity in pulmonary and systemic arteries.","authors":"P W Shaul,&nbsp;M A Farrar,&nbsp;R R Magness","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostacyclin (PGI2) is an important local mediator of vasomotor tone in the fetus and newborn, acting via stimulation of cAMP production by vascular smooth muscle (VSM) adenylate cyclase. In this investigation PGI2 and prostaglandin (PG) E2 synthesis and stimulation of cAMP production were compared in vitro in ovine fetal pulmonary versus systemic (mesenteric) arteries. PGI2 synthesis was similar in the pulmonary and systemic arteries (2.4 +/- 0.2 and 2.6 +/- 0.3 ng/mg protein.h, respectively), as was PGE2 synthesis (1.9 +/- 0.2 and 1.5 +/- 0.2 ng/mg protein.h, respectively); synthesis was greater for PGI2 versus PGE2 in both artery types. 65-71% of PGI2 synthesis and 51-59% of PGE2 synthesis occurred in the endothelium. Basal (nonstimulated) cAMP production was fully attenuated by indomethacin, indicating that it is mediated exclusively by endogenous PG. Basal cAMP production was 3.8-fold less in pulmonary versus systemic arteries, and this was related to a 9.7-fold difference in responsiveness to PG. A 14.7-fold difference in the response to forskolin indicates that underlying mechanism may be a disparity in the quantity and/or function of the adenylate cyclase enzyme complex. Thus, prostacyclin and PGE2 synthesis are comparable in ovine fetal pulmonary versus systemic arteries, but the cAMP response to the prostanoids is markedly greater in the latter artery type due to differences in the activation of adenylate cyclase. This heterogeneity in VSM intracellular signalling may contribute to differential vasomotor tone and responses in the fetal pulmonary and systemic circulation.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12457872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A possible 5-HT3 component of thyrotropin-releasing hormone-induced increases in gastric motility in developing rats. 促甲状腺激素释放激素诱导发育大鼠胃运动增加的可能的5-HT3成分。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01 DOI: 10.1159/000457465
M M Heitkemper, E F Bond, M K Gruver, A Horita
{"title":"A possible 5-HT3 component of thyrotropin-releasing hormone-induced increases in gastric motility in developing rats.","authors":"M M Heitkemper,&nbsp;E F Bond,&nbsp;M K Gruver,&nbsp;A Horita","doi":"10.1159/000457465","DOIUrl":"https://doi.org/10.1159/000457465","url":null,"abstract":"<p><p>Intracisternal injection of thyrotropin-releasing hormone (TRH) increases gastric motility primarily via a vagal cholinergic mechanism. However, a serotonergic (5-HT) component may also exist. Rats (7, 10, 14, and > or = 50 days of age) were anesthetized and gastric motility monitored via an extraluminal strain gauge. Following baseline, ICS 205-930 which blocks 5-HT3 and 5-HT4 receptors (0.01, 0.10, or 1.0 mg/kg) was administered intraperitoneally, then 30 min later intracisternal TRH (5 or 10 micrograms). ICS 205-930 0.1 and 1.0 mg/kg blocked TRH-induced motility in 7-day-old rats. Results support a 5-HT3 or 5-HT4 receptor contribution to TRH-induced gastric motility stimulation, and suggest that receptor expression is dynamic during development.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12513589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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