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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":"19 2-3","pages":"80-9"},"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":"19 2-3","pages":"118-30"},"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":"18 3-4 1","pages":"139-44"},"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":"314 1","pages":"9-13"},"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":"26 1","pages":"161-8"},"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
Ontogeny of vascular smooth muscle responsiveness in the postweaning rat. 断奶后大鼠血管平滑肌反应的个体发生。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01
E E Soltis, P S Newman
{"title":"Ontogeny of vascular smooth muscle responsiveness in the postweaning rat.","authors":"E E Soltis,&nbsp;P S Newman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study investigated the ontogeny of contractile and relaxation responses in aortic and tail artery preparations from 3-, 7-, and 11-week-old male Sprague-Dawley rats. Contractile responses to norepinephrine, serotonin, KCl, electrical stimulation, and potassium-free physiological solution were significantly increased in vascular smooth muscle from 3-week-old rats when compared to 7- and 11-week-old rats. Endothelium-dependent acetylcholine-induced relaxation and beta-adrenoceptor mediated isoproterenol-induced relaxation were significantly attenuated with maturation. These data demonstrate that significant changes occur in aortic and tail artery smooth muscle responsiveness during the postweaning maturational period of the rat. The alterations may have significant implications with regard to cardiovascular and thermoregulatory function as well as the age of the animal when utilized as an experimental model for identifying pathogenic mechanisms involved in various disease states such as hypertension. As such, further studies are warranted to determine if similar ontogenic changes in vascular function occur at the level of the resistance vessel.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":"18 1-2","pages":"44-54"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12653621","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
Age-related changes in calcium antagonist receptors in rabbit ureter. 兔输尿管钙拮抗剂受体的年龄相关性变化。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01
M Yoshida, J Latifpour, R M Weiss
{"title":"Age-related changes in calcium antagonist receptors in rabbit ureter.","authors":"M Yoshida,&nbsp;J Latifpour,&nbsp;R M Weiss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>(+)-[3H]PN 200-110 (a dihydropyridine calcium channel antagonist) binding sites were studied in ureters of 1-day (neonatal), 6-week (premature), 6-month (young) and 4.5- to 5-year (old) female rabbits. Specific binding of (+)-[3H]PN 200-110 to ureteral membrane particulates was saturable, reversible and of high affinity. The densities (Bmax) of (+)-[3H]PN 200-110 binding sites were 46.7 +/- 2.5, 22.6 +/- 2.0, 12.7 +/- 1.8 and 11.9 +/- 1.6 fmol/mg protein in 1-day, 6-week, 6-month and 4.5- to 5-year rabbit ureters, respectively. The affinity constants (KD) of the binding sites for (+)-[3H]PN 200-110 were similar in all groups. Calcium agonists and antagonists inhibited (+)-[3H]PN 200-110 binding to 1-day and 6-week rabbit ureters with the following rank order of Ki values: nitrendipine < nifedipine < BAY K 8644 < verapamil. There were no significant differences in Ki values between the neonatal and premature groups. The data demonstrate the presence of an age-related down-regulation of (+)-[3H]PN 200-110 binding sites in rabbit ureteral membrane particulates.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":"18 1-2","pages":"100-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12654388","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
Effects of nimodipine on brain blood flow following acute brain ischemia in the newborn piglet. 尼莫地平对新生仔猪急性脑缺血后脑血流的影响。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01
C S Easley, F S Wartman, A E Kopelman, T M Louis
{"title":"Effects of nimodipine on brain blood flow following acute brain ischemia in the newborn piglet.","authors":"C S Easley,&nbsp;F S Wartman,&nbsp;A E Kopelman,&nbsp;T M Louis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We examined the effect of the calcium channel blocker nimodipine on postischemic hypoperfusion in the newborn piglet brain. A severe pneumothorax (SP) was induced by injecting air into the right thorax until the mean arterial blood pressure fell to 25% of baseline and was maintained for 4 min. Blood flow was immediately reduced 70-90% from baseline in each brain region during SP. In untreated animals postischemic hypoperfusion existed at 60 min, following recovery from SP with regional brain blood flow reduced 20-30% from baseline. Nimodipine infusion after SP prevented postischemic hypoperfusion in all brain regions and increased blood flows by as much as 40% above baseline in midbrain and brainstem structures. Nimodipine infusion began after severe brain ischemia prevented postischemic hypoperfusion and enhanced brain blood flow in this model.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":"18 1-2","pages":"65-70"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12653623","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
Relationship of prenatal caffeine exposure and zinc supplementation on fetal rat brain growth. 产前咖啡因暴露与补锌对胎鼠脑发育的影响。
Developmental pharmacology and therapeutics Pub Date : 1992-01-01
M Yazdani, F Fontenot, S B Gottschalk, Y Kanemaru, F Joseph, T Nakamoto
{"title":"Relationship of prenatal caffeine exposure and zinc supplementation on fetal rat brain growth.","authors":"M Yazdani,&nbsp;F Fontenot,&nbsp;S B Gottschalk,&nbsp;Y Kanemaru,&nbsp;F Joseph,&nbsp;T Nakamoto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pregnant rat dams were divided into four groups on the 3rd day of gestation. Group 1 dams were fed a 20% protein diet as controls. Dams of group 2 were fed a 20% protein diet supplemented with zinc (0.6 g ZnCl2/kg diet). Group 3 dams were fed a 20% protein diet supplemented with caffeine (2 mg/100 g body weight) and dams of group 4 were fed a 20% protein diet supplemented with both caffeine and zinc. Fetuses were surgically delivered on day 22, and brains were removed and analyzed for alkaline phosphatase activity, protein, zinc, cholesterol and DNA concentrations. Fetal brain caffeine levels, as well as maternal and fetal plasma caffeine levels, were determined in caffeine-supplemented groups. The body weight of group 4 and brain weights of groups 3 and 4 were higher than those of groups 1 and 2. Alkaline phosphatase activity of group 3 was less than that of group 1. The brain zinc concentration of group 2 was higher than in the other groups, but that of group 4 was less than that of group 1. The present study indicated that the supplementation of caffeine to the maternal diet decreased zinc levels in the fetal brain, and the addition of extra zinc to this diet did not return the zinc level to that of the control level as we had expected. In addition, the supplementation of caffeine and zinc together increased the body weights of the fetuses compared to the controls, but the addition of only one of these substances had no effect, suggesting that the combination of caffeine and zinc may have unique effects on fetal growth.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":"18 1-2","pages":"108-15"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12654389","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
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":"18 1-2","pages":"89-99"},"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
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