Developmental pharmacology and therapeutics最新文献

{"title":"Synergistic effect of triiodothyronine and dexamethasone on renal tubular transport of p-aminohippurate in rats of different ages.","authors":"H Bräunlich,&nbsp;W Pils","doi":"10.1159/000457462","DOIUrl":"https://doi.org/10.1159/000457462","url":null,"abstract":"<p><p>Postnatal maturation of the renal tubular transport of p-aminohippurate (PAH) was verified in rats both in diuresis experiand on renal cortical slices in vitro. Following treatment with various doses of triiodothyronine (T3) or dexamethasone (3 days, once a day), the increase in renal tubular transport of PAH was more distinct in young rats with immature kidney function. The synergistic effects of simultaneous treatment with both hormones indicate differences between T3 and dexamethasone in the modulation of cellular function.</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/10.1159/000457462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12481065","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}

{"title":"Comparison of the effect of midazolam or vecuronium on blood pressure and cerebral blood flow velocity in the premature newborn.","authors":"H L van Straaten,&nbsp;C M Rademaker,&nbsp;L S de Vries","doi":"10.1159/000457484","DOIUrl":"https://doi.org/10.1159/000457484","url":null,"abstract":"<p><p>The effect of midazolam and vecuronium on mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) was evaluated in premature infants (birthweight 550-2,560 g; gestational age 26-36 weeks) randomised to receive either 0.1 mg/kg midazolam (n = 7) or 0.05 mg/kg vecuronium (n = 8) intravenously. MAP, by means of an indwelling arterial catheter, and MCBFV, by means of non-invasive pulsed-Doppler of the middle cerebral artery, were measured every 5 min, starting at 10 min prior to until 1 h after drug administration. A transient 25-43% decrease in MCBFV (mean 0.06 m/s) dependent on a 8-23% decrease in blood pressure (mean 9 mm Hg) was noted in all patients within 15 min following administration of midazolam, which returned to baseline values within 1 h. In 2 out of 7 infants, a plasma expander was required. In contrast, vecuronium only decreased the MCBFV in 3 of 8 infants. Thus, a bolus of midazolam transiently decreased blood pressure and MCBFV, and should be used cautiously in sick preterm infants.</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/10.1159/000457484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12538395","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}

{"title":"Pharmacokinetics of high-dose methylprednisolone in children.","authors":"S Ito,&nbsp;Y Kusunoki,&nbsp;T Oka,&nbsp;Y Ito,&nbsp;A Okuno,&nbsp;H Yoshioka","doi":"10.1159/000457470","DOIUrl":"https://doi.org/10.1159/000457470","url":null,"abstract":"<p><p>Disposition of methylprednisolone was characterized in 11 children receiving the high-dose therapy (26.0 mg/kg on average). After intravenous infusion, methylprednisolone hemisuccinate was rapidly converted to methylprednisolone with a half-life of about 20 min. Methylprednisolone in serum, eliminated monoexponentially in 8 patients and biexponentially in the remaining three, had the mean residence time of about 3 h, and a terminal half-life of 2.5 h. The volume of distribution at steady state, and the clearance were 1.3 liters/kg and 0.5 liters/kg/h, respectively. Although these average pharmacokinetic parameters were comparable to those determined in other studies with conventional low doses, the clearance values in our data were characterized by 5-fold interindividual difference, suggesting large variations in exposures to methylprednisolone among children on the high-dose pulse therapy.</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/10.1159/000457470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12513594","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}

{"title":"Effects of prenatal cocaine on the ventilatory response to hypoxia in newborn rabbits.","authors":"D E Weese-Mayer,&nbsp;L M Klemka-Walden,&nbsp;G A Barkov,&nbsp;J L Gingras","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recently, investigators have reported an alteration of postnatal respiratory pattern, deficient hypoxic arousal from sleep, and an increased incidence of sudden infant death syndrome (SIDS) among human infants exposed to cocaine prenatally, thus suggesting that prenatal cocaine exposure may perturb the maturation of respiratory control thereby increasing the risk for SIDS. To investigate the effects of prenatal cocaine on postnatal respiration, we evaluated the ventilatory response to 0.21 FIO2 (baseline) and at 0.15, 0.10, and 0.08 FIO2 by the barometric method on days 4-5 of life in 23 New Zealand White rabbit pups born to cocaine-exposed (30 mg/kg/day of cocaine HCl by continuous subcutaneous infusion), pair-fed and free-fed does. The chamber pressure deflection (proportional to VT after appropriate calculation) was computer-sampled at 200 Hz when the unanesthetized pups were resting quietly with no gross body movements. Recording was made after 10 min acclimatization to a specific FIO2. We found that baseline ventilation did not differ significantly among study groups. However, minute ventilation (VI), inspiratory flow (VT/TI), tidal volume (VT), increased significantly with hypoxia to peak values at 0.08 FIO2 in pair-fed and free-fed pups but these measurements did not increase significantly in cocaine-exposed pups. Our finding of a deficient second phase of the hypoxic ventilatory response among cocaine-exposed pups supports the hypothesis that prenatal cocaine perturbs the maturation of respiratory control.(ABSTRACT TRUNCATED AT 250 WORDS)</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":"12654390","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}

{"title":"Functional changes implicating dopaminergic systems following perinatal treatments.","authors":"T. Archer, A. Fredriksson","doi":"10.1159/000480623","DOIUrl":"https://doi.org/10.1159/000480623","url":null,"abstract":"A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-hydroxydopamine (6-OHDA) (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound, or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphetamine-induced activity. It was shown that prenatal metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d-amphetamine-induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded according to the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine-induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85% depletion compared to control values) caused notable impairments. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered.","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":"88986922","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}

{"title":"Pharmacodynamics and pharmacokinetics of cyclosporin A in the newborn pig.","authors":"P. Tsao, S. Ito, P. Wong, I. Radde, S. Bryson, D. Young, J. Caspi, R. J. Diaz, M. Martell, J. Augustine","doi":"10.1159/000480594","DOIUrl":"https://doi.org/10.1159/000480594","url":null,"abstract":"The disposition kinetics of cyclosporin A in the neonates as well as age-related differences in lymphocyte responses to cyclosporin A are unknown. A single intravenous infusion of cyclosporin A was given to neonatal (2.5 or 5 mg/kg) and mature pigs (10 mg/kg) and blood cyclosporin A levels were measured by RIA. The neonates had longer elimination half-life and lower drug clearance than mature animals. Suppression in lymphocyte proliferation was only observed in mixed lymphocyte reaction and phytohemagglutinin-stimulated cultures of the 2-hour samples from neonates receiving 5 mg/kg. We conclude that neonatal pig exhibit different cyclosporin A pharmacokinetics and show higher sensitivity to cyclosporin A than mature animals.","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":"85418087","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}

{"title":"Vasodilators in persistent pulmonary hypertension of the newborn: a need for optimal appraisal of efficacy.","authors":"J B Gouyon,&nbsp;M Françoise","doi":"10.1159/000457466","DOIUrl":"https://doi.org/10.1159/000457466","url":null,"abstract":"<p><p>Tolazoline hydrochloride is usually the first choice pulmonary vasodilator in persistent pulmonary hypertension of the neonate (PPHN). The analysis of 26 articles including 467 tolazoline-treated infants has been hindered by many methodological drawbacks. Tolazoline has always been administered to infants suffering refractory hypoxemia, but, unfortunately, pulmonary hypertension has not usually been investigated. Moreover, 80% of the tolazoline-treated neonates had an underlying pulmonary parenchymal disease as a potential cause of severe hypoxemia. Noteworthy is that similar comments apply to all studies dealing with the use of other pulmonary vasodilators in PPHN. Pulsed Doppler echocardiography (PDE) should allow a qualitative and quantitative approach for PPHN and an analysis of both success and failure of vasodilator therapeutics. In the meantime, the use of PDE requires more intense investigation prior to wide application in PPHN.</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/10.1159/000457466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12513590","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}

{"title":"The valproic acid metabolite E-2-n-propyl-2-pentenoic acid does not induce spina bifida in the mouse.","authors":"K Ehlers,&nbsp;H Stürje,&nbsp;H J Merker,&nbsp;H Nau","doi":"10.1159/000457485","DOIUrl":"https://doi.org/10.1159/000457485","url":null,"abstract":"<p><p>The antiepileptic drug valproic acid (VPA) has been implicated as a human teratogen causing spina bifida aperta. Recently we developed a mouse model inducing spina bifida aperta and occulta with VPA. In a search for novel antiepileptic agents the VPA metabolite E-2-n-propyl-2-pentenoic acid (2-en-VPA) had been developed. In the mouse, 2-en-VPA exhibits anticonvulsive potency similar to VPA but very low teratogenic potency (induction of exencephaly). We have now compared VPA and its metabolite 2-en-VPA in regard to induction of spina bifida in our mouse model. 2-en-VPA was administered 3 times during the period of gestation most sensitive for the induction of spina bifida aperta with VPA: on day 9 of gestation at 0, 6 and 12 h. The following doses were injected (in mmol 2-en-VPA-Na/kg): (a) 3 x 2.1, (b) 3 x 2.7 (the equimolar dose of VPA is the threshold dose for induction of spina bifida aperta) and (c) 3 x 3.0 (the equimolar VPA dose produced spina bifida aperta). 2-en-VPA did not induce spina bifida aperta in the mouse in any of these groups. We then investigated the induction of spina bifida occulta in the three dose groups. Spina bifida occulta is a less serious form of spina bifida and may provide a sensitive method to estimate the potency of a compound to induce more severe forms of spina bifida. This malformation was demonstrated in alcian-blue- and alizarin-red-stained fetal skeletons by measurements of the distance between the cartilaginous ends of each vertebral arch.(ABSTRACT TRUNCATED AT 250 WORDS)</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/10.1159/000457485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12516763","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}

{"title":"Effects of prenatal cocaine on the ventilatory response to hypoxia in newborn rabbits.","authors":"D. Weese-Mayer, L. Klemka-Walden, G. Barkov, J. Gingras","doi":"10.1159/000480605","DOIUrl":"https://doi.org/10.1159/000480605","url":null,"abstract":"Recently, investigators have reported an alteration of postnatal respiratory pattern, deficient hypoxic arousal from sleep, and an increased incidence of sudden infant death syndrome (SIDS) among human infants exposed to cocaine prenatally, thus suggesting that prenatal cocaine exposure may perturb the maturation of respiratory control thereby increasing the risk for SIDS. To investigate the effects of prenatal cocaine on postnatal respiration, we evaluated the ventilatory response to 0.21 FIO2 (baseline) and at 0.15, 0.10, and 0.08 FIO2 by the barometric method on days 4-5 of life in 23 New Zealand White rabbit pups born to cocaine-exposed (30 mg/kg/day of cocaine HCl by continuous subcutaneous infusion), pair-fed and free-fed does. The chamber pressure deflection (proportional to VT after appropriate calculation) was computer-sampled at 200 Hz when the unanesthetized pups were resting quietly with no gross body movements. Recording was made after 10 min acclimatization to a specific FIO2. We found that baseline ventilation did not differ significantly among study groups. However, minute ventilation (VI), inspiratory flow (VT/TI), tidal volume (VT), increased significantly with hypoxia to peak values at 0.08 FIO2 in pair-fed and free-fed pups but these measurements did not increase significantly in cocaine-exposed pups. Our finding of a deficient second phase of the hypoxic ventilatory response among cocaine-exposed pups supports the hypothesis that prenatal cocaine perturbs the maturation of respiratory control.(ABSTRACT TRUNCATED AT 250 WORDS)","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":"79073298","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}

{"title":"Adrenal responsiveness in very-low-birth-weight infants treated with dexamethasone.","authors":"A Strauss,&nbsp;M Brakin,&nbsp;K Norris,&nbsp;H D Modanlou","doi":"10.1159/000457476","DOIUrl":"https://doi.org/10.1159/000457476","url":null,"abstract":"<p><p>This study was designed to investigate the effect of steroid administration in ill premature neonates. Twenty high-risk very-low-birth-weight (VLBW) infants [birth weight (BW) < or = 1,300 g] with a mean BW 948 +/- 220 g, gestational age (GA) 27 +/- 1.7 weeks underwent 1-hour ACTH (Cortrosyn) stimulation tests and determination of 17-hydroxyprogesterone (17OHP)/dehydroepiandrosterone sulfate (DHEAS) at 23.6 +/- 15.9 days poststeroid treatment for bronchopulmonary dysplasia (BPD)/airway obstruction. Metyrapone tests were also obtained in 18 infants. Baseline (nonsteroid-exposed) values for pre-/post-ACTH cortisol, 17OHP, DHEAS, and pre-/post-metyrapone compound S values were obtained in 5 infants. Eight of 18 (44%) infants had evidence of secondary (hypothalamic-pituitary) adrenal suppression based on abnormal metyrapone tests. No difference was found in BW, GA, time on O2 or AV, steroid dose/kg, or neonatal/postneonatal mortality between the suppressed and nonsuppressed groups. Two of 4 infants with borderline ACTH tests had subnormal compound S levels postmetyrapone. No relationship was found between steroid dose/kg and cortisol response post-ACTH. Additionally, corrected GA was not related to change in cortisol, 17OHP, and DHEAS pre-/post-ACTH. Two infants exhibited recovery of adrenal suppression documented by repeated metyrapone testing at 63 and 186 days poststeroid treatment. In conclusion, this study documents the apparent high incidence of secondary adrenal suppression in VLBW infants treated with dexamethasone. Clinical significance of these findings deserves further investigation.</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/10.1159/000457476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12514421","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}