Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reports correlations among gamma-glutamyltransferase (GGT), fetal haemoglobin (fH), alpha-fetoprotein, 5'-nucleotidase, ceruloplasmin, and direct, indirect, and total bilirubin in the serum of blood taken from the umbilical cords of 128 newborns delivered after 37-42 weeks of gestation. GGT was significantly correlated with alpha-fetoprotein, but not with direct bilirubin, indirect bilirubin, total bilirubin, fH, or %fH. Neither fH nor %fH were correlated with alpha-fetoprotein, but there was highly significant negative correlation between both fH and %fH on the one hand, and gestational age and weight at birth on the other. The %fH was also correlated negatively with ceruloplasmin, which in turn exhibited negative correlation with alpha-fetoprotein. The predominant forms of GGT in umbilical cord and adult sera were, respectively, those with alpha 1 and alpha 2 mobility. In cord sera, delipidation with n-butanol brought about loss of GGT activity and a shift from an alpha 1 to an alpha 2 position, whereas no significant effect of this kind was observed in adult sera. Affinity chromatography through Concanavalin A-Sepharose showed cord sera to contain a proportion of bound-GGT (68.5 +/- 5.5%) that was significantly greater (p less than 0.001) than that found in adult sera (59.8 +/- 10.2%). It is concluded that the high GGT activity of cord sera is probably due to hepatic immaturity rather than maternal sources, enzymatic induction or microsomal lesions; that the predominant form of GGT in cord serum may be a complex with HDL and less sialized than the adult enzyme; and that, of the factors examined, the best indicator of neonatal maturity is fetal haemoglobin.
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PMID:Cord serum gamma glutamyltransferase in newborns. 244 3

Leprechaunism is a rare genetic disorder characterized by physical abnormalities, intrauterine and postnatal growth retardation, poorly developed subcutaneous fat and muscle at birth, and early death. This patient, who was a 1.5 year-old female with typical clinical features of leprechaunism, had relatively high levels of plasma GH and IGF-I/SMC but no glucose intolerance or insulin resistance. Studies were undertaken to elucidate (1) the differences among some kinds of methods for IGF-I/SMC measurement, (2) the distribution patterns of IGF-I/SMC between two kinds of its binding protein (SMBP) in plasma, and (3) the dynamics of IGF-I/SMC receptor in her erythrocytes and liver microsomal membranes. The results were as follows: (1) The level of IGF-I/SMC measured by Nichols radioimmunoassay kit was 1.33U/ml, which was higher than that of infants the same age. Conversely, it was lower than that of the control which was measured by radioimmunoassay using recombinant IGF-I/SMC after acid-ethanol or Seppak C18 extraction. (2) By Sephadex G150 gel-chromatography, immunoreactive IGF-I/SMC was eluted predominantly in 150K region, and two apparent peaks of unsaturated somatomedin binding protein (USBP) were determined in a neonatal infant (appropriate to date), a normal adult and an infant of the same age as this patient. On the other hand, immunoreactive IGF-I/SMC was located only in the fractions corresponding to 40K region, and only one peak of USBP could be estimated in the region of 40K dalton. (3) The IGF-I/SMC receptor in the patient's erythrocytes possessed significantly lower binding affinity but higher binding capacity in comparison with that of the normal neonate and adult. In addition, the receptor in liver microsomal membranes obtained from this patient at autopsy also indicated lower affinity but higher capacity than that of fetuses at more than 19 weeks of gestation. This was coincident to that of fetuses less than 19 weeks of gestation. These results suggested that this patient resembled the intrauterine fetus before midgestation not only in the co-relationship among GH, IGF-I/SMC and its binding proteins, but also in the characteristics of its receptor. The severe growth retardation existing in this patient may be, at least partly, due to the abnormality and/or immaturity of IGF-I/SMC function. It is speculated that leprechaunism could be classified in relation to fetal growth mechanism by aspects of biological functions of IGF-I/SMC during development.
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PMID:[A case of leprechaunism with disorders of insulin-like growth factor-I(IGF-I)/somatomedin C(SMC) binding protein and its receptor]. 247 74

DNA damage and repair in kidney and liver of mouse fetuses exposed to selected doses of N-nitrosodimethylamine (NDMA) (CAS No. 62.75.9) were studied using the alkaline elution technique. CD1 female mice (15 days pregnant) were treated i.p. with 2 and 10 mg/kg b.w. of NDMA; a slight increase in DNA damage was observed in their fetuses compared to untreated controls. A 2-fold higher extent of DNA damage was induced when mice were treated by intrafetal injections of a rat S9 activating fraction (S9) immediately before exposure to the same dose of NDMA by transplacental means. The DNA-strand breaks disappeared as a function of time in animals treated with NDMA alone. In contrast, a significant persistence of DNA damage was detected in the liver and lung of fetuses which were treated with S9 and NDMA in sequence. These experiments demonstrate the metabolic immaturity of unborn mice as far as the carcinogenic activation of NDMA is concerned and show the high susceptibility of fetal tissues to DNA-damaging agents. The alkaline elution applied in vivo by the transplacental route combined with the intrafetal injection of an exogenous activating microsomal fraction allow to extend our knowledge on the interaction of metabolism-dependent chemicals with fetal tissues.
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PMID:A new method to reveal the genotoxic effects of N-nitrosodimethylamine in pregnant mice. 334 94

The binding of human [125I]GH, ovine [125I]GH, bovine [125I]GH, and ovine [125I]PRL, to hepatic microsomal membranes (100,000 g) prepared from fetal, neonatal, and infant lambs and adult ewes has been examined. The specific binding of hGH increases (P less than 0.01) from 3.4 +/- 0.8% in the fetus (n = 7) to 20.0 +/- 2.1% (n = 6) in lambs at least 6 days postpartum. The binding of oGH is low in the fetus (0.7 +/- 0.2%; n = 13) and neonatal lamb (1.3 +/- 0.5%; n = 5) and increases (P less than 0.01) in older lambs (14.6 +/- 4.7%; n = 6) and adult sheep (14.9 +/- 5.3%; n = 4). Similarly, the binding of bGH is less (P less than 0.05) to fetal tissues. In contrast, the binding of oPRL is similar in fetal and postnatal preparations. Cross-reaction studies suggest that the binding of GHs is to a site with lactogenic characteristics in the fetus. In contrast, in lambs at least 4 days postpartum and in adult sheep, binding is to a site with somatogenic characteristics. The inability to detect somatogenic sites in the fetal liver is not due to saturation by endogenous GH or chorionic somatomammotropin, as the binding characteristics do not change after MgCl2 pretreatment of the membrane fractions. No change in binding is observed 25 days after fetal decapitation at 69 days (n = 3), suggesting that circulating GH does not down-regulate the fetal GH receptor. These observations suggest an immaturity of the somatogenic receptor in the ovine fetal liver and its appearance in the perinatal period. Immaturity of this receptor is likely to be the basis for the lack of a major effect of fetal GH on fetal somatic growth.
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PMID:The ontogeny of somatotropic binding sites in ovine hepatic membranes. 613 14

The effects of gestational age on the pharmacokinetics of cefotaxime and its desacetyl metabolite during the first days of life was investigated in a group of four full-term infants and 12 preterm infants of less than 35 weeks gestation. Half of the preterm infants had received betamethasone, a drug known to facilitate hepatic microsomal drug metabolism, whilst the others had not. No significant differences in the pharmacokinetics of cefotaxime were observed between the various groups, with elimination half-life (T 1/2 beta) of cefotaxime ranging from 4.04 +/- 1.52 to 4.56 +/- 1.31 h. The desacetyl metabolite of cefotaxime was present in all post-dose serum samples, irrespective of the gestational age of the baby. Its formation was apparently unaffected by prior exposure to betamethasone. The elimination half-life of cefotaxime is significantly longer in newborn infants than in older children or adults, this increase probably results from decreased renal excretion of the drug, rather than from immaturity in its metabolism. A dose of 50 mg/kg of cefotaxime given every 12 h is appropriate for infants of less than seven days old.
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PMID:Pharmacokinetics of cefotaxime in neonates. 633 19

Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition (ie, distribution, metabolism and excretion) processes during the neonatal period. These alterations affect the plasma concentrations as well as the concentrations of drug attained at the receptor site. Some characteristics of the neonatal period include greater absorption from the gastrointestinal tract, lower extent of plasma protein binding, increased apparent volume of distribution of drugs that distribute in extracellular fluid or total body water, increased permeability of the 'blood-brain' barrier and slower elimination of many drugs. The hepatic microsomal oxidative reactions and glucuronide conjugation are deficient metabolic pathways for a varying period of time, usually up to six weeks after birth or even longer in some species. Decreased metabolism can affect the duration of action of lipid-soluble drugs. Functional immaturity of the kidneys decreases the renal excretion of polar drugs and drug metabolites. Overall renal function appears to reach maturity within two weeks after birth in ruminant species and pigs, while maturation may take at least four weeks in other species of domestic animals. Considerable physiological and biochemical development takes place during the first five days after birth with maturation continuing more slowly over the succeeding five weeks. The time it takes for any process to reach functional maturity depends on the process in question and varies with the species of animal. The absorption, disposition and pharmacological response to drugs during the first 24 h after birth may be unique to that time and, because of lack of information, are impossible to predict.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug disposition in the neonatal animal, with particular reference to the foal. 647 35

Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg/kg, respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines). Unlike in human in vitro or in vivo, 1,3,7-DAU (6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil) was an important metabolite (9.7% of total caffeine metabolites). Pregnandiol inhibited N-1, N-3 and N-7 demethylation in vitro (-33%, -33% and -28%, respectively, at 5 mg/kg/day), but it had no effect on N-1 demethylation at 1.25 or 2.50 mg/kg/day. Pregnandiol at all doses had no effect on 1,3,7-trimethyluric acid and 1,3,7-DAU formation. These results are consistent with the hypothesis that C-8 hydroxylation and demethylation of caffeine are mediated by different isoenzymes. They indicate that pregnandiol is a potent inhibitor of microsomal drug metabolism, specifically of cytochrome P450 IA, which could explain the immaturity of some metabolic pathways of caffeine in neonates.
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PMID:Effect of pregnandiol on caffeine metabolism in female rats. 824 2

Adult white Leghorn chickens exhibited a sexual dimorphism in hepatic microsomal monooxygenases determined from the concentrations of total cytochromes P450 and b5, and the metabolism of drug (hexobarbital, coumarin and ethoxyresorufin) and steroid (androstenedione and testosterone) substrates that were 2- to 4-fold greater in roosters than in hens. Caponizing at 6 weeks of age reduced the activities of the monooxygenases to levels comparable to those found in intact hens. In spite of the fact that testosterone replacement maximally stimulated comb growth in the capons and elevated (i.e. masculinized) hepatic monooxygenase activities in the hens to male-like levels, androgen replacement was ineffective in increasing the subnormal enzyme levels in the capons. While the failure of testosterone administration to restore monooxygenase levels in the capons may be explained by the immaturity of the birds at orchiectomy, the present results demonstrate, that like some mammals, birds may display gender differences in hepatic monooxygenases that are regulated by the testes.
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PMID:Sexual dimorphism in avian hepatic monooxygenases. 837 39

Physiologic changes influence the pharmacokinetics of drugs relevant to anesthesia in neonates and infants. The neonatal phase is the phase of life with the most rapid and dramatic changes of organ-functions responsible for pharmacokinetics of most anesthetics. Changes in body composition and the content of plasma proteins influence volume of distribution, the drug distribution to different compartments and the amount of free fraction in plasma. Due to the immaturity of hepatic microsomal enzyme systems there is a decreased metabolism particular of agents which undergo low hepatic extraction like Diazepam, Morphine or some local anesthetics. In the first year of life capacity of the enzymatic systems increases and also clearance increases. Until puberty the clearance of some drugs is greater than the adult level. There are also pharmacodynamic changes like modified sensitivity to some drugs like volatile anesthetics or neuromuscular blocking agents. In summary neonates and infants are a highly heterogenous group with large interindividual differences. Therefore the dosage of anesthetic agents must be individualized to achieve optimal pharmacodynamic effects without toxicity in this age group.
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PMID:[Pharmacokinetics in newborns and infants]. 1054 58

In this study, we explored the paradox that in suckling rats the serum concentration of LDL is high although the liver secretes only minimal quantities of VLDL, the presumed precursor of LDL. Freshly isolated hepatocytes and hepatocytes in primary culture obtained from adult (90 days old) and suckling (17 days old) rats were used to investigate the synthesis and secretion of apolipoprotein B (apoB) and lipids as well as the density profile of secreted apoB-containing lipoproteins. Furthermore, the effects of dexamethasone and oleate on apoB biogenesis were investigated in primary cultures of hepatocytes from adult and suckling rats. Hepatocytes from suckling rats were unable to assemble mature VLDL but secreted apoB as primordial lipoprotein particles in the LDL-HDL density range. Intracellular degradation of apoB was also reduced in hepatocytes from suckling rats compared with that in hepatocytes from adults. The immaturity in VLDL assembly and apoB degradation of hepatocytes from suckling rats could be overcome by treating the cultures with dexamethasone plus oleate or dexamethasone alone. The lower microsomal triacylglycerol transfer protein (MTP) mRNA concentrations in hepatocytes from suckling rats in comparison with hepatocytes from adult rats were not reflected in lower MTP activity levels. Furthermore, dexamethasone plus oleate treatment had no effect on MTP activity although VLDL assembly and secretion were clearly stimulated. We conclude that, during the suckling period of the rat, serum LDL is directly produced by the liver. This is a result of impaired hepatic VLDL assembly, which is a consequence of low triglyceride synthesis and an inefficient mobilization of bulk lipids in the second step of VLDL assembly.
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PMID:Postnatal development of hepatocellular apolipoprotein B assembly and secretion in the rat. 1171 56


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