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)

In order to pursue peculiarities of fetal metabolism, fluorometric measurements of intracellular nicotinamide adenine dinucleotide (NAD) were made in perfused adult and fetal guinea pig livers following the administration of various agents before and after anoxia loadings. Oxygen and glucose concentrations of the drainage from perfused livers were also measured. The following results were obtained: (1) NAD reduction, oxygen uptake and glucose production were observed to be lower in fetal livers in response to lactate, pyruvate, octanoate and ethanol than the adult ones, suggesting immaturity of fetal intracellular metabolism. (2) However, on the basis of NAD reduction following norepinephrine (NE) administration, fetal plasma membraneous receptors were considered to be similarly active, although induced glucose production was lower than the adult ones. Sequential NE administrations yielded consecutive changes in NAD reduction and glucose production, suggesting active response of fetal plasma membrane to NE. (3) After one hour and three hours of anoxia loadings, adult NAD reduction rates by NE were decreased remarkably to 37% and 11%, respectively, of the control values on average, while fetal rates were reduced to only 61% and 45% of the control values, suggesting anoxic tolerance of fetal plasma membrane. (4) After three hours of anoxia loading, NAD reduction was observed following succinate administration in adult livers, indicating membraneous damage due to anoxia. No such changes were observed in fetal livers. (5) Scanning spectrophotometric studies demonstrated activities of mitochondrial cytochromes in perfused adult and fetal livers, indicating the efficacy of non-destructive in vivo measurements.
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PMID:[Comparative studies on perfused adult and fetal guinea pig liver metabolism before and after anoxia loadings, with special reference to intracellular redox state]. 687 38

Glucose, insulin and C-peptide were determined in amniotic fluid from 28 normal and 46 insulin-treated diabetic pregnant women. Glucose, insulin and C-peptide concentrations in amniotic fluid were higher in the diabetics than in the normal subjects. In diabetic women insulin levels did not correlate with birth weight or birth weight adjusted for gestational age, but C-peptide did. C-peptide correlated poorly with insulin (p < 0.05) in diabetics but closely (p < 0.002) in normal subjects. These results suggest that amniotic fluid investigations in insulin-treated diabetic women should use C-peptide assays as these seem to reflect more closely the insulin production of the fetus than do insulin assays. There were no differences in amniotic fluid glucose, insulin and C-peptide concentrations where the amniotic fluid lecithin-sphingomyelin ratio indicated fetal pulmonary maturity or immaturity.
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PMID:Amniotic fluid C-peptide in normal and insulin-dependent diabetic pregnancies. 699 99

The low cerebral energy requirements of most mammals at birth reflect an immaturity of the central nervous system, and it has been suggested that energy demands in fetuses are even less well developed than in newborns. Furthermore, fetal cerebral energy requirements are presumed to be met predominantly or exclusively by anaerobic glycolysis. To clarify these issues, we investigated cerebral oxidative metabolism in 9-, 14-, 16-, and 19-day-old chick embryos and in newly hatched peeps. Animals were decapitated and quick-frozen in liquid Freon 0--5 min post-mortem. Forebrain extracts were prepared and assayed for ATP, phosphocreatine, glucose, and lactate. Alterations in these metabolites post-decapitation were used to calculate cerebral metabolic rates (delta similar to P) and rates of maximal anaerobic glycolysis (delta lactate). Rates of lactate accumulation during cerebral ischemia increased progressively from embryonic day 9 through hatching. Cerebral metabolic rates were not different in 9-, 14-, and 15-day-old embryos, but increased steadily thereafter. The extent to which total cerebral energy utilization could be derived from anaerobic glycolysis (delta lactate/delta similar to P) increased from a low at day 9 (0.29) to a maximum at day 16 (0.78). The data suggest that, despite the low cerebral metabolic activity of the chick embryo, at no time during development is anaerobic glycolysis capable of entirely supporting the energy needs of the developing brain.
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PMID:Ontogeny of cerebral oxidative metabolism in the chick embryo. 706 56

Twenty-one Thai patients with beta-thalassemia/haemoglobin E and haemoglobin H diseases, 8-20-years-old, were studied. These patients had receive none or minimal blood transfusion. The important clinical endocrine abnormalities were growth retardation and sexual immaturity. GH secretion was found to be impaired in the majority of patients. Oral GTT showed chemical diabetes in one out of sixteen tests, a much lower incidence than in thalassaemic patients treated by hypertransfusion in the West. The mean insulin levels basally and after glucose loading were lower than those of the normal controls. Thyroid function was normal in all of the patients. Serum cortisol and 24-h urinary oxogenic steroids 917 OGS) levels were normal, as was adrenal cortical reserve in all the patients. The literature on endocrine function in in thalassaemia is reviewed.
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PMID:Endocrine function in thalassaemia. 726 14

The inability of the human fetal beta cell to secrete insulin in response to glucose has been exhaustively studied. In comparison, little attempt has been made to understand if the kinetics of insulin synthesis are as mature as those of an adult beta cell. Using a purified cell population in which 41% of the cells are beta cells, we generated a dose-response curve to glucose with half-maximal synthesis at 4.6 mM glucose, identical to that seen in adult islets. Unlike adult islets, however, in the absence of glucose, agents that raise cyclicAMP (cAMP) (theophylline and forskolin) generated dose-response curves similar to those obtained for glucose. cAMP levels in these cells were enhanced twofold in response to glucose and fourfold to theophylline. Inhibition of cAMP metabolism with 1 mM MDL 12,330A (RMI) reduced insulin synthesis stimulated by glucose and completely inhibited insulin synthesis stimulated by theophylline. Substances that block glucose transport (100 microM cytochalasin B) and protein synthesis (1 mM cycloheximide) also markedly reduced insulin biosynthesis. These results indicate that the regulation of insulin biosynthesis in the human fetal beta cell is cAMP dependent, although glucose transport is a limiting factor when glucose is used as the stimulus. Thus, the human fetal beta cell is relatively mature in its synthesis of insulin, unlike its immaturity in insulin release.
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PMID:Control of insulin biosynthesis in the human fetal beta cell. 766 44

The choice of anesthesia during pregnancy and fetal operations is controversial. Halothane frequently is used, but its direct effects on fetal cardiac performance are unknown. The effects of halothane on fetal cardiac mechanics were studied in 8 fetal lamb hearts (135 days' gestation) using a modified Langendorff model connected to a membrane oxygenator. The perfusate consisted of oxygenated maternal blood at a constant flow temperature, hematocrit value, and glucose level. Coronary blood flow, left ventricular systolic pressure, left ventricular end-diastolic pressure, and the developed left ventricular pressure at a fixed volume were evaluated at baseline and after the addition of incremental concentrations of halothane to the perfusate through the oxygenator. Perfusate halothane levels were maintained in a clinical range. Systolic and diastolic cardiac function were adversely affected by the administration of even low doses of halothane, despite a concomitant increase in coronary blood flow. Because of the immaturity of their calcium transport system, fetal hearts may be particularly sensitive to the known calcium channel-blocking properties of halothane.
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PMID:Effects of halothane on the immature lamb heart. 788 14

The cause of hyperphenylalaninemia in sick preterm infants has yet to be determined; one reason may be reduced tolerance to phenylalanine as a consequence of immaturity of phenylalanine hydroxylase. Phenylalanine metabolism was studied in vivo in 23 ventilated preterm infants of gestational age 23 to 36 wk within the first 6 d of life using a continuous i.v. infusion of the stable isotope-labeled amino acids [2H5]phenylalanine, [2H4]tyrosine, and [2H2]tyrosine. Phenylalanine hydroxylation was calculated from two different methods. In the first method, used in all 23 infants receiving glucose and in seven of these infants who subsequently received parenteral nutrition, phenylalanine hydroxylation was calculated from the plasma enrichments of [2H5]phenylalanine and [2H4]tyrosine and from the molar ratio of tyrosine to phenylalanine in mammalian tissue protein. In this instance, the mean hydroxylation was 16.0 (SD 10.9) and 48.4 (SD 14.9) mumol/kg/h, which was 17.3% (SD 8.4%) and 33.2% (SD 9.8% of the total phenylalanine flux for infants receiving glucose and parenteral nutrition, respectively. Additionally, in six infants receiving glucose, hydroxylation was calculated from the measured phenylalanine (2H5), independent tyrosine (2H2) fluxes, and the plasma enrichments of (2H5) phenylalanine and its hydroxylation product [2H4]tyrosine. In this case, hydroxylation was 20.5 (SD 13.0) mumol/kg/h, which represented 22.3% (SD 9.8%) of the phenylalanine flux. In the same six infants, phenylalanine hydroxylation derived using the first method was 22.2 (SD 13.1) mumol/kg/h, 23.6% (SD 9.9%) of the total phenylalanine flux.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenylalanine kinetics in sick preterm neonates with respiratory distress syndrome. 789 79

To determine seizure propagation patterns, we analyzed ictal positron emission tomography (PET) studies of regional cerebral glucose utilization in 18 children (11 male and 7 female aged 2 weeks to 16 years) with epilepsy (excluding infantile spasms IS). Three major metabolic patterns were determined based on degree and type of subcortical involvement: Nine children had type I; asymmetric glucose metabolism of striatum and thalamus. Of these, the 7 oldest children showed unilateral cortical hypermetabolism (always including frontal cortex) and crossed cerebellar hypermetabolism. Two infants (aged < 1 year) had a similar ictal PET pattern but no cerebellar asymmetry, presumably owing to immaturity of corticopontocerebellar projections. Five children had type II, symmetric metabolic abnormalities of striatum and thalamus; this pattern was accompanied by hippocampal or insular cortex hypermetabolism, diffuse neocortical hypometabolism, and absence of any cerebellar abnormality. Four children had type III, hypermetabolism restricted to cerebral cortex. This classification can accommodate ictal PET and single photon emission computed tomography (SPECT) patterns described by other investigators. Future studies should be directed at the clinical relevance of this classification, particularly with regard to epilepsy surgery.
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PMID:Ictal patterns of cerebral glucose utilization in children with epilepsy. 808 28

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.
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PMID:Pathophysiological mechanisms of brain damage from status epilepticus. 838 2

To ascertain whether the inability to suppress glucose production and increase glucose utilization in response to glucose infusion is an inherent characteristic of immature individuals, we determined glucose rate of appearance (R(a)) in minimally stressed, clinically stable, extremely premature infants (approximately 26-wk gestation) at two glucose infusion rates (6.2 +/- 0.4 and 9.5 +/- 0.5 mg/kg per min). We also assessed whether an increase in glucose delivery suppresses proteolysis by measuring the R(a) of phenylalanine and leucine. Glucose R(a) (and utilization) increased significantly at the higher glucose infusion rate (7.9 +/- 0.5 vs. 9.8 +/- 0.6 mg/kg per min). Glucose production persisted at the lower glucose infusion rate but was suppressed to nearly zero at the higher rate (1.7 +/- 0.5 vs. 0.3 +/- 0.1 mg/kg per min). Proteolysis was unaffected by the higher glucose infusion rate as reflected by no change in the rates of appearance of either phenylalanine (96 +/- 5 vs. 95 +/- 3 mumol/kg per h) or leucine (285 +/- 20 vs. 283 +/- 14 mumol/kg per h). Thus, clinically stable, extremely premature infants suppress glucose production and increase glucose utilization in response to increased glucose infusion, demonstrating no inherent immaturity of these processes. In contrast, increasing the rate of glucose delivery results in no change in whole body proteolysis in these infants. The regulation of proteolysis in this population remains to be defined.
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PMID:Intravenous glucose suppresses glucose production but not proteolysis in extremely premature newborns. 840 27


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