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)

When compared to adults, muscle mass in children is lower and the relative development of aerobic and anaerobic pathways is different. The main consequences are the following: 1) The aerobic metabolism, evaluated by measurement of maximal oxygen uptake (VO2max), is either the same as in adults or more developed when VO2 max is related to body mass or lean body mass. 2) The maximal anaerobic power developed during force-velocity test and Wingate test is lower than in adults even if it is expressed by total or lean body mass unit. Blood lactate concentration is also lower. This immaturity of the anaerobic metabolism, especially the "lactic pathway" may result from lower anaerobic enzyme activities (lactico-dehydrogenase, phosphofructokinase, etc) and glycogen content. During puberty, "lactic metabolism" starts to develop significantly, simultaneously with muscle mass. It has been suggested that sexual hormones (testosterone in boys, oestrogens in girls) and other factors, such as growth factors, are implicated in this phenomenon. During this period, the aerobic metabolism remains unchanged. In prepubertal children there is neither aerobic nor anaerobic specialization: the highest anaerobic performance is associated with the highest VO2 max. Moreover, it seems that before puberty, bioenergetic profile is not modified by training. 3) Despite a high VO2 max, performance in endurance events is not as high in children as in adults because of a lower running economy. Cardiovascular responses are characterized by higher maximal and infra-maximal heart rates, and lower systolic stroke volume and arterial blood pressures than in adults. During prolonged exercise, the hormonal adaptations for energy substrate utilization is quite different from adults: a lower decrease in insulin and increase in catecholamines and glucagon in response to exercise could be responsible for a less effective regulation of glycemia with a risk of hypoglycemia. Therefore, an adequate carbohydrate intake is recommended.
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PMID:[Physiology of muscular exercise in children]. 784 28

Six extragonadal teratomas that contained pancreatic tissue were retrieved from archival material at the University of Minnesota Hospital, Minneapolis. The neuroendocrine cells were studied immunohistochemically for insulin, glucagon, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, gastrin, chromogranin, and synaptophysin. Pancreatic tissue from autopsies of 10 stillbirths (20 to 40 weeks' gestational age) was evaluated similarly. The features of the teratomatous pancreatic tissue were compared with those of the fetal pancreata and with data from previous studies of normal pancreatic development and adult pancreata. The pancreatic tissue in all six teratomas contained abundant mature islets that contained beta, alpha, delta, and pancreatic polypeptide cells; however, they also showed widespread nesidioblastosis with the same cell types, resembling third-trimester fetal and neonatal pancreata. Increased proportions of alpha and delta cells were observed in three and five cases (relative to those of adult tissue), respectively, providing further evidence of immaturity. Two cases showed a lack of alpha cells. None of the teratomas contained pancreatic cells that were positive for vasoactive intestinal polypeptide or gastrin. Mechanisms that regulate neuroendocrine cell differentiation in the normal pancreas also seem to operate in the teratomatous pancreas; they may eventuate in features similar to those of the late fetal and neonatal pancreas. Abnormal differentiation in teratomas may result in deficient hormone production.
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PMID:Immunohistochemical characterization of teratomatous and fetal neuroendocrine pancreas. 831 55

The cause of the poor secretion of insulin in response to glucose by the beta-cell in the fetal rat pancreas is thought to be immaturity of the metabolism of glucose. Glucokinase (GK), a key enzyme in glycolysis, is the glucose sensor that maintains glucose homeostasis in the adult beta-cell; its role in the fetal beta-cell has not been determined. The aim of this study was to examine whether GK was functional in phosphorylation of glucose in the fetal islet, and if so, to determine what factors regulated this activity. Similar Km values were found in both fetal and adult islets: 7.4 vs. 7.7 mmol/l. The maximal GK velocity (Vmax) of the fetal islet and the contribution of GK to total glucose phosphorylation were also not significantly different from their adult counterparts. Western blot analysis of protein extracts from fetal and adult islets confirmed the presence of GK at 52 kDa. To determine if glucose had any effect on the Vmax of GK, islets were cultured for 7 days in medium containing low (1.4 or 2.8 mmol/l), normal (5.6 mmol/l), or high (11.2 or 16.8 mmol/l) concentrations of glucose. The maximal GK velocity increased linearly with increasing concentrations of glucose (r = 0.93; P < 0.01). To determine whether it was possible to up- and down-regulate Vmax of GK, islets were cultured in either a low (1.4 mmol/l) or high (30 mmol/l) concentration of glucose for 7 days and then switched to the opposite concentration for a further 3 days. The Vmax of GK in the fetal islet was upregulated 3.8-fold when the glucose concentration was raised. Conversely, the Vmax was downregulated 3.6-fold when the glucose concentration was lowered. The same phenomenon was also observed in the adult islet. These data indicate that GK is the glucose sensor for the fetal rat islet, just as it is for the adult islet. Since glucose did not cause insulin secretion from the fetal islet, it was important to examine whether this substrate had any effect on its own metabolism. Glucose utilization was estimated, and its Vmax was found to increase linearly with increasing concentrations of glucose (r = 0.96; P < 0.01). We conclude that the inability of the fetal rat beta-cell to secrete insulin in response to glucose cannot be explained by immaturity of GK or the glycolytic pathway.
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PMID:Glucose regulates the maximal velocities of glucokinase and glucose utilization in the immature fetal rat pancreatic islet. 869 Jan 54

Glucokinase (GK) is the glucose sensor in the adult beta-cell, resulting in fuel for insulin synthesis and secretion. Defects in this enzyme in the beta-cell are responsible for the genetic disorder maturity-onset diabetes of the young, with the beta-cell being unable to secrete insulin appropriately when challenged with glucose. The human fetal beta-cell is also unable to secrete insulin when exposed to glucose, but whether GK is present and functional in this developing cell is unknown. To determine the expression of GK in human fetal pancreatic tissue, cytosolic protein was extracted from human fetal islet-like cell clusters (ICCs) at 17-19 weeks gestation and examined for protein content and enzyme activity. On Western blots, a single band corresponding to GK was seen at 52 kDa, and this was similar to that obtained from human adult islets. The maximal velocity (Vmax) of GK was less in fetal ICCs than that in adult islets (8.7 vs. 20.7 nmol/mg protein x h); similar K(m) values were found in both ICCs and islets. No attempt was made to determine which cells in an ICC contained GK. Glucose utilization was determined radiometrically; the Vmax of the high K(m) component was less in ICCs than in islets (31.3 pmol/ICC x h vs. 101.4 pmol/islet.h). Culture of ICCs for 3-7 days in medium containing 11.2 mmol/L glucose resulted in a 3.7-fold increase in the Vmax of GK and a 1.8-fold increase in glucose utilization. These enhanced activities of glucose phosphorylation and glycolysis, however, did not lead to the beta-cell being able to secrete insulin when exposed to glucose. In conclusion, glucokinase is present and functional in human fetal ICCs, but the inability of the human fetal beta-cell to secrete insulin in response to an acute glucose challenge is not due to immaturity of this enzyme.
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PMID:Expression of glucokinase in glucose-unresponsive human fetal pancreatic islet-like cell clusters. 906 11

Prepubertal years of insulin-dependent diabetes mellitus are protected from the nephropathic effects of this disease, yet this effect of immaturity has not been investigated in an animal model. Male Munich-Wistar rats were made diabetic with streptozocin at two ages: weanling (approximately 4 wk) and pubescent (approximately 10 wk). After 5 wk of untreated diabetes, weanling diabetic animals showed relatively greater growth of the medulla, whereas relative proportions of these areas were constant in the older animals. Glomerular volume increased by approximately 35% in older diabetic animals, but no glomerular enlargement was demonstrated in weanling rats with diabetes. Glomerular ultrastructure was not significantly altered during the short course of this study. The renal structural response to diabetes is age-dependent in the rat, with prepubertal animals protected from glomerular hypertrophy. Longer studies are needed to see if these differences will eventually parallel those demonstrated in patients with onset of diabetes before and after puberty. This model may ultimately prove to be valuable in determining the mechanism via which prepubertal kidneys are protected from the nephropathic effects of insulin-dependent diabetes mellitus.
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PMID:Age of onset of streptozocin diabetes determines the renal structural response in the rat. 916 8

Several groups have reported a risk of fetal macrosomia in pregnancies with maternal glucose intolerance which is intermediate between gestational diabetes (GDM) and normal glucose tolerance. The present study was designed to determine whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and placental villous immaturity. 325 women with risk factors for GDM underwent a 75 g OGTT interpreted according to the O'Sullivan criteria. All women who met the criteria for GDM were managed with diet therapy. Insulin therapy was added for women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile. Patients not meeting the GDM criteria were managed without special intervention. Primary outcome variables were measures of neonatal weight and skinfold thickness, fetal and neonatal insulin and glucose concentration, and placental villous maturation. Outcome parameters were compared among three groups: pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1 abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value in the OGTT was different from those with normal OGTT. Regarding fetal growth, rates of LGA were approximately twice as high in groups with one abnormal value and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1 and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control only). Regarding fetal hyperinsulinism, AFI concentrations were similar in control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p < 0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1 abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1 abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in the one abnormal value than in the control group (49% vs 34% of infants) and intermediate in the GDM group (40%). Severe placental villous immaturity was more than twice as frequent in the 1 abnormal value group compared to controls (24% vs 9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs controls). Pregnancies with glucose intolerance below the thresholds for diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism, postpartum hypoglycemia and placental immaturity. These findings indicate the continuum of risk for fetal morbidity associated with increasing maternal glucose intolerance in pregnancy.
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PMID:Hyperinsulinism, neonatal obesity and placental immaturity in infants born to women with one abnormal glucose tolerance test value. 959 64

So far, gestational diabetes treated with tolbutamide has never been associated with severe hypoglycaemia in the newborn when the mother's diabetes was well controlled. We report a case of a premature neonate, gestational age 34 weeks, with severe and long-standing hypoglycaemia from birth. The mother had well-controlled gestational diabetes, treated with tolbutamide from the 24th week of gestation until delivery. The neonate had inappropriately high levels of serum proinsulin, insulin and C-peptide relative to blood glucose concentrations. From day 19 after birth, the levels were normalized. Serum tolbutamide was 140.6 micromol/l (38 microg/ml) at 3 h after birth. Zero-order kinetics were seen during the first 90 postnatal hours. The half-life of serum tolbutamide decreased from 46 to 6 h. It is suggested that tolbutamide, when given to the mother until delivery, may cause severe and prolonged hyperinsulinaemic hypoglycaemia in premature neonates. The initially prolonged tolbutamide half-lives and zero-order kinetics suggest immaturity of hepatic elimination during the first 2 days of postnatal life.
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PMID:Prolonged elimination of tolbutamide in a premature newborn with hyperinsulinaemic hypoglycaemia. 967 39

The Diabetes Mellitus is the pathology that frequently is associated to the pregnancy and it is responsible for perinatal mobility specially by the respiratory distress syndrome since exists delay in the conversion of myoinositol-phosphatidyl inositol-phosphatidyl glycerol. To demonstrate the reliability of the DO tho 650 nm with standard of 20 in the determination of fetal lung maturity of the infant of diabetic mother. There were included 143 patient with pregnancy > or = 37 weeks with amenorrhea reliable and gestational age confirmed by ultrasound, of those 94 corresponded to gestational Diabetes Mellitus, 49 to pregestational (46 non insulin-dependent and 3 insulin-dependent). In all of them amniotic fluid studies was perform at 37 week and the resolution of the pregnancy was when DO to 650 nm showed fetal lung maturity. It was found a correlation among the DO to 650 nm of 20 and absence of RDS in 130 cases (true positive); there were seven cases with immaturity results by DO that they did not express RDS (false negative) and six cases with results that showed immaturity by DO and there were manifestations of RDS (true negative). We did not find results of false positive. The frequency of RDS was of 4.9% with a positive predictive value of the 100% an negative predictive value of 46%, a specificity of 100% and a sensitivity of 94%. An interesting finding was the fact that six cases true negative cases had poor maternal metabolic control of different degrees. For our results can be deduced that DO to 650 nm with standard of .20 it is reliable for the diagnosis of fetal lung maturity in the pregnancies complicated with Diabetes Mellitus, in addition to be an easy elaboration test and low cost.
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PMID:[Reliability of optic density at 650 nm in determining lung maturity in children of diabetic mothers]. 982 5

There is increasing evidence to suggest that insulin-like growth factors (IGF) I and II play a crucial role in fetal lung development. Expression of IGF-I and II has been demonstrated to be predominant during fetal life and decreases prior to birth. Antenatal glucocorticoids are reported to improve lung immaturity. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on IGF-I and II expression in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. A CDH model was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term = 22 days). Dexamethasone (0.25 mg/kg) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21. The fetuses were divided into three groups: I, normal controls; II, nitrofen-induced CDH; and III, nitrogen-induced CDH with antenatal dexamethasone treatment. mRNA was extracted from whole lung and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of IGF I and II mRNA. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a housekeeping gene known to be expressed at a constant level. Immunohistochemistry using anti-rat IGF I and II antibody was also performed in each group. Levels of IGF I mRNA were significantly increased in group II (0.50 +/- 0.08) compared to group I (0.34 +/- 0.10) or group III (0.32 +/- 0.06) (P < 0.05). Levels of IGF II mRNA were also significantly increased in group II (0.95 +/- 0.20) compared to group I (0.42 +/- 0.07) or group III (0. 31 +/- 0.09) (P < 0.05). Strong IGF I and II expression was observed in the hypoplastic CDH lung (group II), mainly in the bronchiolar epithelium. IGF I and II expression in group I and III lungs was either absent or weak. The finding of significant reductions in IGF I and II mRNA and protein levels in dexamethasone-treated CDH lung suggest that dexamethasone may accelerate the fetal stage of lung development.
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PMID:Effect of antenatal glucocorticoid administration on insulin-like growth factor I and II levels in hypoplastic lung in nitrofen-induced congenital diaphragmatic hernia in rats. 1037 16

Although extensive data are available on the impact of nutrient and protein administration on growth, plasma amino acids, and nitrogen balance in the newborn and growing infants, relatively few studies have carefully examined the dynamic aspects of protein metabolism in vivo and particularly in the micropremie or ELBW infant. These studies show that the very preterm infants, either because of immaturity or because of the intercurrent illness, have high rates of protein turnover and protein breakdown. This high rate of proteolysis is not as responsive to nutrient administration. Intervention strategies aimed at promoting nitrogen accretion, such as insulin, human growth hormone, or glutamine, have not thus far resulted in enhanced protein accretion and growth. This may be, in part, due to limitations in delivery of adequate calorie and nitrogen.
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PMID:Protein metabolism in the extremely low-birth weight infant. 1069 May 63


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