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)

Response of the fetal kidney to metabolic acidosis was studied in five fetal lambs, 115-125 days gestation, in order to evaluate the renal contribution to elimination of hydrogen ion during intra-uterine development. Experiments were conducted on healthy unanesthetized fetuses, intact in utero, with catheters implanted at hysterotomy into a fetal femoral artery and vein and into the bladder via the urachus, four or more days prior to the study. A metabolic acidosis was induced by infusion of isotonic lactic acid, 15 m mole/kg, intravenously over a period of 90 minutes. Serial arterial samples were taken and urine collected in fractions before, during and for three hours following the infusion, for measurements of pH, bicarbonate, lactate and electrolytes as well as urine output. During the infusion, urine pH fell from 6.65 to 6.25 and was 6.34 three hours later (Figs. 1 to 4, Tabs. III to IV). Lactic acid infusion caused a prompt increase in urine output from a mean rate of 0.12 to a maximum of 0.28 ml/kg/min at the end of the infusion, returning to control rates three hours later. Lactate excretion increased from 0.05 to a maximum of 4.6 mumole/kg/min at the end of infusion; titratable acid increased from 0.22 to a maximum of 4 muEq/kg/min; the rates of excretion of lactate and titratable acid were still higher than control at the end of three hours. Ammonia excretion increased from 0.21 to a maximum of 0.56 muEq/kg/min three hours after the end of infusion. The acid infusion caused a small but significant fall in excretion of bicarbonate. During the 90 minutes of infusion and over the following three hours, about 800 mumole lactate was excreted while net acid excretion over the same period was no more than half that amount. The diuresis was also accompanied by a net loss of sodium and chloride, the excretion of these ions increasing more than threefold following acid infusion; excretion of potassium decreased to one-third its rate prior to the infusion. During the 90 minutes of infusion, blood pH fell from 7.36 to 7.13, base deficit rose from 3.8 to 16.4 mEq/L and lactate rose from 2.2 to 14.8 mM/L; there was also a small but significant rise in both blood PCO2 and PO2 (Figs. 1 to 2, Tabs. I to II). During the following three hours of recovery, pH rose gradually to 7.29, base deficit and lactate fell to 7.4 mEq/L and 8.7 mM/L respectively. Since renal excretion of net acid and lactate was small, the decrease in blood base deficit and lactate levels during the recovery must therefore be mainly due to equilibration in various fetal compartments as well as placental transfer. These experiments indicate that, in the lamb fetus, intact in utero, the kidney although limited by immaturity of several mechanisms, is capable of responding to an acid load and thus can make a small contribution to fetal homeostasis. The increase in excretion of net acid is accompanied by loss of sodium and chloride in the urine.
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PMID:Renal response to acid loading in the developing lamb fetus, intact in utero. 0 Apr 79

To test the hypothesis that intarpartum acidosis has a role in the etiology of hyaline membrane disease (HMD), blood was collected from the umbilical artery (UA) at birth from 110 premature infants and analyzed for hydrogen ion concentration ([H+]), PCO2, standard bicarbonate, and lactic acid. The infants were followed until a definite diagnosis was made of HMD (33 infants), type II respiratory distress syndrome (16 infants) or the absence of respiratory distress (61 infants). In general, infants with HMD were more premature and had lower Apgar scores than nondistressed infants; however, there were no significant differences between the two groups in any acid-base measurement. Only in those patients of 32 to 37 weeks' gestational age was it possible to detect a significant increase in UA [H+] in infants with HMD compared to those without respiratory distress. There was evidence that the reduced Apgar score of infants with HMD may be due to immaturity and abnormal pulmonary function secondary to lung disease. It is concluded that acidosis at birth is not a factor in the development of HMD except possibly in more mature infants.
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PMID:The role of acidosis at birth in the development of hyaline membrane disease. 95 Nov 32

The effects of the low neutral endopeptidase (24.11/CD10) exhibited by cord blood neutrophils on response to the peptide mediator of cell function f-met-leu-phe (fMLP) were investigated. Oxidative radical release (superoxide and hydrogen peroxide) and chemotactic responses to fMLP were determined and compared to the responses of normal adult neutrophils. The effect of fMLP on CD10 expression as measured by flow cytometry also was evaluated. The data show that cord blood neutrophils produce increased amounts of O2- and H2O2 largely because of a prolonged reaction time to fMLP. In addition, adult polymorphonuclear neutrophil leukocytes increase the intensity of their expression of CD10 following fMLP stimulation, whereas cord blood CD10 expression does not change. Evaluation of chemotaxis demonstrated that cord blood neutrophils exhibited a shift in the fMLP dose-response relationship showing relatively better chemotaxis to lower concentrations. In support of this observation, the inhibition of endopeptidase on adult polymorphonuclear neutrophils leukocytes by phosphoramidon was associated with an augmentation of chemotaxis to 10(-9) and 10(-10) mol/L fMLP. These studies demonstrate that cord blood and adult neutrophils respond differently to fMLP and suggest that membrane endopeptidase plays a role in the observed response patterns. The low level of expression of CD10 on cord blood neutrophils and the failure to increase its expression after fMLP stimulation suggests that adult neutrophils have preformed intracellular CD10 that is not present in the newborn. We propose that the lack of endopeptidase on cord blood neutrophils together with other known features of immaturity may play a role in the overall compromised host defense exhibited by the newborn.
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PMID:Effect of low neutral endopeptidase expression on response to fMLP. 145 99

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in near-term rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO2 was observed in rabbit fetuses. The CO2 reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO2 reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.
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PMID:CO2 reactivity and autoregulation in fetal brain. 176 8

Dietary intake, bacterial metabolites, and the secretion of factors (eg, proteins, electrolytes, lipid-soluble molecules, and water) by the body each contribute to the physicochemical environment of the gastrointestinal tract. Peristalsis regulates the changes along the length of the intestine. However, coordinated peristaltic responses develop as premature infants mature. In addition, the physicochemical environment of the center of the intestinal lumen differs from that of the epithelial surface. The area adjacent to the small intestinal epithelium is more acid than the bulk phase. Na+/H+ exchange antiporters in the epithelial cell apical membrane generate this acidity. Mucus maintains the acid microclimate by preventing free diffusion of hydrogen ions into the bulk phase. Development also affects these mechanisms. Changes in the lumenal environment may alter the synthesis of signaling molecules expressed by the intestinal epithelium. Thus, the epithelium, through changes in gene regulation, may act as an active interface that transmits information about the composition of the intestinal lumen to the mucosal immune system. Premature neonates are at risk of necrotizing enterocolitis, a disease almost exclusively associated with oral feeds. The pathogenesis of this condition may, in part, be due to the immaturity of the interactions between the physicochemical environment of the lumen and intestine.
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PMID:The physicochemical environment of the neonatal intestine. 1023 45

Administration of supplemental oxygen, despite being an important clinical therapy, can cause significant lung damage. Because they have underdeveloped lungs, prematurely born human infants frequently require supportive therapies that employ elevated oxygen concentrations, which put them at risk for developing pulmonary oxygen toxicity. This risk is made even greater by the immaturity of their cellular antioxidant defenses. Although the exact mechanisms of oxygen toxicity are still not fully defined, cellular damage is probably mediated by increased production of chemically reactive oxygen species (ROS) in the mitochondria. Cellular protection against ROS is provided by a variety of antioxidant molecules and enzymes, including the glutathione (GSH)-dependent antioxidant system. The GSH-dependent antioxidant enzyme system provides vital cellular protection against ROS, particularly hydrogen peroxide and certain organic hydroperoxides, under pathological and toxicological conditions, by using selenium-dependent and -independent peroxidases to reduce hydrogen peroxide or lipid peroxides to water or the respective alcohols, with the concurrent oxidation of GSH to glutathione disulfide (GSSG). In the mitochondria, limitations of GSH synthesis and transmembrane transport suggest that optimal functioning of the mitochondrial GSH system, and maintenance of adequate thiol-disulfide redox tone is essential to protect against the injurious effects of ROS. Manipulation of endogenous GSH concentrations can alter cellular responses to oxidant injury. Beneficial effects are evident when intracellular GSH concentrations are increased. In conditions that increase mitochondrial production of ROS, such as exposure to high concentrations of oxygen, therapies based on enhancing mitochondrial GSH concentrations could be highly beneficial.
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PMID:Mitochondrial glutathione and oxidative stress: implications for pulmonary oxygen toxicity in premature infants. 1100 27

Proton magnetic resonance spectroscopy(1H-MRS) can be used for looking at cerebral metabolites in vivo. However, measurement of concentrations of cerebral metabolites in patients with disturbances of cerebral development have not been successful. Our purpose was to measure the concentrations of cerebral metabolites in such patients. We carried out quantitative 1H-MRS in eight patients with cortical dysplasia, four with lissencephaly and three with heterotopic grey matter and six age-matched normal controls. Regions of interest for 1H-MRS were set over the affected cortex in the patients and the occipital cortex in controls. The calculated concentration of N-acetylaspartate ([NAA]) was significantly lower in the affected cortex in patients with cortical dysplasia (P < 0.05), lissencephaly (P < 0.01), and heterotopia (P < 0.05) than in controls, idnicating a decreased number and/or immaturity or dysfunction of neurones in the affected cortex. The concentration of choline ([Cho]) was significantly lower in patients with lissencephaly (P < 0.01) than in controls, indicating glial proliferation and/or membrane abnormality.
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PMID:Proton magnetic resonance spectroscopy in disturbances of cortical development. 1151 91

The neonatal brain appears to be selectively vulnerable to oxidative stress. Several potential mechanisms associated with altered reactive oxygen species metabolism would explain the increased susceptibility. They include increased accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced neurotoxicity from H2O2 accumulation may be related to inadequate scavenging abilities of the immature nervous system, such as lower glutathione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glutathione stores. The immature nervous system is rich in iron, and has more free iron than the mature nervous system. As H2O2 accumulates because of these improper defense mechanisms, it is exposed to this free iron. This exposure results in the generation of OH radical (Fenton reaction), a more potent free radical that can cause severe damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up the immature nervous system for increased cytotoxicity. Understanding the molecular mechanisms of oxidative stress will lead to better therapies for neonatal hypoxia-ischemia.
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PMID:Oxidant mechanisms in neonatal hypoxia-ischemia. 1159 20