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

Studies on the correlation between hyperosmolality and brain damage, especially intracranial hemorrhage, were carried out on young and newborn rabbits following infusion with 7% sodium bicarbonate. 1) All the young rabbits injected with 7% sodium bicarbonate died of hyperosmolality at over 380 mOsm/L (the mean was 462 mOsm/L) after drip infusion at the rate of 20-60 ml/kg/hr. Young rabbits under a 10% hypoxic environment died even at the 350 mOsm/L level (the mean was 392 mOsm/L) during infusion of 7% sodium bicarbonate. Half of the case of newborn rabbits injected with 7% sodium bicarbonate at 10 ml/kg, intraperitoneally, had intracranial hemorrhage at 335 mOsm/L. When the hyperosmolality reached 392 mOsm/L (50 ml/kg), intracranial hemorrhage was observed in all cases. 2) The main cause of death in young and newborn rabbits was subdural hemorrhage in the subtentorial region. Intraventricular hemorrhage was observed in about 40% of the cases of young and newborn rabbits. 3) The blood pH was elevated by the drip infusion, but when the hyperosmolality reached about 400 mOsm/L, the blood pH began to fall. At the same osmolality, pCO2 showed a marked elevation. It is likely that the decrease of the blood pH was caused by the elevation of pCO2 and the outflow of H+ from intracellular compartments resulting from the hyperosmolality. These results apparently indicate that fatal intracranial hemorrhage was induced by hyperosmolality and was enhanced by the combination of hypoxia and immaturity.
 ...
PMID:Intracranial hemorrhage following administration of sodium bicarbonate in rabbits. 626 52

Centrally-mediated responses to plasma hyperosmolality include compensatory drinking and pituitary secretion of vasopressin and oxytocin in both adult and neonatal rats. However, the anorexia that is produced by plasma hyperosmolality in adult rats is not evident in neonates, perhaps due to functional immaturity of osmoresponsive hindbrain circuits. To examine this possibility, the present study compared treatment-induced brain expression of the immediate-early gene product c-Fos as a marker of neural activation in adult and two-day-old rats after subcutaneous injection of 2 M NaCl (0.1 ml/10 g body weight). This treatment produced marked hypernatremia in adult and two-day-old rats without altering plasma volume. Several brain regions (including components of the lamina terminalis, the paraventricular and supraoptic nuclei of the hypothalamus, and the area postrema) were activated to express c-Fos similarly in adult and two-day-old rats after 2 M NaCl injection, consistent with previous reports implicating a subset of these regions in osmotically-stimulated drinking and neurohypophyseal secretion. In contrast, other areas of the brain that were activated to express c-Fos in adult rats after 2 M NaCl injection were not activated in neonates: these areas included the central nucleus of the amygdala, the parabrachial nucleus and catecholamine cell groups within the caudal medulla. This study demonstrates that certain brain regions that are osmoresponsive in adult rats (as defined by induced c-Fos expression) are not osmoresponsive in two-day-old rats. When considered in the context of known differences between the osmoregulatory capacities of adult and neonatal rats, our results are consistent with the idea that osmoresponsive forebrain centres are primarily involved in osmotically-stimulated compensatory drinking and neurohypophyseal secretion, whereas osmoresponsive regions of the hindbrain are important for concomitant inhibition of feeding and gastric emptying.
 ...
PMID:Central c-Fos expression in neonatal and adult rats after subcutaneous injection of hypertonic saline. 921 75

In ovine and human pregnancy, fetal swallowing contributes importantly to amniotic fluid homeostasis. Fetal dipsogenic responsiveness to short-term plasma hyperosmolality develops in late gestation, although fetal swallowing is not stimulated in response to long-term plasma osmolality increases (2 to 3%), which typically stimulate adult drinking behavior. To explore the near-term fetal plasma osmolality threshold for swallowing stimulation, we examined the effects of i.v. hypertonic saline-induced subacute increases in plasma hypertonicity on fetal swallowing behavior. Central sites of activation were examined by c-fos expression in putative dipsogenic nuclei. The results demonstrate that subacute 2 to 3% plasma osmolality increases do not stimulate near-term ovine fetal swallowing. However, fetal swallowing activity significantly increased (3 times) after plasma osmolality increased >6% above basal values. Consistent with a specific dipsogenic response, i.v. hypertonic saline induced c-fos expression in the anterior third ventricle region, a putative dipsogenic center, as well as in the fetal hindbrain. The stimulation of fetal swallowing under conditions of higher osmotic stimulation and the correlation with forebrain c-fos expression indicates that near-term fetal osmoregulation mechanisms are functional, although not completely mature. Reduced fetal dipsogenic responsiveness may result from altered osmoreceptor sensitivity, downstream neuronal or synaptic immaturity, or potentially inhibitory actions of stimulated hindbrain nuclei.
 ...
PMID:Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term ovine fetus. 1132 52

The basic mechanism of kernicterus and bilirubin encephalopathy has not been unequivocally determined. Much knowledge has been gained about phenomena that contribute to bilirubin neurotoxicity, and this knowledge has implications for clinical practice. Conditions that impact on blood-brain barrier function, increase brain blood flow, or impact on bilirubin metabolism, including its transport in serum, should be avoided, if possible. Such conditions include drugs and drug stabilizers that compete with bilirubin binding to albumin, or that inhibit P-glycoprotein in the blood-brain barrier, prematurity/immaturity, and clinically significant illness in the infant that involves hemolysis, respiratory and metabolic acidosis, infection, asphyxia, hypoxia and (perhaps) hyperoxia, and hyperosmolality. If these conditions are not avoidable then there should be a more aggressive approach to the treatment of hyperbilirubinemia. The limits of tolerance for hyperbilirubinemia varies among neonates and there are no tools to determine with certainty when a particular infant is approaching the danger zone. Neurological symptoms in a jaundiced infant require extreme vigilance, and, in most cases, immediate intervention.
 ...
PMID:Mechanisms of bilirubin toxicity: clinical implications. 1251 45