Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High serum bilirubin levels (SBL), over 20-25 mg/dl are toxic for the Central Nervous System (CNS) of newborn infants. However, the possible toxicity on the CNS of "intermediate" SBL both in term and preterm neonates are still a matter of debate. An extensive review of the literature in this respect did not provide conclusive evidence for a dose-response pattern of toxicity for SBL 18-20 mg/dl in infants without hemolysis and/or other risk factors (such as extreme prematurity, hypoxia, hypercapnia, acidosis, sepsis, hyperosmolarity, etc.). Therefore, an aggressive approach to the treatment and/or prophylaxis of neonatal jaundice when SBL are below 20 or even 25 mg/dl is not justified on the basis of the present knowledge. This is particularly true when treatment includes phototherapy and/or exchange-transfusion which are associated with clinically significant complications and side effects. Guidelines for treatment of neonatal hyperbilirubinemia in full-term and preterm infants, with and without added complications and/or risk factors, are provided in the attempt of encouraging a more critical approach to neonatal jaundice, which is coherent with the data available in the literature and which should optimize the risk/benefit ratio.
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PMID:[Controversial aspects and rational bases of the treatment in neonatal jaundice]. 158 31

We have studied the entry of 3H-bilirubin and 125I-albumin into brain regions in young rats during short-term (1 h) hyperbilirubinemia. Bilirubin enters the brain both under control, displacer (sulfisoxazole 50 mg/kg), hypercarbic (PCO2 18-21 kPa; pH approximately 6.9), and hyperosmolar (serum osmolality approximately 400 mosm/l) conditions. No significant differences in bilirubin uptake were found between brain regions. Thus preferential staining of basal ganglia ('kernicterus') may not be a phenomenon related to uptake. Albumin does not cross the blood-brain barrier under control or displacer conditions, but does enter the brain to some extent in hypercarbia, and to a greater extent in hyperosmolality. During control and displacer conditions, only unbound bilirubin appears to enter the brain. In hypercarbia bilirubin enters primarily in the unbound form, but some is also albumin-bound. In hyperosmolality a significant fraction of the bilirubin entering the brain is albumin-bound.
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PMID:Effects of sulfisoxazole, hypercarbia, and hyperosmolality on entry of bilirubin and albumin into brain regions in young rats. 250 67

Despite intensive investigation it remains uncertain how bilirubin enters the brain and how it exerts a toxic effect on neurones. Studies of induced hyperbilirubinemia in animal models in vivo have failed to reproduce bilirubin encephalopathy without additional factors such as hypoxia, asphyxia, hypercapnia, and disruption of the blood-brain barrier. The aim of this study was to investigate, using 31P NMRS, whether hyperbilirubinemia alone or in association with hyperosmolar opening of the blood-brain barrier caused any disturbance of cerebral energy metabolism in vivo. Spectra were acquired using a surface coil positioned over the right cerebral hemisphere of anaesthetized adult rats placed in the bore of a 1.9 Tesla magnet. Hyperbilirubinemia alone at a maximum mean serum concentration of 1063 +/- 175 mumol/L (mean +/- SD, n = 7) caused no apparent disruption in brain energy metabolism. However, in combination with hyperosmolar blood-brain barrier opening a serum bilirubin concentration of 483 +/- 52 mumol/L (mean +/- SD, n = 9) was associated with a reduction in PCr/(PCr + Pi) ratio from 0.68 +/- 0.06 to 0.44 +/- 0.14 (mean +/- SD, p less than 0.001). A significant correlation was demonstrated between cerebral hemisphere bilirubin content and the reduction in PCr/(PCr + Pi) (r = 0.84, n = 9, p less than 0.01). These results demonstrate in vivo a disruptive effect of bilirubin on cerebral energy metabolism in the presence of an open BBB. This mode of entry and mechanism of toxicity may be factors in the pathophysiology of bilirubin encephalopathy in the newborn infant.
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PMID:The effects of bilirubin on brain energy metabolism during hyperosmolar opening of the blood-brain barrier: an in vivo study using 31P nuclear magnetic resonance spectroscopy. 279 49

The aim of this study was to investigate (i) whether bilirubin encephalopathy with lasting sequelae could be created in a rat model, and (ii) putative differences in brain toxicity between bound and unbound bilirubin. Hyperbilirubinemia was produced by infusing bilirubin 20 mg/kg/h during 3 h into 6-week-old male Sprague-Dawley rats. In addition to the hyperbilirubinemia, different groups were created by exposing the rats to hyperosmolality, hypercarbia, and sulfisoxazole. Three weeks after the infusion the rats were studied in an open-field apparatus during 10 daily sessions of 15 min duration. A data collection program was used to study the following measures of activity: crossings in cage, peeks, rearing, latency to enter field, crossings in middle and in outer field, and time outside cage. The data were subjected to multivariate analyses of variance (MANOVA). Generally, the level of activity was higher in the bilirubin-treated rats as compared to the control animals. The difference in activity between bilirubin-treated and control rats changed systematically both between and within sessions. The data show that both unbound and albumin-bound bilirubin are neurotoxic, but they indicate a more pronounced effect of unbound bilirubin. The sequelae of bilirubin brain toxicity appear to include changes in stimulus processing. This is compatible with findings from neuropsychological tests of children who have had significant neonatal hyperbilirubinemia.
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PMID:Open-field behavior of rats previously subjected to short-term hyperbilirubinemia with or without blood-brain barrier manipulations. 369 Mar 1

The effect of metabolic and respiratory acidosis on bilirubin and albumin entry into the brain was studied in 24 awake and unanesthetized rats. Hyperbilirubinemia was established by infusion of unconjugated bilirubin at a rate of 30 mg/kg/h for three hours. After two hours, metabolic acidosis was produced in eight rats by infusion of 0.5 N hydrochloric acid at a rate of 0.02 mL/g/h. This reduced the pH level to 7.03 +/- 0.01 (mean +/- SEM) with a normal value for PCO2. Respiratory acidosis was produced in another group of eight animals who breathed 20% CO2 in a balanced gas mixture for the last hour of the study period. This resulted in a reduction of pH to 7.04 +/- 0.01 with PCO2 of 100.4 +/- 2.3 mm Hg. A third group of eight rats served as controls and were given equal volumes of saline infusion. No increase in brain bilirubin or brain albumin was found in the group with metabolic acidosis, but in the group with respiratory acidosis both bilirubin and albumin concentrations in the brain increased significantly. No significant differences were found between the groups in serum total or apparent unbound bilirubin, albumin, or osmolality. The results indicate that a brief period of acidosis per se does not increase bilirubin entry into the brain, but hypercarbia does so by opening of the blood-brain barrier.
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PMID:Effect of acidosis on bilirubin deposition in rat brain. 670 23

In recent years kernicterus at autopsy has been observed in sick premature infants in the absence of markedly elevated levels of serum bilirubin. Potentiating factors have been suggested to explain kernicterus in such a setting. In order to establish which factors are associated with increased risk for kernicterus in these small babies, this retrospective matched control study was undertaken. Thirty-two infants with kernicterus at autopsy were matched for gestational age, birth weight, length of survival, and year of birth to 32 control infants without kernicterus. Multiple historical, clinical, and laboratory factors were compared, including therapy, sepsis, hypothermia, asphyxia as reflected by Apgar score, hematocrit, acidosis, hypercarbia, hypoxia, hypoglycemia, and hyperbilirubinemia. No statistically significant differences between the kernicteric and nonkernicteric infants were demonstrated for any of these factors, including peak total serum bilirubin levels. Multivariant analysis also failed to determine a group of factors associated with increased risk for kernicterus. It was not possible to separate those infants with and without kernicterus at autopsy on the basis of the clinical factors evaluated.
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PMID:Lack of identifiable risk factors for kernicterus. 743 34

Brain bilirubin concentrations are increased by hyperosmolality and hypercarbia, but the mechanism is not known. The same applies to the mechanism for preferential localization of bilirubin to basal ganglia. Young Sprague-Dawley rats were used. Groups were: control (n = 15), hypercarbia (n = 16, pH approximately 6.95), and hyperosmolality (n = 13, serum osmolality approximately 390 mosm/L). Hyperbilirubinemia was induced by a 5-min infusion of 50 mg/kg bilirubin, containing approximately 20 microCi [3H]bilirubin. Rats were killed at 15-min intervals up to 60 min, and the brains were flushed in situ, dissected into seven regions, weighed, and dissolved. Brain bilirubin was determined by scintillation counting. The half-life of bilirubin in brain was calculated by exponential fitting, which also allowed an estimation of brain bilirubin at the end of the bilirubin bolus. The kinetics of bilirubin clearance from brain were first order. The half-life of bilirubin in brain was significantly prolonged in hyperosmolality (38.2 +/- 28.8 min [mean +/- SD]) compared with control (16.1 +/- 7.7 min) and hypercarbia (12.6 +/- 8.6 min) (F = 12.6, p < 0.0001 after log transformation) results. The estimated acute entry of bilirubin into brain was significantly increased in hypercarbia (13.9 +/- 7.4 nmol/g) compared with control (5.6 +/- 2.1 nmol/g) and hyperosmolality (6.5 +/- 2.1 nmol/g) (F = 19.2, p < 0.0001 after log transformation) results. There were no significant differences between brain regions in acute entry or clearance of bilirubin. The kinetics of increased brain bilirubin differ between hypercarbia (increased acute entry) and hyperosmolality (delayed clearance). Preferential localization of bilirubin to basal ganglia is not produced under, and may not be explained by, the conditions investigated.
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PMID:Bilirubin entry into and clearance from rat brain during hypercarbia and hyperosmolality. 882 88