Fusidic acid binding to serum albumin and interaction with binding of bilirubin

Sodium fusidate, an antibiotic used in staphylococcal infections, is strongly bound to human serum albumin, competitively with bilirubin. It is given in molar amounts sufficient to occupy a considerable fraction of circulating albumin. In order to avoid a risk of bilirubin encephalopathy, induced by displacement of bilirubin, fusidate should be given with caution to newborn infants, particularly if patients are prematurely born, icteric or acidotic. Fusidate does not interfere with albumin binding of warfarin or diazepam.     

Wavelength dependence of the geometric and structural photoisomerization of bilirubin bound to human serum albumin

The two quantitatively important photoisomers in bilirubin metabolism during phototherapy are (ZE)-bilirubin and (EZ)-cyclobilirubin. We describe in vitro studies on the wavelength dependence for the geometric (delta 4Z, delta 15Z----delta 4Z, delta 15E) and structural (endovinyl cyclization) photoisomerization of bilirubin bound to human serum albumin by a high performance liquid chromatography method. For the geometric photoisomerization from (ZZ)-bilirubin to (ZE)-bilirubin, the most effective wavelength in vitro was 410 nm. For the structural photoisomerization, green light at 510 nm is the most efficient for causing cyclization of (ZZ)-bilirubin to (EZ)-cyclobilirubin via (EZ)-bilirubin and this may depend on a larger cross-section of (EZ)-bilirubin than (ZZ)-bilirubin in this spectral region and/or on a larger quantum yield for cyclization than geometric photoisomerization.     

Increase in bilirubin binding to albumin with correction of neonatal acidosis.

Twenty-six serial measurements of free bilirubin concentration and apparent association constant of bilirubin for albumin (Ka) at a bilirubin: albumin molar ratio of 0.8 were performed and compared with baseline values in 11 newborn infants with acidosis before treatment and during recovery from acidosis. When arterial pH was corrected from 7.12 +/- 0.02 (Mean +/- S.EM.) to 7.34 +/- 0.02, there was a significant decrease in serum free bilirubin concentration and a significant increase in the Ka at molar ratio 0.8. The data offer in vivo evidence that correction of acidosis in the neonate results in an improvement of the apparent bilirubin binding affinity of albumin.     

Relationship of serum bilirubin levels and hearing impairment in newborn infants

A comparison has been made between 39 infants with a birthweight of 1500 g or less and a bilirubinlevel of 240 mumol/l or above, born between January 1980 and December 1983 and 19 infants with the same criteria, born between January 1984 and December 1985. Eight of the 22 high risk and two of the 17 low risk infants were diagnosed to have sensorineural deafness (SND) during the first period and this was strongly associated with the duration of the hyperbilirubinaemia. During the second period, more active intervention for hyperbilirubinaemia led to an increased number of exchange transfusions and a marked drop in the mean duration of hyperbilirubinaemia (less than 240 mumol/l). None of the very low birth weight (VLBW) infants born in the second period have developed SND. To investigate the independent effect of hyperbilirubinaemia on hearing, six low risk infants with bilirubin levels less than 320 mumol/l were studied by serial auditory brainstem responses (ABR). Impairment of the ABRs was found in four infants, with further deterioration with the persistence of high bilirubin levels in two. Although recovery of hearing thresholds was noted in all infants with impaired ABRs, an absence of wave I was noted in three infants at 6 months of age, which could indicate damage to the auditory nerve-cochlear complex. These findings suggest that hyperbilirubinaemia in itself can have an adverse effect on hearing and that careful management of hyperbilirubinaemia may reduce the incidence of sensorineural deafness.     

Reduced albumin binding of MADDS--a measure for bilirubin binding--in sick children

The reserve albumin concentration for binding of MADDS (monoacetyldiaminodiphenyl sulphone) in plasma is used as a measure of the reserve albumin concentration for binding of unconjugated bilirubin. The aim of the present study was to investigate whether a reduction in the reserve albumin concentration for binding of MADDS could exist in sick children after 5 months of age, where the bilirubin binding properties of the albumin has reached the adult level. The material included 75 children, 1-15 years of age with mild infections, severe bacterial infections, acute viral hepatitis, chronic hepatic diseases or uraemia, and a control group of 22 healthy children. The reserve albumin concentration was significantly lower in children with severe bacterial infections, acute viral hepatitis, and uraemia, than in healthy children (p less than 0.01), while the reserve albumin concentration in children with mild infections and chronic hepatic diseases did not differ significantly from that of the control group (p greater than 0.05). The total albumin concentration in plasma in either of the groups of sick children did not differ significantly from that of the healthy children. The plasma concentration of unconjugated bilirubin was elevated in the group of children with acute viral hepatitis, but not enough to influence the concentration of reserve albumin for binding of MADDS to a significant degree. The reserve albumin concentration was significantly lower in children with acute viral hepatitis than in children with severe bacterial infections (p less than 0.05).     

Albumin binding properties in relation to bilirubin and albumin concentrations during the first week of life

In 19 non-jaundiced and 22 jaundiced neonates, the serum albumin and bilirubin concentrations were measured during the first week of life. Some of the neonates were followed longitudinally. The albumin binding properties were evaluated by determining the reserve albumin concentration for monoacetyldiaminodiphenyl sulphone (MADDS), a deputy ligand for bilirubin. The reserve albumin concentration for MADDS increased with postnatal age. The reason for this increase is still unexplained. There was an inverse relation between the bilirubin and the reserve albumin concentrations, but when the bilirubin concentration increased by 1 mumol/l, the reserve albumin concentration for MADDS decreased by only 0.2 mumol/l. This shows that the reserve albumin concentration for MADDS does not give a direct measure of the bilirubin binding ability of the serum albumin molecule. In spite of this, it is still possible that a low reserve albumin concentration for MADDS is a risk factor for bilirubin encephalopathy.     

Normal serum bilirubin levels in the newborn and the effect of breast-feeding

We measured the serum bilirubin concentrations in 2,416 consecutive infants admitted to our well-baby nursery. The maximum serum bilirubin concentration exceeded 12.9 mg/dL (221 mumol/L) in 147 infants (6.1%), and these infants were compared with 147 randomly selected control infants with maximum serum bilirubin levels less than or equal to 12.9 mg/dL. In 66 infants (44.9%), we identified an apparent cause for the jaundice, but in 81 (55%), no cause was found. Of infants for whom no cause for hyperbilirubinemia was found, 82.7% were breast-fed v 46.9% in the control group (P less than .0001). Breast-feeding was significantly associated with hyperbilirubinemia, even in the first three days of life. The 95th percentile for bottle-fed infants is a serum bilirubin level of 11.4 mg/dL v 14.5 mg/dL for the breast-fed population, and the 97th percentiles are 12.4 and 14.8 mg/dL, respectively. Of the formula-fed infants, 2.24% had serum bilirubin levels greater than 12.9 mg/dL v 8.97% of breast-fed infants (P less than .000001). When compared with previous large studies, the incidence of "readily visible" jaundice (serum bilirubin level greater than 8 mg/dL) appears to be increasing. The dramatic increase in breast-feeding in the United States in the last 25 years may explain this observation. There is a strong association between breast-feeding and jaundice in the healthy newborn infant. Investigations for the cause of hyperbilirubinemia in healthy breast-fed infants may not be indicated unless the serum bilirubin level exceeds approximately 15 mg/dL, whereas in the bottle-fed infant, such investigations may be indicated if the serum bilirubin exceeds approximately 12 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)