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Biomedical subjects

W J Cashore

Publications and source records attributed to W J Cashore.

53 records · Page 3Linked to original sources

Effects of bilirubin on fat cell metabolism and lipolysis.

Bilirubin (0.45 mM) inhibited lipolysis and stimulated [1-14C]glucose oxidation by rat fat cells in the presence of an equimolar concentration of bovine serum albumin. Bilirubin was an insulinlike agent with respect to inhibition of lipolysis and stimulation of glucose oxidation. There was a marked inhibition of adenylate cyclase activity of fat cell ghosts by 0.001--0.1 mM bilirubin in the absence of albumin, which was largely reversed by the addition of albumin. Although both bilirubin and free fatty acids bind to albumin, the primary binding sites appear to be separate. The effects of bilirubin at a molar ratio to albumin of 2 or less were not influenced by free fatty acid-to-albumin ratios up to 3. Triglyceride lipase activity of partially purified rat fat cell homogenates was inhibited by bilirubin in the presence of an equimolar concentration of bovine albumin. These data indicate that the antilipolytic action of bilirubin is probably due to direct inhibition of triglyceride lipase through a mechanism that does not involve competition with free fatty acids for binding to albumin.

Adenylyl Cyclase Inhibitors↗

Influence of gestational age and clinical status on bilirubin-binding capacity in newborn infants. Sephadex G-25 gel filtration technique.

Total bilirubin-binding capacity was measured by Sephadex G-25 gel filtration in 43 clinically well and 45 clinically ill newborn infants between 26 and 41 weeks' gestation. In the well patients, bilirubin-binding capacity, serum albumin concentration, and the molar-binding ratio of bilirubin to albumin were directly related to gestational age. In the sick patients, serum bilirubin-binding capacity and albumin concentration also correlated with gestational age; however, from 32 to 41 weeks' gestation, the mean values for the sick infants were significantly lower than for the well infants. In the sick infants, the molar binding ratio of bilirubin to albumin was also lower than in the well patients and did not correlate with gestational age. The data are in agreement with previous clinical findings indicating an increased risk for low-bilirubin kernicterus among immature infants and suggest that some critically ill term infants may be at risk for kernicterus at serum bilirubin levels below 20 mg/100 ml.

Bilirubin↗

Effect of postnatal age and clinical status of newborn infants on bilirubin-binding capacity.

Serial determinations of bilirubin-binding capacity were performed in 61 newborn infants during the first 10 days of life. 27 infants were classified as term (gestational age greater than or equal to 36 weeks) and 34 as preterm (gestational age less than or equal to 33 weeks); 34 were classified as 'sick' and 27 as 'well'. Bilirubin-binding capacity was measured by Sephadex gel filtration. In relation to postnatal age, total bilirubin-binding capacity (TBBC) remained stable in well term and preterm infants, decreased slightly in sick preterm infants, and decreased significantly in sick term infants. TBBC, serum albumin, and molr binding ratio (B/A) were significantly higher in well than in sick infants in both term and preterm groups; there were no significant differences between sick term and sick preterm infants. Clinical recovery in 16 infants was associated with a significant rise in TBBC and in B/A. The data suggest that in healthy infants, the serum bilirubin-binding capacity remains relatively unchanged during the first 10 days of life. Clinically ill infants show wide patient-to-patient variability in TBBC. Because of the tendency of TBBC to decrease with postnatal age in sick infants, repeated determinations of TBBC may be indicated for the management of sick jaudiced newborns.

Age Factors↗

The lack of effects of phototherapy on neonatal oxygen dissociation curves and hemoglobin concentration in vivo.

Phototherapy has been shown to cause hemolysis of fetal red cells and a shift to the right in the neonatal oxygen dissociation curve (deltaP50) in vitro. To determine if these parameters act similarly in vivo, we have studied 16 icteric infants before and after phototherapy and compared them with eight control infants studied at birth and at 3 days of age, measuring the change in P50, 2,3-diphosphoglycerate (2,3-DPG), serum bilirubin, the percent of bilirubin/albumin saturation, and the hemoglobin concentration in the two groups. Following phototherapy, in the icteric infants there was a shift to the right in the O2 dissociation curve of + 1.7 mm Hg, a rise in 2,3-DPG of 2.26 micronmol/gm Hb, a fall in serum bilirubin of 4.3 mg/100 ml, a decrease in percent bilirubin/albumin saturation of 12.4%, and a drop in hemoglobin of 1.1 gm/100 ml. The control group showed a deltaP50 of + 2.0 mm Hg, a rise in 2,3-DPG of 3.67 micronmol/gm Hb, an increase in serum bilirubin of 3.2 mg/100 ml, an increase in percent bilirubin/albumin saturation of 9.3%, and a fall in hemoglobin of 0.3 gm/100 ml. Significant differences between the groups were seen only in the changes in bilirubin concentration and percent bilirubin/albumin satruation. The magnitude of changes in P50, 2,3-DPG, and hemoglobin concentration was similar in the phototherapy and control groups and was related to the expected changes with reference to postnatal age. These results suggest that phototherapy in vivo neither affects (fetal erythrocytic affinity for oxygen nor causes hemolysis. Pediatrics, 59:1027-1031, 1977 PHOTOTHERAPY, 2,3-DIPHOSPHOGLYCERATE, HEMOLYSIS, NEWBORN INFANT.

Diphosphoglyceric Acids↗

The inhibition of pulmonary maturation in the fetal rabbit by maternal treatment with phenobarbital.

Phenobarbital was administered to pregnant rabbits, 7 to 10 days before the delivery of their fetuses at 27 to 30 days of gestation. There were no differences in body weight or wet or dry lung weights between control animals and phenobarbital-treated pups at similar gestational ages. The phospholipid content (PLC) of the alevolar wash was lower in the phenobarbital-treated group, but there was no difference in the lung tissue PLC between the treated and control groups. Phenobarbital-treated pups had higher opening pressures and fewer lamellar bodies than the control animals. These data suggest that phenobarbital may have an inhibitory effect on surfactant production and/or release.

Animals↗

Acceleration of fetal lung maturation by aminophyllin in pregnant rabbits.

To test the hypothesis that fetal lung maturation can be accelerated by one of the xanthine derivatives, aminophyllin was given to 40 pregnant rabbits beginning on the 20th gestational day for a period of 7-10 days. The fetuses were delivered by cesarean section and fetal lung maturity was assessed by determining the biochemical, functional, and ultrastructural characteristics of aminophyllin-treated vs. control animals. The phospholipid content of the lung tissue homogenate from the aminophyllin-treated group was significantly higher than in the control subjects (saline injected) at 28 days of gestation (421 +/- 9 vs. 368 +/- 12 mug/mg wet wt, mean +/- SEM) and at 29 days of gestation (531 +/- 10 vs. 475 +/- 20). The alveolar wash phospholipid content of the aminophyllin-treated group was higher at 30 days (167 +/- 9 mug/mg dry wt, mean +/- SEM vs. 117 +/- 17). The lung compliance derived from pressure volume curves was also significantly higher in the aminophyllin-treated group when compared with controls at 27 days of gestation (0.023 +/- 0.0005 ml/cm H2O, mean +/- SEM vs 0.010 +/- 0.0002) and at 28 days of gestation (0.048 +/- 0.0003 vs 0.035 +/- 0.0006). There was no significant difference in the number of lamellar bodies in the type II cells between the aminophyllin-treated and the control groups. The data show that aminophyllin has accelerating effects on fetal lung maturation in rabbits when the drug is given to pregnant rabbits during the last 7-10 days of gestation.

Aminophylline↗

The lack of effect of phototherapy on serum bilirubin-binding capacity in newborn infants.

Using a Sephadex G-25 separation technique, the total bilirubin-binding capacity was measured in 18 jaundiced infants before and after phototherapy. The initial total bilirubin-binding capacity obtained at 20 to 113 hours of age averaged 17.5 +/- 4.4 mg/dl (mean +/- SD) and was unchanged during phototherapy at 34 to 135 hours of age. In ten infants, the total bilirubin-binding capacity was measured before, during, and 24 hours after the cessation of phototherapy. Here too, phototherapy did not significantly influence the TBBC. These data indicate that in vivo, phototherapy does not alter the serum bilirubin binding capacity of newborn infants.

Bilirubin↗

Nutritional supplements with intravenously administered lipid, protein hydrolysate, and glucose in small premature infants.

Nutritional support with intravenously administered fat, protein hydrolysate, and glucose was given to 23 premature infants weighing less than 1,500 gm at birth. Growth in the 19 survivors approximated intrauterine growth rates in all dimensions. Complications included sodium imbalance and transient intolerance of the smallest and sickest infants to all components: carbohydrate, protein, fat, and even water. Autopsies in four patients who died did not reveal any untoward findings clearly related to the use of intravenously given lipids. Intravenously given fat has a potentially useful role in the nutritional support of small premature infants.

Animals↗

Pseudomembranous colitis in a preterm neonate.

This preterm female infant abruptly developed diarrhea and bowel distention at 25 days of age and died within 60 h with fulminating pseudomembranous colitis and proctitis. Toxin-producing C. difficile was recovered from the stool. The pseudomembranous colitis developed 12 days after the last dose of ampicillin was given to the baby. Necrotizing enterocolitis, a condition pathologically distinct from pseudomembranous colitis, was also present.

Ampicillin↗