Search PubMed⌕ Search

Biomedical subjects

F J Suchy

Publications and source records attributed to F J Suchy.

83 records · Page 5Linked to original sources
PubMed1982

Uptake of taurocholate by hepatocytes isolated from developing rats.

To further define developmental changes in bile acid metabolism, we determined the kinetics of taurocholate uptake by hepatocytes isolated from Sprague-Dawley rats at 7, 14, 21, 28, and 56 days of age. There was a progressive increase in taurocholate uptake with age. The uptake process exhibited saturable kinetics in every age group with a maximum uptake velocity attained above a taurocholate concentration of 200 microM. There were no differences in Km values but Vmax increased progressively between 7 and 56 days of age. These data suggest that the deficit in hepatic excretory function observed in immature mammals of several species may, in part, be related to decreased transport of bile acids.

Aging↗
PubMed1982

Bile salt metabolism in the first year of life.

Bile salt metabolism was examined in 12 infants (ages 7 weeks to 10 months) who had recovered from protracted infantile diarrhea. Cholic acid kinetics were measured with the isotopic dilution technique. Cholate pool size was 938 +/- 89 mg/m2 (means +/- S.E.), synthetic rate was 478 +/- 52 mg/m2/day, and the fractional turnover rate was 0.537 +/- 0.060 day -1. Estimated chenodeoxycholate pool size was 607 +/- 103 mg/m2. similar cholic acid pool sizes were previously observed in older children; however, the synthetic and turnover rates were significantly lower, p less than 0.05 and 0.025, respectively. A significant inverse relationship between age and fractional turnover rate (r = -0.577, p less than 0.05) was observed in the first 10 months of life. Fasting serum cholylglycine measured by radioimmunoassay was significantly higher (p less than 0.01) in infants than in children. Peak postprandial concentrations were higher in infants than in older children. Accelerated hepatic bile salt synthesis rapidly increases the size of small pools at birth. Intraluminal bile salt concentrations concurrently increase, thereby normalizing fat solubilzation. Slow maturation of intestinal transport mechanisms may result in normal cycling of bile salts by 3 to 7 months of age. Persistent immaturity of hepatic uptake and/or excretion of bile salts leads to intrahepatic retention of a portion of the pool, with resultant regurgitation into the serum during the first months of life.

Adult↗
PubMed1981

Pathologic versus physiologic cholestasis: elevated serum concentration of a secondary bile acid in the presence of hepatobiliary disease.

Serum levels of the primary bile acids cholic and chenodeoxycholic acid are transiently elevated in normal neonates and infants; this represents a state of "physiologic cholestasis." In this study we determined, using specific radioimmunoassay, the concentration of a secondary bile acid, sulfated lithocholate, in serum obtained from healthy infants and from those with various hepatobiliary diseases. The serum levels of sulfated lithocholate were low in 69 neonates (less than 5 days of age: mean +/- SEM = 0.45 +/- 0.05 mumoles/L) and in 78 normal infants (less than one year of age: 0.49 +/- 0.02); there was no postprandial rise. These values were similar to those seen in 95 older children (0.56 +/- 0.03) and in maternal (0.49 +/- 0.04) and cord blood (0.44 +/- 0.03) of the neonates. In contrast, in patients with neonatal cholestasis of any nature there was a consistent marked rise in serum concentrations of sulfated lithocholate (mean = 4.46 +/- 0.39, P less than 0.001). In infants monitored during the course of parenteral nutrition, elevated values of sulfated lithocholate often occurred in the presence of normal results of other liver function tests. Serum sulfated lithocholate concentration is an accurate index of neonatal hepatobiliary disease; the sensitivity and specificity of this test remain to be further defined.

Biliary Tract Diseases↗
PubMed1981

Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants.

Immaturity of hepatic excretory function resulting in a period of "physiologic cholestasis" may occur during early life. Serum bile acids should accurately reflect maturation of the enterohepatic circulation; we therefore determined serum concentrations of the primary bile acids in normal infants to define age-related changes. There was a striking rise in serum cholylglycine and conjugates of chenodeoxycholate during the first few days of life over levels detected in cord sera; the values attained were significantly greater than maximal postprandial concentrations found in children over 1 yr of age (p less than 0.01). There was a gradual decline in bile acid concentration; however cholylglycine remained higher than the postprandial values of older children until 4 mo and chenodeoxycholate until 6 mo of age. In 12 infants a liquid feeding stimulated a greater maximal postprandial cholylglycine concentration and integrated area under the meal curve than that achieved in children (p less than 0.01). There was no difference in the postprandial response in chenodeoxycholate in these infants compared with the older subjects. We conclude that serum bile acids are elevated in normal infants and that the subsequent decline to levels of the child and adult demonstrates the evolving maturation of liver function during infancy.

Age Factors↗
PubMed1980

Serum bile acid response to a test meal stimulus: a sensitive test of ileal function.

We assessed ileal functional integrity, as reflected in the capacity to reabsorb the bile acid, cholylglycine, by sequential measurement of postprandial serum levels of this compound. A consistent increase in cholylglycine concentration (mean +/- SEM, peak above fasting baseline = 1.86 +/- 0.14 microM) occurred in eight normal children. Five patients with ileal resection and two with primary bile acid malabsorption had a minimal postprandial increase (0.27 +/- 0.08 microM; P less than 0.005 vs controls) and excess bile acid loss in feces. Similarly, in seven patients with Crohn disease involving the ileum the postprandial increase (0.38 +/- 0.06) was less than controls (P less than 0.001). In eight patients with cystic fibrosis, the administration of pancreatic enzymes normalized the blunted response demonstrated when enzymatic therapy was interrupted suggesting an intact ileal active transport mechanism. Meal-stimulated response of serum cholylglycine concentration is a sensitive indicator of altered ileal integrity and bile acid malabsorption due to ileal resection, inflammation, or dysfunction.

Adolescent↗
PubMed1980

Enterohepatic circulation of bile acids in infants and children with ileal resection.

Seven children who had undergone ileal resection of varying lengths as neonates were studied to determine later gastrointestinal function with specific emphasis on the enterohepatic circulation of bile acids. Fecal homogenate and aqueous supernatant bile acid concentrations and serum bile acids were analyzed. Cholic acid kinetics were measured by the isotopic dilution technique, with multiple duodenal bile samples obtained within 48 hr after intravenous 14C--cholic acid. As compared to those of age-matched controls, significantly increased fecal homogenate bile acid concentrations (p less than 0.05) and fecal aqueous supernatant bile acid concentrations (p less than 0.01) were present. Fasting and postcibal serum bile acid concentrations were significantly reduced (p less than 0.001). Increased FTRs for cholic acid (p less than 0.001) were present in children with resection. The FTR correlated significantly with resection length (p = 0.012). Fasting pool sizes of chenodeoxycholic and cholic acid measured after an overnight fast were variable. Three children had significantly reduced cholic acid and chenodeoxycholic acid pools, and one had a reduction in the cholic acid pool only. The cholic acid pool size correlated directly with the postprandial rise in serum CG concentration (p = 0.003). The fecal coefficient of fat excretion and fecal weights were only moderately increased. Although rapid turnover of bile acids was present following neonatal ileal resection, efficient compensatory mechanisms during infancy and childhood allowed adequate intraluminal bile salt concentrations for normal fat solubilization throughout the day and resultant mild steatorrhea and diarrhea in our study patients.

Bile Acids and Salts↗
PubMedDate not supplied

Physiologic cholestasis II: serum bile acid levels reflect the development of the enterohepatic circulation in rats.

We have shown that serum bile acid concentrations are elevated in human infants reflecting physiologic immaturity of the enterohepatic circulation. To define further the ontogeny of bile acid metabolism in mammals, we examined maturational changes in the serum concentration of total cholate conjugates by radioimmunoassay in fetal, neonatal, suckling, and mature Sprague-Dawley rats. Fetal (21st day) levels were low (1.4 +/- 0.23 microM; X +/- S.E.), possibly due to minimal enterohepatic cycling in utero. The concentrations in samples obtained minutes after birth, prior to suckling were significantly elevated (12.6 +/- 2.37; p less than 0.001 vs. fetal); these high values persisted after feeding was initiated (6 hr = 13.5 +/- 0.99), but fell at 12 hr (5.2 +/- 0.81) and remained unchanged for the duration of the first day. Serum values fluctuated briefly, being 9.6 +/- 0.73 on Day 4, and the rose progressively through the suckling period (Day 10 = 7.2 +/- 9.57; Day 14 = 10.4 +/- 1.70; Day 21 = 16.8 +/- 1.93); there was a dramatic peak after weaning (Day 28 = 21.8 +/- 1.53). The serum concentration of cholate conjugates then fell (5.6 +/- 0.68 on Day 42) to achieve adult levels by 56 days (4.0 +/- 0.55), a value substantially different from that of all developing animals (p less than 0.025). These data corroborate studies which suggest that a period of physiologic cholestasis occurs in the developing rat. Serum cholate conjugate concentrations likely reflect interrelated morphologic alterations (bile canalicular structure and portal blood flow) and physiologic changes (bile acid synthesis, pool size, and transport) occurring in the enterohepatic circulation during early life.

Age Factors↗