Helen McNamara

Intestinal osmolality and carbohydrate absorption in rats treated with polymerized glucose

The effect of passive antibody (p.a.) on the antibody response to ingested Bovine Seriun Albumin (USA) was compared to intravenous (i.v.) and subcutaneous (s.c.) immunization. Antibody to BSA was measured by the Farr-technique and quantitatively expressed as μg BSA-N binding capacity/ml of serum (ABC 33). 18 rabbits, passively imunized to BSA fron a pool of high titered antiserum had a mean ABC 33 of 17.2. Four of these animals received no antigen (group I), 5 were fed 0.156 BSA in witer (gr. II), and 3 received 5 rag BSA s.c. (gr. III); 50 mg BSA was given i.v. to 3 aniraala (gr. IV) and 20 ag BSA i.v. to another 3 (gr. V). Control animals for groups II - V were actively immunized in the same way without prior administration of p.a. Catabolism of p.a. was similar in groups I and II (mean ABC 33 on day 25: gr: I 1.4 ± 0.5, gr. II 0.9 ± 0.5). Subsequently, serum anti-BSA in gr. II increased to 6,6 ± 5.7 on day 63 (control 3.6 ± 2.2, p> 0.05). In gr. III, mean ABC 33 was lowest on day 14 (2.2 ± 1.4) and increased to 51.7 ± 21.7 (control 9.4 ± 8.4, p<0.02). In gr. IV mean ABC 33 increased from day 7 (0.4 ± 0.7) to 3.1 ± 2.8 (control 0.3 ± C.5, P<0.05). No active immunity developed in gr. V (control 0.17 ± 0.21). Confirming previous data, p.a. enhanced or suppressed parenteral immunization depending on routes of immunization and antigen/antibody ratios. In contrast, p.a. did not influence oral immunization and its catabolism was not affected by the ingested antigen.Summary: The intestinal osmolal physiology and absorption of comparable preparations of polymerized glucose and glucose were evaluated in isolated segments of rat duodenum. The acute rise in the osmolality of the succus entericus after 5% polymer injections (298 mOsm/kg at 3 min, 311 mOsm/kg at 30 min) was significantly less than that noted after 5% glucose (387 mOsm/kg at 3 min, 351 mOsm/kg at 30 min). At 60 min a steady state had been established and no significant difference was found. Ten percent polymer was superior to 10% glucose as it also produced a lower luminal osmolality (351 mOsm/kg versus 427 mOsm/kg at 30 min). Luminal polyethylene glycol concentrations revealed comparable increases in intraluminal water content after 10% polymer and 5% glucose (22% versus 25% at 30 min). After polymer injections, 4 times as much glucose was present in the mucosa as in the succus, whereas, after 5% glucose injections, a high concentration of glucose remained in the succus.These results indicate that polymer solutions produce lower luminal osmolality than glucose solutions of similar weight. Additionally, enhanced glucose absorption by the mucosal cell is suggested in animals injected with polymer. Polymerized glucose should, therefore, provide twice the calories of glucose without a disparate increase in the intestinal osmolality and intraluminal diffusion of extracellular water.Speculation: A polymerized glucose preparation, when administered orally, produces a lower immediate intraluminal solute content and osmolality than a glucose solution of the same concentration by weight when each has comparable electrolytes. Hydrolysis of the polymer within the intestinal lumen and on contact with the brush border of the intestine provides nutrient without increase in water movement into the proximal small bowel. Because of these properties, such a polymer may be useful in the oral nutritional rehabilitation of neonates and infants with diarrhea. It remains to be seen whether the pathogenesis of the diarrheal state may also prove to be of significance in determining the beneficial effect of this therapy.

Effect of lead exposure on the activity of some hepatic enzymes in the rat.

Summary: Seven-day-old rats were fed 1% lead acetate tetrahydrate solution for 2,4, or 7 days. Adult rats were fed the same lead solution for 6–8 wk. In the newborn rats, hepatic UDP-bilirubin glucuronyl transferase (GT) and gamma glutamyl transpeptidase (GGTP) activities were markedly increased. GT activity was increased after 4 days as compared to the controls (6.3 ± 0.3 vs. 4.3 ± 0.3, P < 0.001), and was maximal after 7 days of treatment (7.5 ± 0.4 vs. 4.6 ± 0.4, P < 0.001). GGTP activity was already maximally increased after 2 days of lead treatment (1.4 ± 0.2 vs. 0.4 ± 0.1, P < 0.001). Hepatic GT and GGTP activities were similarly increased in adult rats (7.9 ± 0.3 vs. 5.1 ± 0.1, P < 0.001, and 0.7 ± 0.1 vs. 0.4 ± 0.1, P < 0.005, respectively). In vitro studies adding lead citrate to liver homogenates did not produce any direct effect on GT and GGTP activities.Speculation: The increase in hepatic GT and GGTP activities in lead treated animals appears to be a response to lead induced cellular damage or may result from interference with regulatory mechanisms responsible for production of these enzymes and not related to hepatic enzyme induction. The hepatic metabolism of drugs ingested by children with an increased lead burden may, therefore, be significantly altered.

EFFECTS OF PHOTOTHERAPY ON INTESTINAL DISACCHARIDASE ACTIVITY IN THE RAT

Diarrhea occurs in some newborns undergoing phototherapy for hyperbilirubinemia presumably due to decreased intestinal lactase activity. Such an effect may result directly from photo-energy or photo-oxidative products on the enzyme. To study the mechanism of this diarrheal state, a congenitally jaundiced homozygote Gunn rat (jj) and a non-icteric heterozygote litter mate (Jj) were used. Both jj and Jj adult rats were shaved of hair, treated with phototherapy for 48 hours, sacrificed, and the activity of lactase and sucrase determined in intestinal mucosal scrappings. In 5 therapy treated jj rats, lactase and sucrase activities were 2.1 and 14.1 umol/g/min respectively, compared to 4.7 and 24.0 in 5 untreated jj controls (p < .05 lactase, and p < .001 sucrase). There were no significant changes in disaccharidase activities in a group of 13 similarly treated Jj rats. A stable mucosal peptidase, GGTP, was unaffected in jj and Jj phototherapy treated rats. Bile collected from a treated jj rat had no effect on disaccharidase activities when incubated with mucosa in vitro. Incubation of mucosa with serum from a treated jj rat similarly had no effect on disaccharidase activities. The in vivo decrease in disaccharidase activities in phototherapy treated jaundiced rats (jj) but not in their anicteric litter mates (Jj) suggests that the photo-oxidative products and not direct light-energy alters disaccharidase activities. The mechanism for inhibition remains unknown.

The effect of phototherapy on intestinal mucosal enzyme activity in the Gunn rat.

Infants undergoing phototherapy may develop loose stools. Acquired lactase deficiency secondary to this treatment modality was suggested as a cause for the diarrhea. The effects of light energy directly on intestinal enzymes and indirectly through bilirubin photooxidation products were studied. Adult homozygote and heterozygote Gunn rats were treated with light for varying periods while littermate controls were kept in the dark. Intestinal lactase, sucrase and GGTP activities and serum bilirubin concentrations were determined. Jaundiced and non-jaundiced 1-week-old suckling Gunn rats were treated with light for 96 h, and intestinal lactase activity determined. No decreases in lactase, sucrase or GGTP activities were observed suggesting the reported diarrheal states following phototherapy are not related to light energy or photooxidation products.

Effect of Na benzoate on serum bilirubin in the Gunn rat

That Na benzoate will displace bilirubin from albumin has been demonstrated in vitro; however, bilirubin-albumin kinetics may not be altered in vivo by Na benzoate because of its rapid conversion to Na hippurate. Of particular concern is whether the available injectable diazepam, which contains Na benzoate in its liquid vehicle, is safe to administer to newborns for such conditions as seizures or narcotics withdrawal. The Gunn rat was used as an experimental model for the displacement of bilirubin from albumin by serially measuring the fall in serum bilirubin following I.P. or I.M. administration of Na benzoate. Control animals were injected with saline. 26 animals were given 7 or 35mgs/kg of Na benzoate (equivalent to 2 or 10mg diazepam in a 3kg infant) as a single injection and 7 rats were given the same doses repeated 2 times at 1 hour intervals Serum bilirubin was determined at 10, 20 and 60 minutes after injection. No differences were found in mean bilirubin levels between control and treated rats. With repeated benzoate injections of 35mg/kg or a single dose of 100mg/kg some depression of serum bilirubin occurred; but only at 200mg/kg did bilirubin levels fall to the extent observed in the Gunn rat with similar doses of sulfasoxazole. These data suggest that recommended doses of diazepam for neonates do not contain sufficient Na benzoate to alter bilirubin binding capacities in vivo and thus are safe.