D. Grant Gall

POSTNATAL MATURATION OF HEPATIC BILE FORMATION IN THE RABBIT

The ontogenesis of hepatic bile formation was studied in 4 groups of rabbits:suckling infants at ages 10-14, 18-22, and 26-30 days, and adults. Bile was collected directly from the common duct during three 1 h periods: a basal period followed by adding 1 and then 2 μmol/min/kg of glycodeoxycholic acid. 14C-erythritol and 3H-inulin clearances assessed canalicular bile flow and membrane permeability,respectively.Bile flow and bile salt secretion were significantly (p<.001) less in 10-14 d infants and progressively increased with increasing age.Bile flow was linearly related to bile salt secretion.Bile salt-dependent flow,the increment in flow per mass bile salt secreted(μl/μmol), was greater (p<.01) in the two youngest groups,10-14 d (80) and 17-22 d (70) compared to the adult (50) and 25-30 d (44) rabbits.The chloride:bile salt ratio was also higher in the two youngest groups.Bile salt-independent flow at theoretic zero bile salt secretion was absent in the younger groups, but evident in the adult and 25-30 d rabbits. Canalicular flow estimated by erythritol clearance was linearly (p<.01) related to bile salt secretion.Inulin clearance relative to erythritol clearance was higher in 10-14 d infants than adults.Thus, bile flow and bile salt secretion are reduced in young adults, but rise to near adult levels at the time of weaning,25-30 d. The increase in flow results from increased bile salt secretion and the appearance of bile salt-independent flow.In the young, increased biliary permeability maintains bile flow and chloride output despite increased bile salt secretion.

Acute liver disease and encephalopathy mimicking Reye syndrome. A report of three cases.

Three patients are described whose clinical presentation suggested Reye syndrome, and in whom the initial laboratory investigations supported the diagnosis. The subsequent clinical and biochemical evolution of the illness differed from that of Reye syndrome. The liver biopsy of each patient revealed changes in centrilobular hepatocytes rather than the diffuse small droplet fatty change characteristic of Reye syndrome. In each of them normal liver functions were regained. The findings in these patients suggest that a firm diagnosis of Reye syndrome cannot be made without histologic examination of the liver.

Sodium ion transport in isolated intestinal epithelial cells. The effect of actively transported sugars on sodium ion efflux

Abstract A technique to measure Na+ efflux from isolated intestinal epithelial cells has permitted us to examine the mechanisms responsible for Na+ transport in absorptive cells without contamination by other cell types. We examined the effect of actively transported sugars on Na+ efflux from isolated rat jejunal epithelial cells to evaluate the mechanism by which actively transported non-electrolytes stimulate Na+ absorption. Glucose, galactose and 3-O- methylglucose , sugars known to be actively transported by the small intestine, stimulate total Na+ efflux from isolated epithelial cells. This stimulation results from an increase of active Na+ transport, since it is inhibited by ouabain. Glucose stimulation is significantly greater than that produced by galactose or 3-O- methylglucose , 2-Deoxyglucose, a sugar that is not actively transported, has no effect on total Na+ efflux from isolated cells. Phloridzin, which has no effect on Na+ efflux in a sugar-free medium, completely abolishes the effect of galactose. These findings (a) support the hypothesis that the increase in intestinal absorption of Na+ in the presence of actively transported non-electrolytes occurs by a transcellular route; and (b) are consistent with the ion-gradient model. The results are not compatible with the direct energy-coupling model.

Recent Developments in Viral Gastroenteritis

In recent years impressive advances have been made in understanding viral gastroenteritis. A specific causative agent has been identified in infants and young children, and studies of a similar but distinct enteritis in piglets have given new insight into the pathogenesis of viral diarrhea. This article discusses these recent findings in veterinary and human medicine.

Protein intolerance and immunocyte and enterocyte interaction.

Food allergy is an untoward immunologic reaction to food. The number of conditions that need to be considered in the differential diagnosis is large and includes adverse reactions to foods that do not have an immunologic basis. Intestinal immune elements are an integral feature of the intestinal mucosa and, besides modulating gastrointestinal function, represent a significant part of the hosts overall immune system. Despite increasing knowledge, the precise disturbances in immune function that lead to the appearance of food allergy are still unclear. Food allergy will remain primarily a clinical diagnosis, relying on history and response to dietary elimination and rechallenge until more specific tests become available.

Effects of Chronic Protein-Calorie Malnutrition on Small Intestinal Repair after an Acute Bacterial Enteritis: A Study in Infant Rabbits

ABSTRACT: The aim of this study was to determine if recovery of intestinal function in infant rabbits subjected to protein-calorie malnutrition was delayed as a result of inflammatory injury induced by an experimental bacterial enteritis. Rabbits were malnourished by expanding litter size at 7 days of age and infecting undernourished animals and dietary controls with Yersinia enterocolitica at either 17 or 21 days of age. Intestinal morphology and function were evaluated in infected and noninfected animals from both dietary groups at 27 days of age. Undernutrition alone significantly reduced animal weight, small intestinal weight, segmental jejunal and ileal mucosal weight, villus height, crypt depth, disaccharidase activities, mucosal protein and DNA contents, but increased ileal short-circuited glucose-stimulated Na+ absorption compared to controls. The jejunum of undernourished rabbits at 6 days postin-fection exhibited an intestinal injury, as evidenced by a miJd inflammatory infiltrate and further reductions in villus height, mucosal weight, lactase activity, protein and DNA content, not seen in infected dietary controls. Jejunal recovery was complete by 10 days postinfection. In the ileum of infected animals of both dietary groups at 6 days post-infection, a severe inflammatory response, decreased villus height, elongated crypts, and depressed stimulation of Na+ absorption by glucose was observed. By 10 days after infection, while recovery was nearly complete in dietary controls, intestinal damage persisted in the undernourished rabbits, as evidenced by absent glucose-stimulated Na+ absorption, continued severe inflammation and microabscess formation. We conclude that intestinal injury is more severe and chronic in the undernourished, compared to dietary control infant rabbits subjected to an acute bacterial enteritis.ABSTRACT: The aim of this study was to determine if recovery of intestinal function in infant rabbits subjected to protein-calorie malnutrition was delayed as a result of inflammatory injury induced by an experimental bacterial enteritis. Rabbits were malnourished by expanding litter size at 7 days of age and infecting undernourished animals and dietary controls with Yersinia enterocolitica at either 17 or 21 days of age. Intestinal morphology and function were evaluated in infected and noninfected animals from both dietary groups at 27 days of age. Undernutrition alone significantly reduced animal weight, small intestinal weight, segmental jejunal and ileal mucosal weight, villus height, crypt depth, disaccharidase activities, mucosal protein and DNA contents, but increased ileal short-circuited glucose-stimulated Na+ absorption compared to controls. The jejunum of undernourished rabbits at 6 days postin-fection exhibited an intestinal injury, as evidenced by a miJd inflammatory infiltrate and further reductions in villus height, mucosal weight, lactase activity, protein and DNA content, not seen in infected dietary controls. Jejunal recovery was complete by 10 days postinfection. In the ileum of infected animals of both dietary groups at 6 days post-infection, a severe inflammatory response, decreased villus height, elongated crypts, and depressed stimulation of Na+ absorption by glucose was observed. By 10 days after infection, while recovery was nearly complete in dietary controls, intestinal damage persisted in the undernourished rabbits, as evidenced by absent glucose-stimulated Na+ absorption, continued severe inflammation and microabscess formation. We conclude that intestinal injury is more severe and chronic in the undernourished, compared to dietary control infant rabbits subjected to an acute bacterial enteritis.

Refeeding Enhances Intestinal Repair during an Acute Enteritis in Infant Rabbits Subjected to Protein-Energy Malnutrition

ABSTRACT: We examined the effects of refeeding during an acute bacterial enteritis on small intestinal repair in infant rabbits subjected to protein-energy malnutrition and in noninfected and infected dietary controls. Malnutrition was induced by litter expansion at 7 d of age. Randomly selected litters from both dietary groups were infected on d 17 with Yersinia enterocolotica. Inflammation and intestinal damage were observed in the jejunum and ileum at the “acute stage‘’ of infection in 23-d-old animals from both dietary groups, as evidenced by an inflammatory infiltrate, blunted villi, and reduced disaccharidase activities. In addition, ileal glucose-stimulated Na+ absorption was depressed. On d 24, a 7-d period of ad libitum refeeding of breast milk and rabbit feed was initiated in randomly selected litters of infected-malnourished animals and all dietary controls. Mucosal repair was nearly complete at 31 d of age in infected dietary controls and in the infected-malnourished animals that were refed, as demonstrated by the recovery of segmental mucosal mass and ileal glucose-stimulated Na+ transport in association with the resolution of inflammation and diarrhea. Only mucosal disaccharidase activities remain depressed. In contrast, in 31-d-old infected-malnourished animals subjected to ongoing nutrient deprivation, severe intestinal damage persisted as evidenced by increased mortality, ongoing intestinal inflammation, mucosal hypoplasia, depressed disaccharidase activities, and reduced glucose-stimulated Na+ transport. We conclude that a refeeding regimen introduced during an acute bacterial enteritis is well tolerated and promotes recovery of intestinal mass, structure, and function in malnourished infant rabbits and dietary controls.

Effect of Cortisone on Postnatal Development of Ion Transport in Rabbit Small Intestine

Summary: To study the effect of corticosteroids on postnatal maturation of Na+ transport in the small intestine, we studied 10–12-day-old suckling rabbits after they had received cortisone acetate, 20 mg/kg SC on days 3, 4, and 5 of life. When killed, the cortisone-injected animals weighed significantly less than saline-injected controls. In jejunal villus enterocytes isolated from this cortisone-treated group, the specific activities of sucrase and Na+-K+-ATPase were significantly greater than those in control enterocytes. Studied in Ussing chambers, a significant electrical and ion-flux response to glucose was observed hi the jejunal epithelium of the treated group, but not in controls. We conclude that exogenous cortisone, administered early in life, can stimulate the precocious development not only of certain epithelial enzymes but also glucose-facilitated Na+ transport in the jejunum of the rabbit.

The Effect of Massive Small Bowel Resection and Oral Epidermal Growth Factor Therapy on SGLT-1 Distribution in Rabbit Distal Remnant

Small bowel resection decreases brush border membrane (BBM) glucose uptake kinetics. Oral epidermal growth factor (EGF) returns net glucose transport across intact tissue to control levels despite persistence of a defect in BBM glucose uptake. The purpose of this study was to examine the effects of resection and EGF treatment on sodium-dependent glucose cotransporter 1 (SGLT-1) expression in distal remnant tissue. New Zealand White rabbits (1 kg) underwent 70% small bowel resection (R). One group of resected animals (R-EGF) received oral EGF (40 μg/kg, days 3–8). Distal remnant tissue was harvested 10 d after surgery, and compared with controls (C). Mucosal SGLT-1 mRNA was measured by Northern blot, BBM SGLT-1 content by Western blot, and villus distribution of SGLT-1 protein and mRNA by immunofluorescence and in situ hybridization. Western blot indicated BBM from both resected and EGF-treated tissue had decreased SGLT-1 content (C, 0.55 ± 0.04; R, 0.35 ± 0.04; R-EGF, 0.35 ± 0.03 trace OD; n = 5; p < 0.05). Northern blot revealed no alterations in mucosal SGLT-1 mRNA content in any group. SGLT-1 protein and mRNA localization in control tissues was characterized by a gradual increase in stain intensity from the base of the villus to the villus tip. Resection altered SGLT-1 protein and mRNA expression along the villus axis with intensity being strongest in the mid-villus region and little expression at the tip of the villus. Oral EGF normalized SGLT-1 protein and mRNA expression to control patterns. Resection alters SGLT-1 protein and mRNA expression along the villus axis, despite no change in total mucosal SGLT-1 mRNA content. EGF normalized villus SGLT-1 protein and mRNA distribution, without altering overall BBM SGLT-1 content or mucosal mRNA levels.

Sodium ion transport in isolated intestinal epithelial cells. II.Comparison of the effect of actively trasported sugars on sodium ion efflux in cells isolated from jejunum and ileum

Na+ transport studies in intestinal epithelial cells indicate that enterocytes from different regions of the small intestine differ in their response to actively transported sugars. 1. Compared with sugar-free medium total Na+ efflux rate constants from isolated rat jejunal cells were significantly increased when medium contained actively transported sugars, glucose and galactose, but not when medium contained fructose. 2 In contrast total Na+ efflux rate constants from isolated rat ileal cells did not respond to actively transported sugars, glucose and galactose. 3. Similar results for the effect of actively transported sugars on Na+ ellux were obtained for isolated rabbit jejunal and ileal epithelial cells. 4. Passive Na+ efflux rate constants for isolated jejunal and ileal enterocytes are not significantly different, indicating similiar permeability characteristics.