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Biomedical subjects

D G Gall

Publications and source records attributed to D G Gall.

At least 109 records · Page 6Linked to original sources

Effect of intestinal anaphylaxis on gut function in the rat.

We examined the effect of intraluminal antigen on intestinal function in an animal model of anaphylaxis using Hooded-Lister rats sensitized to ovalbumin. Older rats were more difficult to sensitize than younger ones; younger rats more consistently developed antiovalbumin titers of greater than or equal to 1:64 as measured by passive cutaneous anaphylaxis. That these immunoglobulins were of the immunoglobulin E class was suggested by the fact that heating of the sera to 56 degrees C for 3 h eliminated the response. Net fluxes of water and electrolytes were measured in sensitized rats with serum titers greater than or equal to 1:64 and compared with nonsensitized sham-treated controls during two periods: when the perfusate was antigen-free and after the addition of antigen. Intraluminal antigen challenge had no effect in controls but caused a rapid and dramatic reduction in water, Na+, Cl-, and K+ absorption in experimental animals (greater than or equal to 1:64). There was no evidence of recovery after antigen withdrawal, and the response was antigen-specific. Mucosal homogenates prepared after antigen challenge in sensitized animals contained significantly less histamine than homogenates prepared from controls, and granulated mucosal mast cell numbers were reduced. Light microscopy did not reveal any alteration of villus height or crypt depth, but mucosal edema was apparent in sections from sensitized animals. The findings suggest that anaphylactic reactions to food proteins in the intestine lead to abnormalities of water and electrolyte absorption and that histamine, or other mast cell mediators, or both, may be responsible.

Anaphylaxis↗

A simple and safe method of anesthetizing infant rabbits for abdominal surgery.

There is a great lack of information about general anesthesia in small infant animals. We developed a safe method using Halothane to maintain anesthesia in 20 infant rabbits weighing 100-150 g. Halothane was administered through a modified T piece using a small finger cot in order to minimize the dead space of the system. Halothane concentrations of 0.5 to 1.5% were safe and efficient to perform a laparotomy and to keep the rabbits alive after surgery.

Abdomen↗

Postnatal development of glucose transport in the proximal small intestine of the rabbit.

Developmental change in intestinal solute transport was examined by studying glucose transport in rabbit jejunal tissue at age intervals after birth. Net D-glucose absorption was greater in jejunum from suckling rabbits (10-14 days old) compared to older animals when studied in Ussing-type short-circuited chambers, and jejunal tissue slices from these younger animals accumulated more intracellular D-glucose. Net fluxes of 3-0-methyl-D-glucose were also greater in jejunum from the younger age group, excluding this effect being due to substrate metabolism. Increased permeability of jejunal epithelium in immature animals was evidenced by larger unidirectional fluxes and higher conductance. The findings suggest that the developing jejunum, although more permeable, has an increased capacity for active sugar transport, a pattern differing from that seen with most other intestinal absorptive functions.

3-O-Methylglucose↗

Cholestasis and total parenteral nutrition: in vivo studies on dogs.

The effect of total parenteral nutrition (TPN) on bile formation was evaluated in 10 studies performed on three adult dogs. The bile duct was directly cannulated via a Thomas cannula while bile salt secretion was maintained by intravenous [14C]taurocholic acid infusion. After a 1.5-h basal period, either an amino acid solution (2.5% Travasol) with 10% glucose, or a lipid emulsion (10% Intralipid) was added intravenously for 2 h, followed by a second control period. The amino acid-glucose solution resulted in a significant (p less than 0.05) increase in bile flow which rose (+33%) while bile salt secretion increased transiently (+11%) and then returned to basal levels. The specific activity of taurocholate secreted did not decrease during the amino acid-glucose infusion, indicating that the unexpected increase in bile salt secretion was mainly due to a washout of the biliary tree rather than to enhanced synthesis. Cholesterol, phospholipid, and bilirubin outputs did not change significantly. Intralipid had no effect on bile flow or solute secretion. Thus, short-term TPN therapy with amino acids and glucose had no cholestatic effect in dogs, but rather produces a transient choleresis which is largely independent of bile salts.

Amino Acids↗

Effect of body weight on postnatal development of the proximal small intestine of the rabbit.

The effect of oral intake and body weight on postnatal maturation of the small intestine was examined in infant rabbits with accelerated weight gain. Intestine from immature animals is characterized by large unidirectional Na fluxes, failure of Na absorption to respond to glucose but increased ability to absorb monosaccharides, and an enzyme pattern of high lactase and thymidine kinase and low sucrase. Postnatal development was monitored by measuring Na and glucose transport in short-circuited jejunum and enzyme activities in jejunal mucosa. Accelerated weight gain was achieved in the experimental group by reducing litter size to 3 animals at 24-48 hours of age. Under glucose-free conditions unidirectional Na fluxes were significantly smaller in tissue from the heavier experimental animals compared to controls. The addition of glucose had no effect on Na fluxes in control tissue but significantly increased Na absorption in the experimental group. Unidirectional and net fluxes of 14C-D-glucose were significantly smaller in the heavy experimental animals compared to controls. Isolated villus enterocytes from the experimental group had reduced lactase and thymidine kinase activities. Sucrase activity, which did not differ in isolated cells, was increased in total mucosa from the experimental group. Solute transport and the enzyme profile in jejunum from the heavier experimental suckling rabbits is characteristic of intestinal epithelium from more mature animals, indicating accelerated postnatal maturation. The findings suggest that oral nutrient intake and body weight, rather than chronologic age, act as the physiologic trigger for postnatal maturation of the small intestine.

Aging↗

Intestinal glucose transport in acute viral enteritis in piglets.

1. We studied intestinal glucose transport in pigs during the acute and convalescent phases of an invasive viral enteritis, transmissible gastroenteritis. 2. When diarhoea was severe 40 h after experimental infection, net absorption of glucose, Na+ and water, measured by marker perfusion in the jejunum, was reduced; the enhancement of Na+ and water absorption in response to increasing perfusate glucose concentrations up to 120 mmol/l was diminished compared with the response observed in control and convalescent pigs. 3. Measured in vitro, 40 h after infection, unidirectional fluxes of 3-O-methyl-D-glucose across the jejunal epithelium were reduced and net absorption of the sugar was obliterated. Phlorizin (0.05 mmol/l), which completely inhibited net 3-O-methyl-D-glucose absorption in control tissue, had no significant effect on transmissible gastroenteritis jejunum. 4. Our data suggest that in this invasive viral enteritis, which closely resembles human rotavirus enteritis, glucose absorption is impaired as a result of defects in both active and passive glucose flux. 5. Differences between the mechanisms of viral diarrhoea, demonstrated by our study and those of the enterotoxigenic diarrhoeas, should be taken into consideration in formulating active therapeutic measures for children with acute viral diarrhoea.

3-O-Methylglucose↗

Effect of cortisone on postnatal development of ion transport in rabbit small intestine.

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 Using chambers, a significant electrical and ion-flux response to glucose was observed in 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.

Animals↗

Response of the rat small-intestine epithelium to methotrexate.

We studied jejunal epithelial structure and function in rats 24, 48, 96, and 192 hours after a single intravenous injection of methotrexate (MTX) 30 mg/kg. The acute effect of the drug on the gut at 24 and 48 hours was characterised, as expected, by reduced mitoses in crypts, shortened villi, and depressed activity of thymidine kinase (an enzyme normally confined to intestinal crypt cells). At 96 hours, when MTX was no longer detectable in serum, the intestine had entered a proliferative phase characterised by increased crypt mitoses, accelerated migration of enterocytes along villi, and the presence on villi of epithelial cells with the enzyme profile of crypt cells, decreased disaccharidase, alkaline phosphatase, and Na+-K+ATPase activities and increased thymidine kinase activity. Although the enzyme data suggested that enterocyte maturation was defective during this proliferative phase, glucose-stimulated Na+ transport, normally a function of fully differentiated villus cells, was normal at 96 hours. Measured both in Ussing chambers and in suspensions of enterocytes isolated from villi, Na+ transport responded normally to glucose at 96 hours, although the response had been significantly depressed at 24 hours. These findings cannot be attributed to MTX-induced malnutrition, as all comparisons included pair-fed controls. We conclude that, in the MTX-induced malnutrition, as all comparisons included pair-fed controls. We conclude that, in the small intestine under conditions of altered epithelial renewal, some components of enterocyte function may be affected more than others. Comparing the present experimental model with another intestinal disorder, acute viral enteritis, in which proliferative activity is excessive, it is clear that the nature of the original intestinal injury is a significant determinant of the pattern of enterocyte response.

Animals↗

The postnatal development of sodium transport in the proximal small intestine of the rabbit.

To investigate the postnatal development of intestinal Na+ transport, a major determinant of fluid absorption, we measured spontaneous and glucose-coupled Na+ transport across short-circuited epithelium and in isolated villus enterocytes from rabbit jejunum at age intervals after birth. Villus cells from suckling animals actively transported Na+ and responded to glucose, but their capacity to do so was less than that of villus cells from older animals. Net Na+ fluxes across short-circuited epithelium from suckling animals failed to respond to glucose, remaining negligible and less than adult values. This lack of response to glucose in tissue from younger animals was associated with marked paracellular shunting as evidenced by greater unidirectional fluxes and greater tissue conductance. Villus enterocytes from suckling animals compared to those from adults had reduced (Na+-K+)ATPase activity, but were rich in thymidine kinase. We conclude that proximal intestinal epithelium in suckling animals has a limited capacity for active Na+ transport, is incompletely differentiated, and is leaky, with a greater permeability for ions compared with adult intestine.

Age Factors↗

A clinical study of young infants after small intestinal resection.

We prospectively studied 15 infants who, before 3 months of age, underwent resection of the small intestine-proximal in 3 infants, mid in 6, and distal in 6. Two died before one year of age. Many required prolonged parenteral nutrition, but by one year, 12 of the 13 survivors were on oral feedings only, and seven were above the third percentile for height and weight. Developmental delay occurred in the early postoperative period but diminished with time. There was compensatory adaptation of the remaining gut, shown by improving fat and B12 absorption and duodenal bile-salt concentrations. Bacterial contamination complicating end-to-side anastomoses occurred in two cases (P), gastric hyperacidity in four of 12 (1P, 3M), and hyperoxaluria in eight of 14 (1P, 5M, 2D). Studies of immune competence revealed normal cellular immune function (11/11), transient hypogammaglobulinemia (3/14), hypocomplementemia (1/12), and serum autoantibodies (3/10). Thus, massive resection of the small intestine did not preclude spontaneous improvement in absorptive function, growth, and development.

Child Development↗

Determinants of diarrhea in viral enteritis. The role of ion transport and epithelial changes in the ileum in transmissible gastroenteritis in piglets.

To understand mechanisms of viral diarrhea further, we studied ileal ion transport in vitro in relation to mucosal changes and epithelial differentiation in transmissible gastroenteritis in piglets, an invasive viral enteritis thought to involve mainly proximal intestine. In infected pigs, at the height of diarrhea, short-circuited ileal epithelium failed actively to transport Na+ and Cl-, and there was a defect of glucose-mediated Na+ transport. The Cl- secretory response to theophylline remained intact. Conductance measurements indicate that paracellular permeability may be reduced and transcellular transport may be altered. A mucosal lesion was observed at the time of the transport changes, characterized by villus blunting, crypt hyperplasia, and immature crypt-type enterocytes on the villus epithelium, deficient in disaccharidase and (Na+, K+)ATPase activity but rich in thymidine kinase. Consideration of the major determinants of diarrhea in this invasive enteritis must take into account not only altered mucosal function and differentiation but also the extent of intestinal involvement, including the ileum, a major site of fluid absorption in the intestine.

Animals↗

Hepatic function following portoenterostomy for extrahepatic biliary atresia.

Liver structure and function in 10 patients with extrahepatic biliary atresia were studied after portoenteric anastomosis (Kasai operation). Bile flow adequate to reduce the serum bilirubin concentration was established in five patients (improved group), three of whom became anicteric. The serum bilirubin concentration did not decrease in the remaining five patients (unimproved group). Hepatic effluent collected postoperatively from both groups contained small amounts of cholesterol and bilirubin; bile salts, however, were present in the hepatic effluent of only the improved patients. Liver biopsy specimens obtained postoperatively from the five improved patients showed partial (in two) or complete (in three) relief of cholestasis; hepatic fibrosis, however, was unchanged (in one) or worse (in four). The serum concentrations of bile salts were markedly elevated, despite normal excretion of sodium sulfobromophthalein and rose bengal, in two anicteric patients studied 14 and 24 months postoperatively. It is concluded that neither structure nor function of the liver is normalized by portoenterostomy even in clinically well, anicteric patients.

Bile Ducts↗