Michel Doffoel

Idiopathic biliary ductopenia in adults: a report of five cases.

The clinical and pathological findings of five adult cases of idiopathic nonsyndromatic paucity of interlobular bile ducts are reported. Patients were 18-32 years old at the onset of the disease; four presented with pruritus and/or jaundice and one with bleeding of the esophageal varices. Two patients were siblings. Serum alkaline phosphatase counts ranged from 1 to 16 times the upper normal value, and total bilirubin counts ranged from 0.6 to 8.8 mg/dL (10 to 150 mumol/L). Initial liver biopsy showed portal and periportal fibrosis with cholangiolar proliferation and reduction in the number of interlobular bile ducts. Antimitochondrial antibodies were absent, and bile ducts were normal after opacification. The patients were observed for 3-11 years. Repeated liver biopsies in the five patients showed progression of the lesions, with development of biliary type cirrhosis in four. Two of the four patients with cirrhosis died of hepatic failure 3 and 11 years after onset of the disease. In the two other cases, liver transplantation was performed successfully. These cases suggest that chronic cholestasis with marked ductopenia resembling the nonsyndromatic paucity described in infancy and childhood may reveal itself at an adult age. This disorder, possibly familial, may rapidly progress to severe and even fatal liver disease and could be a new indication for liver transplantation.

Effects of Amino Acids in Mixtures Given by Enteral or Parenteral Route on Intestinal Morphology and Hydrolases in Rats

This study compares the effects of amino acid addition to an elemental liquid diet containing carbohydrates and triglycerides given either intragastrically or intravenously on the morphology and on hydrolase activities in the jejunum and ileum of adult rats. The isocaloric mixtures were administered for 4 days and control rats received an isocaloric laboratory diet orally. Independent of their content in amino acid, all mixtures given intravenously caused a drop in mucosal weight and a shortening of the height of the villi in both the jejunum and ileum. By enteral route, the addition of amino acids to a carbohydrate-triglyceride liquid diet led to the maintenance of normal villus height (this effect being prominent in the ileum) and to a significant increase of jejunal sucrase and aminopeptidase activities when compared with the carbohydrate-triglyceride mixture. Feeding the mixtures by parenteral route caused a significant drop of both enzyme activities. In contrast, lactase activity was generally not modified by the route of nutrient administration or by the composition of the diets. However, the absence of amino acid in the mixture given intravenously caused a specific drop of lactase activity in the ileum. Ileal sucrase activity was lowered dramatically by intragastric or intravenous feeding of the elemental diets. This effect was not modulated by the presence of amino acids. The presence of amino acids caused a significant drop of aminopeptidase activity in the ileum independently of the route of administration when compared with animals receiving the carbohydrate-triglyceride liquid diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Age influence on sucrose hydrolysis and on monosaccharide absorption along the small intestine of rat.

The consequences of aging on the hydrolysis and absorption of hexoses was assessed in vitro using everted intestinal segments. Glucose and fructose were given either as a mixture of free monosaccharides or as a disaccharide solution (sucrose). The jejuno-ileum of 3- and 24-month-old rats was everted and divided into four equal segments. For each segment, the mucosal medium contained either sucrose (140 mM) or an equimolar mixture of glucose and fructose (70 mM). Monosaccharide concentrations in the mucosal ans serosal media were measured after 1 h of incubation at 37 degrees C. In the young adult, glucose absorption was enhanced when given as sucrose. In contrast, in the aged rat, free glucose or glucose released from sucrose hydrolysis were similarly absorbed. Independently of age, fructose was better absorbed when provided in a mixture of free monosaccharides. The intestinal segments (and especially the ileum), of the aged animals exhibited higher abilities to hydrolyse sucrose and to absorb monosaccharides indicating a normal or increased intestinal hydrolytic activity and absorptive capacity for dietary sugars.

Effect of Intravenous and Intragastric Fat Infusion on Intestinal Brush Border Enzyme Activities in Rats

Intralipid was given to adult rats for 4 days either by intragastric or intravenous infusion. The villus height, protein content and the levels of sucrase, lactase and aminopeptidase activities were determined in the jejunum. The results were compared to values found in control rats fed orally with an equilibrated isocaloric diet. Intragastric or intravenous infusion of Intralipid caused a 50% reduction in the protein content of the brush border membrane, a significant drop of the specific (expressed per milligram protein) and segmental (expressed per centimeter intestinal length) activities of the disaccharidases, the maintenance of aminopeptidase activity and the lengthening of the villi in the jejunum. The major loss in disaccharidase activities was obtained when fat was given intravenously. Arguments favoring a hormone-mediated effect of the infused lipids on the intestinal function are presented and discussed.A portacaval shunt (PCS) model is frequently employed to study phenomena inherent in portal-systemic shunting of splanchnic blood. In many species, a PCS induces hepatic insufficiency, accompanied by encephalopathy. Rats operated on with a nonsuture technique tolerate a PCS better and exhibit no or only slight encephalopathy. Age and environment seem to have a large impact on the ability to tolerate a PCS. This explains the discrepancies between the results of different investigators and the varying time periods reported between the PCS operation and the optimal time for experiments. To characterize the PCS model (button technique) in rats with respect to metabolic parameters in our field of interest, we studied three groups of male Sprague-Dawley rats--non-operated (n = 12); sham-operated (n = 12) and PCS (n = 13)--for 4 weeks following surgery. Body weight in the PCS group decreased for 1 week after surgery and then increased at about the same rate as in the control groups. Plasma immunoreactive insulin, plasma immunoreactive glucagon (IRG) and aromatic amino acid concentrations were highest 1 week after surgery and tended to normalize in the next weeks. Plasma branched-chain amino acid (BCAA) concentrations were decreased in the 1st, 2nd and 3rd week after surgery, after which normalization occurred. These data demonstrate that after 3-4 weeks, male Sprague-Dawley rats start to recover from the metabolic disturbances caused by PCS with regard to the parameters measured. Therefore, experiments in this area, especially those relating to BCAA metabolism, should be carried out 2-3 weeks after the shunt operation (button technique).

A Comparison of Intestinal Adaptation to Short-Term Intravenous Versus Intragastric Diet in Adult Rats

This study was designed to determine, on intestinal function, the comparative effects of a fat emulsion, a carbohydrate solution, and a mixture of lipids and carbohydrates given for 4 days to adult rats either intragastrically or intravenously. The rats were separated into three groups (n = 24 in each group). Each group was divided into two populations fed either intragastrically or intravenously. Each group received one of the following nutrients: a 20% Intralipid emulsion, a mixture (1:1, V/V) of Intralipid 20% and Vamine N containing 25% glucose (W/V), a solution of Vamine-glucose supplemented with fructose to reach a final concentration of 20% (W/V). Sham-operated rats that received laboratory chow orally were used as controls. The daily caloric intake was 0.21 to 0.22 kcal/g body weight. The studies on villus morphology and on brush border enzyme activities were performed on the proximal part of the jejunum. For all nutrients, intragastric infusion provoked an increase in the villus height. The lipids were the only nutrients to cause villus lengthening by the intravenous route. Intragastric or intravenous infusion of fat provoked a deficiency in intestinal disaccharidases; the presence of carbohydrates in the diet inhibited this effect slightly. Carbohydrates given alone, either intragastrically or intravenously, caused an elevation of lactase activity. Independent of diet composition, aminopeptidase activity was reduced after intravenous feeding. In conclusion, the disaccharidase activities are largely dependent on changes occurring in the nutrient composition given either intragastrically or intravenously, whereas amino-peptidase activity was related to the route of diet administration.

Stimulation of Disaccharidase Activities in the Jejunal Brush Border Membrane of Adult Rat by Total Parenteral Nutrition

This study examined the morphological and functional adaptations occurring in the jejunum of adult rats fed totally by parenteral nutrition during a 4-day period. Comparison was made with sham-operated animals receiving orally a similar isocaloric diet. The intravenously fed rats exhibited a 20% shortening of the villus height. The specific activity of aminopeptidase showed remarkable stability in all conditions. A major stimulation (2.5-fold) was measured for lactase-specific activity. Daily administration of thyroxine completely inhibited the rise of lactase activity. Thyroidectomy caused a significant increase of lactase activity in the orally fed controls, but did not exert any synergistic effect with parenteral nutrition on intestinal enzyme activities. In our experimental conditions intravenous feeding led to a 3-fold decrease in the concentration of thyroid hormones detected in the serum. The results show that total parenteral nutrition leads to a stimulation of the specific activity of brush border lactase in the intestine of adult rat which might be related to the level of thyroid hormones.

Prenatal exposure to alcohol in rat: Effect on intestinal enzymes in offspring

Intestinal hydrolase activities were studied during postnatal development in the offspring of rats exposed to 20% ethanol during gestation; alcohol was withdrawn at birth. Controls received water during gestation. Sucrase, lactase, glucoamylase and aminopeptidase activities were determined 2 and 4 weeks after birth in the proximal jejunum. Offspring prenatally exposed to ethanol showed a deficit in body weight and lower aminopeptidase activity during the suckling period (2 weeks). These effects were reversible by 4 weeks when alcohol was withdrawn at birth. The prenatal exposure to ethanol did not change the pattern of sucrase maturation in the intestine of offsprings. The activities of lactase and glucoamylase were not modified following prenatal exposure to ethanol. In conclusion, exposure to ethanol during gestation caused decreased abilities for the intestine of the offspring to digest protein.

Imbalance between Jejunum and Ileum in the Response of Brush Border Hydrolases to Oral Feeding after Intravenous Alimentation in Rats

The effect of oral refeeding after total parenteral nutrition (TPN) on brush border hydrolases was measured in the proximal jejunum and ileum of adult rats. The animals received intravenously for 4 days a mixture of Intralipid 10% and Vamine-Glucose. At the end of TPN, oral feeding was reinstituted and the rats were fed with an isocaloric standard diet (60% carbohydrate, 17% protein, 3% lipid). Sucrase, isomaltase, lactase, and aminopeptidase N activities were measured at the end of TPN and at 1, 3, and 5 days after TPN. Sham-operated rats nourished orally with the standard diet were used as controls. In both intestinal segments, lactase activity showed no significant changes at the end of TPN or during oral realimentation. Isomaltase, and especially sucrase activities, exhibited an important drop at the end of TPN. After TPN, a complete restoration of isomaltase and sucrase activities was obtained in the jejunum only. During oral refeeding a 40% deficit in sucrase activity persisted in the ileum throughout the experimental period, whereas normal isomaltase activity was restored in this segment. Aminopeptidase N activity was lowered by TPN and recovered normal values within a few hours after oral realimentation. Thus, reinstitution of oral feeding after TPN should take into account that the intestine is capable of digesting normal amounts of dietary protein but has a reduced tolerance for carbohydrates.