Biotin-responsive in vivo carboxylase deficiency in two siblings with secretory diarrhea receiving total parenteral nutrition

1. Intravenous infusion of endotoxin into rats over 18 h caused a reduction in food intake to 20% of normal levels, weight loss, hypoalbuminaemia and a fall in rates of protein synthesis in vivo in heart and skeletal muscle. 2. Measurements of protein turnover in vitro in skeletal muscle of endotoxaemic animals, showed a 50% fall in protein synthesis rates and a 200% increase in rates of protein degradation. 3. Total parenteral nutrition was only partially able to reverse endotoxin-induced weight loss. Total parenteral nutrition did not reverse endotoxin-induced catabolism in cardiac or skeletal muscle, but was able to reverse the catabolism of protein in skeletal muscle produced by starvation. 4. Endotoxin treatment elevated rates of protein synthesis in vivo in liver. The combination of parenteral nutrition and endotoxaemia further increased the rate of protein synthesis in the liver. Parenteral nutrition did not influence endotoxin-induced hypoalbuminaemia.

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Speed of Onset of Adaptive Mucosal Hypoplasia and Hypofunction in the Intestine of Parenterally Fed Rats

Clinical Science ◽

10.1042/cs0590317 ◽

1980 ◽

Vol 59 (5) ◽

pp. 317-327 ◽

Cited By ~ 138

Author(s):

C. A. Hughes ◽

R. H. Dowling

Keyword(s):

Parenteral Nutrition ◽

Total Parenteral Nutrition ◽

Unit Length ◽

Control Group ◽

Control Groups ◽

Mean Values ◽

Mucosal Mass ◽

And Function ◽

Speed Of Onset

1. To establish the speed of onset of jejunal and ileal mucosal hypoplasia and hypofunction in parenterally fed rats, we measured three indices of mucosal mass, three mucosal enzymes and quantitative histology after 3, 6, 10 and 15 days of total parenteral nutrition and compared the results with those in two orally fed control groups, one with and one without intravenous catheters and metabolic cage restraint. The kinetics of galactose absorption in vivo were also measured after 10 days of total parenteral nutrition and in both control groups. 2. The most striking decrease in both jejunal and ileal mucosal wet weight and protein and DNA content per 10 cm length of intestine, occurred after only 3 days of total parenteral nutrition; thereafter the mean values showed only a slight further decrease. 3. The results of the morphometric studies showed that the hypoplasia affected the villi slightly more than the crypts. Within 3 days of starting total parenteral nutrition, mean jejunal mucosal thickness decreased by 16% and after 15 days it had fallen by 28%. The ileum showed similar, although less marked, changes. In the jejunum (not the ileum) modest cellular hypotrophy accompanied the mucosal hypoplasia; there were more epithelial cells/unit length of mid-villus and there was more DNA per g of mucosa in the total parenteral nutrition group than in the control group of rats. 4. Jejunal galactose absorption from the 16, 32 and 64 mmol/l solutions was significantly less in the 10-day total parenteral nutrition rats than in the controls, the apparent Vmax being five times greater in the orally fed animals. The apparent Michaelis constant (Km) was also significantly less than normal in the jejunum of the parenterally fed rats, suggesting increased affinity of the hypothetical carrier for galactose, perhaps as a result of functionally hypermature cells. 5. Mucosal alkaline phosphatase and catalase activities per unit length of intestine decreased and α-d-glucosidase activity increased in the jejunum and ileum of the total parenteral nutrition rats. 6. These results show that during total parenteral nutrition, the ileum and particularly the jejunum show marked reductions in mucosal mass and function after only 3 days of total parenteral nutrition and that there is a more gradual and progressive loss of mucosal mass thereafter up to 15 days.

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