Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of diarrhea caused by rotavirus infection was studied in miniature swine piglets. The animals were inoculated orally with 2 X 10(7) plaque-forming units of porcine rotavirus (OSU strain). During the height of diarrhea, intestinal function was investigated by in vivo perfusion of a 30-cm segment of proximal jejunum and a 30-cm segment of distal ileum. Absorption of Na+ and water decreased and 3-O-methylglucose transport was markedly reduced, P less than 0.01 compared to control animals. Mucosal lactase and sucrase levels were depressed in both the jejunum and ileum, P less than 0.001. Na+,K+-ATPase activity was significantly depressed only in the ileum, P less than 0.001. These changes were associated with a marked reduction in villous height, suggesting that the diarrhea could be an osmotic diarrhea due to nutrient (carbohydrate) malabsorption. Fresh stool samples were obtained and analyzed immediately for NA+,K+, osmolarity, glucose, and lactose; the osmotic gap was also determined. Stool osmolarity continually increased from 248 +/- 20 mosm/liter prior to inoculation to 348 +/- 20 mosm/liter at 75 +/- 1 hr postinoculation (P less than 0.005); the majority of the fecal osmotic gap could be accounted for by the amount of lactose present in the stools. Stool sodium increased from 34 +/- 6 mM prior to inoculation to a maximum of 65 +/- 4 mM at 53 +/- 1 hr postinoculation, P less than 0.001. There was no significant change in potassium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathogenesis of rotavirus-induced diarrhea. Preliminary studies in miniature swine piglet. 648 82

Azathioprine is employed for its immunosuppressive properties, as a steroid-sparing agent or as monotherapy. Its most traditional clinical indications are connective tissue diseases, vasculitis, post-transplant, and immunobullous dermatoses. The main disadvantages of azathioprine therapy are a delayed onset of action (6-8 weeks), and rare profound bone marrow toxicity. Susceptibility to bone marrow toxicity is due to a genetically determined metabolic defect (1 in 300). Patients at risk of such toxicity may be identified by a Thiopurine methyltransferase enzyme assay. We have undertaken a retrospective study, looking at the use of azathioprine as monotherapy for non-bullous inflammatory dermatoses. We studied a total of 24 patients (10 male, 14 female). The dermatoses comprised: atopic eczema (10), pompholyx (6), plaque psoriasis (6), and chronic actinic dermatitis (2). All patients had severe refractory disease warranting systemic second line therapy. The mean age was 49.4 years (range 17-86 years). The starting dose of azathioprine was 100-150 mg/day, and the maintenance dose 50-100 mg/day. The mean duration of treatment was 33.5 months(range 1-132 months). Eighteen patients (75%) showed a good to excellent sustained clinical response to azathioprine. This response rate was evenly represented in the 4 dermatoses studied. The adverse reactions encountered were raised MCV (6), leucopenia (2), raised hepatic enzymes (6), and dyspepsia (4). Azathioprine had to be discontinued due to adverse reactions in 2 patients (dyspepsia, raised hepatic enzymes) followed by normalization. Other factors that potentially contributed to the observed adverse events were present in 5 patients: alcoholism (2), erythromycin toxicity (1), and malabsorption (2). Our study demonstrates the efficacy of azathioprine monotherapy for severe atopic eczema, pompholyx, plaque psoriasis, and chronic actinic dermatitis. Furthermore, azathioprine is a low cost and generally well tolerated drug.
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PMID:Azathioprine in dermatological practice. An overview with special emphasis on its use in non-bullous inflammatory dermatoses. 1059 68

This study explored the potential of using the gene therapy approach, based on adenovirus-mediated expression of pancreatic lipase in the hepatobiliary tract, to increase lipid digestion in the intestinal lumen and promote lipid absorption through the gastrointestinal tract. Recombinant adenovirus containing the human pancreatic lipase cDNA (AdPL) was shown to transduce and mediate pancreatic lipase biosynthesis in rat IEC-6 epithelial cells in vitro. Retrograde infusion of recombinant adenovirus (3 x 10(8) plaque-forming units) containing the bacterial LacZ gene (AdLacZ) into the bile duct of rats resulted in positive X-gal reaction products in the periportal liver cells 7 days after AdLacZ infusion. A high level of human pancreatic lipase was detected in bile after retrograde bile duct infusion of rats with AdPL but not in the bile of animals infused with AdLacZ. Triglyceride hydrolytic activity in the bile of AdPL-infused rats was equivalent to that present in pancreatic juice. In contrast, serum obtained from these animals did not contain any detectable pancreatic lipase activity. These results suggest that ectopic expression of pancreatic enzymes in the hepatobiliary tract may be an alternative therapeutic strategy for treating fat malabsorption due to pancreatic insufficiency.
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PMID:Adenovirus-mediated human pancreatic lipase gene transfer to rat bile: gene therapy of fat malabsorption. 1105 1