Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:036187 (gut)
 73,132 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulphasalazine consists of 5-aminosalicylic acid and sulphapyridine both linked together by an azo bond. Sulphasalazine is clearly useful in long-term management of ulcerative colitis and may be useful in Crohn's disease. The absorption, metabolism and excretion of sulphasalazine is similar in volunteers and patients with ulcerative colitis or Crohn's disease. Sulphasalazine serves as a vehicle to deliver its possible active components, 5-aminosalicylic acid and sulphapyridine, to the colon in higher concentrations than could be achieved by oral administration of either one alone. Sulphasalazine reaches the colon mostly unchanged and is split by gut bacteria at the azo linkage, releasing 5-aminosalicylic acid and sulphapyridine. 5-Aminosalicylic acid may act locally and is not absorbed to any great extent. On the contrary, sulphapyridine is mostly absorpbed from the colon and may act both locally, during mucosal absorption, and systemically. A positive correlation exists between serum total sulphapyridine concentration and both therapeutic efficacy and toxicity. Sulphapyridine metabolism is largely determined by inherited acetylator phenotype, either slow or fast. Slow acetylators have higher levels of free sulphapyridine and lower levels of acetylated sulphapyridine than fast acetylators, and are likely to have more toxic symptoms on equivalent doses of sulphasalazine. Therapeutic effects of sulphasalazine in ulcerative colitis and Crohn's disease correlate with serum concentrations of total sulphapyridine (20 to 50 microng/ml), and toxicity with total sulphapyridine concentration greater than 50 microng/ml. Side-effects are mostly observed among slow acetylators. In long-term therapy of ulcerative colitis doses of 2 to 3g/day of sulphasalazine are most likely to sustain remissions and avoid toxicity. During therapy with sulphasalazine, determination of acetylator phenotype and total sulphapyridine concentration can guide effective dosage and avoid side-effects. A single serum sample for free and acetylated sulphapyridine concentrations is sufficient for this purpose.
Clin Pharmacokinet
PMID:Clinical pharmacokinetics of sulphasalazine. 1 52

The study of vitamin B12 release from the ileal enterocyte has been hampered by the fact that B12 does not cross the serosa of traditional everted ileal sacs. We studied this release by perfusing the superior mesenteric arteries of starved, heparinized, etherized rats and collecting perfusate from the superior mesenteric vein. The rats were fed 57CoB12 well before study. The standard perfusion medium was Krebs-Henseleit-NaHCO3 buffer containing glucose, dextran, albumin, propranolol, and dexamethasone. The preparation utilized glucose and O2, produced lactate, and was relatively impermeable to [14C]inulin, to D-xylose, and to 57CoB12 bound to an inert human IF. Glucose placed in the gut lumen was transported much more rapidly than D-xylose. Vitamin B12 emerged in the perfusate bound to a protein with a molecular size similar to that of TC II. IF could not be identified in the perfusate. Rat serum, independently of its unsaturated TC II content, increased the rate of transfer of B12 into the perfusate.
J Lab Clin Med 1979 Dec
PMID:Vitamin B12 absorption studied by vascular perfusion of rat intestine. 4 Oct 23

Human feces contain enzymes produced by enteric bacteria that degrade the A, B, and H blood group antigens of gut mucin glycoproteins. We have studied their production in fecal cultures to determine if such cultures can be a source for enzyme purification and to explore how blood group antigen-degrading enzymes are adapted in individual human colon ecosystems. They were present in fecal cultures from each of 27 healthy subjects, including ABH nonsecretors. Heat-sensitive obligate anaerobes are their major source. From 39 to 85% of the total enzyme activity produced by growing cultures was extracellular. Commercial hog gastric mucin and salivary glycoproteins, including Lea saliva which lacks A, B, and H antigens, enhance production of A-, B-, and H-degrading activity in anaerobic fecal cultures irrespective of the glycoprotein's blood group specificity. There is evidence that the host's ABO blood type and secretor status affects the specificity of blood group-degrading enzymes produced by his fecal bacteria in vitro. Thus, fecal inocula from B secretors incubated with hog gastric mucin (A and H specificity) or with Lea saliva produced greater levels of B-degrading than A- or H-degrading activity, and inocula from A secretors in similar media produced greater levels of A-degrading than B- or H-degrading activity. Blood group-degrading enzymes produced in fecal cultures are glycosidases and not proteases. The B-degrading enzyme cleaves the B antigenic determinant alpha-D-galactose from the oligosaccharide side chains of mucin glycoproteins with B specificity. Anaerobic fecal cultures containing blood group substances are a feasible source for purifying blood group antigen-degrading enzymes. Prior adaptation to blood group antigens in the gut mucins of type A and type B secretors affects the specificity of the enzymes produced in vitro.
J Clin Invest 1976 Jan
PMID:Degradation of blood group antigens in human colon ecosystems. I. In vitro production of ABH blood group-degrading enzymes by enteric bacteria. 5 65

The autosomal dominant ABH secretor gene together with the ABO blood type gene control the presence and specificity of A, B, and H blood group antigens in human gut mucin glycoproteins. Certain obligate anaerobes in feces produce extracellular antigen-specific glycoside structures. We estimated the populations of these bacteria in feces of 22 healthy subjects by determining the greatest dilution of feces that yielded A, B, or H blood group-degrading enzyme activity after 24 h incubation in anaerobic cultures. Comparatively small populations of fecal bacteria produce blood group-degrading enzymes; their estimated populations were 10(8) per g or less in 21 subjects. Fecal populations of B-degrading bacteria were stable over time, and their population density averaged 50,000-fold greater in blood group B secretros than in other subjects. We present evidence that the greater fecal populations of B-degrading bacteria in B secretors is due in part to a competitive nutritional advantage gained by their ability to enzymatically cleave the B antigenic determinant alpha-D-galactose from gut mucins of B secretors. Fecal populations of bacteria producing A and H antigen-degrading enzyme activities were comparable in all subjects to the fecal population of B-degrading bacteria in B secretors. The large populations of fecal anaerobes may be an additional source of A antigen substrate for A-degrading bacteria; thus, antigens cross-reacting with A antigen were detected on cell walls of anaerobic bacteria from 3 of 10 cultures inoculated with 10(-10) g feces. Bacteria producing B-degrading activity likely represent a separate population from those producing A- or H-degrading activity since their fecal populations differed numerically in 14 subjects. These findings suggest that adaptation of blood group-degrading enzymes to mucin structures in human colon ecosystems is chiefly by mutation-selection of comparatively small populations of constitutive enzyme-producing strains rather than by substrate induced enzyme synthesis in many strains.
J Clin Invest 1976 Jan
PMID:Degradation of blood group antigens in human colon ecosystems. II. A gene interaction in man that affects the fecal population density of certain enteric bacteria. 5 66

Workers exposed to chlordecone (Kepone), a toxic organochlorine pesticide, excreted larger amounts of chlordecone in bile than in stool, suggesting that it may undergo enterohepatic recirculation. We found in a single subject that equal amounts of chlordecone and of its reduced metabolite, chlordecone alcohol, were excreted in bile at a rate four times as great as in stool. When biliary contents were diverted from the intestine through a T tube, fecal excretion of chlordecone alcohol was abolished, presumably due to interruption of its passage via bile to intestine. This change was not accompanied by disappearance of chlordecone from the stool. The amount of chlordecone in stool when bile was diverted was increased six- to tenfold over that when diverted bile was continuously infused into the duodenum. Analogous experiments with [14C]-chlordecone-treated rats in which bile flow was exteriorized through a plastic cannula showed that the excretion of radioactivity in feces was in the same range when bile was reinfused in the duodenum or was totally diverted. Moreover, in rats with bile diverted, cholestyramine, an anion-exchange resin which binds chlordecone in vitro, doubled the excretion of radioactivity in stool. A similar effect was observed in intact animals. We conclude that chlordecone enters the intestinal lumen from a nonbiliary source, probably the gut, and that net excretion of chlordecone from this source can be augmented by cholestyramine.
Clin Pharmacol Ther 1979 May
PMID:Excretion of chlordecone by the gastrointestinal tract: evidence for a nonbiliary mechanism. 8 3

The data presented confirm the advantages of Fe(III)-EDTA as a salt for iron fortification. This iron compound exchanges completely with intrinsic wheat iron in the lumen of the gut. The iron absorption data from this salt tested with six different food vehicles compared with the absorption of ferrous sulfate administered with the same vehicles indicate that while the mean absorption from ferrous sulfate varies from 2 to 30% according to the food vehicle mixed with the salt, the absorption from Fe(III)-EDTA remains practically the same. Apparently, the iron absorption from Fe(III)-EDTA complex is slightly or not affected by the presence of vegetable foods or milk. All these data suggest that only a small amount of iron from this salt, about 10 mg/day, would be necessary to prevent iron deficiency anemia even in those populations relying for their subsistence on vegetable food only.
Am J Clin Nutr 1979 Apr
PMID:Fe(III)-EDTA complex as iron fortification. Further studies. 10 84

The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham-operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally-fed, hypophysectomized. and pair-fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake. Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal alpha-glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair-fed, sham-operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair-fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.
Eur J Clin Invest 1979 Apr
PMID:Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat. 11 42

The radioactivity in the blood, bile, and contents from different parts of the gastro-intestinal tract was estimated for different time intervals up to 24 h after 3H-SDMH injection to rats. 65% of the radioactivity was excreted in the urine. Of the total quantity of radioactive products entering the intestine, 96% is brought with bile and only 4% from the circulation through the wall of the intestine. This latter small amount of SDMH metabolites plays a leading role in the genesis of intestinal tumours. This conclusion was proved by the observation that the intestinal tumours developed in different isolated segments of the gut where the entry of bile was excluded and by published data indicating that SDMH is excreted unchanged in the bile. It was shown that the carcinogenic effect depends upon the dose schedule of carcinogen treatment, probably, due to the changes in the SDMH metabolism. The optimal conditions for induction of intestinal tumours occur after administration of SDMH in a dose of 21 mg/kg body weight once a week. Hypothetic SDMH metabolic pathways leading to tumour production have been considered in the light of available experimental data.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976 Sep 24
PMID:Distribution and carcinogenic action of 1,2-dimethylhydrazine (SDMH) in rats. 13 14

Drugs entrapped in liposomes (artificial lipid vesicles) exhibit different pharmacokinetics after intravenous application than drugs injected in a free form. The folidacidantagonist methotrexate can be entrapped in liposomes in a therapeutically useful concentration (0.5 mg MTX/ml) and can be stored with high stability of entrappment. After intravenous injection into the tail vein of mice liposomes entrapped methotrexate is found more enriched in cell systems with high rate of endocytosis and not eliminated by the kidneys within 3 h like free methotrexate. It can be shown, that for the organs liver, spleen, kidney, gut, lung, and blood over a 6 h period liposomes entrapped methotrexate is enriched in the tissues and that for example after 6 h the methotrexate level in the liver is 20 fold higher in comparison to free injected methotrexate.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977 Nov 18
PMID:[The carrier potential of liposomes for methotrexate. Changing of the tissue levels of methotrexate in the organs of mice (author's transl)]. 14 58

Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbCl. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the following of its analogues: a) with extended peptide chains at the N-terminal (including "hormonogens") Nalpha-glycyl-glycyl-lysine-vasopressin, Nalpha-glycyl-glycyl-glycyl-arginine-vasopressin and Nalpha-D-valyl-lysine-vasopressin, b) "carba" modifications desamino-carba6-arginine-vasopressin, desamino-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarba-arginine-vasopressin and c) other steric alterations - desamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 60 min. The presence of steric alterations in the C-terminal tripeptide of the molecule- D-arginine or N-methylarginine in sequence position 8 - practically completely eliminated vascular activity. The same was true for Nalpha-D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of a lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-S-, -CH2CH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and constitute the limiting factor determining complex duration, or persistence of the active peptide in the "receptor compartment". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and uterus and for induction of menstruation.
Eur J Clin Invest 1975 Apr
PMID:Regional and systemic haemodynamic effects of some vasopressins: structural features of the hormone which prolong activity. 16 85


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