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Intestinal absorption and tissue retention of cadmium and calcium in normal adult rats and rats given an active metabolite of vitamin D (1,25-dihydroxycholecalciferol).

1. Nine-months-old male rats were divided into a normal control group and one experimental group which received eight daily intraperitoneal injections 15 pmol of 1,25-dihydroxycholecalciferol/100 g body weight. After 5 days, 20 muCi of 109CdCl2 or 20muCi of 45CaCl2 was administered by stomach tube. The intestinal absorption and tissue retention of the radioisotopes were analysed during the next 3 days, the animals being kept in metabolic cages. 2. The administration of 1,25-dihydroxycholecalciferol caused significantly increased net absorption of intestinal calcium, hypercalcaemia and increased incorporation of calcium into bone. In comparison, there was no significant effect on the intestinal absorption of trace doses of cadmium or upon the accumulation of cadmium in the liver and kidneys.

Animals

Isolation, chemical characterization, and immunohistochemical localization of a protein from the basolateral plasma membrane of the rat intestinal absorptive cell.

The protein pattern of the basolateral membrane (BLM) of the rat small intestinal absorptive cell shows about 20 major and a multitude of minor bands. A simple and efficient method is described for isolation and purification of a major protein in the 17 kDa molecular weight (MW)-range called Prot 17. The isolated BLM of intestinal epithelial cells was dissolved in buffer 1 (Tris/HCl, 2% SDS, 10% glycerol, 5% beta-mercaptoethanol, pH 6.8) and subsequently dialyzed for 4 h against buffer 2 (Tris/glycine, pH 8.3) and then for 12 h against buffer 2 containing 25% methanol. The resulting precipitate contained Prot 17 and phospholipids in the form of liposomes. All other BLM proteins remained dissolved in the supernatant. Chemical characterization of Prot 17 suggested that it is an integral membrane protein amounting to about 5% of the total BLM protein. Amino acid analysis revealed a MW of 17.6 kDa. The Prot 17 molecule did not contain any PAS-positive carbohydrates. In its isolated form, and apparently also in the BLM, Prot 17 occurred as a polymerized structure with a MW of about 90 kDa. By dissolution in buffer 1 and heating to 100 degrees C for 1 min the complex was split into its 17 kDa subunits. By oxidation with performic acid it was also broken down into its subunits. A specific antiserum against Prot 17 was obtained from immunized Balb/c mice. Immunofluorescence labelling of rat small intestinal sections with this serum showed that Prot 17 was not a BLM-specific protein. It occurred in both plasma membrane domains of the intestinal absorptive cell.

Animals

Intestinal absorption of 5-fluorouracil and its alkylcarbamoyl derivatives in the rat small intestine.

The intestinal absorption of 5-fluorouracil (1) and its alkylcarbamoyl derivatives possessing various lipophilic pro-moieties including the butylcarbamoyl, hexylcarbamoyl, octylcarbamoyl, and nonylcarbamoyl groups, was investigated in the rat using both in situ and in vitro techniques. All compounds showed greater apparent partition coefficients and lipophilic indices (k') (by HPLC) and lower solubilities in water than 1. Although enhancement of uptake by the everted intestine in vitro was observed when the alkylcarbamoyl chain length was increased, the appearance of the prodrugs in the mesenteric vein in the in situ intestinal loop (complete venous collection) was decreased and sustained. The conversion of alkylcarbamoyl derivatives to 1 was noted in the absorption process.

Animals

The effect of di- and trivalent iron on the intestinal absorption of aluminum in rats.

The effect of iron (Fe) on the intestinal absorption of aluminum (A1) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The gut was perfused with media containing 0.0, 10.0, 15.0, 20.0, and 25.0 mmol/liter Al chloride and 5 mmol/liter Fe(II) or Fe(III) chloride at pH 3.0. Neither luminal disappearance nor intestinal absorption of A1 were affected by Fe(III). Fe(II), however, enhanced luminal disappearance and reduced absorption of Al.

Aluminum

Intestinal absorption of folic acid, glucose, sodium and water in chronic pancreatitis.

Intestinal absorption of folic acid, glucose, water and sodium in 10 patients with chronic pancreatitis who have abstained from alcohol for at least 2 months is compared with 18 agematched outpatients without gastrointestinal disorders and a daily alcohol intake less than 30 g. Intestinal absorption was measured by segmental perfusion of the jejunum using a triple lumen tube. Patients with chronic pancreatitis showed a significantly decreased absorption of folic acid and glucose, whereas the net absorption of water and sodium was not disturbed.

Adult

[Functional diagnosis of intestinal absorption in gastroenterology surgery].

Clinical tests for measuring the intestinal absorption in abdominal surgery, especially surgery of the GI-tract, are of great importance. The absorption of the proximal small intestine can be investigated via a modified D-xylose-test. The distal small intestine may be studied by using the vitamin-B12 urinary excretion test. The bacterial overgrowth syndrome and the absorption of bile salts can be diagnosed on the basis of a 14C-glykocholate test.

Biopsy

Electron microscope autoradiographic study of intestinal absorption of decanoic and octanoic acids in the rat.

Intestinal absorption of [3H]octanoic acid and [3H]decanoic acid was investigated in the rat by electron microscope autoradiography. The common duct (bile and pancreatic common duct) of the rats was diverted and a loop of the duodenum was cannulated 24 h later. The lipid mixture to be investigated was introduced into each experimental loop, and after 15 min or less the loop was removed. One part of each loop was used to determine the distribution of radioactivity in different lipid fractions, and an autoradiographic study was performed on the other part of the loop. Radioactivity distribution studies confirmed that medium chain fatty acids are absorbed in their nonesterified form and established that these fatty acids are absorbed much more rapidly than oleic acid. Autoradiographic studies indicated that the medium chain fatty acids are taken up in a molecular or aggregate molecular form, leave the epithelial cells by way of the lateral plasma membrane, and are next found in the blood capillaries. Our results suggest that the Golgi complex does not play an important role in the absorption of unesterified fatty acids.

Animals

[Kinetics of intestinal absorption in cases of dumping syndrome following partial gastrectomy and pyloric stenosis (author's transl)].

By means of analyses of intestinal absorption using the modified D-Xylose test the absorption kinetics of nutrients in cases of dumping syndrome after partial gastrectomy and in cases of pyloric stenosis could be traced. There was no decrease of absorption in the small gut. Changes of the intestinal absorption in cases of gastric dumping were caused by rapid gastric emptying. The delayed gastric emptying in cases of pyloric stenosis is followed by a decrease of Xylose resorption due to the reduction of resorption. The D-Xylose-test allows disorders of gastric emptying to be differentiated from those of enteral resorption.

Adult

[Comparison of 2 technics (ninhydrin vs. TNSB) for estimating circulating amino acid nitrogen, applied to the study of the intestinal absorption of solutions of free amino acids or small peptides].

The intestinal absorption of nitrogen from amino acids present in a solution of small peptides or of free amino acids with the same pattern, perfused intraduodenally, has been studied using two analytical techniques [2, 4, 6 trinitrobenzene-1-sulfonic acid (TNBS) after dialysis of the blood vs ninhydrine after chromatography] to determine post-perfusion porto arterial differences and to measure blood flow rate in the portal vein. The results obtained on blood nitrogen level with the chromatographic method were always higher than those obtained using the TNBS method. The differences in the values varied from 8 to 24% according to post-perfusion time and to blood sample origin (arterial or portal). On the contrary, the absorbed amounts of nitrogen measured by either analytical technique were not very much different: no significant and systematic deviation was found between the two. The TNBS method is thus useful as a preliminary approach to very elaborate studies on intestinal absorption. In these conditions, the nitrogen of amino acids from duodenally-perfused small peptides was absorbed earlier and more rapidly than that from a perfusion of a solution of free amino acids. The amount of nitrogen appearing in the portal vein five hours after perfusion exceeded the perfused amount owing to considerable recycling of endogenous nitrogen.

Amino Acids

Intestinal absorption mechanisms of thyrotropin-releasing hormone.

Intestinal absorption mechanisms of thyrotropin-releasing hormone (TRH) following the oral administration of TRH-tartrate (TRH-T) were studied in animals. When TRH-T was orally administered to rats or beagle-dogs, absorption of TRH showed apparent saturation and decreased with food ingestion. TRH is very stable against gastrointestinal digestive enzymes, homogenized intestine and epithelial cells. First pass effect in the liver was not observed in beagle-dogs. Absorption site specificity was found in rats, namely TRH can be absorbed from only the upper part of the small intestine. A saturation phenomenon was also observed in in situ and everted sac experiments. TRH absorption was inhibited by the existence of oligopeptides and some beta-lactam antibiotics that had been reported to be absorbed by active transport or carrier-mediated transport systems. The transfer of TRH from mucosal to serosal solutions was inhibited by the replacement of medium Na ions by K ions and by the existence of oligopeptides. The transfer rate from serosal side to mucosal side was much slower than that from mucosal side to serosal side. These results suggested that there should be a certain carrier-mediated transport system in the absorption process of TRH.

Animals

In vivo intestinal absorption of manganese in the rat.

The mechanisms of intestinal absorption of Mn in rats and the effects of low-molecular-weight ligands in this process were investigated using an in vivo perfusion system. Segments of either jejunum or ileum were perfused with isotonic solutions containing 0.0125 to 0.1 mM MnSO4 X 7H2O, in the presence or absence of double its concentration of either L-histidine (His) or citrate (Cit). In all cases the absorption of Mn declined with time; for example, in the absence of ligand Mn absorption fell from (means +/- SEM) 16.0 +/- 2.2 at 30 minutes to 2.3 +/- 4.1 pmol/(minute X cm) after 90 minutes of perfusion. Comparable declines occurred both in the jejunum and in the ileum in the presence of His or Cit. The initial absorption rates of Mn, obtained by extrapolation, were higher in the jejunum when His or Cit were present than when no ligands were included in the perfusate [means +/- SD, with His, 66.4 +/- 11.9; with Cit, 79.5 +/- 6.2; none = 17.8 +/- 3.3 pmol/(minute X cm)]. In the ileum, optimum absorption with His was observed between pH 7 and 8. The kinetics of in vivo Mn ileal absorption in the presence of His yielded a Kt of 0.056 mM and an estimated Vmax of 158 pmol/(minute X cm). The coefficient of diffusion was calculated to be 1.5 X 10(-3) cm2/minute. These data are compatible with a high affinity, low capacity, active transport mechanism for Mn in the rat intestine and suggest a limited role for small-molecular-weight ligands associated with both diffusional or active translocation processes.

Animals

Calbindin D28k in mammalian intestinal absorptive cells: immunohistochemical evidence.

Calbindin D28k and D9k are two cytosolic calcium-binding proteins abundant in intestinal absorptive cells which appear to play a role in calcium translocation. Until today, calbindin D28k was found in avian and reptilian absorptive cells but not in mammalian ones. We have described the presence of calbindin D28k-immunoreactivity in intestinal absorptive cells of pig and jerboa (Jaculus jaculus). Pig calbindin D28k-immunoreactive absorptive cells were prominent in duodenum, they were scattered along the villi and nearly absent in the crypts. Jerboa labelled absorptive cells were located along the colonic mucosal surface. No calbindin D28k could be detected in mouse, rat and goat absorptive cells. Topography of calbindin D28k absorptive cells was compared with calbindin D9k distribution. Our results confirmed the data of the literature showing a gradient of labelling increasing from the crypt to the top of the villus and no positive endocrine cell. Young (48 h old) pigs did not expressed calbindin D28k in absorptive cells although calbindin D9k was detected. Calbindin D28K was also observed in endocrine cells which were numerous in pig and goat duodenum and very rare in mouse and jerboa. Western blot experiments confirmed the presence of calbindin D28k in the adult pig intestine, in the jerboa colon and the absence of cross-reactivity between calbindin D28k antibody and calbindin D9k.

Animals

Reduced intestinal absorption of arginine during sepsis.

OBJECTIVE: To investigate the effect of sepsis on the intestinal absorption of arginine. DESIGN: Controlled, nonintervention study. SETTING: Surgical research laboratories of Sinai Hospital of Baltimore. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Experimental sepsis induced by cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: Sepsis assessed by peritoneal and blood cultures. Intestinal absorption estimated by measuring the transfer of 3H-arginine by everted jejunal sacs prepared from septic and control animals (n = 6 per group) at multiple time points after the induction of sepsis (6, 12, 24, 48, and 72 hrs after cecal ligation and puncture; 6 and 12 hrs after intraperitoneal injection of lipopolysaccharide). Induction of peritonitis in the rat by cecal ligation and puncture significantly reduced the in vitro uptake of arginine by everted jejunal sacs at 12, 24, and 48 hrs after laparotomy. Arginine transfer by everted jejunal sacs was also significantly reduced in rats as early as 6 hrs after intraperitoneal injection of endotoxin (endotoxin 273 +/- 14; saline 377 +/- 14 nmol/sac/hr). Data are expressed as mean +/- SEM. Recovery from sepsis was associated with normalization of arginine transfer by intestinal sacs. CONCLUSIONS: Experimental sepsis, induced by either cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide, resulted in impaired intestinal amino acid uptake. Impaired intestinal arginine absorption may explain the lack of benefit of enteral, compared with parenteral, arginine therapy on survival from a septic insult.

Animals

Enhanced intestinal absorption of cyclosporine in rats through the reduction of emulsion droplet size.

The intestinal absorption of cyclosporine was measured in situ in rats using an olive oil emulsion prepared by either stirring or homogenization. The surface area of the homogenized dosage form was twice that of the stirred dosage form. The apparent permeability of cyclosporine from the homogenized emulsion was about twice that of the emulsion prepared by stirring. The examination of absorption in different intestinal segment lengths suggested the presence of an "absorption window." The absorption of cyclosporine appeared to be concentration independent and, therefore, non-carrier mediated. The dependence of absorption upon the intestinal perfusion rate suggested that the stagnant aqueous layer is the rate-limiting barrier in cyclosporine absorption. These results indicate that the bioavailability of cyclosporine administered in an emulsion can possibly be increased by enhancing its rate of absorption through the reduction of droplet size.

Animals