Enhancement effect of methylxanthines on the intestinal absorption of poorly absorbable dyes from the rat small intestine.
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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.
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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.
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.
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.
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.
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.
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.
Intestinal absorption and first-pass elimination of 2',3'-dideoxynucleosides (ddNs), including 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (DDI) and 2',3'-didehydro-3'-deoxythymidine (D4T), following oral administration was investigated in rats. Enzymatic degradation of ddNs in rat intestinal washing and in the intestinal homogenate showed them to be stable in the washing with half lives of more than 140 h, whereas degradation of DDI in the intestinal homogenate was more than ten times as rapid as those of AZT and D4T. Intestinal absorption was studied in three segments of the rat intestine (duodenum, jejunum and colon) using an in situ closed-loop method. The area under plasma ddN concentration curve (AUC) and the residual percent of dose 1 h after dosing indicated a greater absorption of AZT and D4T in the upper intestinal tract than in the colon, very poor absorption of DDI in all segments, and considerable absorption of AZT in the colon. The AUC and the mean residence time (MRT) of ddNs following four different routes (intravenous: i.v., intra portal vein: i.p.v., intra duodenal: i.d. and intra gastric: i.g.) were measured using the in viva multiple sites of input method in rats. AZT and D4T were rapidly absorbed from the gastrointestinal tract and their bioavailability was more than 90%. DDI was less absorbed (33.02%) following i.d. administration compared with AZT and D4T. This poor absorption of DDI was partly attributable to its metabolism in the intestine.
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.
The ultrastructural changes in the intestinal absorptive cells of the rat during the absorption of triglycerides, Particularly medium chain triglyceride (MCT), were studied by electron microscopy. In the absorptive cell of rats fed with MCT, the agranular endoplasmic reticulum in tubular form was remarkably proliferated throughout the cytoplasm as compared with that of fasting rats. The granular endoplasmic reticulum was mostly transformed into the same tubulo-vesicular form as the agranular endoplasmic reticulum. Chylomicra, which were consistently observed in the endoplasmic reticulum of the intestinal absorptive cell of rats fed with long chain triglyceride (LCT), did not appear in that of MCT-fed rats, although small lipid particles were noticed within it. The Golgi lamellae decreased in number and length. During the absorption of MCT, the central lacteal contained some lipid particles which were smaller in size than the chylomicron which appeared in the LCT-fed rats. These evidences might suggest that the majority of MCT administered was transported through the absorptive cell without reesterification in the endoplasmic reticulum into the portal vein system, and only a minor part of the MCT given was transported via the central lacteal after reesterification.
The apparent absorption of nitrogen and minerals was studied in 8 ileostomy subjects. Four different test diets containing 60 g of meat, rice and bread protein, or a 25% replacement of the protein with soy flour, soy concentrate or soy isolate, were randomly assigned to the subjects in 2-d periods. All animal protein was replaced by soy isolate for a fifth 2-d period in two of the subjects. Ileostomy contents were collected in 2-h intervals during the day and in one portion during night and immediately deep-frozen. The fiber components and the phytic acid in the diet were almost completely recovered in the ileostomy contents, whereas unabsorbed starch was less than 2% of the intake. A significantly lower protein digestibility was observed when the diets containing soy protein were fed. No difference in protein digestibility was found between the different soy protein products. A 25% replacement by soy protein had no obvious effect on apparent mineral absorption. A low protein digestibility was also observed when soy was the main source of protein, and a negative apparent absorption of zinc was found in both subjects. Although 25% of soy protein in the diet does not seem to impair mineral absorption significantly, small intestinal net absorption of nitrogen is less from the soy diets than from the meat diet.
The effect of renal failure (RF) on intestinal absorption of dietary fatty acids is not known. We studied the intestinal absorption of arachidonic acid (AA) in rats with experimental short-term (2 weeks post-subtotal nephrectomy) and long-term (5-6 weeks post-subtotal nephrectomy) RF. The results were compared with those obtained in sham-operated animals on liberal food intake (NL) and in those pair-fed (PF) with the respective RF groups. In vivo perfusion and in vitro incubation experiments were performed at a wide range of AA concentrations. The rates of AA transport determined both in vivo and in vitro were significantly lower in the short-term RF group than those found in the NL controls and the PF animals who showed comparable values. In contrast animals with long-term RF exhibited an increased rate of AA transport as compared with the respective controls. The observed changes in the transport rates appeared to parallel directional changes in mucosal mass which was reduced in animals with short-term RF and restored in those with long-term RF.
The part played by calcium in genesis of essential hypertension may be suspected. Yet, the whole of epidemiological research as well in the animal as in man is still not very convincing. The objective of such a research has been to appreciate the calcium intestinal absorption before and after nicardipine treatment in 11 subjects (5 M/6 F) aged between 32 and 82. The group is made up of 7 hypertensive patients (2 M/5 F) and 4 normotensive ones (3 M/1 F). Subjects showing bone disease, kidney insufficiency and stone in kidneys or under such a treatment as to interfere with calcium metabolism had been excluded. Dosage of calcium and phosphate, Na, K, aldosterone, in blood and urine and PTH and PRA in blood had been effectuated. Estimation of true calcium absorption has been made by double isotope deconvolution method. Blood pressure has been measured by semi-ambulatory monitoring method. Similar evaluation has been made after four weeks treatment (60 mg of nicardipine a day). Without any treatment, normotensive subjects have a lower intestinal absorption coefficient than the hypertensive ones, which is normal (non significative statistical results: NS). Under nicardipine, hypertensive patients seem to get lower intestinal absorption (NS); other clinical, biological parameters show no change, except a rise of apoprotein A after nicardipine treatment (P less than or equal to 0.05). So, the intestinal absorption of calcium would become higher in hypertensive subjects and diminished by calcium antagonist treatment.
The effects of age on intestinal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied using adult male Fischer-344 rats of 3 different age groups: 13 weeks old (young), 13 months old (mature), and 26 months old (senescent). Absorption was measured with an in situ intestinal recirculation perfusion procedure. Absorption expressed in terms of ng TCDD absorbed/g intestinal dry weight/h was 166, 149 and 143 ng/g/h in the young, mature and senescent groups, respectively. When absorption was calculated in terms of ng TCDD absorbed/g mucosal dry weight/h, the decrease between the senescent rats and the 2 younger age groups, from 544 ng/g/h (young) to 351 ng/g/h (senescent), was not statistically significant (P less than 0.05). It was demonstrated that absorption of TCDD was unaffected by the presence of 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) in the perfusate, but that HCB absorption was (P less than 0.01) enhanced by the presence of TCDD.