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PubMed1984

Gastro-intestinal absorption and in vitro release of boric acid from water-emulsifying ointments.

Boric acid taken orally by six male volunteers in a cross-over study was absorbed to equal extents from a water solution and a 3% waterless, water-emulsifying ointment, though with a slight initial delay in the latter case. Virtually complete gastro-intestinal absorption and renal excretion were indicated by the 96-hr urinary recovery, amounting to 89.1-98.3% (mean 93.9%) and 89.2-97.5% (mean 92.4%) of the dose ingested as solution and ointment, respectively, normal daily boron excretion having been taken into account. The in vitro release of boric acid, measured for 24 hr by dialysis in water at 37 degrees C, reached 95% from a purely water-based jelly but only about 5% from the water-emulsifying ointment. The low boric acid release from the ointment was not significantly influenced when the ointment was dialysed against buffer solutions of pH 2.5 and 9.6 instead of water, or when the maximum possible amount of water (26.9% w/w) was incorporated into the ointment before dialysis. The 24-hr boric acid release from a number of other oil-based ointments, either hydrophobic or water-emulsifying and containing 1-3% boric acid and 0-28.5% water, was also low (0.9-18.3% of the boric acid content). This indicates that the formulation of the ointment is an important factor in determining the extent of release of boric acid when the ointment is applied externally, but that it does not alter the absorption of boric acid should the ointment be ingested.

Administration, Oral↗
PubMed1985

Intestinal absorption and renal excretion of biotin in patients with biotinidase deficiency.

We have investigated four patients from three unrelated families with typical clinical and biochemical features of "late-onset" multiple carboxylase deficiency. All patients suffered from biotinidase deficiency (plasma biotinidase activities 1.4%-3% of normal). Intestinal absorption of biotin, measured in three of the patients using a single load of 1.5 micrograms/kg, was found to be normal. Deficient activities of the mitochondrial biotin-dependent carboxylases in lymphocytes of one of these patients increased from 25% of mean basal control values to 33%-36% within 45 min and to 46%-47% within 2 h of the 1.5 micrograms/kg biotin load. After a high biotin load of 100 micrograms/kg, the values normalised within 45 min in all three patients studied. These results indicate normal cellular transport of biotin and normal holocarboxylase synthesis. After cessation of biotin supplementation, the plasma and urinary biotin in patients decreased to subnormal levels. In one patient, available for more detailed studies, both plasma and urinary biotin declined about twice as fast as in controls (apparent half-life 12-14 h in the patient and 26 h in controls). These results point to increased excretion of free biotin in our patient. Renal loss of biotin is one of the factors contributing to the high biotin requirement observed in patients with biotinidase deficiency.

Amidohydrolases↗
PubMed1986

Enhancement of small intestine absorption by intraluminal gastrin.

Several studies have suggested that gastrointestinal peptides can produce trophic changes in the small intestine epithelium. In a previous study utilizing a rat fetal intestine transplant model, we reported that chronic, continuous, systemic administration of gastrin-17 increased carbohydrate absorption 2.5-fold and protein absorption 1.3-fold. The present study was designed to evaluate the effect of chronic luminal perfusion of gastrin on substrate absorption in rat mature small intestine. A 10-cm segment of mid small intestine was isolated with both ends brought out as abdominal wall stomas (creating a Thiry-Vella loop) and bowel continuity was established by end-to-end anastomosis. After a 1-week recovery, the tips of two catheters were positioned at approximately 3 and 6 cm from the proximal end of the isolated small intestine segment. A 14-day continuous luminal perfusion was accomplished by connecting the other ends of the catheters to subcutaneously placed osmotic pumps filled to deliver saline (control; N = 10) or gastrin-17 (13.5 nM/kg/day; N = 7). At the completion of the luminal perfusion, intestinal absorption was determined with labeled substrates [14C]galactose and [14C]glycine) using a closed, recirculation technique. Absorption (microM/cm2 small intestine) of galactose in the control animals was 1.44 +/- 0.18 and for the gastrin infused rats, it was 6.56 +/- 0.46. Glycine absorption was 1.63 +/- 0.31 for the control group and 7.83 +/- 0.62 for the gastrin infused group. Thus, in this rat model, intraluminal gastrin infusion was capable of increasing carbohydrate (galactose) absorption 456% (P less than 0.01) and protein (glycine) absorption 480% (P less than 0.01). These data represent the first demonstration that intraluminal gastrin can influence small intestine mucosal function by enhancing substrate absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of tumour necrosis factor-alpha (cachectin) on glucose metabolism in the rat. Intestinal absorption and isolated enterocyte metabolism.

Intravenous administration of a single dose (20 micrograms) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats decreased the rate of intestinal glucose absorption. In vivo, the oxidation of [U-14C]glucose to 14CO2 was significantly increased by the cytokine. In addition, [14C]lipid accumulation from [U-14C]glucose was increased both in liver and brown adipose tissue of the TNF-injected animals. The decrease observed in intestinal glucose absorption was not associated with changes in intestinal metabolism. There was no difference in glucose metabolism by isolated enterocytes from either control or TNF-injected rats whether in the absence or presence of different concentrations of the cytokine in the incubation medium. In contrast, tumour necrosis factor altered the rate of gastric emptying as measured by the gastrointestinal distribution of 3[H]inulin following an intragastric glucose load. These results suggest that the cytokine profoundly alters glucose metabolism by increasing its whole-body oxidation rate and delaying intestinal absorption through a reduced gastric emptying.

Adipose Tissue, Brown↗
PubMed1989

Oxalate metabolism in renal stone disease with special reference to calcium metabolism and intestinal absorption.

Hyperoxaluria and hypercalciuria are common features of renal calcium stone disease. The purpose of the present investigation was to examine the relationships between the intestinal absorption and the renal handling of oxalate and calcium in patients with idiopathic renal stone disease and in patients with enteric hyperoxaluria following jejunoileal bypass (JIB), in comparison with healthy controls. Hyperoxaluria was associated with a higher frequency of both stone episodes and stone operations than a lower urinary oxalate concentration. Patients with idiopathic stone disease showed increased intestinal uptake of both oxalate and calcium, which was probably of importance for their propensity to form calcium oxalate-containing stones. Hyperoxaluria in patients with JIB was found to be a result of hyperabsorption of oxalate, and these patients displayed altered oxalate kinetics with continued urinary excretion of orally administered 14C-oxalate for more than 48 hours. The prolonged excretion is assumed to be due to a prolonged absorption and/or an increased oxalate pool. Malabsorption of calcium and low fasting urinary calcium excretion in the JIB patients were associated with high tubular reabsorption of calcium, the latter presumably attributable to a compensatory increase in circulating parathyroid hormone (PTH). In most recurrent renal stone formers the urinary calcium concentration was increased, with an inverse relationship to serum PTH, indicating intestinal hyperabsorption of calcium. A subgroup of hypercalciuric patients showed increased urinary calcium due to reduced tubular reabsorption of calcium. It is suggested that this is a renal defect resulting in a compensatory rise in PTH. Two different mechanisms of similar prevalence might explain enhanced secretion of PTH in normocalcaemic stone disease, namely reduced calcium absorption and a renal defect in the form of reduced tubular reabsorption of calcium. Glycosaminoglycans efficiently inhibit calcium oxalate crystal growth by binding to the surface of calcium oxalate crystals. In this study the binding was dependent on ionic strength. Higher affinity to the crystals may be the reason why highly charged glycosaminoglycans were more efficient inhibitors of calcium oxalate crystal growth. A calcium-containing organic marine hydrocolloid with the capacity to bind oxalate in vitro was shown to reduce enteric hyperoxaluria. In addition to biochemical effects considerable improvements in diarrhoeal symptoms were reported.

Adult↗
PubMed1988

[Effect of roasted wheat flour on the intestinal absorption and zinc metabolism of rats].

24 experiences have been carried in 8 younger Wistar female rats that been submitted to three different diets considering fibers and phytates, with the purpose to demonstrate if "gofio de trigo" of popular consumption in Canary Islands, and rich in these substances affects intestinal absorption of zinc in the diet. Authors have observed a very significant elevation of zinc in feces, during the control period. An important decrease of zinc in hair has been observed indicating a deficit of corporal ion although zinc in serum remained in its normal limit. Authors emphasize the fact that under these circumstances, removal of urinary zinc is not a useful guide for diagnosis of deficiency state.

Animals↗
PubMed1993

Site-dependent effect of aprotinin, sodium caprate, Na2EDTA and sodium glycocholate on intestinal absorption of insulin.

In order to determine an advantageous site for intestinal insulin absorption, the hypoglycemic effects of insulin after administration to the duodenum, the jejunum, the ileum and the colon were investigated using an in situ loop method. Insulin solution was administered to the various loops of fasted rats with or without aprotinin (AP) as a protease inhibitor, or absorption enhancers such as sodium caprate, Na2EDTA or sodium glycocholate. An obvious hypoglycemic effect of insulin alone was seen only in the ileum loop washed with phosphate buffered saline. When coadministered with AP, the most remarkably amplified effect was again observed in the ileum. In the ileum, the area under the serum insulin levels vs. time curve from 0 to 4 h was linearly related to the logarithm of the AP dose. Both sodium caprate and Na2EDTA significantly promoted the hypoglycemic effect of insulin at all sites, and their intensity increased towards the distal regions of the intestine. On the other hand, sodium glycocholate improved only colonic insulin efficacy. These results suggest that the ileum seems to be the most useful region in the small intestine for insulin absorption; however, insulin must be protected from proteolysis to enhance its absorption. In addition, the insulin efficacy could be increased by absorption promoters more effectively in the colon than in the small intestine.

Animals↗
PubMed1996

Unchanged intestinal absorption in rats fed a high sweet paprika-containing diet.

The absorption rate of radiolabelled nutrients (22Na, 45Ca, [35S]methionine, [3H]leucine) was investigated in vivo in Sprague-Dawley rats at the end of a feeding period of 135 days on a semisynthetic diet containing 32% sweet paprika powder. No effect was seen on the intestinal absorption of these compounds, nor on the nutritive experimental parameters in these animals.

Animals↗
PubMed1996

Water-in-oil microemulsions containing medium-chain fatty acids/salts: formulation and intestinal absorption enhancement evaluation.

PURPOSE: Water-in-oil (w/o) microemulsions have been developed which, in addition to non-ionic medium-chain glycerides, incorporate ionic lipids, primarily medium-chain fatty acids, such as caprylic (C8) capric (C10) and lauric (C12) acids and their corresponding sodium salts. The absorption enhancing activity of w/o microemulsions incorporating these lipids was evaluated in the rat using Calcein (MW = 623) a water-soluble and poorly absorbed marker molecule. METHODS: Phase diagrams were constructed where C8/C10 or C12 fatty acids were treated as lipophilic surfactants and their sodium salts as hydrophilic ones. The anesthetised rat model was employed to evaluate Calcein absorption upon a single intraduodenal administration from a solution and the various w/o microemulsions. RESULTS: A wide range of clear and transparent w/o microemulsions were obtained at ambient temperature either in liquid or solid form when a fixed blend of medium chain fatty acid/salt was titrated by a fixed ratio of the oil containing the oil-soluble mono- and diglycerides and deionized water or physiological saline. Upon intraduodenal administration in the anesthetised rat, the absorption of Calcein was improved from about 2% in aqueous solution up to about 37% in w/o microemulsions. Solid and liquid formulations were equally effective in improving bioavailability. The absorption enhancement activity of the fatty acids/salts followed the order C8 approximately C10 > C12. Absorption enhancement of Calcein was significantly reduced in the absence or presence of low levels of C8/C10 mono-/diglycerides. CONCLUSIONS: These results further support the use of medium-chain glycerides and fatty acids/salts in microemulsion formulations to improve intestinal absorption of water-soluble compounds.

Animals↗
PubMed2002

Intestinal absorption and lymphatic transport of a high gamma-linolenic acid canola oil in lymph fistula Sprague-Dawley rats.

A new canola strain capable of producing >30% gamma-linolenic acid [GLA, 18:3(n-6)] in the seed oil has been developed in our laboratories. This study compares the intestinal absorption and lymphatic transport of this newly developed high GLA content canola oil (HGCO) with traditional GLA-rich borage oil (BO) using a lymph fistula rat model. To assess the extent that 1 mL of GLA in the supplemented oil was absorbed and transported, the fatty acid compositions of triglycerides in mesenteric lymph were compared over a 24-h collection period. The digestion, uptake and lymphatic transport of HGCO and the normal physiologic changes associated with fat absorption (e.g., lymph flow and an increase in lymphatic endogenous lipids outputs, triglycerides, cholesterol and phospholipids) were similar in the HGCO-and the BO-fed rats. The original differences in gamma-linolenic acid content in HGCO and BO were preserved in the fatty acid composition of the rats' lymph lipid. We conclude that the HGCO derived from the genetically modified canola plant is absorbed and transported into lymph similarly to BO.

Animals↗
PubMed1996

Interaction of taurine on baclofen intestinal absorption: a nonlinear mathematical treatment using differential equations to describe kinetic inhibition models.

Previous studies showed that the in situ absorption of baclofen in rat jejunum was inhibited by beta-alanine, a nonessential amino acid, and therefore mediated, at least in part, by some beta-amino acid carrier. In this paper a similar study was undertaken using taurine, a sulfonic beta-amino acid, in order to evaluate its effect and to establish a general inhibition model. To achieve this goal, remaining concentrations of inhibitor were also measured and incorporated into the model. Previously, kinetic absorption in situ parameters for taurine in free solution were obtained: Vm = 27.73 +/- 9.99 mM h-1, K(m) = 8.06 +/- 2.82 mM, Ka (passive difussion component) = 0.40 +/- 0.28 h-1. Isotonic solutions containing 0.5 mM baclofen with starting taurine concentrations ranging from 0 to 100 mM were perfused in rat jejunum, and the remaining concentrations of both compounds were measured. The apparent rate pseudoconstant of the drug clearly decreased as the remaining taurine concentration increased. The interaction can be described as a complete competitive inhibition plus a second component, K, noninhibited, K = 0.58 (+/- 0.03) h-1, Ki = 20.62 (+/- 4.04) mM, Vmi = 28.12 (+/- 6.12) mM h-1, Kmi = 11.71 (+/- 2.53) mM, Kai = 0.47 (+/- 0.10) h-1. A residual absorption of baclofen in the presence of high taurine concentrations was observed, which should be attributed to another transport system not associated with the taurine carrier. In order to elucidate whether or not taurine and beta-alanine carriers are two separate entities that baclofen can use for absorption, further experiments using beta-alanine and taurine together as inhibitors (baclofen, 0.5 mM; beta-alanine, 50 mM, and taurine, 50 mM) were developed. Results indicated that baclofen and both amino acids share the same carrier in the intestinal absorption process. We have completed studies using leucine, taurine, and GABA together as inhibitors of drug absorption. An isotonic perfusion solution of 0.5 mM baclofen in the presence of 50 mM leucine, 25 mM taurine, and 25 mM GABA was perfused. Under these conditions the absorption rate pseudoconstant of baclofen decreases until 0.080 h-1 (+/- 0.069). Practical implications of these phenomena are briefly discussed.

Animals↗
PubMed1985

Intestinal absorption of nutrients in animals dosed orally with retinoids: considerations for chemopreventive studies.

Biochemical measurements demonstrate that, in some species, various retinoids administered in the diet, can reduce the tissue contents of several lipid-soluble compounds: vitamin K, alpha-tocopherol, cholesterol, and vitamin A itself. The effect is probably due to an interference with intestinal absorption, as indicated by use of radioactive compounds and administration of bile acids. In male rats, a vitamin K deficiency induced by retinoids in the diet can lead to fatal hemorrhaging. Although retinoids inhibit the uptake of dietary cholesterol, they do not change plasma and tissue concentrations of the endogenous compound. Conversely, cholesterol in the diet appears to interfere with the absorption of retinyl esters. alpha-Tocopherol deficiency caused by retinoids results in tissues with low antioxidant and high peroxide concentrations. Humans may be less susceptible to these effects of retinoids, which, however, still deserve consideration in the planning of clinical trials.

Administration, Oral↗
PubMed1989

Studies on intestinal absorption, distribution and metabolism of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro[4-14C]stigmast-5-ene in mice.

A method for the analysis of 3 beta-chloro steroids by high-performance liquid chromatography is described. These compounds are known to occur in commercial protein hydrolysates. The gastro-intestinal absorption, distribution and metabolism of chlorinated steroids were studied after their intragastric application to mice. At 2 hr after stomach intubation of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro-[4-14C]stigmast-5-ene, large proportions of radioactivity had passed through the small intestine and were found to be concentrated in the contents of the caecum and colon. Very small amounts of 3 beta-chlorocholest-5-ene were absorbed by the intestinal mucosa and distributed to organs and tissues outside the alimentary canal, whereas intestinal permeability of 3 beta-chlorostigmast-5-ene was negligible. After administration of labelled 3 beta-chlorocholest-5-ene, the highest value of radioactivity, 120 Bq/g tissue, outside the intestinal tract was detected in liver. Altogether, less than 0.5% of the total radioactivity applied to the animals was found to be transported through the intestinal wall and less than 0.5% of the total radioactivity was detected in various metabolites. In general, 3 beta-chlorostigmast-5-ene was transported in smaller proportions and metabolized to a lesser extent than the corresponding cholesterol derivative. Moreover, metabolites of the two radioactive substrates formed by enzymatic attack of enteric micro-organisms were not detected in the contents of the caecum and colon. It appears that 3 beta-chlorinated steroids are fairly stable products that are metabolized poorly both by the cells of the intestinal mucosa and by enteric micro-organisms of mice.

Animals↗
PubMed1992

Further studies of the effect of zinc on intestinal absorption of calcium in man.

In a previous study dietary supplementation with 140 mg zinc (Zn) as Zn sulfate (ZnSO4) per day significantly decreased absorption of calcium (Ca) during a low Ca intake (230 mg/day) but not during a normal Ca intake (800 mg/day). The purpose of the present study was to determine whether smaller doses of Zn would also inhibit Ca absorption during the 230 mg Ca intake, and whether the 140 mg dose of Zn would inhibit Ca absorption during a Ca intake less than 800 mg/day. To investigate the first aspect, 100 mg Zn as ZnSO4, was given daily during a low Ca intake (230 mg/day) in six studies, and in the second phase, 140 mg Zn as ZnSO4 was given during a Ca intake of of 500 mg/day in five studies. Intestinal absorption of Ca was determined with tracer doses of 47CaCl2 in control studies and in the two Zn supplementation studies. Results showed that 100 mg Zn/day during a low Ca intake (230 mg/day) did not inhibit Ca absorption and that 140 mg Zn given during the 500 mg Ca intake also did not affect the absorption of Ca.

Aged↗
PubMedDate not supplied

L-glutamine supplementation in home total parenteral nutrition patients: stability, safety, and effects on intestinal absorption.

A study was conducted to determine safety and efficacy of L-glutamine when added to total parenteral nutrition (TPN) solutions of patients receiving TPN in the home. Stability studies were first performed on various concentrations of L-glutamine in TPN solutions mixed by the Pharmix method. These showed that glutamine was stable in home TPN solutions for at least 22 days. The daily home TPN solutions of seven stable patients were then supplemented with glutamine at a dose of 0.285 g/kg of body weight for 4 weeks. The glutamine-TPN solutions were prepared weekly. Five patients received the full 4 weeks of glutamine-TPN. In two patients, administration of glutamine-TPN mixtures was stopped at the end of week 2 and week 3 because of elevations in liver enzymes. A third patient's liver enzymes rose at the end of week 4. These abnormalities subsided after discontinuation of the glutamine-TPN solution. Plasma levels of glutamine increased during the first 3 weeks of supplementation but these increases were not statistically significant. D-Xylose absorption studies performed before and after the administration of glutamine-TPN did not reveal any improvement in small-bowel absorptive capacity. In conclusion, stable glutamine-TPN solutions for use by home TPN patients can be formulated. However, supplementation of home TPN solutions at this dose was associated with apparent hepatic toxicity and did not demonstrate a beneficial effect on intestinal absorptive capacity as measured by D-xylose absorption. Therefore, on the basis of this study, routine supplementation of home TPN solution with glutamine cannot be recommended.

Adult↗
PubMed2001

Chitosan and its derivatives as intestinal absorption enhancers.

Chitosan is a non-toxic, biocompatible polymer that has found a number of applications in drug delivery including that of absorption enhancer of hydrophilic macromolecular drugs. Chitosan, when protonated (pH<6.5), is able to increase the paracellular permeability of peptide drugs across mucosal epithelia. Chitosan derivatives have been evaluated to overcome chitosan's limited solubility and effectiveness as absorption enhancer at neutral pH values such as those found in the intestinal tract. Trimethyl chitosan chloride (TMC) has been synthesized at different degrees of quaternization. This quaternized polymer forms complexes with anionic macromolecules and gels or solutions with cationic or neutral compounds in aqueous environments and neutral pH values. TMC has been shown to considerably increase the permeation of neutral and cationic peptide analogs across Caco-2 intestinal epithelia. The mechanism by which TMC is enhancing the intestinal permeability is similar to that of protonated chitosan. It reversibly interacts with components of the tight junctions, leading to widening of the paracellular routes. This chitosan derivative does not provoke damage of the cell membrane, and does not alter the viability of intestinal epithelial cells. Co-administrations of TMC with peptide drugs were found to substantially increase the bioavailability of the peptide in both rats and juvenile pigs compared with administrations without the polymer.

Animals↗