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In vitro percutaneous absorption of benzidine in complex mechanistically defined chemical mixtures.

Little work has been done on the topical absorption of the bladder carcinogen benzidine. Since humans are more likely to be exposed to chemical mixtures than to a single chemical, a program was developed in these laboratories to examine the cumulative effect of complex mixtures on percutaneous absorption of important toxicants such as benzidine. In this investigation, a mixture is defined as a physical combination consisting of a marker chemical and several other chemicals, each of which can have independent and/or synergistic effects on dermal penetration and absorption of the marker chemical. Ten mixtures, consisting of a marker chemical (benzidine, B), a solvent (acetone, A or DMSO, D), a surfactant (0 or 10% sodium lauryl sulfate, SL), a vasodilator (0 or 180 microg methyl nicotinate, M), and a reducing agent (0 or 2% SnCl2, s) were employed in this study. Isolated perfused porcine skin flaps (IPPSFs), which have proven to be a suitable in vitro model for assessing dermal absorption and toxicity, and flow-through diffusion cell systems were utilized. The extent of benzidine absorption in skin sections dosed with either B + A (0.94% dose) or B + D (1.01% dose) was similar to that when IPPSFs were dosed with either B + A (0.54% dose) or B + D (1.31% dose). However, flux vs time profiles were different when the two in vitro methods were compared. For mixtures containing (1) DMSO only or acetone only or (2) solvents containing SL + M, benzidine absorption was enhanced when compared with other mixtures. Compared to acetone, DMSO appears to enhance dermal penetration of benzidine in most of the mixtures. Compared to other mixtures evaluated, SnCl2 inhibited benzidine absorption irrespective of solvent present. SnCl2 also appears to inhibit benzidine penetration in DMSO mixtures containing SL only, but not in acetone mixtures. It is proposed that chemical-chemical interactions between benzidine and SnCl2 may be inhibiting benzidine absorption and chemical-biological interactions between M + SL and skin may be enhancing benzidine absorption. Across all mixtures, maximum observed benzidine absorption was almost 3% of the topical dose over 8 hr, but maximum penetration was 22% over the same time period which would suggest a potential for greater systemic exposure over longer time frames. This work underscores the need to study potentially toxic chemicals in mixture exposure scenarios since the interactions observed would confound risk assessment based on single chemical data.

Animals↗

The influence of diethyl-m-toluamide (DEET) on the percutaneous absorption of permethrin and carbaryl.

Simultaneous exposure to DEET and permethrin was recently proposed to be associated with the "Gulf War Syndrome." However, no studies have reported the percutaneous absorption of DEET and permethrin when applied simultaneously to the skin as a mixture, the relevant route of exposure in the Persian Gulf. The present study quantitates percutaneous absorption of DEET and permethrin after coadministration to rodent and pig skin in vitro. Dosing solutions were also prepared with either acetone, dimethyl sulfoxide (DMSO), or ethanol to compare vehicle effects on percutaneous absorption of permethrin and DEET. The influence of DEET on carbaryl absorption and dermal disposition was also assessed in pig studies to statistically demonstrate DEET effects in acetone or DMSO and different solvent concentrations. Topical application of permethrin + DEET resulted in absorption of DEET (1-20% dose), but no permethrin. Permethrin (1.2-1.7% dose) was detected only when mouse skin was dosed solely with permethrin, a finding suggesting that DEET decreased permethrin absorption. DEET also inhibited carbaryl absorption in acetone mixtures, but had no effect on DMSO mixtures. Irrespective of solvent, DEET did not enhance carbaryl penetration into skin. For DEET, absorption was greater in mouse skin (10.7-20.6% dose) than in rat skin (1.1-5.2% dose) and pig skin (2.8% dose). The extent of DEET absorption was greater with DMSO and acetone than with ethanol in rat and mouse skin. These studies support DEET, but not permethrin or carbaryl, as having sufficient systemic exposure to potentially cause signs of toxicity when simultaneously applied with pesticides. Furthermore, these studies demonstrated that DEET does not necessarily enhance dermal absorption of all toxicants as was originally hypothesized.

Administration, Cutaneous↗

Pentachlorophenol dermal absorption and disposition from soil in swine: effects of occlusion and skin microorganism inhibition.

Residue of the environmentally relevant biocide pentachlorophenol (PCP) is found mainly in soil, making dermal contact one of the primary routes for PCP exposure. To quantify exposure effects on dermal absorption and systemic disposition, [14C-UL]PCP was dosed nonocclusively or occlusively at 40 micrograms/cm2 in a soil-based mixture in an in vivo swine model. Additionally, antibiotics were also codosed with occlusive PCP in soil to examine the impacts of skin microbial PCP biodegradation on total dermal absorption. Under nonocclusive, occlusive, and occlusive-antibiotic conditions, total radiolabel absorption by 408 hr was 29.08, 100.72, and 86.21% dose, respectively. Tissue accumulation of PCP and its labeled metabolite(s) was very significant in swine since one-half to two-thirds of the absorbed dose was still present in tissues by 17 days after PCP dermal exposure. High 14C concentrations were found in liver, kidney, lung, ovary, and uterus. Urine and fecal routes were equally important for label excretion from the body. Occlusion enhanced total dermal absorption and changed the shape of the absorption profiles in the blood and plasma. Skin microorganism inhibition retarded 14C dermal absorption, altered local and systemic tissue distribution, and increased plasma/blood concentration ratios, suggesting skin microbial PCP degradation might play an important role in the altered absorption and disposition by occlusion. This study demonstrated significant dermal absorption and extensive tissue persistence of PCP after soil exposure. Occlusion and skin microflora growth may greatly impact dermal absorption, cutaneous disposition, and systemic toxic input. Therefore, exposure-specific PCP absorption and disposition profiles must be taken into consideration in risk analysis.

Animals↗

Effects of fusarenon-X and T-2 toxin on intestinal absorption of monosaccharide in rats.

In order to delineate the effects of Fusarenon-X (FX) and T-2 toxin (T-2) on intestinal absorption of monosaccharide, jejunal absorption in vivo and uptake in vitro of 3-0-methyl glucose (m-glucose) and L-glucose were studied in rats. Jejunal absorption in vivo was assessed by determining the rate of appearance of the sugars in plasma of the mesenteric vein draining the jejunal segment, which was perfused with the medium containing radiolabelled m-glucose or L-glucose. Jejunal uptake in vitro was assessed by determining the m-glucose or L-glucose uptake by the everted jejunum taken from toxin-treated rats. m-Glucose absorption was reduced 1 or 3 h after either toxin was injected into the jejunal lumen. A reduction of m-glucose absorption was also noted after intravenous injection of the toxins, although the timing and magnitude of the reduction were slightly different from those seen after the luminal injection. These results suggest that both toxins impair the jejunal function relating to monosaccharide absorption in the early stages of intoxication. The reduction in m-glucose absorption was associated with a reduction in L-glucose absorption and unchanged or increased uptake of L-glucose. The active transport component, which was indicated by the difference between absorption or uptake of the two sugars, was also reduced in association with the reduction of m-glucose absorption. These results suggest that the toxins cause specific damage in the active transport system for monosaccharides on the one hand, and impairment of their diffusional movement from the epithelial layer to the mesenteric vein on the other.

3-O-Methylglucose↗

Variations in percutaneous absorption of testosterone in the rhesus monkey due to anatomic site of application and frequency of application.

This study determines if the anatomic region affected percutaneous absorption in the rhesus monkey, an animal model with some relevance to man. Percutaneous absorption of testosterone (13.3 microgram/cm2) from the ventral forearm was 8.8 +/- 2.5%. Absorption from the chest was slightly less (5.3 +/- 0.6%) while that from the cheek was about the same (9.6 +/- 0.2%). Absorption from the scalp was greatly increased (20.4 +/- 2.7%), that from the vagina was the greatest (63.1 +/- 2.6%). As previously noted in man, anatomic variation in skin absorption exists in the rhesus. The ratio of scalp absorption to ventral forearm absorption in the rhesus was similar to that in man. The next objective was to determine the percutaneous absorption of testosterone when applied as a single dose or on a repetitive basis. There was no substantial difference in total absorption when 13.3 microgram/cm2 was applied as a single dose or when the 13.3 microgram/cm2 was applied three times, totaling 40 microgram/cm2. However, when 40 microgram/cm2 was applied as a single dose, absorption was substantially increased over 13.3 microgram/cm2 applied either once or three times. These results confirm previously reported results done with single versus repetitive doses of hydrocortisone.

Animals↗

Inhibition of iron absorption by omeprazole in rat model.

Since gastric acid is an important luminal factor in the absorption of non-heme iron, the effect of omeprazole on the absorption of iron in a rat model was studied. Iron absorption studies were performed on rats on a normal diet (N = 42) and rats fed an iron-deficient diet (N = 43) for three weeks. Rats were orally dosed with 40 mumol/kg of omeprazole or placebo daily for two days prior to iron absorption studies. Rats were orally dosed with 1 mmol of ferrous chloride, ferric chloride or food iron (dietary suspension) containing 11 micrograms of iron and labeled with 1 microCi of 59Fe. Omeprazole-treated rats on the normal diet had no significant reduction in the absorption of ferric, ferrous, or food iron. In the rats on the iron-deficient diet, the absorption of ferrous iron decreased from 76 +/- 7.5% (mean +/- SE) in control rats to 38 +/- 8.5% in the omeprazole-treated rats (P less than 0.003) and the absorption of food iron decreased from 65 +/- 7.5% in control rats to 37 +/- 6.5% in the omeprazole-treated rats (P less than 0.016). There was no significant reduction in the absorption of ferric iron. Omeprazole therapy is unlikely to be associated with significant iron malabsorption in normal patients but may reduce iron absorption in pathological states associated with increased iron absorption such as iron deficiency.

Absorption↗

Colonic absorption of unconjugated bile acids: perfusion studies in man.

Colonic absorption of three major unconjugated bile acids--cholate, chenodeoxycholate, and deoxycholate--was measured under steady-state conditions using a technique of colonic perfusion in healthy volunteers. Aqueous solutions at pH 8.0 and varying in concentration from 1 mM to 10 mM were used. The rate of chenodeoxycholate absorption averaged nine times that of cholate absorption; deoxycholate absorption was somewhat less than that of chenodeoxycholate absorption, averaging six times that of cholate. At concentrations below 5 mM, the rate of absorption of bile acids was directly proportional to concentration, so that "clearance" could be calculated. Clearance values for a 1-mM solution (ml/min/colon, mean +/- SE) were: chenodeoxycholate, 9.84 +/- 1.0; deoxycholate, 7.0 +/- 1; and cholate, 0.82 +/- 0.10. Since absorption was proportional to concentration in the lumen, and was more rapid for the dihydroxy acids, the major mechanism of absorption was thought to be passive nonionic diffusion. Maximal rates of bile acid absorption were calculated from a 1-mM solution and found to be as high as 4.2 g/day for chenodeoxycholate, 3.2 g/day for deoxycholate, and 0.5 g/day for cholate, and the rate would be still greater for more concentrated solutions. Colonic absorption may contribute significantly to conservation of the dihydroxy bile acid pool, especially in conditions of bile acid malabsorption.

Bile Acids and Salts↗

Mixture component effects on the in vitro dermal absorption of pentachlorophenol.

Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal risk assessment process, would be greatly improved by the elucidation and characterization of these interactions. Pentachlorophenol (PCP), a compound known to penetrate the skin readily, was used as a marker compound to examine mixture component effects using in vitro porcine skin models. PCP was administered in ethanol or in a 40% ethanol/60% water mixture or a 40% ethanol/60% water mixture containing either the rubefacient methyl nicotinate (MNA) or the surfactant sodium lauryl sulfate (SLS), or both MNA and SLS. Experiments were also conducted with 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB). Maximal PCP absorption was 14.12% of the applied dose from the mixture containing SLS, MNA, ethanol and water. However, when PCP was administered in ethanol only, absorption was only 1.12% of the applied dose. There were also qualitative differences among the absorption profiles for the different PCP mixtures. In contrast with the PCP results, absorption of TCB or PCB was negligible in perfused porcine skin, with only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being maximally absorbed. The low absorption levels for the PCB congeners precluded the identification of mixture component effects. These results suggest that dermal absorption estimates from a single chemical exposure may not reflect absorption seen after exposure as a chemical mixture and that absorption of both TCB and PCB are minimal in this model system.

Administration, Topical↗

Influence of a high-oxalate diet on intestinal oxalate absorption.

Hyperoxaluria is a major risk factor for renal stones. In most cases, it is sustained by increased dietary loads. In healthy individuals with a normal Western diet, the majority of urinary oxalate is usually derived from endogenous metabolism. However, up to 50% may be derived from the diet. We were interested in the effect of a high-oxalate diet on oxalate absorption, not merely on the frequently studied increased oxalate excretion. In study I, 25 healthy volunteers were tested with the [13C2]oxalate absorption test once while following a low-oxalate (63 mg) and once while following a high-oxalate (600 mg) diet for 2 days each. In study II, four volunteers repeated study I, and afterwards continued with a high-oxalate diet (600 mg oxalate/day) for 6 weeks. In the last week, the [13C2]oxalate absorption test was repeated. After 4 weeks of individual normal diet, the oxalate absorption test with a high-oxalate diet was performed again. The results of study I show that the mean [13C2]oxalate absorption under low-oxalate diet was 7.9 +/- 4.0%. In the presence of oxalate-rich food, the percent absorption for the soluble labelled oxalate almost doubled (13.7 +/- 6.3%). The results of study II show that the mean [13C2]oxalate absorption of the four volunteers under low-oxalate diet was 7.3 +/- 1.4%. The absorption increased to 14.7+/-5.2% under 600 mg oxalate. After 6 weeks under a high-oxalate diet, the [13C2]oxalate absorption was significantly decreased (8.2 +/- 1.7%). After the wash-out phase, the absorption was again high (14.1 +/- 2.2%) under the 600 mg oxalate challenge.

Adult↗

L-glucose absorption in house sparrows (Passer domesticus) is nonmediated.

We previously demonstrated in intact house sparrows substantial absorption in vivo of L-glucose, the stereoisomer of D-glucose that is assumed not to interact with the intestine's D-glucose transporter. Results of some studies challenge this assumption for other species. Therefore, we tested it in vitro and in vivo, based on the principle that if absorption of a compound (L-glucose) is mediated, then absorption of its tracer will be competitively inhibited by high concentrations of either the compound itself or other compounds (e.g., D-glucose) whose absorption is mediated by the same mechanism. An alternative hypothesis that L-glucose absorption is primarily paracellular predicts that its absorption in vivo will be increased (not decreased) in the presence of D-glucose, because the permeability of this pathway is supposedly enhanced when Na(+)-coupled glucose absorption occurs. First, using intact tissue in vitro, we found that uptake of tracer-radiolabeled L-glucose was not significantly inhibited by high concentrations (100 mM) of either L-glucose or 3-O-methyl-D-glucose, a non-metabolizable but actively transported D-glucose analogue. Second, using intact house sparrows, we found that fractional absorption of the L-glucose tracer was significantly increased, not reduced, when gavaged along with 200 mM 3-O-methyl-D-glucose. This result was confirmed in another experiment where L-glucose fractional absorption was significantly higher in the presence vs. absence of food in the gut. The greater absorption was apparently not due simply to longer retention time of digesta, because no significant difference was found among retention times. Our results are consistent with the idea that L-glucose is absorbed in a non-mediated fashion, largely via the paracellular pathway in vivo.

3-O-Methylglucose↗

Quantitative evaluation of reconstruction methods after gastrectomy using a new type of examination: digestion and absorption test with stable isotope 13C-labeled lipid compound.

BACKGROUND: Digestive and absorptive disorders may negatively influence patients' nutrition, thus resulting in weight loss after gastrectomy. A relationship thus seems to exist between the fat absorptive function and body weight after gastrectomy; however, so far there has been no evidence to prove this hypothesis. Therefore, in this study we evaluated fat absorption ability using a stable isotope, (13)C-trioctanoin, based on the range of the gastrectomy and the method of reconstruction, and we also determined the feasibility of this test. METHODS: Among patients who had undergone gastrectomy for gastric cancer, 40 patients who had been operated on between 1 and 3 years previously were evaluated. Ten patients had undergone the double-tract (DT) method, and 10 patients had received the Roux-en-Y (RY) method after a total gastrectomy. Twenty patients who had undergone the Billroth I (BI) method after a distal gastrectomy were the control group. In addition, 10 volunteers formed a healthy control group for the (13)C-trioctanoin test. We also examined other six factors related to nutrition after gastrectomy. RESULTS. The (13)C-trioctanoin test showed, in relation to the reconstruction procedure, the highest average peak of fat absorption in the BI group (which had food passage through the duodenum), followed by the average peak of fat absorption in the DT group and the RY groups. In a comparison of duration, at 60 min and 90 min after administration, the BI group and DT group showed a significantly higher level than the RY group. The peaking time (average time at peak level) showed a significant difference between the RY group and the other groups. The absorption amount at an early stage of absorption and the percent (%) dose showed a significant difference between the RY group and the other groups. The RY group had significantly lower fat absorption than the healthy controls. CONCLUSION: According to this study, which evaluated fat absorption after different reconstructive procedures after gastrectomy, the procedure that accommodated for the passage of food through the duodenum showed better results for the absorption of medium-chain triglycerides, and the patients also showed a better physiological state.

Aged↗

Relationships between intestinal calcium absorption, serum vitamin D metabolites and smoking in postmenopausal women.

Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27); p = 0.004], as were serum calcitriol (p<0.001) and parathyroid hormone (PTH) (p<0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r = 0.38) and non-smokers (r = 0.28); hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH-calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH-calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation.

Aged↗

Site-specific variations in basal and meal-stimulated intestinal absorption.

The ingestion of a meal increases water and electrolyte absorption in the proximal jejunum. The purpose of these experiments was to elucidate any site-specific variations in intestinal absorption, comparing jejunum to ileum, in both the basal and the meal-stimulated states. Twenty-five-centimeter proximal jejunal and distal ileal Thirty-Vella fistulae were constructed in four dogs. Simultaneous jejunal and ileal absorption studies were performed using [14C]PEG to calculate net absorption of water and electrolytes. Two groups were studied: in Group 1 no meal was ingested, while in Group 2, the animals ingested a mixed meal. Each study consisted of a 1-hr basal period and a 3-hr experimental period. In the basal state ileal absorption significantly exceeded jejunal absorption (P less than 0.0001). The ingestion of mixed meal significantly increased water and electrolyte absorption in both the jejunum and the ileum, (P less than 0.001), with the magnitude of meal-stimulated ileal absorption significantly exceeding the magnitude of meal-stimulated jejunal absorption (P less than 0.001). These studies demonstrate distinct site specific variations in intestinal water and electrolyte absorption in both the basal and the meal-stimulated states.

Animals↗

Effects of atropine and guanethidine on canine intestinal absorption and blood flow.

The possibility of tonic autonomic control over intestinal Na and H2O absorption and whether the cardiovascular system was involved was tested by administration of atropine or guanethidine. 3H2O and 22Na in saline perfused through the lumen were used to calculate unidirectional fluxes and total and absorptive site blood flow in canine ileum. Both atropine and guanethidine had qualitatively similar effects on absorption and blood flow with atropine being quantitatively greater. Net Na and H2O absorption were not increased significantly but their absorptive and secretory unidirectional fluxes were increased significantly. Total blood flow was not affected but absorptive site blood flow was increased and resistance decreased. The absorptive site blood flow was correlated with the absorptive Na fluxes similarly in all groups. The secretory fluxes of Na and H2O were correlated with estimated capillary pressure when all three groups were considered together. It was concluded that there is tonic cholinergic control over intestinal absorption which is mediated, in part, through cardiovascular effects. The findings were consistent with tonic parasympathetic activity having primarily a direct effect on gut absorption and blood flow but tonic sympathetic activity primarily modulating the direct effects of other regulatory mechanisms.

Animals↗

Absorption of Theo-Dur Sprinkle with food: importance of types of meals and medication times.

The bioavailability and absorption pattern of theophylline from Theo-Dur Sprinkle were investigated in adults both in fasting conditions and after two different meals. Theophylline administered intravenously was used as a reference. Furthermore, the importance of the time of medication in relation to the meal consumption for the effect of food on absorption was studied. The preparation was well absorbed under fasting conditions. A high water-content meal (apple sauce) delayed the absorption of theophylline slightly but did not influence the extent of absorption (bioavailability, 83%). A dry meal (corn flakes and bread) markedly affected both absorption pattern and bioavailability. Long delays in absorption and periods of rapid absorption of theophylline were found, and the bioavailability was reduced from 92% (fasting) to 65% (p less than 0.05). Substantial interindividual variations in absorption were observed. Taking the preparation 5 minutes before the dry meal instead of immediately after markedly reduced the effect of food on absorption. Bioavailability increased to about 84%, and the absorption profiles became much more reliable.

Adult↗

Absorption of hexose and pentose sugars in vivo in perfused intestinal segments in the fowl.

1. Rates of absorption of two hexose (D-glucose and D-galactose) and two pentose (D-xylose and D-arabinose) sugars were measured by in vivo perfusion, in jejunum, ileum and (distal) caecum, in immature hens conditioned to either a standard (ST) or "high fibre" (ST + 20% grass) diet. 2. Each bird was tested in one intestinal segment with all four (U-14C-labelled, 10 mM) sugars, with either the hexoses preceding the pentoses or vice versa. 3. With all treatments, absorption rates of the hexoses were alike, as were those of the pentoses. Hexose absorption was twice as fast as pentose absorption in jejunum and ileum with both dietary pretreatments, whereas in caecum hexose and pentose rates were similarly high, except when pentose (and its associated fluid transfer) was apparently inhibited by prior hexose absorption with the ST diet. 4. With the ST diet, hexose absorption (per unit length and dry weight) was faster in caecum than in jejunum and ileum, and pentose absorption was also fastest in caecum when all pentose data from testing after hexose were excluded. 5. With the ST/grass diet, hexose absorption was faster in jejunum than in ileum and caecum when expressed per unit length, and pentose absorption was fastest in caecum on a dry weight basis. 6. Hexose absorption was faster in jejunum and slower in caecum with the ST/grass pretreatment than with ST. However, the dietary comparison was not conclusive because it involved birds form (two) different hatches (of similar age and weight) tested at different times.

Absorption↗

Promotive effects of non-digestible disaccharides on rat mineral absorption depend on the type of saccharide.

OBJECTIVE: We examined the effects of feeding non-digestible disaccharides, difructose anhydride III (DFAIII), maltitol, melibiose and, cellobiose, on calcium, magnesium, and iron absorption in comparison with fructo-oligosaccharide (FOS) in normal and ovariectomized rats. METHODS: In experiment 1, six groups of male Sprague-Dawley rats were fed a control diet (100 g of cellulose/kg of diet), test diets containing 30 g of FOS, or the four non-digestible disaccharides in place of the cellulose in the control diet for 4 wk. In experiment 2, two groups of female Sprague-Dawley rats (sham or ovariectomized) were assigned to one of four subgroups and fed the control or test diet containing FOS, DFAIII, and melibiose for 5 wk. Feces and cecal contents were collected to evaluate mineral absorption and cecal fermentation. RESULTS: In experiment 1, calcium absorption in all the disaccharides groups except the cellobiose group, magnesium absorption in all test diet groups, and iron absorption in the FOS, DFAIII, and melibiose groups were higher than those in the control group. In ovariectomized rats (experiment 2), calcium absorption in the DFAIII and melibiose groups, magnesium absorption in all test diet groups, and iron absorption in the DFAIII group alone were higher than those in the control group. Cecal organic acids were positively and pH was negatively correlated with the absorption of these minerals, although the effects varied. CONCLUSION: Non-digestible disaccharides increase calcium, magnesium, and iron absorption in normal and ovariectomized rats; however, the effects depend on the disaccharide tested, a fact that may be partly associated with the cecal fermentation of these disaccharides.

Analysis of Variance↗

Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk.

Triglycerides and cholesterol are important biological lipids, and their excessive intake in the diet is relevant to the development of two prevalent cardiovascular risk factors, obesity and hypercholesterolemia. Because most lipids are essentially water-insoluble molecules, their transport within and absorption from the aqueous medium of intestinal contents is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific esterases, micellar transport, mucosal absorption, re-synthesis of parent molecules in enterocytes, and assembly with apolipoproteins and other molecules to form chylomicrons, the secretory product of intestinal cells. Many of these processes, however, are not well characterized at the molecular level. While in health the intestinal absorption of triglycerides is very efficient, the same does not apply to cholesterol absorption. Besides being generally inefficient, cholesterol absorption is highly variable, with a between-subject variability that depends in part on genetic factors and an intra-individual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal lipid absorption can be interfered with by dietary components or drugs and thus are potential therapeutic targets for inducing a controlled malabsorption of triglyceride, useful in the treatment of obesity, or for rendering cholesterol absorption even more inefficient in an attempt to lower blood cholesterol levels. Nevertheless, intestinally derived cholesterol available to the liver exerts complex feedback regulation on whole-body cholesterol homeostasis that limits the efficacy of cholesterol absorption inhibitors to lower blood cholesterol. This review focuses first on present knowledge of the physiology of intestinal fat absorption, necessary to understand the ways to manipulate it in order to obtain the desired effects on dietary triglyceride and cholesterol disposition. The second part discusses old, present and future ways, both dietary and pharmacological. of interfering with cholesterol and triglyceride absorption to reduce blood cholesterol and energy acquisition, respectively.

Animals↗