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Cefixime absorption kinetics after oral administration to humans.

Cefixime (CFX) absorption kinetics after oral administration to humans was studied. Four distinct models, incorporating a delay of absorption and first-order elimination kinetics, i.e. first-order absorption (M1), zero-order absorption (M0), Michaelis-Menten type absorption (MM) and Michaelis-Menten type absorption with 'an absorption window' (MM-delta t) were used to fit concentration data of CFX in 10 Chinese men following an oral dose of 400 mg. r2 and AIC were selected as measures of goodness-of-fit. The results show that the MM-delta t model provided a better fit than the other three models. The kinetic parameters were estimated as follows: Vmax' = 10.80 +/- 3.80 mg.l-1.h-1; K(m)' = 88.31 +/- 2.75 micrograms.ml-1; delta t = 4.75 +/- 0.85 h; T1/2 = 4.20 +/- 0.92 h; Tmax = 5.20 +/- 0.92 h; and Cmax = 6.04 +/- 1.70 mg.l-1.

Absorption↗

Comparative study of the intestinal absorption of three salts of calcium in young and elderly women.

A daily ingestion of 1000 to 1500 mg elemental calcium associated with vitamin D supplement is presently considered to be the adequate and least expensive therapy for senile osteoporosis. There exists only scarce data about calcium absorption with available calcium salts in elderly patients. We have compared the digestive absorption of calcium (Ca) citrate in soluble and solid form and calcium gluconolactate-carbonate in 15 young and 20 elderly, healthy women using the oral calcium loading test. The subjects were divided into two groups. In the first group, the absorption of solid Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) both in young (n = 7) and elderly women (n = 10). In the second group, the absorption of soluble Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) in young (n = 8) and elderly (n = 10) women. In the preload phase, basal calciuria was increased in elderly women (p < 0.01) although basal calcemia was similar in young and elderly women. After oral administration of the calcium salts, an increase in plasma Ca was observed in both groups which was greater for soluble Ca citrate and Ca gluconolactate than for solid Ca citrate. In young women, the increase in plasma calcium was significantly higher with soluble Ca citrate compared to Ca gluconolactate (p < 0.05). In elderly women, the postload calciuria was significantly higher for soluble Ca citrate (p < 0.05) and Ca gluconolactate (p < 0.05) compared to solid Ca citrate. A similar pattern was observed in young women, although it was not significant. In conclusion, an oral load of 1000 mg soluble Ca citrate and Ca gluconolactate-carbonate induces significant biochemical changes suggesting a better digestive absorption compared to Ca citrate in solid form, both in young and elderly women. We did not observe different response, between young and old patients.

Adult↗

Cholecystokinin mediation of colonic absorption via peptide YY: foregut-hindgut axis.

Peptide YY (PYY), a 36-amino-acid polypeptide, is found in abundance in the colon, a region where its physiologic roles are unknown. Previous studies have revealed a substantial increase in plasma PYY after cholecystokinin (CCK) administration. PYY is released from the hindgut in response to a meal and inhibits CCK release. In this study we evaluated the effects of CCK and PYY on intestinal absorption of water and electrolytes. Colonic, ileal, or jejunal Thiry-Vella fistulas (TVFs) were created in 12 dogs, and intestinal continuity was reestablished. The TVFs were perfused with an isotonic buffer solution containing [14C] PEG as a volume marker. Electrolyte and water transport were measured every 15 minutes, and plasma PYY and CCK levels were measured by radioimmunoassay. Group 1 dogs received an intravenous bolus of MK329, a specific CCK receptor antagonist, at 20 nmol/kg after a standard mixed meal; group 2 colonic TVF dogs received a meal and an intravenous bolus of PYY polyclonal antibody at 1 mg/kg. Postprandially, all three regions of the bowel became significantly proabsorptive for water, sodium, and chloride. In the colon postprandial absorption was abolished by MK329 starting 60 minutes after a meal, whereas specific CCK receptor blockade blunted ileal absorption. CCK receptor blockade did not affect postprandial absorption in the jejunum. Postprandial PYY levels did not rise in MK329-treated animals. PYY antibody reduced colonic absorption during the postprandial phase. Reduction of meal-induced colonic absorption and PYY release by MK329 in awake dogs suggests an important foregut-hindgut hormonal feedback loop. Foregut-derived CCK stimulates hindgut PYY release, which in turn stimulates colonic absorption while inhibiting further CCK release.

Animals↗

Effect of altered iron metabolism on markers of haem biosynthesis and intestinal iron absorption in mice.

In this study, well-characterised animal models of altered iron metabolism were used to investigate link(s) between haem biosynthesis and intestinal iron absorption. Mice rendered iron deficient by feeding a low-iron diet for 3-4 weeks showed low levels of hepatic non-haem iron and hepcidin mRNA, with reduced urinary 5-aminolaevulinic acid (ALA) excretion and enhanced intestinal iron absorption. Hepatic ALA synthase activity was reduced while ALA dehydratase activity was increased. Iron-loaded mice had markedly increased liver non-haem iron and hepcidin mRNA, with increased urinary ALA excretion. Intestinal iron absorption was decreased mainly due to a reduction in transfer of absorbed iron from mucosa to the carcass. Hepatic ALA synthase activity was increased and ALA dehydratase activity moderately reduced. Mice exposed to hypoxia (0.5 atm) for 1-3 days had reduced hepatic hepcidin mRNA and urinary ALA excretion, while intestinal iron absorption was increased. Hepatic ALA synthase activity was reduced. The ALA dehydratase activity in liver and spleen was markedly enhanced. Injection of ALA to iron-deficient mice or hypoxic mice reduced their intestinal iron absorption to normal levels. This study further supports the hypothesis that alterations in haem biosynthesis influence duodenal iron absorption. ALA in particular appears to function as a modulator in controlling intestinal iron absorption.

5-Aminolevulinate Synthetase↗

Effects of inulin-type fructans of different chain length and type of branching on intestinal absorption and balance of calcium and magnesium in rats.

BACKGROUND: Inulin-type fructans or chains with mainly beta[2-1] linked fructose molecules escape the ingestion procedure in the small intestine and are fermented by the microflora, and are known to increase colonic absorption of minerals in animals. The fermentation rate in the large bowel into short-chain fatty acids depends on the molecular mass and the structure of these food ingredients. It is thought that this colonic fermentation is the basis for the reported increase in mineral absorption. AIM OF THE STUDY: The purpose of the present study was twofold: a) to compare different types of fructans that differ in the sugar chain length and in chain branching; b) to determine the potential synergistic effect of a combination of inulin-type fructans with different chain lengths. METHODS: For this purpose, 50 adult male Wistar rats weighing 170 g each were used in this study. The rats were distributed into 5 groups and fed for 28 days a fiber-free basal purified diet or diet containing 10 % oligofructose (OF) (DP(av) 4), or 10 % HP-inulin (DP(av) 25), a blend of 50 % OF and 50 % HP-inulin, or a branched-chain inulin. RESULTS: During the first period, the rats went into a gradual adaptation, during which the rats received 2.5 % for 1 week and then 5 % for 1 week of the tested products. During the last 4 days of the experiment, feces and urine were monitored for mineral balance study. The animals were then sacrificed and blood, cecum and tibia were sampled for mineral status assessment. Our results showed that the ingestion of all the tested fructans led to a considerable cecal fermentation. All tested compounds increased the intestinal absorption and balance of Mg significantly. Interestingly, in the present experimental set-up, all tested compounds increased the intestinal absorption and balance of Ca numerically, but only the blend OF + HP-inulin increased apparent intestinal absorption and balance of Ca significantly. CONCLUSIONS: The different types of fructans studied in the present experiment seem to have similar activity on mineral absorption. However, the combination of OF and HP-inulin showed synergistic effects on intestinal Ca absorption and balance in rats. Further studies with other combinations of fructans need to be done to extend these findings.

Analysis of Variance↗

Diet composition and age determine the effects of inulin-type fructans on intestinal calcium absorption in rat.

BACKGROUND: Although several studies in animals and humans have established that inulintype fructans (inulin, oligofructose, fructooligosaccharides) enhance intestinal Ca absorption, there are also reports that failed to demonstrate any effects of added fructans on Ca absorption. AIM OF THE STUDY: We investigated in a rat model what variables determine inulin actions on mineral absorption with special focus on the basic diet. METHODS: To determine apparent intestinal mineral absorption, whole body retention and mineral accumulation in bone, we performed feeding experiments with a balance technique by which mineral intake, faecal and urinary output are determined. RESULTS: In a first study we compared the effects of an inulin oligofructose mixture (0 and 10%,respectively) when added either to a standard diet or a semi-synthetic diet. Rats fed the semi-synthetic diet were younger (adolescent) than rats on standard diet (young adult). We observed that the apparent Ca absorption ratio was significantly increased by inulin and oligofructose only when provided in the semisynthetic diet and not in the standard diet that intrinsically already contained some fructans from wheat. In our second study with a semi-synthetic diet fed to growing (adolescent) rats, inulin and oligofructose increased not only Ca but also Mg and Zn absorption, whole body mineral retention and femur mineral content. CONCLUSION: Inulin-type fructans at dietary levels of 10 % (w/w) do increase mineral absorption, retention and accumulation in bone in the case of Ca, Mg and Zn, but only when the basic diet for the control group contains no intrinsic fructans and when the mineral demand is particularly high as during growth.

Age Factors↗

Ingestion of difructose anhydride III partially restores calcium absorption impaired by vitamin D and estrogen deficiency in rats.

BACKGROUND: Vitamin D (VD) and estrogen deficiencies impair Ca absorption and bone mineralization, and the relevance of the interaction between these factors has not been fully understood. AIM OF THE STUDY: The aim of the present study was to clarify the effects of a nondigestible saccharide, difructose anhydride III (DFAIII), on the interaction of VD and estrogen deficiencies involved in Ca malabsorption by assessing changes in intestinal Ca absorption and bone mineralization by feeding of DFAIII in rats with VD or estrogen deficiency or with a combined loss of VD and estrogen. METHODS: Three-week-old female Sprague-Dawley rats were divided into four groups: two groups were ovariectomized (OVX) and two were laparotomized (sham). One group each of OVX and sham rats were fed an AIN93G-based normal diet, and the other groups were fed a VD-deficient diet for 8-weeks. Rats from the four groups were divided into two subgroups and fed the normal or VD-deficient diet with or without DFAIII for next 4-weeks. RESULTS: VD deficiency decreased Ca absorption and bone mineralization with reductions in duodenal calbindin D9k mRNA and serum Ca levels. There were no additional reductions in these parameters in the OVX. The reductions in Ca absorption and femoral Ca were restored partially or fully by DFAIII. Recovery of Ca absorption rate by DFAIII was greater in the OVX than in the sham showing an interaction between OVX and VD deficiency in, at least, the DFAIII-fed groups. The cecal pH was lower and the level of short-chain fatty acids in the cecal contents was higher in all the DFAIII groups than those in the control groups. CONCLUSIONS: VD deficiency impaired Ca absorption and bone mineralization, and feeding DFAIII partially restored Ca malabsorption and fully recovered bone Ca in VD-deficient rats. No additional reductions in these parameters with a combination of VD deficiency and OVX were noted. However, interactions were found between these factors in the DFAIII-induced increase in Ca absorption.

Animals↗

Effects of non-esterified stanols in a liquid emulsion on cholesterol absorption and synthesis in hypercholesterolemic men.

UNLABELLED: BACKGROUND Numerous studies have shown that dietary plant sterols (phytosterols and phytostanols) and their esters can decrease cholesterol absorption. However, few researchers have examined the effects of plant sterols on cholesterol absorption and synthesis using stable isotope tracers, instead of relying on endogenous pathway precursors. Further, we have worked with non-esterified lecithin-solubilized stanols as opposed to the more frequently studied esterified sterols and stanols. The vehicle was an oil-in-water liquid emulsion rather than the more common spread vehicle typically employed. AIM OF THE STUDY: To determine the effects of relatively low doses of lecithin-solubilized non-esterified stanols in liquid emulsions on cholesterol absorption and synthesis in mildly hypercholesterolemic subjects. METHODS: In a randomized, double blind crossover design, 12 mildly hypercholesterolemic men received either a free phytostanol supplement (3 g/d in 3 servings) or a control treatment for 3 days. Cholesterol endogenous synthesis rate was determined using the rate of incorporation of deuterium from body water into newly formed cholesterol molecules. Cholesterol absorption at the intestinal level was determined using the dual isotope method using 13C cholesterol injected intravenously and 180 cholesterol given orally. RESULTS: Cholesterol absorption was 55.7 +/- 6.5 % for the control and 33.5 +/- 5.3% for the phytostanol treatment. This massive reduction of the cholesterol absorption did not induce, on average, a difference in cholesterol endogenous synthesis which was measured at 0.074 +/- 0.0015 pool/d for plant sterols and 0.0736 +/- 0.0015 pool/d for controls (p > 0.05). CONCLUSIONS: The results demonstrated that lecithin-solubilized stanols administrated during a short period of time (3 days) in an oil-in-water emulsion can dramatically decrease cholesterol absorption, without a consistent, concomitant increase in synthesis, which is highly suggestive of effective LDL cholesterol lowering. The effects of synthesis should be verified in a longer study with more subjects.

Adult↗

Effects of experimental conditions on absorption of glycol ethers through human skin in vitro.

OBJECTIVES: To determine effects of experimental variables on the dermal absorption of 2-ethoxyethanol (EE), 2-butoxyethanol (BE) and 1-methoxy-2-propanol (M2P) through human skin in vitro. METHODS: Percutaneous absorption of EE, BE and M2P, in aqueous solution (3 mg ml(-1), 200 microl) or undiluted (10.5 microl), though full thickness or dermatomed human breast skin (0.64 cm(2) exposed area) was measured for 24 h using flow-through diffusion cells. Tissue culture medium was used as receptor fluid, with 2% (w/v) bovine serum albumin (BSA) or 2%-6% (w/v) polyethylene glycol 20 oleyl ether (PEG 20) added for some studies. Volatilised test compounds were trapped on charcoal filters placed above cells. RESULTS: In aqueous solution, steady-state flux of BE (544+/-64 nmol cm(-2) h(-1)) exceeded that of EE (143+/-19 nmol cm(-2) h(-1)) and M2P (48+/-6 nmol cm(-2) h(-1)). Reducing the dose volume to 100 microl decreased the steady-state flux of BE by about 55%, though the flux of EE was approximately doubled. Doubling the dose concentration of EE increased the flux by about eight-fold. Using full thickness skin increased tau of both EE and BE and reduced the steady-state flux of BE. Absorption rates of undiluted solvents in finite doses exceeded those measured with aqueous solutions, though the apparent permeability coefficient was higher with aqueous doses. Addition of BSA or PEG 20 to receptor fluid markedly increased absorption in both aqueous and undiluted doses. CONCLUSIONS: The dermal absorption potential of M2P from a liquid application was markedly lower than from EE or BE in all but infinite undiluted doses. The influence of receptor fluid on dermal absorption of glycol ethers could be relevant to prediction of absorption in vivo.

Chromatography, Gas↗

Influence of ammonia on sodium absorption in rat proximal colon.

The influence of ammonia on sodium and chloride fluxes in rat proximal colon was studied in Ussing chamber experiments. Under short-circuit conditions, the proximal colon absorbed sodium and secreted chloride. The presence of ammonia (30 mmol 1(-1) mucosal) diminished Na+ absorption, but had hardly any influence on Cl- fluxes. Blocking the apical Na+/H+ exchanger isoform NHE2 by amiloride or HOE642 diminished absorptive Na+ and Cl- fluxes. In contrast, the NHE3-specific antagonist S3226 was ineffective. Amiloride and HOE642 also inhibited the effect of ammonia on net sodium absorption. In bicarbonate-free buffer solution, ammonia failed to alter the absorptive fluxes of sodium and chloride, but increased the secretory fluxes of Na+ and Cl-. The latter effect was blocked by HOE642. These results suggest that basal NaCl absorption in rat proximal colon depends to a large extent on NHE2. Mucosal ammonium decreases Na+ absorption and this effect can be antagonized by blocking NHE2. This observation suggests that ammonium interacts with the apical Na+/H+ exchanger, thereby diminishing sodium absorption.

Amiloride↗

Measurement of potassium absorption during hypokinesia in potassium supplemented and unsupplemented healthy subjects.

Measuring potassium (K+) absorption, and K+ levels in plasma, urine and feces during and after hypokinesia (HK) and K+ supplementation, the aim of this study was to determine if prolonged HK could depress K+ deposition significantly more with or without K+ supplementation. Studies were conducted during 30-days pre-HK, 364-days HK and 30-days post-HK. Forty male healthy volunteers 24.2+/-5.5 years of age were chosen as subjects. They were equally divided in four groups: unsupplemented active control subjects (UACS), unsupplemented hypokinetic subjects (UHKS), supplemented active control subjects (SACS), and supplemented hypokinetic subjects (SHKS). Hypokinetic subjects were walking average distances of 0.5+/-0.2 km day(-1). Active control subjects were running average distances of 5.8+/-1.2 km day(-1). Both SHKS and SACS consumed daily 2.17 mEq elemental potassium per kg body weight. Potassium absorption, fecal and urinary K+ excretion, sodium (Na+) loss, plasma K+ and Na+ level and plasma aldosterone (PA) level did not change in SACS and UACS compared with their pre-HK values. During HK, K+ absorption decreased significantly (P < 0.05) with time, and fecal and urinary K+ loss, urinary Na+ loss, plasma K+ and Na+ levels and PA level increased significantly (P < 0.05) with time in SHKS and UHKS compared with their pre-HK values and their respective active controls (SACS and UACS). During initial 15-days of post-HK, K+ absorption increased significantly (P < 0.05), fecal and urinary K+ excretion, urinary Na+ excretion and plasma K+ and Na+ levels and PA level decreased significantly (P < 0.05) in hypokinetic compared with active control subjects; by the 30th day they approached the control levels. During HK and post-HK, K+ absorption, fecal and urinary K+ losses, urinary Na+ excretion, plasma K+ and Na+ levels and PA level, changed significantly (P < 0.05) more in SHKS than UHKS. Decreased K+ losses during post-HK showed K+ depletion during HK. Decreased K+ absorption with K+ depletion during HK showed decreased K+ deposition. The greater K+ changes in SHKS than UHKS, during HK and post-HK, demonstrated that K+ deposition decreased more with than without K+ supplementation. It was concluded that dissociation between K+ absorption and K+ depletion showed decreased K+ deposition as the main mechanism for K+ depletion during HK.

Absorption↗

Effect of structure and form on the ability of plant sterols to inhibit cholesterol absorption in hamsters.

We investigated the effect of three types of plant sterols (4-desmethylsterols, 4,4'-dimethylsterols, and pentacyclic triterpene alcohols) in three forms (free, esterified with FA, or with phenolic acids) on cholesterol absorption. Plant sterol fractions derived from soybean (99% 4-desmethylsterols), rice bran (70% 4,4'-dimethylsterols), or shea nut (89% pentacyclic triterpene alcohols) were fed to male hamsters (n = 20/group) as free sterols or esterified with FA or phenolic acids (cinnamic or ferulic). Cholesterol absorption was measured after 5-8.5 (mean, 7) wk by a dual-isotope technique. Soybean sterol intake significantly reduced cholesterol absorption efficiency (23%) and plasma total cholesterol (11%). Rice bran sterols tended to lower cholesterol absorption efficiency by 7% and plasma total cholesterol by 5%, whereas shea nut sterols had no effect. In hamsters, dietary 4-desmethylsterols were more effective than 4,4'-dimethylsterols in lowering cholesterol absorption and levels of cholesterol in blood. Pentacyclic triterpene alcohols had no effect on the absorption of cholesterol or on its level in blood. Esterification with FA did not impair the ability of 4-desmethylsterols and 4,4'-dimethylsterols to inhibit cholesterol absorption, whereas esterification with phenolic acids reduced this ability. This study supports the use of 4-desmethylsterols, esterified with FA to increase solubility, as the most effective cholesterol-lowering plant sterols in the diet.

Animals↗

Effect of 1,25-dihydroxyvitamin D3 on calcium and magnesium absorption in the healthy human jejunum and ileum.

In calcium deficiency states such as chronic renal failure, 1,25-dihydroxyvitamin D3 increases calcium and magnesium absorption toward normal levels. In the present study, the ability of exogenous 1,25-dihydroxyvitamin D3 to increase calcium and magnesium absorption above normal rates in healthy subjects was investigated. Steady-state perfusion studies were performed in 30 cm segments of jejunum and ileum before and after one week of 1,25-dihydroxyvitamin D3 administration (2 micrograms per day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration increased from 25.8 +/- 2.5 pg/ml to 56.4 +/- 6.6 (mean +/- SEM, p less than 0.05). In the basal state, calcium absorption was significantly higher in the jejunum than in the ileum. Vitamin D administration resulted in a significant increase in calcium absorption which was quantitatively similar in both the jejunum and ileum. The changes in net movement were due to an increase in lumen-to-plasma flux of calcium; the plasma-to-lumen flux remained unchanged. Jejunal magnesium absorption also was enhanced by 1,25-dihydroxyvitamin D3. These studies demonstrate that in healthy persons, exogenous 1,25-dihydroxyvitamin D3 increases calcium absorption in both the jejunum and the ileum, and increases magnesium absorption in the jejunum.

Adult↗

Meal-induced jejunal absorption requires intact neural pathways.

A signal for meal-induced absorption originates from the small intestine and is transmitted to a luminally excluded segment of the proximal jejunum (Thiry-Vella [TV] fistula). Using intraluminal topical anesthesia with oxethazaine, this study assessed the role of intestinal neural pathways in basal and postprandial jejunal water and electrolyte absorption. Studies (n = 45) were performed on dogs with 25-cm proximal jejunal TV fistulae and feeding jejunostomies, using luminal perfusion with 14C-polyethylene glycol. The animals were randomized into five study groups: (1) jejunostomy oxethazaine alone, (2) jejunostomy water and jejunal meal, (3) jejunostomy oxethazaine and jejunal meal, (4) TV fistula water and jejunal meal, and (5) TV fistula oxethazaine and jejunal meal. The jejunal meal significantly increased TV fistula absorption, whereas oxethazaine significantly reduced basal absorption when administered via the TV fistula and postprandial absorption when administered via the jejunostomy (p less than 0.05). TV fistula oxethazaine did not diminish the magnitude of postprandial absorption. We conclude that intact intestinal neurotransmission is necessary for maintenance of the normal basal absorptive state of the proximal jejunum and for the generation of a normal meal-stimulated proabsorptive signal from the small intestine. A nonneural mechanism appears to be of predominant importance in transmitting the proabsorptive signal from the intact gastrointestinal tract to the TV fistula.

Anesthetics, Local↗

Enhanced glucose absorption in the jejunum of patients with cystic fibrosis.

After oral D-xylose ingestion, cystic fibrosis patients have significantly higher blood levels of xylose than controls. The aim of this study was to examine whether nutrient absorption at the mucosal level is altered in cystic fibrosis. Steady-state perfusion experiments using isotonic test solutions were performed in 11 healthy controls and 10 cystic fibrosis patients. Net D-glucose absorption was higher in cystic fibrosis when the perfusate contained a glucose concentration of less than or equal to 50 mM. Kinetic analysis by three different methods, including Lineweaver-Burk analysis, revealed a lower apparent Km as well as a lower apparent Vmax in cystic fibrosis as compared with healthy controls (33.9 mM and 52.5 mmol/20 cm . h vs. 81.8 mM and 68.3 mmol/20 cm . h, respectively, p less than 0.01). Absorption of D-fructose and glycine demonstrated a tendency for increased net absorption in cystic fibrosis but the results were not significantly different. L-Xylose absorption and electrolyte movement were not altered in cystic fibrosis. Among several possible mechanisms investigated, a decrease in the apparent Km for glucose absorption would be consistent with a decrease in diffusion barriers overlying the jejunal mucosa in cystic fibrosis. Using an electrical method, the unstirred water layer thickness was significantly decreased in cystic fibrosis (546 +/- 41 micron in cystic fibrosis vs. 780 +/- 110 micron in controls, p less than 0.05). A decrease in the mucosal surface area in the cystic fibrosis group or an intrinsic defect in the mucosal glucose transport system could account for differences in the apparent Vmax values. We suggest, however, that enhanced absorption in cystic fibrosis is most likely due to a decrease in intestinal diffusion barriers possibly due to abnormal mucus overlying the intestinal mucosa.

Adolescent↗

Influence of infusate viscosity on intestinal absorption in the rat. An explanation of previous discrepant results.

Previous studies of the influence of increased luminal viscosity on intestinal absorption have yielded conflicting results ranging from no effect to a marked diminution. We measured the absorption of three probes (carbon monoxide, [14C]warfarin, 5.5 mM glucose) from a saline infusate or from saline containing 0.6% guar, which yielded a 20-fold increase in viscosity. Two animal models were used: (a) conscious nonlaparotomized rats with chronically implanted cannulas and (b) anesthetized laparotomized rats. In the anesthetized laparotomized rats, absorption was independent of perfusate viscosity. In the conscious nonlaparotomized rats, the absorption of each of the three probes was significantly greater than in the anesthetized laparotomized rats and increased viscosity caused a 60%-70% decrease in the clearance of the three probes. In anesthetized laparotomized rats, we have shown that fluid moves with laminar flow, and increased infusate viscosity cannot further reduce luminal stirring (or absorption). In conscious, nonlaparotomized rats, laminar flow is disrupted by normal gut motility causing better luminal stirring. Such stirring is inhibited by a viscous infusate resulting in decreased absorption. We conclude that the conflicting results seen in previous studies can be attributed to the model used. In conscious animals where luminal stirring was good, a viscous infusate caused decreased absorption.

Animals↗

Passive jejunal bile salt absorption alters the enterohepatic circulation in immature rats.

BACKGROUND: Developmental changes in passive bile salt absorption may alter the enterohepatic circulation. METHODS: 14-, 21-, and 40-day-old anesthetized male Sprague-Dawley rats were studied. Jejunum and ileum were isolated, cannulated, and injected or perfused with a taurocholate, [3H]taurocholate, and nonabsorbable marker solution. Bile was collected. RESULTS: Using bolus injection, jejunal taurocholate absorption rates and total taurocholate absorption were nonsaturable, linearly related to taurocholate dose, and decreased from 14 days (1.62 nmol.cm-1.min-1) to 21 days (1.05 nmol.cm-1.min-1) and 40 days (0.54 nmol.cm-1.min-1). While total taurocholate absorption decreased (14 days, 52.4%; 21 days, 43.7%; 40 days, 30.5%), hepatic taurocholate clearance increased (14 days, 18.2%; 21 days, 23.7%; 40 days, 37.3%). Hepatic taurocholate clearance was saturated only at 14 days. Using jejunal perfusion, total taurocholate absorption (14 days, 62.0%; 21 days, 43.1%; 40 days, 45.3%) and taurocholate absorption rate decreased with age (14 days, 941.13 nmol.cm-2.min-1 per micromole of taurocholate; 21 days, 411.28 nmol.cm-2.min-1 per micromole of taurocholate; 40 days, 334.50 nmol.cm-2.min-1 per micromole of taurocholate). CONCLUSIONS: Passive jejunal bile salt absorption and decreased hepatic bile salt clearance could account for the low intraluminal and high serum bile salt levels observed in immature animals and in human neonates.

Aging↗

The role of cholesterol absorption and hepatic cholesterol content in high and low responses to dietary cholesterol and fat in pedigreed baboons (Papio species).

Selective breeding has produced baboon families with low and high plasma cholesterol responses to dietary cholesterol and fat. We used 12 high- and 12 low-responding (mainly in low-density lipoprotein [LDL] cholesterol) pedigreed baboons to determine whether cholesterol absorption and hepatic cholesterol concentration are associated with these responses. We measured cholesterol absorption first on the chow diet, which was low in cholesterol and fat, and after 3 and 13 weeks on the challenge diets, which contained 0.45 mg cholesterol/kcal and 40% of calories as either coconut oil or corn oil. Plasma, lipoprotein, and hepatic cholesterol concentrations were measured 1 week after cholesterol absorption measurements. High-responding baboons had higher percentage cholesterol absorption than low-responding baboons on both chow and challenge diets, regardless of the type of dietary fat. Both high and low responders had higher percentage cholesterol absorption with corn oil than with coconut oil. High responders also had higher hepatic cholesterol concentrations than low responders on chow and after consuming the challenge diets for 4 weeks. After consuming the challenge diets for 14 weeks, low responders fed coconut oil had hepatic cholesterol levels equal to those of high responders, while low responders fed corn oil continued to have low hepatic cholesterol levels. Thus, percentage cholesterol absorption is consistently higher in high-responding baboons regardless of diet, but hepatic cholesterol concentration varies with duration of challenge and type of fat. The results suggest that both cholesterol absorption and hepatic cholesterol concentration regulate cholesterolemic responses to diet, but by different mechanisms.

Animals↗