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Simultaneous measurement of renal clearance and plasma clearance of 99mTc-labelled diethylenetriaminepenta-acetate, 51Cr-labelled ethylenediaminetetra-acetate and inulin in man.

The present investigation was undertaken to study the kinetics of 99mTc-labelled diethylenetriaminepenta-acetate (DTPA) as compared with inulin and 51Cr-labelled ethylenediaminetetra-acetate (EDTA). Twenty patients with various degrees of decreased renal function were studied. The renal clearance, plasma clearance and volume of distribution of all three tracers were measured after a simultaneous single injection. The average renal clearance ratio 99mTc-DTPA to inulin was 0.97; the average renal clearance ratio 99mTc-DTPA to 51Cr-EDTA was 1.02. In all patients the plasma clearance of inulin exceeded that of 99mTc-DTPA. No difference was seen between the plasma clearance of 99mTc-DTPA and 51Cr-EDTA. The plasma clearance of all three tracers overestimated the simultaneously measured renal clearance; on average this was, for 99mTc-DTPA 5.7 ml/min, for 51Cr-EDTA 6.0 ml/min and for inulin 8.1 ml/min. The plasma clearance of 99mTc-DTPA correlated well with the renal clearance of inulin, but overestimated this by 3.5 ml/min on average. The volume of distribution of inulin was less than that of 99mTc-DTPA and 51Cr-EDTA. No difference was seen between the volume of distribution of 99mTc-DTPA and 51Cr-EDTA. It is concluded that the difference in the kinetics of 99mTc-DTPA and 51Cr-EDTA in patients with decreased renal function was small and without clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Reassessment of the single intravenous injection method with inulin for measurement of the glomerular filtration rate in man.

1. Factors influencing the total body and renal clearances of inulin were investigated in a total of 37 healthy adult volunteers and 10 patients with stable chronic renal failure after the single intravenous injection of a dose of 70 mg/kg given over 5 min. 2. The elimination of inulin was highly concentration-dependent, and in healthy volunteers the renal clearance fell from 103.7 +/- 14.4 ml min-1 1.73 m-2 during the first hour after administration to 49.1 +/- 20.9 ml min-1 1.73 m-2 over the period 6-8 h. In the patients with renal failure the renal clearance fell correspondingly from 39.7 +/- 16.5 to 26.6 +/- 8.6 ml min-1 1.73 m-2. There were no changes in the simultaneously measured clearances of creatinine. 3. The values obtained for the total body clearance of inulin after a single injection depend critically on dose, the number and timing of blood samples, the choice of pharmacokinetic model, the number of data points chosen for estimation of the slope of the terminal elimination phase for analysis by the methods of residuals, and the weighting used for curve fitting by non-linear regression analysis. 4. With standardized conditions of sampling from 0 to 2 h and weighted non-linear regression analysis of the plasma concentration-time data, the total body and renal clearances of inulin were almost identical in subjects with normal renal function at 105.2 +/- 10.2 and 102.9 +/- 13.0 ml min-1 1.73 m-2. In the patients with chronic renal failure sampling was continued for 3 h and the corresponding clearances were 40.4 +/- 15.3 and 38.9 +/- 15.7 ml min-1 1.73 m-2. 5. The 0-2 h total body and renal clearances of inulin were measured by the single injection method and the renal clearance was measured by the standard constant infusion method on different occasions in 10 healthy volunteers. The respective clearances were similar at 101.4 +/- 6.6, 94.9 +/- 11.9 and 88.4 +/- 12.1 ml min-1 1.73 m-2. 6. The reproducibility of the single injection and constant infusion methods was compared by measuring the inulin clearance with both techniques on three occasions in separate groups of eight and nine healthy volunteers. The mean coefficient of variation for the total body clearance with the single injection method was only 3.9% compared with 9.5% for the renal clearance determined the same way and 12.0% for the renal clearance during constant infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Comparative kinetics of microvascular inulin and 99mTc-labelled diethylenetriaminepenta-acetic acid exchange.

1. After simultaneous intravenous injection as a mixture, 99mTc-labelled diethylenetriaminepentaacetic acid (99mTc-DTPA; molecular mass 492 Da) and inulin (approximately 6000 Da) gave arterial plasma clearance curves consisting of three exponentials, the time courses of which were not significantly different between the two solutes. 2. The ratio of 99mTc-DTPA to inulin concentration in antecubital venous plasma (normalized to the ratio in arterial plasma at 30 s) was 0.6, significantly less than unity, within 2 min after intravenous injection, but increased to reach unity by 60 min. The minimum concentration ratio of 99mTc-DTPA to inulin in arterial plasma was 0.75 at 4 min, also rising to just above unity at 60 min. 3. The extraction fraction from plasma to interstitial space was higher for 99mTc-DTPA (approximately 0.5) than for inulin (approximately 0.2). For both solutes, the net extraction fraction decreased with time, becoming negative at about 25 min after injection. Thereafter, the net extraction fractions remained negative, between -0.05 and -0.1, and not significantly different between the two solutes. 4. 99mTc-DTPA time-activity curves recorded over the limbs with scintillation probes were biphasic, with an initial phase corresponding closely in time with the first exponential of the arterial 99mTc-DTPA plasma clearance curve. The second phase corresponded in time to the intermediate exponential of the arterial 99mTc-DTPA plasma clearance curve. 5. The time course of net 99mTcm-DTPA extraction fraction across the forearm vascular bed was bi-exponential, with phases corresponding in time with the two phases of the limb uptake curves. 6. Deconvolution analysis of the limb time-activity curves, using the arterial time-concentration curve as the input function, gave bi-exponential 99mTc-DTPA impulse response curves in which the time courses of the exponentials corresponded with the first and intermediate exponentials of the arterial 99mTc-DTPA clearance curve. 7. The bi-exponential nature of the equilibrium of 99mTc-DTPA between vascular and interstitial compartments suggests the presence of two separate functional volumes within the interstitial space. Although 99mTc-DTPA and inulin clearly diffuse at different rates across the endothelium, as would be expected from their disparate sizes, the similarity in the time courses of their initial exponentials and simultaneous equalization of transfer rates (i.e. when net extraction fraction was zero) is consistent with the hypothesis that inulin moves initially into a smaller functional interstitial fluid volume than 99mTc-DTPA. The total distribution volumes, however, are not significantly different between the two solutes.

Adult↗

Iothalamate measured by capillary electrophoresis is a suitable alternative to radiolabeled inulin in renal micropuncture.

BACKGROUND: Inulin remains the gold standard for measurements of fluid reabsorption (Jv) and single nephron glomerular filtration rate (SNGFR) in micropuncture experiments. However, the method used to measure cold inulin in nanoliter samples is time-consuming, while the use of radiolabeled inulin is disadvantaged by possible radioactive contamination, disposal of radioactive material and cost of the isotope. It has been reported that non-radiolabeled iothalamate may be a suitable alternative for estimation of whole kidney GFR. The present study tested whether iothalamate can be used to measure Jv in microperfusion and free-flow micropuncture experiments. METHODS: Superficial loops of Henle (LOH) were perfused from late proximal to early distal tubules with an end-like proximal solution. In the first set of experiments, the perfusate contained both iothalamate (1.9 mmol/L) and 3H-methoxy-inulin (50 microCi. mL(-1)). To test if iothalamate was able to detect changes in Jv, two additional sets of experiments were performed: (1) mannitol (61 mmol/L) was added to the perfusate to partially replace NaCl, a condition known to inhibit Jv; (2) LOH of remnant kidneys were perfused, which in previous experiments we showed to have a higher Jv. Lastly, free-flow micropuncture experiments were performed by infusing iothalamate IV at 18.3 mg. h(-1). Iothalamate analysis in nanoliter samples of renal tubular fluid obtained in vivo was performed by capillary electrophoresis (CE). RESULTS: In the first set of experiments, liquid scintillation counting of 3H-methoxy-inulin versus iothalamate analysis with CE resulted in almost identical calculated perfusion rates (20.4 +/- 0.6 vs. 20.6 +/- 0.7 nL. min(-1), N = 20) and tubular fluid/perfusate ratios (TF/P; 1.35 +/- 0.04 vs. 1.36 +/- 0.04) and thus also Jv (5.17 +/- 0.50 vs. 5.38 +/- 0.59 nL. min(-1)). In the mannitol experiments, iothalamate measurements showed that the addition of mannitol significantly reduced Jv from 4.98 +/- 0.40 (N = 19) to 0.72 +/- 0.58 nL. min(-1) (N = 33; P < 0.0001). Iothalamate determinations by CE were able to detect a significant increase in Jv in LOH of remnant rats perfused at 40 nL. min(-1)[from to 8.40 +/- 0.73 (N = 20) in sham-operated to 17.8 +/- 2.9 nL. min(-1) (N = 6) in remnant animals; P < 0.0001]. In free flow micropuncture experiments the ratio of tubular fluid to plasma iothalamate (TF/P) along the proximal tubule was 1.62 +/- 0.10 (N = 15). CONCLUSIONS: These data demonstrate that iothalamate can replace inulin to measure Jv in microperfusion and free-flow micropuncture experiments. Since iothalamate analysis by CE technique is a fast, easy and highly reproducible technique, it may become the gold standard method for the detection of fluid reabsorption in microperfused nephron segments.

Animals↗

Transgenic potato (Solanum tuberosum) tubers synthesize the full spectrum of inulin molecules naturally occurring in globe artichoke (Cynara scolymus) roots.

The ability to synthesize high molecular weight inulin was transferred to potato plants via constitutive expression of the 1-SST (sucrose:sucrose 1-fructosyltransferase) and the 1-FFT (fructan: fructan 1-fructosyltransferase) genes of globe artichoke (Cynara scolymus). The fructan pattern of tubers from transgenic potato plants represents the full spectrum of inulin molecules present in artichoke roots as shown by high-performance anion exchange chromatography, as well as size exclusion chromatography. These results demonstrate in planta that the enzymes sucrose:sucrose 1-fructosyltransferase and fructan:fructan 1-fructosyltransferase are sufficient to synthesize inulin molecules of all chain lengths naturally occurring in a given plant species. Inulin made up 5% of the dry weight of transgenic tubers, and a low level of fructan production also was observed in fully expanded leaves. Although inulin accumulation did not influence the sucrose concentration in leaves or tubers, a reduction in starch content occurred in transgenic tubers, indicating that inulin synthesis did not increase the storage capacity of the tubers.

Asteraceae↗

Inulin and oligofructose in the dietary fibre concept.

Dietary fibre consists of remnants of edible plant cell polysaccharides and associated substances resistant to hydrolysis by human alimentary enzymes, which may benefit health through a wide range of physiological effects. Inulin and oligofructose are storage carbohydrates found in a number of vegetables, fruits and whole grains. They resist digestion and absorption in the stomach and small intestine of humans, as shown by their almost full recovery at the end of the ileum of healthy or ileostomised volunteers. Inulin and oligofructose thus enter into the large intestine where they are available to fermentation, as demonstrated by increased breath hydrogen. Fermentation of both substrates is complete and no residue is found in human stools. Inulin and oligofructose improve laxation. Their bulking capacity comprised between 1.2 and 2.1 g of stool per g of ingested substrate, results mainly from increases in microbial biomass in the colon. As water content of bacterial cells is high, stools are softer and easier to expulse. Stool frequency is thus increased, particularly in slightly constipated individuals. In addition, likely due to their fermentation properties, inulin and oligofructose also affect the intestinal epithelium (trophicity, mucin expression, etc.), that may strengthen mucosal protection and reduce the risk of gastrointestinal diseases. In summary, inulin and oligofructose are plant carbohydrates, resistant to digestion in the human small intestine and fermented by colonic bacteria. They exert several intestinal physiological effects contributing to maintenance of health. Therefore, inulin and oligofructose fit well within the current concept of dietary fibre.

Cathartics↗

The nuclear permeability, intracellular distribution, and diffusion of inulin in the amphibian oocyte.

[(3)H]Inulin (mol wt approximately 5,500) solutions are microinjected into the cytoplasm of mature oocytes of Rana pipiens and the subsequent movement of the solute recorded by quantitative ultralow temperature autoradiography. The autoradiographs show transient cellular diffusion gradients, the influence of the nucleus on these gradients, and the nuclear:cytoplasmic distribution of inulin. Analysis leads to the following conclusions: (a) Inulin diffuses in cytoplasm at about 3 x 10(-6) cm(2)/s, or one-fifth as rapidly as in water. Most of this decrease is attributable to the increased tortuosity of the diffusional path due to the presence of inclusions and macromolecules. (b) The nuclear envelope is very permeable to inulin; its resistance to inulin's passage is similar to that of cytoplasm. The envelope appears to play a negligible role in regulating the nucleocytoplasmic movement of solutes smaller than macromolecules, (c) Inulin concentrates in the nucleus to four times its cytoplasmic level; this is attributed to solute exclusion from cytoplasmic water. Evidence is presented that among hydrophilic solutes the degree of exclusion increases with molecular size. The potential significance of cytoplasmic exclusion processes to understanding secretion and the intracellular movement of macromolecules is briefly discussed.

Animals↗

Inulin and oligofructose: safe intakes and legal status.

Inulin and oligofructose are a significant part of the daily diet of most of the world's population. Daily intakes for the U.S. and Europe have been estimated at up to 10 g, specifically 1-4 g for the 97th percentile in the U.S. Because both inulin and oligofructose are macroingredients, it is difficult to apply classical toxicology tests. Although some high dose animal tests have been performed, none have revealed any toxic effects. The safety of inulin and oligofructose for use in foods was evaluated by many legal authorities worldwide. As a result, both inulin and oligofructose are accepted in most countries as food ingredients that can be used without restrictions in food formulations. In the U.S., a panel of experts performed a generally accepted as safe (GRAS) Self-Affirmation Evaluation in 1992 and concluded similarly. At high doses, increased flatulence and osmotic pressure can cause intestinal discomfort. These doses vary widely from person to person and also depend on the type of food in which inulin or oligofructose is incorporated. With regard to labeling, both inulin and oligofructose are gradually being accepted as "dietary fibers" in most countries around the world. The mention of their "bifidogenic effect" on food labels has also been legally accepted in several countries.

Animals↗

Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats.

Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable markers for colon carcinogenesis in animal models. Rat model ACF studies, however, use younger rats, and there are no published reports on the suitability of adult rats for ACF studies. In this study, inulin, a known suppressor of azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344 retired male breeders received two subcutaneous injections of AOM dissolved in saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12 and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment 2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin diets/100 g. All the rats were killed after 11-wk feeding periods. In experiment 1, there was a significant (P < 0.05) AOM dose response on ACF formation. Rats fed >10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a significant increase in cecal weight and a decrease in cecal pH from 7.17 in the control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10 g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence in the colon (P < 0.01). Compared with rats fed the control diet, the percentage reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51, and 65, respectively. The results of this study indicate that mature rats can be used as models in ACF studies, and dietary long-chain inulin dose-dependently suppresses AOM-induced ACF formation in Fisher 344 mature male rats.

Age Factors↗

Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young Fisher 344 rats.

This study was designed to determine the effect of 10% dietary long-chain inulin on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) and small intestinal and colon tumors at the initiation (I), promotion (P) and I + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin. All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7 wk of age followed by a second injection at 8 wk of age. An additional group of five rats received only saline and consumed the control diet. The rats received the assigned diets until asphyxiation by CO(2) at 16 wk of age for the ACF experiment and 45 wk for the end-point tumor experiment. Feed intake, weight gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by approximately 4 wk. Cecal weight was greater in rats fed inulin and cecal pH was lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF compared with the control group. Tumor incidences in the small intestine and colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and 90, 73, 69 and 50%, respectively. The corresponding values for the distal portion of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor-bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups, respectively. All groups differed, P < 0.05. The results of this study indicate that dietary long-chain inulin suppresses AOM-induced ACF formation, an early preneoplastic marker of colon tumorigenesis in rats, and colon tumors, particularly at the promotion stage.

Age Factors↗

Colonic fermentation of inulin increases whole-body acetate turnover in dogs.

Metabolism of acetate from colonic fermentation was investigated in dogs. Beagle dogs (n = 9) were fed a control diet for 17 d followed by a 3% inulin-enriched diet (from chicory) for 4 and 21 d. On 3 occasions, the dogs were administered simultaneously infusions of [1-(13)C]acetate i.v. and [1,2-(13)C(2)]acetate intrarectally. Peripheral acetate concentration and turnover did not change over time after consumption of an inulin-enriched diet for 4 d. After 21 d of consuming the inulin-enriched diet, the whole-body acetate turnover increased significantly by 31% from (mean +/- SEM) 15.6 +/- 2.2 to 20.4 +/- 2.9 micromol/(kg . min) without a change in concentration. The rate of colonic acetate production that reached the peripheral circulation was 4.8 +/- 1.8 micromol/(kg . min). However, no [1,2-(13)C(2)]acetate tracer was recovered in the peripheral circulation. The fraction of oxidized tracer was higher in the gut (64 +/- 3%) than in peripheral circulation (46 +/- 3%) in dogs fed an inulin-enriched diet for 21 d. In conclusion, colonic fermentation of inulin occurred and indirectly stimulated whole-body acetate turnover in dogs fed an inulin-enriched diet for 21 d.

Acetates↗

Properties of fructan:fructan 1-fructosyltransferases from chicory and globe thistle, two Asteracean plants storing greatly different types of inulin.

Remarkably, within the Asteraceae, a species-specific fructan pattern can be observed. Some species such as artichoke (Cynara scolymus) and globe thistle (Echinops ritro) store fructans with a considerably higher degree of polymerization than the one observed in chicory (Cichorium intybus) and Jerusalem artichoke (Helianthus tuberosus). Fructan:fructan 1-fructosyltransferase (1-FFT) is the enzyme responsible for chain elongation of inulin-type fructans. 1-FFTs were purified from chicory and globe thistle. A comparison revealed that chicory 1-FFT has a high affinity for sucrose (Suc), fructose (Fru), and 1-kestose as acceptor substrate. This makes redistribution of Fru moieties from large to small fructans very likely during the period of active fructan synthesis in the root when import and concentration of Suc can be expected to be high. In globe thistle, this problem is avoided by the very low affinity of 1-FFT for Suc, Fru, and 1-kestose and the higher affinity for inulin as acceptor substrate. Therefore, the 1-kestose formed by Suc:Suc 1-fructosyltransferase is preferentially used for elongation of inulin molecules, explaining why inulins with a much higher degree of polymerization accumulate in roots of globe thistle. Inulin patterns obtained in vitro from 1-kestose and the purified 1-FFTs from both species closely resemble the in vivo inulin patterns. Therefore, we conclude that the species-specific fructan pattern within the Asteraceae can be explained by the different characteristics of their respective 1-FFTs. Although 1-FFT and bacterial levansucrases clearly differ in their ability to use Suc as a donor substrate, a kinetic analysis suggests that 1-FFT also works via a ping-pong mechanism.

Asteraceae↗

Muscle capillary permeability for [14C]inulin and [51Cr]EDTA in human forearm.

Capillary permeability of [14C]inulin and [51Cr]EDTA was examined in human forearm in five healthy, subjects by indicator diffusion technique. Injections of, initially [125I]albumin and [14C]inulin, and after 30 min resting, of [125I]albumin and [51Cr]EDTA, were given in a brachial artery. During light exercise of the forearm, blood was sampled in 2-s periods from a deep cubital vein primarily draining muscles. The plasma flow rate, calculated as the dose of [125I]albumin in the injectate divided by the area under the curve for the venous concentration of 125I, was, on average, 8.5 ml min-1 100 g-1 forearm. Assuming [125I]albumin is a partially permeable tracer, a correction for extraction of albumin was performed. This gave extraction fractions of 0.107 +/- 0.015 (mean +/- SEM) for [14C]inulin and 0.377 +/- 0.033 for [51Cr]EDTA, respectively. The capillary permeability surface area product per 100 g tissue (CDC) was for [14C]inulin 0.90 +/- 0.19, and for [51Cr]EDTA 3.31 +/- 0.38 ml min-1 100 g-1 forearm. The average of the ratios of the CDC values of [51Cr]EDTA to those of [14C]inulin, 4.0 +/- 0.5, is significantly higher than the corresponding ratio between the measured free diffusion coefficients in water at 37 degrees C, 3.07 +/- 0.002 (N = 36 and 17, respectively). This indicates that there is some degree of restriction for [14C]inulin (MW 5200) relative to [51Cr]EDTA (MW 340.2) and it points to an 'equivalent pore radius estimate' of about 160 A in human muscle capillaries.

Adult↗

Distribution of inulin, sucrose and mannitol in rat brain cortex slices following in vivo or in vitro equilibration.

1. The distribution spaces of inulin, sucrose and mannitol in rat brain cortex slices were determined in tracer experiments. Tracer equilibration times of 5 hr were used with combined ventriculo-cisternal perfusion and I.V. infusion of tracers. After 5 hr of equilibration the distribution volumes (expressed as mul./100 mg wet wt.) obtained using the perfusion fluid as reference and after correction of tracer amount in residual blood were obtained. Information on cellular uptake was obtained by examining a slow component of wash-out curves from brain slices after in vivo equilibration. Distribution spaces were corrected for intracellular penetration to obtain the extracellular volumes of distribution. Inulin was found to equilibrate with 13.3 mul. extracellular tissue water per 100 mg initial wet weight, sucrose with 16.6 mul. and mannitol with 19.5 mul.2. Marker spaces in rat brain cortex slices were also analysed by compartmental analysis of efflux of tracer inulin, sucrose and mannitol following in vitro incubation in a balanced medium for 60 min. Following in vitro equilibration, inulin was found to equilibrate with 22.4 mul. extracellular tissue water per 100 mg of final wet weight, sucrose to equilibrate with 31.7 mul. extracellular tissue water and mannitol with 42.3 mul.3. Inulin space in vitro when allowance is made for swelling produced during incubation of the slice was similar to the chemically delineated extracellular distribution volume in vivo. Sucrose and mannitol spaces in vitro, however, did not accord with in vivo determinations, most likely due to access of markers to areas of cell damage in the slice arisen during incubation.4. Comparison of fluid spaces delineated by inulin in slices of rat cerebral cortex following in vivo and in vitro equilibration indicated that swelling produced during incubation in vitro mainly occurred in the extracellular space. Swollen glial cells may account for the small, but significant intracellular swelling in incubated slices.

Animals↗

Lactobacillus paracasei subsp. paracasei 8700:2 degrades inulin-type fructans exhibiting different degrees of polymerization.

Ten strains of lactobacilli were assessed for their capacity to degrade inulin-type fructans, which are well-known prebiotics. Both oligofructose and inulin were tested. The dairy isolate Lactobacillus acidophilus IBB 801 degraded only oligofructose. The human isolate Lactobacillus paracasei subsp. paracasei 8700:2 degraded oligofructose and long-chain inulin and grew rapidly on both energy sources. In both cases, fractions of different degrees of polymerization were fermented. Moreover, large and short fractions of oligofructose were degraded simultaneously. When L. paracasei subsp. paracasei 8700:2 grew on oligofructose-enriched inulin, oligofructose was preferentially metabolized. In all cases, lactic acid was the main metabolic end product. Significant amounts of acetic acid, formic acid, and ethanol were produced when long-chain inulin or oligofructose-enriched inulin was used as the sole energy source.

Culture Media↗

Dietary fructo-oligosaccharides and inulin decrease resistance of rats to salmonella: protective role of calcium.

BACKGROUND: We have shown recently that rapid fermentable fructo-oligosaccharides (FOS) decreased resistance of rats towards salmonella. It is not known whether inulin (which is fermented more gradually) has similar effects or whether buffering nutrients can counteract the adverse effects of rapid fermentation. AIMS: To compare the effects of dietary inulin and FOS on resistance of rats to Salmonella enterica serovar Enteritidis and to determine whether calcium phosphate counteracts the effects of fermentation. METHODS: Male Wistar rats (n = 8 per group) were fed a human "Western style diet". Diets with 60 g/kg cellulose (control), FOS, or inulin had either a low (30 mmol/kg) or high (100 mmol/kg) calcium concentration. After an adaptation period of two weeks, animals were orally infected with 2 x 10(9) colony forming units of Salmonella enterica serovar Enteritidis. Colonisation of salmonella was determined by quantification of salmonella in caecal contents. Translocation of salmonella was quantified by analysis of urinary nitric oxide metabolites in time. RESULTS: Inulin and FOS decreased intestinal pH and increased faecal lactobacilli and enterobacteria. Moreover, both prebiotics increased the cytotoxicity of faecal water and faecal mucin excretion. Both prebiotics increased colonisation of salmonella in caecal contents and enhanced translocation of salmonella. Dietary calcium phosphate counteracted most of the adverse effects of inulin and FOS. CONCLUSIONS: Both inulin and FOS impair resistance to intestinal infections in rats. This impairment is partially prevented by dietary calcium phosphate. The results of the present study await verification in other controlled animal and human studies.

Animals↗

Sodium excretion and renal precession of sodium over inulin.

Renal excretory patterns for inulin and 22Na were measured in rats after simultaneous injection into a renal artery. In normal rats, the excretion of 22Na was much faster than inulin. This is referred to as "precession of sodium" and showed that some of the excreted 22Na had bypassed the intratubular route. During water diuresis, 65% of excreted 22Na was excreted before inulin. The quantity of 22Na preceding inulin (0.10 +/- 0.03% of the amount injected) increased eightfold during infusion of atrial natriuretic peptide (ANP). In saline diuresis, 45% of excreted 22Na (1.47 +/- 0.39% of the amount injected) preceded inulin, but precession was not affected by ANP. In rats with a nephrotic syndrome, 13% of excreted 22Na (0.34 +/- 0.12% of the amount injected) preceded inulin during saline diuresis and increased to 1.66 +/- 0.53% of the amount injected during the infusion of ANP. Precession of sodium was completely abolished in kidneys with papillary necrosis, suggesting that 22Na entered the tubular lumen in the inner medulla. These experiments demonstrate that, in rats, a large fraction of excreted sodium enters the tubules by a route other than filtration. The quantity of sodium entering the tubules by this route shows a 10- to 15-fold variation under conditions that modify the rate of sodium excretion.

Animals↗

Rapid determination of glomerular filtration rate by single-bolus inulin: a comparison of estimation analyses.

Rapid measurement of glomerular filtration rate (GFR) by an inulin single-bolus technique would be useful, but its accuracy has been questioned. We hypothesized that reported inaccuracies reflect the use of inappropriate mathematical models. GFR was measured in 14 intact and 5 unilaterally nephrectomized conscious male Sprague-Dawley rats (mean weight 368 +/- 12 g) by both single-bolus (25 mg/kg) and constant-infusion techniques (0.693 mg . kg-1 . min-1). The temporal decline in plasma inulin concentration was analyzed through biexponential curve fitting, which accounted for renal inulin loss before complete vascular and interstitial mixing. We compared our mathematical model based on empirical rationale with those of other investigators whose studies suggest inaccuracy of single-bolus methods. Our mathematical model yielded GFR values by single bolus that agreed with those obtained by constant infusion [slope = 0.94 +/- 0.16 (SE); y intercept = 0.23 +/- 0.64; r = 0.82]. In comparison to the data obtained by constant inulin infusion, this method yielded a very small bias of -0.0041 +/- 0.19 ml/min. Two previously reported models yielded unsatisfactory values (slope = 1. 46 +/- 0.34, y intercept = 0.47 +/- 1.5, r = 0.72; and slope = 0.17 +/- 1.26, y intercept = 17.15 +/- 5.14, r = 0.03). The biases obtained by using these methods were -2.21 +/- 0.42 and -13.90 +/- 1. 44 ml/min, respectively. The data indicate that when appropriate mathematical models are used, inulin clearance after single-bolus delivery can be used to measure GFR equivalent to that obtained by constant infusion of inulin. Attempts to use methods of analysis for simplicity or expediency can result in unacceptable measurements relative to the clinical range of values seen.

Algorithms↗