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PubMed1984

Precorneal factors influencing the ocular distribution of topically applied liposomal inulin.

The primary objective of this study was to investigate the effect of several precorneal factors on the retention of liposomes in tears and their interaction with the corneal and conjunctival surfaces. It was found that adsorption of liposomes onto these surfaces was requisite to the ocular absorption of inulin. Over a range of 10 to 50 microliter, the availability of binding sites at the corneal and conjunctival surfaces rather than the size of the instilled volume controlled the extent of liposomal adsorption and ultimately availability of inulin to the intraocular tissues. The inulin liposomes were in facile association with the adsorptive surfaces, as evidenced by their low resistance to removal by rinsing the eye with saline and by the lack of sustained inulin concentrations in any of the ocular tissues studied. This property of liposomes, coupled with the slow rate (1% per hour) at which they released inulin, was responsible for the absence of inulin in the aqueous humor as late as 240 minutes post-dosing. It was concluded that, for liposomes to be effective in ocular drug delivery, they must show affinity for and be bound to the corneal surface and, in addition, must release their contents at optimal rates.

Absorption↗

PubMed2000

Diets enriched with cereal brans or inulin modulate protein kinase C activity and isozyme expression in rat colonic mucosa.

The role of dietary fibres in colon carcinogenesis is controversial. To elucidate the mechanisms by which different dietary fibre sources may affect colonic tumour development, we studied the effects of diets enriched with cereal brans or inulin on protein kinase C (PKC) activity and isozyme expression in rat colon. Male Wistar rats (twelve per group) were fed one of the following AIN-93G-based diets (Reeves et al. 1993) for 4 weeks: a non-fibre high-fat diet or one of the four high-fat diets supplemented with either rye, oat or wheat bran or inulin at 100 g/kg diet. The fat concentration (20 g/100 g) and fatty acid composition of the non-fibre high-fat diet was designed to approximate that in a typical Western-type diet. In the proximal colon, rats fed the inulin diet had a significantly higher membrane PKC activity and a higher membrane PKC delta level than rats fed the non-fibre diet In the distal colon, rats fed the inulin and oat bran diets had a higher total PKC activity and a higher membrane PKC beta 2 level than rats fed the wheat-bran diet. Rats in the non-fibre and wheat-bran groups had the lowest concentrations of luminal diacylglycerol. In conclusion, feeding of wheat bran resulted in low distal PKC activity and expression of PKC beta 2, a PKC isozyme related to colonic cell proliferation and increased susceptibility for colon carcinogenesis, which may explain in part the protective effect of wheat bran against tumour development in a number of experimental colon cancer studies. The increase in PKC activity and PKC beta 2 expression by feeding inulin may be a drawback of inulin as a functional food.

Animals↗

PubMedDate not supplied

A novel HPLC assay for pentamidine: comparative effects of creatinine and inulin on GFR estimation and pentamidine renal excretion in the isolated perfused rat kidney.

PURPOSE: 1. To develop and validate an analytical method for pentamidine (PTM) by reversed-phase HPLC. 2. To compare the effects of creatinine and inulin on PTM excretion in the isolated perfused rat kidney. METHODS: The HPLC method utilized a base deactivated, 5 micro, C18 column and a mobile phase containing acetonitrile (24%) and 0.025 M monobasic phosphate buffer, pH 3.2 (76%). Mobile phase flow rate and UV detection wavelength were 1 mL/min and 270 nm, respectively. Sulfadiazine (SDZ) was used as the internal standard. The method was used to measure pentamidine in perfusate and urine samples generated from studies with the isolated perfused rat kidney (IPK) model. Perfusion experiments were conducted in the presence of two different GFR markers: creatinine and inulin (PTM dose 800 micro g). Both creatinine and inulin were assayed using colorimetric methods. RESULTS: The HPLC assay is rapid, sensitive and reproducible. The method was validated over two standard concentration ranges: 0.1 to 1 micro g/mL, and 1 to 10 micro g/mL. In control (drug-naïve) IPK perfusions, creatinine clearance was approximately 15% greater than inulin clearance (0.80+/- 0.21 mL/min vs. 0.69+/-0.17 mL/min, p > 0.05). In the presence of PTM, however, creatinine clearance was reduced to 0.56+/-0.27 (p < 0.05 compared to control). Inulin clearance was not altered by PTM administration (0.76+/-0.26 mL/min). Cumulative urinary excretion of PTM (% dose) was 3.0+/-0.47% and 9.6+/-4.2% in the presence of creatinine and inulin, respectively. PTM clearance was significantly reduced (0.06+/-0.01 mL/min vs. 0.13+/-0.01 mL/min, p < 0.05) and % kidney accumulation significantly enhanced (66+/-4.7% vs. 37+/-9.7%, p < 0.05) by creatinine. CONCLUSIONS: Creatinine overestimated GFR in the IPK. The altered renal excretion of PTM by creatinine is consistent with inhibition of PTM tubular secretion. Because of increased kidney accumulation, detrimental effects of PTM on renal function were observed. Based on these findings, creatinine should be used cautiously as an indicator of GFR in IPK experimentation.

Animals↗

PubMed2003

[Effect of oral inulin administration on lipid profile and insulin sensitivity in subjects with obesity and dyslipidemia].

BACKGROUND: Inulin is a non absorbable polysaccharide with prebiotic effects, whose influence on blood lipids or insulin sensitivity is not well known: AIM: To assess the effect of oral administration of inulin on lipid profile and insulin sensitivity in dyslipidemic obese subjects. MATERIAL AND METHODS: A clinical trial, double blind, randomized with placebo was carried out in 12 obese, hypertrygliceridemic and hypercholesterolemic subjects between 19 and 32 years old. The subjects were randomized to receive 7 g/day of inulin or placebo in the morning, during 4 weeks. Biochemical and metabolic profiles and euglycemic-hyperinsulinemic clamp technique for assessing insulin sensitivity, before and after pharmacological intervention were performed. RESULTS: After inulin administration, there was a significant reduction of total cholesterol (248.7 +/- 30.5 and 194.3 +/- 39.8 mg/dL; p = 0.028), low density lipoprotein (LDL), cholesterol (136.0 +/- 27.8 and 113.0 +/- 36.2 mg/dL; p = 0.028), very low density lipoproteins (VLDL) (45.9 +/- 18.5 and 31.6 +/- 7.2 mg/dL; p = 0.046) and trygliceride concentrations (235.5 +/- 85.9 and 171.1 +/- 37.9 mg/dL; p = 0.046). No effect of inulin on insulin sensitivity was observed. CONCLUSIONS: The oral inulin administration reduced total cholesterol, LDL cholesterol, VLDL and trygliceride levels in dyslipidemic and obese subjects, without modifications in the insulin sensitivity.

Administration, Oral↗

PubMed1992

Discrepancy between circadian rhythms of inulin and creatinine clearance.

To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm for inulin clearance with a maximum during daytime and a relative amplitude of 21% +/- 2%. For creatinine clearance a rhythm was either absent or reduced in relative amplitude (p less than 0.01). In all subjects the rate of tubular creatinine secretion was higher at minimum of inulin clearance (night) than at maximum (day). The fractional clearance (relative to inulin) of creatinine was also higher during the night: normal subjects, 1.28 +/- 0.02 versus 1.10 +/- 0.02; patients, 1.78 +/- 0.08 versus 1.45 +/- 0.05 (p less than 0.005). This demonstrates the inaccuracy of creatinine clearance as a measure of glomerular filtration rate (GFR). By subsequent blocking of the tubular secretion of creatinine with cimetidine in four normal subjects, creatinine clearance became similar to inulin clearance during day and night. This confirms that high tubular secretion of creatinine during the night counteracts the normal rhythmicity of glomerular filtration of creatinine. As a result, plasma creatinine concentration is nearly constant during a 24-hour period. In conclusion, tubular creatinine secretion has a circadian rhythm with a phase opposite to the rhythm of GFR, thus blunting or causing absence of a circadian rhythm for creatinine clearance.

Adult↗

PubMed1993

Automated enzymatic analysis of inulin.

We have developed an automated enzymatic assay for quantitation of inulin in plasma and urine that can be performed on the Cobas FARA II. In the assay, inulinase hydrolyzes inulin to fructose, and sorbitol dehydrogenase converts fructose to sorbitol with consumption of NADH, which is detected by spectrophotometry. The method incorporates a sample blank (inactivated inulinase) for each specimen to subtract contributions of endogenous fructose. Recovery of fructose or inulin was near 100%, with linearity to 300 mg/L. The enzymatic assay (y) agreed well with an anthrone comparison method (x) for analysis of inulin in both urine specimens (y = 1.00x - 138; Sy/x = 714) and plasma specimens (y = 1.00x - 3.5; Sy/x = 5.5). Glucose at 300 mg/L yielded an apparent inulin value of 1.3 mg/L in the enzymatic assay, but reacted at nearly 10% equivalency in the anthrone assay. Interferences from sorbitol, mannitol, and xylitol were negligible. CVs for day-to-day precision studies were 1-4%. The automated enzymatic assay of inulin is faster and avoids the use of caustic reagents required by the classical anthrone method.

Anthracenes↗

PubMed1986

Ocular disposition of inulin from single & multiple doses of positively charged multilamellar liposomes: evidence for alterations in tear dynamics and ocular surface characteristics.

The effect of entrapment of inulin, a model medium molecular weight compound, in positively charged, multilamellar liposomes on ocular inulin absorption following instillation of single and multiple doses to the albino rabbit eye was studied. In spite of their affinity for the ocular surfaces, these liposomes provided 5 and 100 times lower ocular concentrations of inulin at 30 minutes post-dosing than aqueous solutions and neutral liposomes, respectively, and failed to sustain inulin concentrations in any anterior segment tissues over 120 min. This negative effect of positive liposomes on the ocular bioavailability of inulin can partly be attributed to a 2-fold faster disappearance rate from the tear pool, which more than offset their intrinsic ability to increase corneal drug permeability. For unknown reasons, multiple doses of these liposomes resulted in further reduction in ocular inulin absorption when compared with single doses.

Absorption↗

PubMed1965

THE PHYSICAL PROPERTIES OF INULIN SOLUTIONS.

1. Carefully recrystallized samples of inulin have been analysed chromatographically for low-molecular-weight contaminants. The analysis of the samples revealed amounts of low-molecular-weight polyfructosans amounting to 5-10% of the inulin. 2. The possible polymorphism of inulin, its solubility behaviour and suggestions of association in solution are discussed. 3. Physical techniques suggest considerable polydispersity. Ultracentrifugation gives a weight-average molecular weight (M(w)) 7250, whereas osmotic-pressure measurements suggest a number-average molecular weight (M(n)) 5600. 4. A probable steric model is suggested of a helix repeating every four residues, of diameter 12A and axial ratio 7.5-10. 5. Fractionation of the inulin on columns of Sephadex G-25 show a pronounced polydispersity. 6. Some doubt is cast on the reliability of inulin as an indicator of physiological volumes of distribution in body fluids.

Chemical Phenomena↗

PubMed1988

Synthesis of 11C-methylated inulin as a radiopharmaceutical for imaging brain edema and pulmonary edema.

11C-methylated inulin, supposedly useful for imaging of brain edema and pulmonary edema, was prepared using cyclotron produced 11CO2. The synthesis consists of the production of 11C-methyl iodide and its coupling with inulin alkoxide sodium in dimethylsulfoxide as solvent. 11C labeled inulin was purified by alcohol precipitation. The radiochemical yield of pure 11C-inulin was 34% of 11CO2 30 min after the end of bombardment. The blood clearance and body distribution of 11C was observed in rabbits after i.v. injection of 11C-inulin. The blood clearance curve was composed of a sum of three exponential functions. The gamma camera image showed that the 11C activity in blood moved quickly to kidneys and urine and a small dose of radioactivity remained persistently in edematous tissues, i.e. the edematous lung tissues produced by oleic acid treatment.

Animals↗

PubMed1987

Dissociation between apparent volumes of distribution for inulin and sodium by salt adaptation in ducks.

In domestic ducks acclimated to 2% saltwater (SW ducks), chronic elevations of plasma osmolality and sodium concentration, and of the circulating levels of antidiuretic hormone and angiotensin II indicate a trend towards dehydration when compared to ducks maintained on freshwater (FW ducks). Under steady state conditions of salt and water balance, with prevailing antidiuresis and no salt gland secretion, the apparent volumes of distribution of 22Na and of radiolabeled inulin were calculated after single injections of the tracers. The sodium spaces as percent body mass of FW ducks (33.3 +/- 0.9) and SW ducks (31.5 +/- 0.5) were not different, but apparent volumes for inulin distribution differed significantly between FW ducks (31.2 +/- 0.7) and SW ducks (24.8 +/- 0.7). Plasma volumes and rates of inulin disappearance from the plasma during both the non-uniform and uniform phases of tracer distribution were closely similar in FW and SW ducks and support the hypothesis that the difference between apparent volumes of inulin distribution reflects a difference in extracellular fluid volume which was estimated as 20.9% in FW ducks and 17.2% in SW ducks. For SW ducks the difference between inulin and sodium spaces was significantly greater than for FW ducks. In relation to the extracellular fluid compartment SW ducks have a larger pool of non-extracellular exchangeable sodium.

Acclimatization↗

PubMed2001

Enrichment of bifidobacteria in the hen caeca by dietary inulin.

Caecal bifidobacterial concentration was increased more than 3-fold in inulin-treated laying hens. The counts of bifidobacteria in birds fed as the control were 9.64, in inulin-diet fed ones 10.17 log CFU/g of caecal content, respectively. Dietary inulin had no effect on caecal microbial metabolite concentration. The proportion of inulin-fermenting bifidobacteria in the total bifidobacteria increased 2-fold in inulin-treated birds.

Animal Feed↗

PubMed2003

Renal length and inulin clearance in the radiologically normal single kidney.

Compensatory hypertrophy of a single functioning kidney is well described and has been shown to occur in utero. The long-term effects of hypertrophy and hyperfiltration in this situation are unknown. This study defined the growth parameters for single kidneys during childhood and correlated them with inulin clearance. Patients were those who had a radiologically "normal" single kidney, where the contralateral kidney was known to be non-functioning from infancy. Data were obtained from 74 children (40 boys and 34 girls) drawn from a registry of cases with a single kidney, and in whom simultaneous measurements of inulin clearance and renal length had been made at around 5, 10, and 16 years of age. Renal length was taken as the maximal bipolar measurement using real-time ultrasound scan. Inulin clearance was by continuous infusion technique. Nomograms for single kidney growth were determined against age, height, weight, and body surface area. Renal growth was correlated with inulin clearance. Renal length was found to correlate best with body surface area ( r=0.85, P<0.001), but this was not significantly superior to correlations with age, height, or weight separately. Inulin clearance per body surface area correlated positively with standardized renal length, i.e., Z score for renal length normalized for body surface area ( r=0.53, P<0.001). The larger kidneys have a higher glomerular filtration rate. Provided that the nephron number in the single kidney is similar to that in a paired kidney, single kidneys are hypertrophied and the single nephron glomerular filtration rate is likely to be abnormally high in these children.

Adolescent↗

PubMed2002

Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis.

PURPOSE: Inflammation is a constant finding in the ileal reservoir of patients with an ileal pouch-anal anastomosis and is associated with decreased fecal concentrations of the short chain fatty acid butyrate, increased fecal pH, changes in fecal flora, and increased concentrations of secondary bile acids. In healthy subjects, inulin, a dietary fiber, is fermented to short chain fatty acids and leads to a lower pH and potentially beneficial changes in fecal flora. The aim of the present study was to investigate the effect of enteral supplementation of inulin on inflammation of the ileal reservoir. METHODS: Twenty patients received 24 g of inulin or placebo daily during three weeks in a randomized, double-blind, crossover design. Stools were analyzed after each test period for pH, short chain fatty acids, microflora, and bile acids. Inflammation was assessed endoscopically, histologically, and clinically. RESULTS: Compared with placebo, three weeks of dietary supplementation with 24 g of inulin increased butyrate concentrations, lowered pH, decreased numbers of Bacteroides fragilis, and diminished concentrations of secondary bile acids in feces. This was endoscopically and histologically accompanied by a reduction of inflammation of the mucosa of the ileal reservoir. CONCLUSION: Enteral inulin supplementation leads to a decrease of inflammation-associated factors and to a reduction of inflammation of pouch mucosa.

Adenomatous Polyposis Coli↗

PubMed1988

Permeability of placenta to inulin.

Inulin was administered to eight volunteer patients at term gestation over a period of 3 hours before cesarean section. Inulin concentrations were repeatedly measured in maternal plasma, in fetal plasma, and in amniotic fluid at the time of delivery. Total inulin uptake of the conceptus was taken to be the sum of the inulin in the amniotic fluid and in the newborn infant. Amniotic fluid volumes were measured by ultrasound examination, and the distribution volume of inulin in the neonate was assumed to be 180 ml/kg on the basis of animal experiments. The mean permeability was 0.15 microliter/(s.g) placenta. This value and the previously measured permeability for cyanocobalamin delimit a range of molecular weights from 1350 to 5200 daltons. In this range permeability to lipid-insoluble molecules is roughly proportional to the coefficients of free diffusion in water without further discrimination of molecular size by the placental barrier.

Amniotic Fluid↗

PubMed1983

Differential blood-brain barrier permeabilities to [14C]sucrose and [3H]inulin after osmotic opening in the rat.

The blood-brain barrier (B-BB) in 3-month-old rats was opened unilaterally by infusing 1.8 m L(+)arabinose in water into the internal carotid artery through a catheter in the external carotid. Two poorly penetrating uncharged test radiotracers of differing molecular weight and size, [14C]sucrose (340 daltons, radius 5 A) and [3H]inulin (5500 daltons, radius 15 A), were simultaneously injected i.v. in untreated rats, or rats at 1, 30, or 50 min after infusion of hypertonic arabinose solution. Evans-blue solution was injected 5 min prior to osmotic treatment as a visual indicator of barrier integrity. In regions of uninfused control brains, the [14C]sucrose permeability-surface area (PA) product approximated 10(-5) s-1, whereas PA was not measurable for [3H]inulin. In arabinose-infused animals, PA products on the ipsilateral hemisphere for both [14C]sucrose and [3H]inulin were markedly elevated 6 min after infusion, but decreased by 35 and 55 min. In nearly all regions, statistically significant differences were not found between 6-min [14C]sucrose- and [3H]inulin-PA values (P greater than 0.05). However, at 35 and 55 min in most regions, the PA for [3H]inulin was significantly lower (P less than 0.05) than PA for [14C]sucrose. The results indicated that the B-BB closed more rapidly to larger than to smaller molecules after osmotic treatment and were consistent with a pore model for osmotic B-BB opening.

Animals↗

PubMed1995

Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin.

BACKGROUND/AIMS: Oligofructose and inulin are naturally occurring indigestible carbohydrates. In vitro they selectively stimulate the growth of species of Bifidobacterium, a genus of bacteria considered beneficial to health. This study was designed to determine their effects on the large bowel microflora and colonic function in vivo. METHODS: Eight subjects participated in a 45-day study during which they ate controlled diets. For the middle 15 days, 15 g.day-1 oligofructose was substituted for 15 g.day-1 sucrose. Four of these subjects went on to a further period with 15 g.day-1 inulin. Bowel habit, transit time, stool composition, breath H2 and CH4, and the predominant genera of colonic bacteria were measured. RESULTS: Both oligofructose and inulin significantly increased bifidobacteria from 8.8 to 9.5 log10 g stool-1 and 9.2 to 10.1 log10 g stool-1, respectively, whereas bacteroides, clostridia, and fusobacteria decreased when subjects were fed oligofructose, and gram-positive cocci decreased when subjects were fed inulin. Total bacterial counts were unchanged. Fecal wet and dry matter, nitrogen, and energy excretion increased with both substrates, as did breath H2. Little change in fecal short-chain fatty acids and breath CH4 was observed. CONCLUSIONS: A 15-g.day-1 dietary addition of oligofructose or inulin led to Bifidobacterium becoming the numerically predominant genus in feces. Thus, small changes in diet can alter the balance of colonic bacteria towards a potentially healthier microflora.

Adult↗

PubMed1990

Intragastric inulin as a measure of mucosal damage caused by aspirin.

In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing 3H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement of 3H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage.

Animals↗

PubMed2005

Mechanisms underlying the effects of inulin-type fructans on calcium absorption in the large intestine of rats.

Inulin-type fructans (inulin, oligofructose, fructooligosaccharides) in the diet do increase intestinal calcium absorption in animals and humans, but the underlying mechanism has not been identified. We therefore assessed the effects of fermentation of inulin-type fructans on transepithelial calcium transport in rat large intestine. Transepithelial calcium fluxes in vitro (Ussing chamber), effects on gene expression, mucosal morphology, and composition of luminal contents were determined in rats fed a standard diet and/or a diet containing 10% (w/w) 1/1 inulin-oligofructose mixture (INOF). Net transepithelial calcium transport in large intestine of rats fed a standard diet was increased by high mucosal calcium concentrations, the presence of 100 mmol/L mucosal short-chain fatty acids (SCFAs), the presence of 10 g/L INOF at the mucosal side, but not by reducing mucosal pH. Tissues from rats fed INOF did not show altered calcium transport when compared to controls. However, when flux data were based on the total caecal surface area, INOF-fed rats nearly doubled absorption rate in caecum. INOF feeding altered transcript levels of several mucosal genes that can be linked to transcellular and paracellular calcium transport processes. In addition, a decreased luminal pH in caecum with markedly increased caecal pools of total, soluble, and ionized calcium resulted from INOF ingestion. Thus, inulin-type fructans increase the large intestinal calcium absorption by different mechanisms including enhanced pools of soluble and ionized calcium, an increase in the absorptive surface predominantly in caecum, the increased concentrations of SCFAs, and by direct interaction with the intestinal tissue.

Animals↗