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Dipyrone and diclofenac do not influence creatinine-clearance, inulin-clearance or PAH-clearance in healthy male volunteers.

The effects of the non-steroidal anti-inflammatory drug diclofenac and the pyrazolone derivative dipyrone on renal function were compared with those of placebo in 12 healthy male volunteers in a randomized, controlled, triple-crossover study with a wash-out period of 4 days between each of the 3 trial periods (dipyrone, diclofenac and placebo) which lasted three days each. The volunteers received dipyrone (1 g, 3 times/day for 2 days, followed by twice 1 g on the main trial day, which was day 3 of each study period) or diclofenac (50 mg, 3 times/day for 2 days, followed by twice 50 mg on the main trial day) or placebo orally. Standardized meals (50 mEq sodium per day) were given from one week before the start until the end of the study and on the main trial days a protein-rich lunch (2 g protein/kg body weight) was taken. Renal function was assessed in each study period by measurement of creatinine-clearance, inulin-clearance and p-aminohippurate (PAH)-clearance to characterize glomerular filtration rate and renal plasma flow. High protein intake induced glomerular hyperfiltration (increased creatinine-clearance, inulin-clearance and PAH-clearance) in all 3 study periods (dipyrone, diclofenac, placebo). Dipyrone and diclofenac had no effect on renal clearance of creatinine, inulin or PAH in comparison to placebo. These results show that dipyrone and diclofenac at therapeutic dosages over 3 days do not decrease glomerular filtration and renal plasma flow in healthy individuals. Furthermore, it is unlikely that prostaglandins play a major role in protein-induced glomerular hyperfiltration.

Administration, Oral↗

Determination of glomerular filtration rate (GFR) on two consecutive days using inulin in a single-sample plasma clearance method.

Reliable estimation of the GFR is essential in nephrological practice for the early recognition and follow-up of latent or residual renal disturbance. The GFR of ten healthy volunteers on two consecutive days and of 40 patients with different renal diseases were investigated by means of a plasma slope clearance technique. After injection of 5 g/50 ml inulin solution, eight plasma samples were taken at 10, 20, 30, 40, 120, 180, 240, 300 min p.i. and analyzed with the aid of a fully enzymatic method. The results were correlated on the basis of 1- and 2-compartment models (1 CM, 2 CM) and the one-sample method (1 S), using only the plasma inulin concentration of the 240 min p.i. sample. The accuracy of the GFR data of volunteers estimated in these models was checked by comparison with the standardized agewise normal values, while for the patient group we found in terms of equations of correlation: 1. GFR (2 CM) = 4.46 + 0.763*GFR (1 S), n = 31, r = 0.985 2. GFR (2 CM) = 1.27*GFR (1 CM)0.9, n = 40, r = 0.996 3. GFR (1 CM) = 0.568*(GFR[1 S] + 5.85)1.11, derived The single-sample method using inulin is closely correlated to multi-sample methods but much more suitable for patients and staff. Therefore, it is recommended for clinical use.

Adult↗

[Effect of oral inulin administration on the fructose 2,6-biphosphate level in the liver tissue of rats with streptozocin diabetes].

The influence of oral inulin administration on glucose and fructose content in blood, glucose and ketone bodies in urine, and fructose-2,6-diphosphate content in liver was investigated in rats with streptozotocin diabetes. Short-term administration (during 5-6 days) of 0.5% inulin solution caused three-fold increase of blood fructose compared with control, normalisation of blood glucose and disappearance of glucose- and ketoneuria. The level of fructose-2,6-di-phosphate in liver increased to the control level. Inulin administration during 12 days caused five-fold increase of blood fructose compares with control, glucose level increased up to the level of uncurred diabetes (22 mmol/1), glucose- and ketoneuria appeared. The content of fructose-2,6-diphosphate in the liver decreased to diabetic level.

Administration, Oral↗

Idiotype of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse.

The serum from non-immunized mice of strains BALB/c, C58, A/He, and RIII contained hemagglutinins for stearoyl inulin-coated SRBC. Immunization with bacterial levan slightly elevated these titers. These same sera also carried cross-specific idiotypic determinants (IdX) that are associated only with inulin-binding myeloma proteins (INBMP) of BLAB/c mice. Three InuldX specificities, A, B, and G, were identified. The InuIdX phenotypes of strains BALB/c, C58, and A/He were InuIdXA+B+G+; strain RIII was InuIdX A+B-G+; strain C57BL/6, C57BL/10, DBA/2, AKR and NH were A-B-G-. Strains CBA, C3H, PL, and C57L could not be typed because of low and inconsistent levels of InuIdX and anti-inulin hemagglutinins. The InuIdXA+B+G+ phenotype was used as a genetic marker in immunoglobulin congenic strains CB-20, BAB-14, and BC-8 and in Bailey RI strains which are derived from crosses of BALB/c (InuIdXA+B+G+) and C57BL/ka or C57BL/6, respectively (InuldXA-B-G-). Linkage of the IdXA+B+G+ to the BALB/c a allotype locus was demonstrated. In addition, the InuldXA+B+G+ marker was used as a phenotype in an analysis of 168 first generation backcorss progeny (C57BL X (C57BL X BALB/c) F). Linkage of the marker to the BALB/c allotype was found again. Two proven recombinant mice having the C57BL a allotype and the InuIdxA+B+G+ markers were identified and progeny tested. Four other potential crossover types are still being progeny-tested.

Animals↗

Cloning of inulin fructotransferase (DFA III-producing) gene from Arthrobacter globiformis C11-1.

A gene encoding an inulin fructotransferase (DFA III-producing) [EC 2.4.1.93] from Arthrobacter globiformis C11-1 was cloned and the nucleotide sequence was determined. The cloned fragment contained a 1353 bp open reading frame. The initiation codon was estimated to be an unusual codon, GTG. The gene encoded a signal peptide (40 amino acid residues) for secretion. The molecular mass of the native enzyme was calculated as 43,400 Da from the sequencing data. The deduced amino acid sequence of the enzyme had 74.0 % homology with that of inulin fructotransferase (DFA III-producing) from Arthrobacter sp. H65-7. It also had 45.1% homology with that of inulin fructotransferase (DFA I-producing) [EC 2.4.1.200] from Arthrobacter globiformis S14-3. The enzyme produced in the culture supernatant of an Escherichia coli clone was purified to the electrophoretically homogeneous stage. The N-terminal amino acid sequence of the cloned enzyme secreted in the broth was the same as that of the native enzyme from A. globiformis C11-1. Therefore, on this enzyme, it is estimated that the cleavage sites by the signal peptidase for secretion of A. globiformis C11-1 and E. coli JM109 are the same.

Journal Article↗

Fermentation of Inulin by Clostridium thermosuccinogenes sp. nov., a Thermophilic Anaerobic Bacterium Isolated from Various Habitats.

Four closely related strains of thermophilic bacteria were isolated via enrichment in batch and continuous culture with inulin as the sole source of carbon and energy by using inoculations from various sources. These new strains were isolated from beet pulp from a sugar refinery, soil around a Jerusalem artichoke, fresh cow manure, and mud from a tropical pond in a botanical garden. The cells of this novel species of strictly anaerobic, gram-positive bacteria were rod shaped and nonmotile. Growth on inulin was possible between 40 and 65 degrees C, with optimum growth at 58 degrees C. All strains were capable of fermenting a large number of sugars. Formate, acetate, ethanol, lactate, H(2), and succinate were the main organic fermentation products after growth on fructose, glucose, or inulin. Synthesis of inulinase in batch culture closely paralleled growth, and the enzyme was almost completely cell bound. Strain IC is described as the type strain of a new species, Clostridium thermosuccinogenes sp. nov., with a G+C content of 35.9 mol%.

Journal Article↗

The clearance of creatinine, inulin, para-aminohippurate and phenosulphothalein in the cat.

Endogenous creatinine, inulin, para-amino-hippurate and phenolsulphothalein clearances for healthy cats are presented. The values for inulin and para-aminohippurate clearances (ml/kg/min) are similar to those for the dog. Creatinine clearance was less than inulin clearance values. Pnenolsulphothalein clearance may be a better index of glomerular rather than tubular function in the cat.

Animals↗

INULIN AND ALBUMIN ABSORPTION FROM THE PROXIMAL TUBULE IN NECTURUS KIDNEY.

In the kidney of the amphibian, Necturus, appreciable quantities of inulin and human serum albumin are transported from the tubular lumen of the proximal tubules into the blood. These findings suggest that inulin may not be a satisfactory indicator for measuring net water movement in the kidney of this species.

Albumins↗

Inulin as a carrier for contrast agents in magnetic resonance imaging.

Magnetic resonance angiography (MRA) has put forth an impetus for the development of macromolecular GdIII complexes that have a prolonged lifetime in the vascular system. Herein, we report the synthesis and GdIII complexation of a new sugar conjugate based on inulin and the DO3A ligand (DO3A = 1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid). Two API-DO3ASQ conjugates (API = O-(aminopropyl)inulin, SQ = squaric acid = 3,4-dihydroxy-3-cyclobutene-1,2-dione) with different degrees of substitution (ds = 0.7 and ds = 1.5) were prepared from API by using the diethyl ester of squaric acid as a linking agent for the DO3A chelate. The efficacies of the resulting GdIII compounds were evaluated by investigation of their water 1H longitudinal-relaxation-rate enhancements at variable field (NMRD). A dramatic increase in relaxivity was observed in the more highly substituted conjugate (ds = 1.5); this prompted us to do a variable-temperature (17)O study in order to further characterize the relaxation parameters involved in this system. [Gd(API-DO3ASQ)] shows promising properties for application as a contrast agent for MRI.

Chelating Agents↗

Measurement of human blood brain barrier integrity using 11C-inulin and positron emission tomography.

Positron emission tomography (PET) using 11C-inulin was demonstrated to be applicable to the clinical measurement of blood brain barrier permeability and cerebral interstitial fluid volume. Kinetic data were analyzed by application of a two compartment model, in which blood plasma and interstitial fluid spaces constitute the compartments. The blood activity contribution was subtracted from the PET count with the aid of the 11CO inhalation technique. The values we estimated in a human brain were in agreement with the reported values obtained for animal brains by the use of 14C-inulin.

Animals↗

The influence of guar gum on the movements of inulin, glucose and fluid in rat intestine during perfusion in vivo.

A two-stage perfusion technique was used to study the effect of guar gum on the inulin-accessible space and the uptake of water and glucose in rat intestine. Pre-perfusion of test loops with low concentrations of guar, dispersed in saline, modified the rate of equilibration of inulin with the mucosal fluid space during a subsequent perfusion. The glucose absorption rate in such loops was reduced at a concentration of 50 mM, but not at 100 or 150 mM glucose. Fluid absorption was inhibited by pre-treatment with guar gum at all glucose concentrations tested. These results suggest that guar forms a layer closely associated with the mucosal surface which modifies the viscosity of the immediate fluid compartment, so that its resistance to diffusion is increased by means of an unstirred layer effect.

Animals↗

Renal clearances of 14C-inulin and polyfructosan in the rat. Effect of increased ureteral pressure.

Polyfructosan has been used as a substitute for inulin in GFR determinations. However, the validity of this substitution in conditions where renal tubular permeability to other substances, such as mannitol, sucrose and other substances, such as mannitol, sucrose and iothalamate, is increased has not been tested. Experiments were performed on 8 rats to compare the clearances of polyfructosan (CPF) and 14C-inulin (CIN) during hydropenia, 3% BW saline expansion, elevation of one ureteral catheter by 30 cm, and following return of increased ureteral pressure to the control level. No significant difference between CPF and CIN could be detected except in the kidney subjected to increased ureteral pressure. However, the magnitude of this difference--which may relate to the different molecular weights of the two compounds--was so small that we conclude that the use of CPF, as an index of GFR, is no less reliable than CIN under the conditions tested.

Animals↗

Estimation of glomerular filtration rate in conscious dogs following a bolus of creatinine. Comparison with simultaneously determined inulin clearance.

The renal clearance of creatinine was measured following orogastric administration in conscious dogs. Values of creatinine clearance were compared with simultaneously determined values of inulin clearance, when urine volume, glomerular filtration rate and volume status were acutely altered by a variety of experimental manoeuvres. At urine volumes greater than 20 microliters X min-1 X kg-1, creatinine clearance was not significantly different from inulin clearance. At low urine volumes there was some evidence of creatinine reabsorption. It is concluded that the bolus creatinine technique provides reliable estimates of glomerular filtration rate and is particularly applicable to long-term studies in conscious dogs.

Animals↗

The molecular configuration of inulin: implications for ultrafiltration theory and glomerular permeability.

A space-filling model of the inulin molecule, based solely on physico-chemical data in the literature, indicates that the gross shape of the solvated molecule is a cylinder having semi-length 25 A and radius 10 A. The axial dimensions of this model very nearly equal the equivalent estimates (25 and 10.5 A) previously determined by studying restricted passage of inulin through artificial membranes of known pore size (E. Middleton, J. Membrane Biol. 20:347, 1975). The good agreement between these independent in-vitro studies--neither of which depends on ultrafiltration theory--strongly suggests that glomerular pore size is considerably greater than predicted by the theory.

Cell Membrane Permeability↗

Changes in the red cell, plasma and inulin spaces and in the total water contents of rat femurs in cortisone induced osteoporosis.

Measurements of the bone vascular space by use of 99mTc-labelled red cells and 131I-serum albumin, and of the 3H-inulin spaces and total water contents were carried out in female rats treated for four weeks by daily subcutaneous injections of 15 mg cortisone acetate. Significant decreases in bone vascularity, inulin space and water contents were noted as compared to controls. These changes were not associated with differences in plasma calcium values, or parathyroid gland weights. They were found to be present together with significant decreases in bone density and ash contents of the femoral shafts in the steroid-treated animals. It is suggested that the changes in the vascular and extravascular fluid spaces of bones were probably consequent upon a generally depressed level of cellular activity and bone turnover, which could be found in steroid induced osteoporosis.

Animals↗

Studies of the uptake and distribution of inulin and alpha-aminoisobutyric acid after intraamniotic injection in the guinea pig.

Pregnant guinea pigs were given intraamniotic injection of 14C-alpha-aminoisobutyric acid and 3H-inulin. Both substances were taken up by the fetus in different concentrations. High levels of alpha-amino-isobutyric acid were found in the placenta, liver, and serum. Inulin on the other hand, being a macro-molecule distributed by diffusion in the extracellular space, was found in high concentrations in the small intestine and in the placenta. Thus the main pathway for transferring nutrient substances from the amniotic fluid to the fetus would seem to be the gastro-intestinal tract. Thus supplementary nutrition of the fetus by the intraamniotic injection of nutrients is a possibility.

Aminoisobutyric Acids↗

Changes in red cell, plasma, inulin, and total water compartments in rat femurs. Comparison of vitamin D deficiency and diphosphonate induced rickets.

The vascular space, as measured with the use of 99m-technetium-labelled red cells and 131I-serum albumin, as well as the 14C-inulin and 3H2O fluid compartments were measured in rats which had been made rachitic by the use of a low phosphate vitamin D-deficient diet. A similar group of rachitic animals fed vitamin D2 50 IU, 5 and 3 days prior to sacrifice and a weight-matched control group were also studied. The same spaces were measured in rats made rachitic by daily s.c. injections of ethane-1-hydroxy-1,1-diphosphonate (EHDP) for 4 weeks and a weight-matched saline injected control group. Findings indicated that the red cell and RISA spaces were unchanged in the untreated D-deficient group as compared to controls but increased after being repleted with vitamin D. By contrast, the vascular space was depressed in the EHDP-treated group. The water content was elevated in D-deficient rickets returning towards normal on healing, whilst both inulin and water spaces were increased in the EHDP-treated animals. Thus, while the extravascular space reflected the presence of osteoid, the vascular space depended on cellular turnover and the process of mineralization.

Animals↗

Selection of yeast strains for ethanol production from inulin.

Of the many yeast species capable of fermenting inulin, some can produce sufficient amounts of ethanol from the substrate, in particular Kluyveromyces fragilis and Torulopsis colliculosa. The results indicate the feasibility of producing ethanol from inulin-rich plants, such as Jerusalem artichoke.

Anaerobiosis↗