Evaluation of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate as markers of intestinal permeability in man

1987 ◽  
Vol 73 (2) ◽  
pp. 197-204 ◽  
Author(s):  
M. Elia ◽  
R. Behrens ◽  
C. Northrop ◽  
P. Wraight ◽  
G. Neale
Keyword(s):  
Urinary Excretion ◽  
Intestinal Permeability ◽  
Large Bowel ◽  
Normal Subjects ◽  
Distribution Volume ◽  
The Body ◽  
Factors Affecting ◽  
51Cr Edta ◽  
Small Intestinal ◽  
Radionuclide Scanning

1. Factors affecting the intestinal uptake and urinary excretion of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), have been investigated in normal subjects and three patients with ileostomy. 2. The distribution volume of markers within the body, the rate of disappearance from plasma and renal clearance were assessed after an intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 μCi), lactulose (0.1 g) and 51Cr-EDTA (5 μCi). 3. The urinary recovery of all the intravenously administered markers was close to 100%. Distribution volumes and patterns of excretion were virtually identical. Oxidation of intravenously administered mannitol accounted for only about 1% of the dose. 4. The passage of an orally administered mixture of markers was traced through the intestine and into urine. Transit time through the gastrointestinal tract was measured by the breath hydrogen method and by radionuclide scanning. 5. The passage of markers from mouth to the large bowel was essentially complete by 3.5 h. In some subjects the marker appeared in the large bowel as early as 30–40 min but in others it took three times as long. 6. After an oral dose the urinary excretion of mannitol fell progressively from 2 to 6 h, whereas the excretion of lactulose and 51Cr-EDTA increased slightly. As a consequence the lactulose/mannitol and 51Cr-EDTA/mannitol ratios in urine collected between 0 and 2 h were more than twofold higher than in urine collected between 4 and 6 h (P < 0.001). After 6 h, the urinary excretion of mannitol and lactulose declined rapidly in all subjects, and was similar to the pattern of excretion of 51Cr-EDTA in subjects with an ileostomy. In contrast, in normal subjects, the excretion of 51Cr-EDTA did not decline rapidly but continued for 24–48 h. 7. Differences in the excretion of mannitol, lactulose and 51Cr-EDTA after oral dosing is due to differences in the temporal pattern of absorption of these markers and not to differences in their distribution volume, oxidation or their clearance by the kidney. 8. The data suggest that the uptake of lactulose by the small intestine persists for longer than the uptake of mannitol, and show that 51Cr-EDTA is readily absorbed in the colon. This study indicates factors which must be considered in the design and interpretation of tests of small intestinal permeability.

Intra-Individual Variation in Serum AZT Concentration is Not Related to Intestinal Absorption or Small Intestinal Inflammatory Changes in Human Immunodeficiency Virus-Infected Subjects

1997 ◽  
Vol 8 (4) ◽  
pp. 327-332 ◽  
Author(s):  
RA Sherwood ◽  
JT Marsden ◽  
CA Stein ◽  
S Somasundaram ◽  
C Aitken ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Urinary Excretion ◽  
Intestinal Permeability ◽  
Absorptive Capacity ◽  
Individual Variation ◽  
Half Life ◽  
Intestinal Inflammation ◽  
Immunodeficiency Virus ◽  
Small Intestinal ◽  
Inflammatory Changes

3′-Azido-3′-deoxythymidine (AZT; zidovudine) either alone or in combination with didanosine or another nucleoside analogue is the first-line treatment for patients with human immunodeficiency virus (HIV) infection, many of whom have concurrent gastrointestinal (GI) disease. This study assessed whether the absorption of AZT was affected by GI disease. The absorption and pharmacokinetics of AZT in 23 HIV-infected individuals was measured after a single dose of AZT and was related in 12 patients to small intestinal function. Levels of AZT and its metabolite 5′-glucopyranuronosylthymidine (G-AZT) were measured by radioimmunoassay. Intestinal permeability was assessed by differential urinary excretion of orally administered lactulose/1-rhamnose; absorptive capacity was measured simultaneously by the urinary excretion of 3-o-methyl-D-glucose, d-xylose and 1-rhamnose. Small intestinal inflammation was assessed by faecal excretion of indium-labelled neutrophils. Peak levels of AZT in serum varied between 170 and 1820 ng mL−1. The metabolite G-AZT was present in serum at peak concentrations varying from 1020 to 9930 ng mL−1. There was up to a sevenfold variation in the area under the curve (AUC). The time to maximum serum concentration for AZT was between 30 and 120 min, with an absorption half-life of between 2 and 38 min. The median elimination half-life was 57 min (range 46–72 min), close to the predicted half-life of 60 min. Intestinal permeability was increased in six of the 12 subjects studied and eight had evidence of reduced absorptive capacity. Ten of the 12 patients had evidence of small intestinal inflammation. We concluded that neither changes in permeability nor absorptive capacity influenced the absorption of AZT. There was no relationship between the presence of intestinal inflammation and AZT absorption. This study showed a significant intra-individual variation of serum AZT levels which cannot be explained on the basis of altered intestinal absorptive capacity or intestinal inflammatory changes.

scholarly journals Effect of running intensity on intestinal permeability

1997 ◽  
Vol 82 (2) ◽  
pp. 571-576 ◽  
Author(s):  
Kay L. Pals ◽  
Ray-Tai Chang ◽  
Alan J. Ryan ◽  
Carl V. Gisolfi
Keyword(s):  
Urinary Excretion ◽  
Intestinal Permeability ◽  
High Performance ◽  
Gastrointestinal Symptoms ◽  
Long Distance ◽  
Mean Values ◽  
Small Intestinal ◽  
C 50 ◽  
Excretion Rates ◽  
Gastric Permeability

Pals, Kay L., Ray-Tai Chang, Alan J. Ryan, and Carl V. Gisolfi. Effect of running intensity on intestinal permeability. J. Appl. Physiol. 82(2): 571–576, 1997.—Enhanced intestinal permeability has been associated with gastrointestinal disorders in long-distance runners. The primary purpose of this study was to evaluate the effect of running intensity on small intestinal permeability by using the lactulose and rhamnose differential urinary excretion test. Secondary purposes included assessing the relationship between small intestinal permeability and gastrointestinal symptoms and evaluating gastric damage by using sucrose as a probe. Six healthy volunteers [5 men, 1 woman; age = 30 ± 2 yr; peak O2 uptake (V˙o 2 peak) = 57.7 ± 2.1 ml ⋅ kg−1 ⋅ min−1] rested or performed treadmill exercise at 40, 60, or 80%V˙o 2 peakfor 60 min in a moderate environment (22°C, 50% relative humidity). At 30 min into rest or exercise, the permeability test solution (5 g sucrose, 5 g lactulose, 2 g rhamnose in 50 ml water; ∼800 mosM) was ingested. Urinary excretion rates (6 h) of the lactulose-to-rhamnose ratio were used to assess small intestinal permeability, and concentrations of each probe were determined by using high-performance liquid chromatography. Running at 80%V˙o 2 peakincreased ( P < 0.05) small intestinal permeability compared with rest, 40, and 60%V˙o 2 peakwith mean values expressed as percent recovery of ingested dose of 0.107 ± 0.021 (SE), 0.048 ± 0.009, 0.056 ± 0.005, and 0.064 ± 0.010%, respectively. Increases in small intestinal permeability did not result in a higher prevalence of gastrointestinal symptoms, and urinary recovery of sucrose did not reflect increased gastric permeability. The significance and mechanisms involved in increased small intestinal permeability after high-intensity running merit further investigation.

Effect of total starvation and very low calorie diets on intestinal permeability in man

1987 ◽  
Vol 73 (2) ◽  
pp. 205-210 ◽  
Author(s):  
M. Elia ◽  
A. Goren ◽  
R. Behrens ◽  
R. W. Barber ◽  
G. Neale
Keyword(s):  
Intestinal Permeability ◽  
Transit Time ◽  
Low Calorie ◽  
51Cr Edta ◽  
Very Low Calorie Diets ◽  
Total Starvation ◽  
Obese Subjects ◽  
Group 3 ◽  
Small Intestinal ◽  
Group 2

1. The effect of total starvation for 4–5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5 g), [14C]mannitol (0.5 μCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 μCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 μCi), lactulose (0.1 g) and 51Cr-EDTA (5 μCi). 2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P < 0.025), 33% in group 2 obese subjects (P < 0.05) and 41% in group 3 obese subjects P > 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose. 3. There was no significant effect of starvation on transit time, whether assessed by the increase in breath hydrogen concentration in expired air or by radionuclide scanning. 4. Starvation produced no significant change in the clearance of the intravenously administered markers from the plasma. Oxidation of intravenous mannitol was estimated to account for about 1% of the clearance both before and during starvation. 5. The data provide evidence of a selective decrease in the absorption and excretion of mannitol during short-term total starvation. The changes in the excretion of mannitol are not due to alterations in renal function or gastrointestinal transit time, or to changes in the oxidation and plasma clearance of mannitol. They are likely to reflect changes in the small intestinal mucosa during early starvation. In contrast, very low calorie diets taken for at least 1 week prevent changes in small intestinal permeability.

Factors affecting the Metabolic Production of Methylguanidine

1975 ◽  
Vol 48 (5) ◽  
pp. 341-347 ◽  
Author(s):  
M. Gonella ◽  
G. Barsotti ◽  
S. Lupetti ◽  
S. Giovannetti
Keyword(s):  
Carbon Dioxide ◽  
Renal Failure ◽  
Gastrointestinal Tract ◽  
Urinary Excretion ◽  
The Body ◽  
Urinary Output ◽  
Solution Ph ◽  
Factors Affecting ◽  
Normal Volunteers

1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested. 2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg diets) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling. 3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high. 4. Creatinine, incubated at 38°C for 24 h in Krebs bicarbonate solution (pH 7.38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur ‘non-enzymatically’.

GENERAL ASPECTS OF IODINE METABOLISM IN SPORADIC GOITRE

1963 ◽  
Vol 42 (2) ◽  
pp. 300-308 ◽  
Author(s):  
B. de Crombrugghe ◽  
C. Beckers ◽  
M. De Visscher
Keyword(s):  
Urinary Excretion ◽  
Rate Constants ◽  
Radioactive Iodine ◽  
Normal Subjects ◽  
The Body ◽  
Thyroid Uptake ◽  
Iodine Metabolism ◽  
Inorganic Iodine ◽  
General Aspects ◽  
Stable Iodine

ABSTRACT Studies on iodine metabolism were performed in 17 patients with sporadic non-toxic goitre. A group of 11 normal subjects served as control. These investigations show that goitrous patients are at least iodine deficient: there is a low urinary excretion of stable and radioactive iodine with high thyroid uptake of radioiodine. Various rate constants of the iodide cycle in the body have been calculated. In particular, the concentration of stable iodide in the plasma as well as the pool of inorganic iodine are significantly reduced as compared with controls. The great avidity of the thyroid allowed an equal accumulation of stable iodine per unit of time in goitrous and non-goitrous subjects. Iodine deficiency undoubtly plays a role in the pathogenesis of sporadic non-toxic goitre in Belgium. The importance of lack of iodine is discussed in relation to other goitrogenic factors.

scholarly journals Radioactive Vitamin B12 Absorption Studies: Comparison of the Whole-Body Retention, Urinary Excretion, and Eight-hour Plasma Levels of Radioactive Vitamin B12

Blood ◽  
1971 ◽  
Vol 38 (5) ◽  
pp. 604-613 ◽  
Author(s):  
M. F. COTTRALL ◽  
D. G. WELLS ◽  
N. G. TROTT ◽  
N. E. G. RICHARDSON
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
The Body ◽  
Whole Body ◽  
Mean Values ◽  
Factors Affecting ◽  
Body Retention ◽  
Single Intramuscular Injection ◽  
Proportional Relationship ◽  
The Individual

Abstract This paper reports the results of investigations designed to compare the whole-body retention, urinary excretion, and 8-hr plasma level of 58Co vitamin B12 in some 80 absorption tests on 50 subjects. Residual levels of radioactivity in the body were measured using a whole-body counter. A proportional relationship is demonstrated between the 9-day whole-body retention, the 8-hr plasma radioactivity and the 48-hr urinary excretion of vitamin B12. The constants of proportionality are determined, enabling the results of absorption tests carried out by different methods to be compared. The mean values and the range of the results obtained are tabulated for subjects in each of four clinical categories. It is shown that approximately one third of the activity absorbed from a 1-µg dose is excreted in the urine following a single intramuscular injection of 1 mg nonradioactive vitamin B12 at 3 hr. The administration of this flushing dose does not significantly alter the activity absorbed as represented by that retained together with that excreted in the urine. The plasma activity at 8 hr is increased by a factor of about 2 over that obtained without the flushing dose. Factors affecting the accuracy of the individual techniques have been studied and the poor reproducibility of successive tests is discussed.

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