Excretion Of 51Cr-EDTA Research Articles

Effects of smoking on the urine excretion of oral51Cr EDTA in ulcerative colitis

Background—Smokers have a reduced risk and ex-smokers an increased risk of ulcerative colitis (UC). Stopping smoking often precedes onset and relapses. Smoking reduces the 24 hour urine excretion of oral...

Ermittlung der passage zweier marker im verdauungstrakt von ochsen mit hilfe unterschiedlicher schätzverfahren: Einfluss des ernährungsniveaus

An sechs ausgewachsenen, mit Pansennstein versehenen Ochsen wurde der Einfluß des Ernährungsniveaus auf die Passage des Verdauungsbreis aus dem Reticulorumen und durch den gesamten Verdauungstrakt untersucht. Die Tiere erhielten eine gemischte Ration, die in der DM im Mittel aus 43 % Grassilage, 25 % Maissilage, 30 % Konzentratfutter und 2 % Mineralfutter bestand und bei drei Ernährungsniveaus vorgelegt wurde: Erhaltungsbedarf und 1,5facher sowie 2facher Erhaltungsbedarf. Gefüttert wurde 2mal täglich, ab 7 Uhr und ab 19 Uhr. Die Versuchsanordnung entsprach einem doppelt besetzten 3×3 lateinischen Quadrat mit Versuchsperioden von 21 Tagen. Zu Beginn jeder Versuchsperiode erhielten die Tiere Einmaldosen der Marker Titan(IV)‐oxid (TiO2) mit dem Konzentratfutter und Cr‐EDTA als unverdünnte Lösung direkt in den Pansen. Kotproben wurden nach der Markergabe rektal über 120 h hinweg entnommen. Passageparameter wurden mit Hilfe unterschiedlicher Schätzverfahren ermittelt, wobei ein monoexponentielles und ein biexponentielles Modell, Modelle mit Gamma‐Zeitabhängigkeit sowie ein Modell, in dem die mittlere Verweildauer des Markers im gesamten Verdauungstrakt als Mittelwert aller Punkte der Marker‐Exkretionskurve berechnet wird, verwendet wurden. Mit steigendem Ernährungsniveau nahm die Passagerate von TiO2 aus dem Reticulorumen zu, die mittlere Verweildauer im gesamten Verdauungstrakt nahm ab. Die Ergebnisse der unterschiedlichen Modellansätze stimmten mit wenigen Ausnahmen gut überein. Außerdem zeigte sich eine gute Übereinstimmung zwischen den Ergebnissen der TiO2‐Passage und den Werten, die andere Versuchsansteller für die Passage kleiner, prinzipiell passagefähiger Teilchen bei ähnlichen Rationstypen ermittelten. Auch für Cr‐EDTA nahm die Passagerate aus dem Reticulorumen mit steigendem Ernährungsniveau zu, die mittlere Verweildauer im Reticulorumen und im gesamten Verdauungstrakt nahm ab. Es zeigten sich jedoch Differenzen zwischen den Modellansätzen mit oder ohne Zeitabhängigkeit. Die Anpassung an den Kurvenverlauf der Cr‐EDTA‐Ausscheidung mit dem Kot war bei den Modellen mit Gamma‐Zeitabhängigkeit unbefriedigend. Für beide Marker ergaben alle verwendeten Modelle übereinstimmend eine deutliche Beschleunigung der Passage aus dem Reticulorumen bzw. eine deutliche Verkürzung der Verweildauer im Reticulorumen und im gesamten Verdauungstrakt, wenn das Ernährungsniveau von der Deckung des Erhaltungsbedarfes auf das 1,5fache des Erhaltungsbedarfes angehoben wurde.

Intestinal mucosal permeability to 51Cr-ethylenediaminetetraacetic acid is increased after bilateral lower extremity ischemia-reperfusion in the rat

Despite successful revascularization of ischemic extremities, multiorgan dysfunction syndrome develops in some patients. Mechanisms responsible for this are not known; however, the gastrointestinal tract has been implicated as a possible mediator. Our objective was to demonstrate increased intestinal mucosal permeability after bilateral hindlimb ischemia-reperfusion (I-R) in a rodent model. Sixteen male Wistar rats were randomized either to 4 hours of bilateral hindlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or control groups (n = 8). The animals received 10 MuCi 51Cr-ethylenediaminetetraacetic acid (EDTA) by gavage, and excretion was measured in urine collected every 8 hours in 16 animals and every 4 hours in 8 animals. Arterial blood pressure was monitored continuously. Intravenous normal saline solution (3 ml/hr) with fentanyl (2 microgram/100 gm/hr) was continuously administered. Immediately before death complete blood count and levels of arterial lactate, creatinine, and urea were obtained. Mesenteric lymph nodes were harvested from the ileocecal region and cultured. Distal small bowel and proximal colon were preserved for histologic analysis. An additional 11 rats, six experimental and five control, were evaluated for mesenteric lymph node cultures only. Urinary excretion of 51Cr-EDTA was significantly greater in the I-R group between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of reperfusion. This increase occurred as early as 4 to 8 hours of reperfusion (p < 0.0001). Urine volume in the I-R group was significantly reduced during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin and lactate level were significantly different in the I-R group. Leukocyte and platelet counts, levels of creatinine and urea, and colony counts from mesenteric lymph nodes were similar in I-R and control groups. Blinded histologic analysis of bowel segments did not reveal morphologic differences. Bilateral hindlimb I-R produces remote intestinal mucosal injury shown by significantly increased permeability to 51Cr-EDTA. Such increased mucosal permeability may be important in the development of multiorgan dysfunction syndrome in patients who sustain lower extremity I-R injury.

Assessing the site of increased intestinal permeability in coeliac and inflammatory bowel disease.

The precise site of intestinal permeability changes in patients with coeliac and inflammatory bowel disease is unknown. To design a non-invasive technique for the localisation of altered gastrointestinal permeability to 51chromium labelled EDTA (51CrEDTA). The method depends on comparing and defining concentration/time profiles in serum of a series of simultaneously ingested indicators with a well defined absorption site (3-0-methyl-D-glucose (jejunal indicator), 57cobalt labelled vitamin B12 (ileal indicator), and sulphasalazine (caecal-colonic indicator)) in relation to simultaneously ingested 51CrEDTA. Five normal controls, six patients with untreated coeliac disease, five with Crohn's ileitis, and five with pan-ulcerative colitis underwent study, which entailed the simultaneous ingestion of the above four test substances followed, during the next 24 hours, by timed serial collection of urine and serum for marker analysis. Urinary excretion of 51CrEDTA was significantly increased in all patient groups. Analysis of serum appearances and profiles of the markers suggested that the increased intestinal permeation of 51CrEDTA took place in the diseased jejunum in patients with coeliac disease, predominantly in the ileum in Crohn's disease and in the colon in the patients with pan-ulcerative colitis. A new non-invasive technique has been assessed that permits the localisation of the site of permeability changes with the gastrointestinal tract.

Assessment of gastrointestinal permeability to small marker probes in the preruminant calf.

The intestinal permeability to markers was assessed in preruminant calves fed different milk substitutes containing skimmed milk powder or whey and soyabean products of differing antigenic activity as the protein sources. In Experiment 1, the 6 h urinary excretion of lactulose transiently decreased with the antigenic soyabean product but not that of sucrose of D-mannitol. In Experiment 2, the 6 h urinary excretion of sucrose and D-mannitol averaged 1-3%, regardless of age and dietary treatment. Cr-EDTA was recovered at rates of 2 and 4% after 6 and 24 h of urinary collection, respectively. The 24 h excretion of Cr-EDTA was lower in the calves fed the antigenic flour than in the controls after 2 weeks of experimental feeding (2.9 vs 6.0%, P < 0.05) but not thereafter. This transient decrease was also observed using D-xylose with the antigenic flour and with the non-antigenic concentrate (17 and 22% respectively vs 37%, P < 0.05). The present markers, including sucrose, may be suitable for assessing intestinal permeability in the calf even though excretion rates differed from one marker to another. Changes in the intestinal permeability to antigenic soya were of low magnitude and were only transiently detected when measured using lactulose, Cr-EDTA or D-xylose, probes which were therefore more sensitive than sucrose or D-mannitol.

Blastocystis hominis Infection and Intestinal Injury

Blastocystis hominis is an enteric protozoan associated with clinical illness. To determine the prevalence of intestinal injury in patients with B. hominis infection, the authors prospectively evaluated 18 patients with B. hominis infection by endoscopy and a test of intestinal permeability. Seventeen patients had gastrointestinal symptoms. Colonic mucosa appeared normal by lower endoscopy in 12 of 13 patients, and was friable slightly in 1. Duodenal mucosa was normal by upper endoscopy in nine patients. Pathologic examination of mucosal biopsy specimens did not demonstrate evidence of mucosal invasion. 51Cr-edetic acid (51Cr-EDTA) was given to the 18 patients with stools positive for B. hominis and to 32 healthy control subjects. Approximately 100 uCi of 51Cr-EDTA was given orally after an overnight fast, and urine was collected for the following 24 hours. Mean 24-hour urinary excretion of 51Cr-EDTA, calculated as a percent of the administered dose, was 1.31% (0.34-2.76%) in patients with B. hominis infection and 1.99% (0.59-3.48%) in the control subjects. The intestinal permeability to 51Cr-EDTA in blastocystis-infected individuals was not increased, but was decreased significantly compared with healthy subjects (p < 0.005). Therefore, in a group of symptomatic patients with B. hominis infection, endoscopy typically did not show evidence of significant intestinal inflammation, and results of intestinal permeability testing with 51Cr-EDTA did not suggest impaired barrier function of the intestinal mucosa. The clinical literature on B. hominis infection and intestinal injury is reviewed.

Antiinflammatory drug-induced small intestinal permeability: the rat is a suitable model.

Excretion of orally administrated 51Cr-EDTA as a marker of small intestinal permeability (a proposed prerequisite for human enteropathy) is increased by corticosteroids and non-steroidal antiinflammatory drugs (NSAIDs). We have investigated the suitability of the rat as an animal model of small intestinal permeability using orally administered 51Cr-EDTA. We dosed Sprague-Dawley rats with NSAIDs and corticosterone followed by 51Cr-EDTA under conditions reported for humans and measured urinary excretion of the marker. In control rats, the urinary excretion of 51Cr-EDTA exhibited a skewed-to-the-left frequency distribution curve with a median of 2.13% of the dose. No sex-related differences were noticed in the baseline permeability. In male rats, single therapeutically equivalent doses of indomethacin, flurbiprofen, ibuprofen, naproxen, diclofenac, sulindac, nambumetone, and corticosterone, increased the intestinal permeability by different extents with indomethacin eliciting the maximum effect, and the last four drugs showing minimal potencies. Therapeutically relevant doses of aspirin did not have any significant effect. The increase in permeability was dependent upon the NSAIDs dose. Administration of glucose/citrate, misoprostol and sulfasalazine significantly reduced the effect of indomethacin. Misoprostol antagonized the effect of naproxen but H2-antagonists and sucralfate did not. All the above observations made in the rat were similar to those previously reported for humans. Thus the rat is a suitable model for studies of small intestinal permeability.

Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid. A test to distinguish colonic from small-intestinal permeability change.

In normal adults intestinal permeation of ingested 51Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.

Intestinal permeability in patients with psoriasis

A possible relationship between intestinal structure and function in the pathogenesis of psoriasis has recently brought about considerable interest. The purpose of this study was to evaluate the intestinal permeability in psoriatic patients by comparing it with healthy controls. 15 psoriatic patients and 15 healthy volunteers entered the study. Intestinal permeability was evaluated using the 51Cr-labeled EDTA absorption test. The 24-h urine excretion of 51Cr-EDTA from psoriatic patients was 2.46 ± 0.81%. These results differed significantly from controls (1.95 ± 0.36%; P < 0.05). The difference in intestinal permeability between psoriatic patients and controls could be due to alterations in the small intestinal epithelium of psoriatics.

The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease

This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability [24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% ± 0.6% (mean ± SE); normal, < 3.0%] and by high fecal excretion of 111In-labeled leukocytes (14.2% ± 1.1%; normal, < 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% ± 0.5%; P < 0.01) and the fecal excretion of 111In (to 5.7% ± 1.0%; P < 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease.

Early detection of damage following bilateral renal irradiation in the mouse

The rate and early pattern of development of radiation-induced renal damage has been determined in the mouse by measuring reductions in both haematocrit and excretion of 51Cr-EDTA, and increases in both urination frequency and urine volume. Kidneys of CBA mice were irradiated bilaterally with 2 fractions of X-rays, one week apart. Renal function was determined immediately prior to irradiation and at 3–4 weekly intervals to 22 weeks post-irradiation. Onset of damage was detected as early as 3–6 weeks using the urination frequency assay. This was confirmed by estimating the volume of urine excreted. A significant fall in haematocrit was not detected until 6–9 weeks post-treatment and a fall in isotope clearance was not detected significantly until 12 weeks. This early detection of damage was consistent with reports using both mouse and other species. The time at which damage was detected first was independent of radiation dose for the frequency and haematocrit assays. For 51Cr-EDTA clearance, there was the suggestion of earlier functional loss for the higher doses. Following the onset of damage, a steady, dose-dependent decline in renal function was measured by all assays. The latency period is defined as the time required to reach a given level of functional damage. This time decreased with increasing radiation dose, to a minimum value set by the time of onset of damage, which varied from 3 to 12 weeks, depending on the assay used. The differences in response measured prior to to 12 weeks post-irradiation represent the first occasion on which a dissociation between these 3 assays has been detected. The radiation-induced anaemia was characterised as normocytic with no evidence of haemolysis.

Elemental diet: a therapeutic approach in chronic inflammatory bowel disease

The therapeutic effect of an elemental diet (Pepti 2000) and blended normal diet (placebo) was investigated in 43 out-patients with chronic inflammatory bowel disease (IBD); 24 with ulcerative colitis (UC) and 19 with Crohn's disease (CD), in a mild to moderate state of disease activity. A pilot study on healthy volunteers was executed to investigate palatability of the two diets. The patients were randomized in a double-blind study to the two diet regimes for 14 d. A simultaneous determination of laboratory data including plasma C3c split product and urinary excretion of 51Cr-EDTA was carried out together with a careful registration of the clinical symptoms and signs. No significant effect on the stage of clinical activity was seen in CD. A significant effect on clinical activity was obtained in both UC groups. The clinical improvement was primarily due to a decrease in number of bowel movements both in the elemental diet group and in the group of patients on the blended normal diet. The gross appearance of rectal mucosa did not improve during the study period in the Pepti 2000 or in the placebo group. The concentration of complement split products in plasma remained unchanged. 51Cr-EDTA excretion, as an expression of a leaky bowel mucosa, also remained unchanged. It was concluded that an effect on inflammation could not be demonstrated even if both diets seem to have a beneficial effect on the stage of clinical activity, especially diarrhoea, in patients with UC.

51Cr-EDTA: A marker of early intestinal rejection in the rat

Intestinal permeability was studied after accessory intestinal transplantation in Lewis rats. Five groups were evaluated: Group 1—isografts ( N = 6); Group 2—Lewis X Brown Norway F1 (LBN-F1) allografts ( N = 6); Group 3—isografts treated with CsA 2 mg/kg/day × 10 days ( N = 6); Group 4—LBN-F1 allografts treated with CsA 2 mg/kg/day × 10 days ( N = 6); Group 5—LBN-F1 allografts treated with CsA 4 mg/kg/day × 28 days ( N = 6). Chromium-labeled ethylenediaminetetraacetate ( 51Cr-EDTA) was given through the proximal stoma of the graft. Renal clearance of ( 51Cr-EDTA and mucosal biopsies were followed post-transplant. The biopsies of the intestinal graft showed no rejection in Groups 1, 3, and 5; fulminant rejection in Group 2; and mild atypical rejection in Group 4. 51Cr-EDTA clearance was elevated in all groups during the first 7 days post-transplant. Thereafter, 51Cr-EDTA excretion fell to lower levels in the animals with histologically normal grafts (Groups 1, 3, and 5). 51Cr-EDTA excretion in Group 4 was increased with the first histological evidence of rejection on Day 14 and remained elevated until sacrifice ( P < 0.02 compared to Groups 3 and 5). A transient permeability defect occurs after intestinal grafting. Once the graft has recovered from this injury, 51Cr-EDTA is a sensitive marker for intestinal rejection.

Age Influence on Digestive Transit Time of Particulate and Soluble Markers in Broiler Chickens

The gastrointestinal transit-time of two markers, Cr-mordanted bran, a solid marker, and Cr-EDTA, a soluble marker, have been studied in chickens (Gallus gallus) at 1, 2, and 3 wk of age. Mean retention time of the particular marker decreased as chicks grew. The excretion of Cr-EDTA took longer as birds grew; this soluble marker was retained in the ceca of the fowl. It was postulated that the ceca are not fully functional until total resorption of the yolk sac content occurs.

Intestinal Permeability of51Cr-labelled Ethylenediaminetetraacetic Acid in Patients with Crohn's Disease and Their Healthy Relatives

An increased intestinal permeability has been proposed as an aetiologic factor in Crohn's disease. The 24-h urinary excretion of 100 muCi 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) was used to test the permeability in 15 patients with Crohn's disease and in 20 healthy first-degree relatives, who are known to have a genetic predisposition to inflammatory bowel disease. Twenty-eight healthy persons not related to patients with inflammatory bowel disease served as control material. The 51Cr-EDTA excretion of the relatives (range, 0.98%-3.87%; median, 1.935%) was not significantly higher than that of the controls (range, 1.17%-3.26%; median, 1.950%), whereas patients with Crohn's disease had a significantly higher excretion (range, 1.64%-8.86%; median, 2.940%) than both the relatives and the controls. Among patients the increased excretion was found only if the small intestine was involved. We conclude that 1) as a group, patients with Crohn's disease in the small intestine have an increased intestinal permeability, in contrast to their healthy relatives, who have a normal permeability; 2) a considerable overlap of the results of the 51Cr-EDTA test was found between the groups studied, and the test is not suitable for evaluating individual patients; 3) our results do not support the hypothesis of an increase in intestinal permeability as an aetiologic factor in Crohn's disease.

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

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 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 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 less than 0.001). After 6 h, the urinary excretion

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

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 (5g), [14C]mannitol (0.5 microCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 microCi), 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 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 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 less than 0.025), 33% in group 2 obese subjects (P less than 0.05) and 41% in group 3 obese subjects P greater than 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)

Radionucleide tests for the assessment of intestinal permeability

14C labelled-D-mannitol and aquo (ethylene-diaminetriacetoacetic acid) 51chromium (III) (51Cr EDTA) have been evaluated as markers of intestinal permeability in twenty-four healthy control subjects, sixteen patients with recently diagnosed coeliac disease and twenty subjects with coeliac disease in remission on a gluten-free diet. The percentage excretion of 14C mannitol in urine collected for 6 h was significantly less in patients with coeliac disease (mean 6.7%) than controls (mean 13.5%). Conversely the excretion of 51Cr EDTA was significantly greater in patients with coeliac disease (mean 1.23%) compared with controls (mean 0.28%). The mean ratio of the percentage excretion of 51Cr to the percentage excretion of 14C was 0.29 in patients with untreated coeliac disease compared with 0.023 for healthy control subjects (P less than 0.001). Patients with untreated coeliac disease were clearly separated from control subjects by use of the 51Cr EDTA: 14C mannitol ratio but not by the excretion of independent markers.

Intestinal permeability to 51Cr-EDTA in rats with experimentally induced enteropathy.

Intestinal permeability has been investigated in the normal rat by measuring the five hour urine excretion of 51Cr-EDTA after intragastric administration. Twelve control animals excreted 2.06% +/- 0.22 (mean +/- SE) of the administered dose. Prolonged intestinal transit times with atropine had no significant effect on the apparent permeability with a urine excretion 2.31% +/- 0.36. The concomitant administration of a hypertonic, but rapidly absorbed glycerol solution, was accompanied by increased urinary excretion (3.05% +/- 0.33) while the administration of a poorly absorbed sugar, lactulose, significantly decreased the apparent permeability (urine excretion 0.61% +/- 0.14) showing that passive intestinal permeability estimations are affected by test dose composition. Enteropathy was induced by ethanol, cetrimide, or methotrexate and each was associated with increased permeability, with urine excretions of 4.19% +/- 0.47, 4.20% +/- 0.66 and 3.97% +/- 0.49 respectively. It is thus suggested that the normal rat mucosa is maximally resistant to the absorption of foreign compounds such as 51Cr-EDTA and intestinal damage will disrupt this barrier.

Radiation induced renal damage in mice: Influence of overall treatment time

The influence of overall treatment time on the radiation response of the mouse kidney was studied by varying the time over which 2 or 5 fractions of X-rays were administered. Two functional assays (urine output and 51Cr-EDTA excretion), and renal weight at sacrifice were used to obtain dose-response curves and estimate isoeffective doses. Split dose experiments showed Elkind recovery of about 5 Gy in 24 h. With a 7-day interval between fractions a transitory increase in isoeffect dose was observed in the first experiment. In the second, more extensive, experiment the recovered dose did not increase significantly even if the interval between two fractions was prolonged up to 25 days. Therefore, if slow repair occurred it was not worth more than 1 Gy because this was the limit of resolution of the assays used. As overall time was prolonged to 60 days an additional 1-2 Gy were recovered: it is difficult to explain this delayed sparing effect on the basis of a compensatory proliferative response, because the labelling indices of the likely target cells in the kidney are so low. Whatever the mechanisms involved, an increase in overall time had only a slight effect on isoeffect dose in these experiments and values for the "T" exponent were low (0.0-0.09). Recovery from sublethal injury between fractions has a much larger effect.