[Primary bile acid diarrhea in a community gastroenterology practice]. / Die primäre chologene Diarrhö in einer gastroenterologischen Praxis.

When first described in 1976, primary bile acid diarrhea (BAD Type 1) was regarded as a very rare cause of chronic diarrhea. Today, the incidence is estimated as > 1 %. Availability of diagnostic tools varies widely and, in Germany, there is no generally consented recommendation for their use. BAD is still widely underdiagnosed.Since the beginning of the '90 s, we have added a therapeutic trial with cholestyramine to our diagnostic approach of chronic diarrhea. Patients with a positive test were offered a Selenium-homocholic acid taurine (SeHCAT) test for confirmation of bile-acid-diarrhea (BAD), using a 7-day-retention of 20 % as cut-off value.From April 1991 to March 2017, after exclusion of other relevant causes for chronic diarrhea like IBD, celiac disease or microscopic colitis, 70 patients with a positive trial treatment of cholestyramine were identified for evaluation. Sixty of them had a SeHCAT test. Patients with BAD Type 1 and Type 3 were excluded, except for cholecystectomy.85 % (35/41) of patients with BAD Type 1 needed continued medical treatment (median follow-up time 8.3 (1 - 23.6) years). Among them, 68.6 % (24/35) took cholestyramine, 31.4 % (11/35) loperamide or another antidiarrheal treatment. 14.6 % (6/41) of patients reported a spontaneous remission after median 2.9 (0.7 - 5.7) years.In the group of patients with BAD after cholecystectomy, 82 % (8/11) still needed treatment after median 7.7 (1 - 24.5) years; 8 having taken cholestyramine, one patient nothing and two with spontaneous remissions.All (8/8) patients with a normal SeHCAT test (7-day retention > 20 %) had spontaneous relief after median 3.6 (1.2 - 6.3) months.Also, 70 % (7/10) of patients who had not been confirmed by the SeHCAT test still needed treatment after median 4.3 (3.7 - 18.3) years.Based on a trial treatment alone, diagnosis of BAD is possible but not assured. Due to its ubiquitous availability, it should be used consequently if other methods are not available. Despite the well-known shortcomings of cholestyramine, a therapeutic trial should be used more consequently. According to the current literature, using the SeHCAT test in the first place will give significantly better results and unnecessary follow-up examinations can be avoided. However, therapeutic consequences might be modest due to the well-known limitations of cholestyramine. A well-tolerated and licensed alternative to cholestyramine is urgently needed.

75SeHCAT scan in bile acid malabsorption in chronic diarrhoea. / Gammagrafía con 75SeHCAT en la diarrea crónica por malabsorción de ácidos biliares.

Chronic diarrhoea is a common entity in daily clinical practice and it leads to a loss in these patients quality of life. It may be the main symptom of multiple ethiologies including bile acid malabsorption (BAM) which has a comparable prevalence to celiac disease. The BAM results from imbalances in the homeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease or ileal dysfunction (BAM type i), it can be considered idiopathic or primary (BAM type ii) or associated with other gastrointestinal entities (BAM type iii). Among the different diagnostic methods available, 75SeHCAT study is the primary current method due to its sensitivity, specificity, safety and low cost. The main disadvantage is that it's not available in all countries, so other diagnostic methods have appeared, such as serum measurement of FGF19 and C4, however they are significantly more complex and costly. The first-line treatment of bile acid diarrhoea is bile acid sequestrant, such as cholestyramine, which can be difficult to administer due to its poor tolerability and gastrointestinal side effects. These are less prominent with newer agents such as colesevelam. In summary, the BAM is a common entity underdiagnosed and undertreated, so it is essential to establish a diagnosis algorithm of chronic diarrhoea in which the 75SeHCAT study would be first or second line in the differential diagnosis of these patients.

Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention.

BACKGROUND: Bile acid diarrhoea is a common, under-diagnosed cause of chronic watery diarrhoea, responding to specific treatment with bile acid sequestrants. We previously showed patients with bile acid diarrhoea have lower median levels compared with healthy controls, of the ileal hormone fibroblast growth factor 19 (FGF19), which regulates bile acid synthesis. AIM: To measure serum FGF19 and SeHCAT retention prospectively in patients with chronic diarrhoea. METHODS: One hundred and fifty-two consecutive patients were grouped according to (75) Se-homocholic acid taurine (SeHCAT) 7-day retention: normal (>15%) in 72 (47%) diarrhoea controls; ≤15% in 54 (36%) with primary bile acid diarrhoea, and in 26 (17%) with secondary bile acid diarrhoea. Fasting blood was assayed for FGF19, 7α-hydroxy-4-cholesten-3-one (C4) and total bile acids. RESULTS: FGF19 was significantly lower in the primary bile acid diarrhoea group compared with the diarrhoea control group (median 147 vs. 225 pg/mL, P < 0.001), and also in the secondary group (P < 0.006). FGF19 and SeHCAT values were positively correlated (rs = 0.44, P < 0.001); both were inversely related to C4. Other significant relationships included SeHCAT and body mass index (BMI)(P = 0.02), and FGF19 with age (P < 0.01). The negative and positive predictive values of FGF19 ≤ 145 pg/mL for a SeHCAT <10% were 82% and 61%, respectively, and were generally improved in an index including BMI, age and C4. In a subset of 28 primary patients, limited data suggested that FGF19 could predict response to sequestrant therapy. CONCLUSIONS: Reduced fibroblast growth factor 19 is a feature of bile acid diarrhoea. Further studies will fully define its role in predicting the response of these patients to therapy.

Translocation of 125I, 75Se and 36Cl to wheat edible parts following wet foliar contamination under field conditions.

Apart from radiocaesium and radiostrontium, there have been few studies on the foliar transfer of radionuclides in plants. Consequently, specific translocation factor (ftr) values for (129)I, (79)Se and (36)Cl are still missing from the IAEA reference databases. The translocation of short - lived isotopes, (125)I and (75)Se, and of (36)Cl to wheat grain were measured under field conditions following acute and chronic wet foliar contamination at various plant growth stages in the absence of leaching caused by rain. The translocation factors ranged from 0.02% to 1.1% for (125)I (a value similar to Sr), from 0.1% to 16.5% for (75)Se, and from 1% to 14.9% for (36)Cl. Both (36)Cl and (75)Se were as mobile as Cs. The phenomenological analysis showed that each element displayed a specific behavior. Iodide showed the lowest apparent mobility because of its preferential fixation in or on the leaves and a significant amount probably volatilized. Selenite internal transfer was significant and possibly utilized the sulphur metabolic pathway. However bio - methylation of selenite may have led to increased volatilization. Chloride was very mobile and quickly diffused throughout the plant. In addition, the analysis underlined the importance of plant growth responses to annual variations in weather conditions that can affect open field experiments because plant growth stage played a major role in ftr values dispersion. The chronic contamination results suggested that a series of acute contamination events had an additive effect on translocated elements. The highest translocation value obtained for an acute contamination event was shown to be a good conservative assessment of chronic contamination if data on chronic contamination translocation are lacking. The absence of rain leaching during the experiment meant that this investigation avoided potential radionuclide transfer by the roots, which also meant that radionuclide retention on or in the leaves was maximized. This study was therefore able to obtain accurate translocation factors, which are probably among the highest that could be recorded.

A mathematical model for the behaviour of Se-79 in soils and plants that takes account of seasonal variations in soil hydrology.

Se-79 is a long-lived radionuclide of potential radiological significance in relation to the deep geological disposal of solid radioactive wastes. In the context of release to the terrestrial environment, its main radiological impact is delivered through food chain pathways. Therefore, its accumulation in soils and uptake by plants is an important consideration in post-closure safety assessment studies. However, representation of its behaviour in the soil-plant system requires consideration of the multiple valence states that it can exhibit under different redox conditions and its susceptibility to volatilisation. A simple model is described that includes seasonal variations in soil hydrology and their effects on the mobility and root uptake of Se-79. Illustrative calculations are undertaken with the model, to demonstrate its capabilities for interpreting experimental data on the behaviour of Se-79 in soils and plants, and for making projections on the long-term behaviour of Se-79 transported to soils.

[Measurement of 75Se-SeHCAT abdominal retention in the initial diagnosis of Bile Acid Absorption (BAM)]. / Medición de la absorción de los ácidos biliares en el diagnóstico inicial de la diarrea crónica.

AIM: To evaluate the usefulness of the (75)SeHCAT abdominal retention (AR) measurement in the early diagnosis of diarrhea syndrome (DS). METHODS: Thirty-seven patients with diarrhea syndrome within the first month of evolution were prospectively evaluated. The (75)Se-SeHCAT abdominal retention was measured 4 and 7 days post-administration of 0.01 mCi of (75)SeHCAT. The test was performed prior to treatment and at 3 months when the baseline study was positive. The test was considered positive if the RA was <25% at 4(th) and <10% on the 7th day. The patients were visited at 3 months. Depending on the response, 3 groups were established: a) complete response: normalization of stool frequency, b) partial response, decrease of frequency or c) no response. RESULTS: Group A: The AR of (75)Se-SEHCAT was normal in 21 patients. Six were diagnosed of colonic diverticulosis, 8 of irritable bowel syndrome, 1 of lymphocytic colitis, 1 of post-gastroenteritis syndrome, 1 of celiac disease and 1 of stenosis of the cardia. Four are still under study. Group B: The AR of (75)Se-SEHCAT decreased in 16 patients. All showed abnormal AR at day 7 and all but 1 at day 4. Following administration of cholestyramine resin, 8 (50%) presented partial response and 8 (50%) complete response. At 3 months, AR had increased at day 4 and 9 at day 7. CONCLUSION: The measurement of (75)SEHCAT abdominal retention allows the early diagnosis of bile acid malabsorption in 43% of the patients with DS. Measurement at 7 days seems more accurate than that at 4 days.

Comparative accumulation of (109)Cd and (75)Se from water and food by an estuarine fish (Tetractenos glaber).

Few data are available on the comparative accumulation of metal(loid)s from water and food in estuarine/marine fish. Smooth toadfish (Tetractenos glaber), commonly found in estuaries in south-eastern Australia, were separately exposed to radio-labelled seawater (14kBqL(-1) of (109)Cd and 24kBqL(-1) of (75)Se) and food (ghost shrimps; Trypaea australiensis: 875Bqg(-1)(109)Cd and 1130Bqg(-1)(75)Se) for 25 days (uptake phase), followed by exposure to radionuclide-free water or food for 30 days (loss phase). Toadfish accumulated (109)Cd predominantly from water (85%) and (75)Se predominantly from food (62%), although the latter was lower than expected. For both the water and food exposures, (109)Cd was predominantly located in the gut lining (60-75%) at the end of the uptake phase, suggesting that the gut may be the primary pathway of (109)Cd uptake. This may be attributed to toadfish drinking large volumes of water to maintain osmoregulation. By the end of the loss phase, (109)Cd had predominantly shifted to the excretory organs - the liver (81%) in toadfish exposed to radio-labelled food, and in the liver, gills and kidney (82%) of toadfish exposed to radio-labelled water. In contrast, (75)Se was predominantly located in the excretory organs (gills, kidneys and liver; 66-76%) at the end of the uptake phase, irrespective of the exposure pathway, with minimal change in percentage distribution (76-83%) after the loss phase. This study emphasises the importance of differentiating accumulation pathways to better understand metal(loid) transfer dynamics and subsequent toxicity, in aquatic biota.

Mimosine mitigates oxidative stress in selenium deficient seedlings of Vigna radiata. Part II: mitochondrial uptake of 75selenium and mimosine.

During the growth of selenium (Se)-deficient seedlings of Vigna radiata, exposure to mimosine [2-amino-3-(3-hydroxy-4-oxo-1H-pyridin-1-yl)-propanoic acid], a nonprotein plant amino acid, effectively mitigated stress at 0.1 mM, as reflected in enhancement of growth and efficiency of mitochondrial functions. Since the changes in the seedlings elicited by exposure to mimosine were similar to those effected by Se at an optimal exposure level of 0.75 ppm (Sreekala et al., Biol Trace Elem Res 70:193-207, 1999), the uptake of Se and that of mimosine itself was individually studied in the respiring mitochondria of Se-deficient seedlings (-Se-stressed group) in comparison with those exposed to mimosine during growth at 0.1 mM (Mim 0.1 group). In both groups, the mitochondrial uptake of (75)Se at 10 microM added Na(2)(75)SeO(3), increased linearly up to 2 min, attaining steady-state levels thereafter. Uptake levels were 2.3-fold higher in the Mim 0.1 group than in the -Se-stressed group. Double-reciprocal plots of mitochondrial (75)Se uptake against 2-20 microM Na(2)(75)SeO(3) in the medium were nonlinear and negative cooperative effects during the uptake were confirmed by Scatchard plots, whereas Hill coefficients were 0.8 and 0.85 for the two groups. Mitochondrial uptake of mimosine, at added levels of 25 or 50 microM, increased linearly up to 1 min and decelerated thereafter. Initial uptake levels of mimosine at 1 min were higher by 6.5-fold at 25 microM and 4-fold at 50 microM in the Mim 0.1 group than those in the -Se-stressed group. Initial uptake levels with added mimosine up to 50 or 100 microM yielded nonlinear double-reciprocal plots; and kinetic analyses at 5 to 50 microM revealed the prevalence of positive cooperativity in the -Se-stressed group and negative cooperativity in the Mim 0.1 group. Involvement of active thiol groups in the uptake of both Se and mimosine were indicated by inhibition studies. Evidence presented for mimosine mediated increase in mitochondrial Se uptake and cooperative interactions thereof underscores the metabolic significance of mimosine.

Uptake and loss of dissolved 109Cd and 75Se in estuarine macroinvertebrates.

Semaphore crabs (Heloecius cordiformis), soldier crabs (Mictyris platycheles), ghost shrimps (Trypaea australiensis), pygmy mussels (Xenostrobus securis), and polychaetes (Eunice sp.), key benthic prey items of predatory fish commonly found in estuaries throughout southeastern Australia, were exposed to dissolved (109)Cd and (75)Se for 385 h at 30 k Bq/l (uptake phase), followed by exposure to radionuclide-free water for 189 h (loss phase). The whole body uptake rates of (75)Se by pygmy mussels, semaphore crabs and soldier crabs were 1.9, 2.4 and 4.1 times higher than (109)Cd, respectively. There were no significant (P>0.05) differences between the uptake rates of (75)Se and (109)Cd for ghost shrimps and polychaetes. The uptake rates of (109)Cd and (75)Se were highest in pygmy mussels; about six times higher than in soldier crabs for (109)Cd and in polychaetes for (75)Se - the organisms with the lowest uptake rates. The loss rates of (109)Cd and (75)Se were highest in semaphore crabs; about four times higher than in polychaetes for (109)Cd and nine times higher than in ghost shrimps for (75)Se - the organisms with the lowest loss rates. The loss of (109)Cd and (75)Se in all organisms was best described by a two (i.e. short and a longer-lived) compartment model. In the short-lived, or rapidly exchanging, compartment, the biological half-lives of (75)Se (16-39 h) were about three times greater than those of (109)Cd (5-12h). In contrast, the biological half-lives of (109)Cd in the longer-lived, or slowly exchanging compartment(s), were typically greater (1370-5950 h) than those of (75)Se (161-1500 h). Semaphore crabs had the shortest biological half-lives of both radionuclides in the long-lived compartment, whereas polychaetes had the greatest biological half-life for (109)Cd (5950 h), and ghost shrimps had the greatest biological half-life for (75)Se (1500 h). This study provides the first reported data for the biological half-lives of Se in estuarine decapod crustaceans. Moreover, it emphasises the importance of determining metal(loid) accumulation and loss kinetics in keystone prey items, which consequently influences their trophic transfer potential to higher-order predators.

Bioavailability of selenium from the selenotrisulphide derivative of lipoic acid.

BACKGROUND/PURPOSE: Selenium is a required micronutrient in mammals, needed for the activity of enzymes that contain selenocysteine at their active site. Several isoenzymes of glutathione peroxidase and thioredoxin reductase contain selenocysteine and thus the nutritional status of selenium in tissues can have significant impact on the steady state level of reactive oxygen species. The aims of this study were to evaluate the bioavailability of selenium derived from the selenotrisulfide derivative of lipoic acid (LASe) and determine the ability of this compound to be absorbed into skin. METHODS: Bioavailability of selenium derived from LASe was determined using a keratinocyte cell model (HaCat). Efficiency of utilization of selenium was assessed by following the decrease in the incorporation of radiolabeled selenite (75Se) in the presence of increasing concentration of selenium compounds. Percutaneous absorption of LASe was measured by determining selenium levels in full thickness biopsy of skin using a Yorkshire pig model. RESULTS: LASe was efficiently absorbed topically into pig skin, a good model of human skin. In a keratinocyte cell line LASe was an efficient source of selenium for selenoprotein synthesis, demonstrating that LASe is a good candidate as a topical selenium micronutrient. Both L-selenomethionine and selenate were found to be poor sources of selenium for selenoprotein synthesis in the skin cell model and L-selenomethionine was poorly absorbed into pig skin. CONCLUSION: These results indicate that stable selenotrisulfides, such as LASe, are good candidates for testing as topical selenium supplements.

A new method for evaluation of radioactive label transport intensity in the predominant direction between blood and liver.

The intensity of (75)Se transport in the predominant direction after intraperitoneal injection of [(75)Se]selenate was compared in 1- and 3-month-old rats receiving common vivarium ration or sucrose diet. The incorporation percent, blood/liver relative radioactivity, and relative radioactivity difference coefficient were evaluated in the blood and liver. The dynamics of label incorporation in the blood of rats fed common diets has two peaks (at 1-3 h and 12-24 h) and a drop at 6 h. Coefficient of difference in 1-month-old rats was characterized by a greater amplitude of fluctuations than in 3-month-old animals.

Estimation of animal transfer factors for radioactive isotopes of iodine, technetium, selenium and uranium.

In post-closure radiological safety assessments of repositories for solid radioactive wastes, transfers of radionuclides to animal products are typically characterised using Transfer Factors (TFs), defined as the ratio of the concentration of the radionuclide in the animal product of interest to the rate of intake in diet. Such transfer factors can be measured directly in experimental studies, but they can also be estimated by use of biokinetic models for uptake and retention of radionuclides in animals. Based on a review of the literature, biokinetic models have been developed for the uptake and retention of iodine, technetium, selenium and uranium. These biokinetic models allow TF values to be estimated for different types of animals and for different animal lifetimes. For each radionuclide considered, reference values and ranges of TF values are estimated. These are summarised in Table 1.

Generic models for radionuclide dosimetry: 11C-, 18F- or 75Se-labelled amino acids.

A generic biokinetic model was developed for use in the assessment of the internal dose received by human subjects injected with amino acids labelled with 11C (T1/2 = 0.34 h, beta+, gamma), 18F(T1/2 = 1.83 h, beta+, gamma) or 75Se (T1/2 = 119.8 d, beta-, gamma). This generic model was used in conjunction with the MIRDOSE 3 computer programme to calculate radiation doses to adults; these radiation doses were compared with those calculated using compound-specific models for two [11C]-, and eight [18F]-labelled amino acids and [75Se]selenomethionine. In general, the effective doses, as well as the organ and tissue doses, calculated using the generic model agreed within a factor of 2 or less, with those calculated using compound-specific models; the generic model tended to over-, rather than underestimate the organ and tissue doses. It was concluded that for 11C- and 18F-labelled amino acids and for 75Se-labelled amino acids or their analogues, the single generic biokinetic model could be applied for general radiation protection purposes.

An external-sample liquid scintillation counting for 75Se and its application to selenoprotein detection.

An external-sample liquid scintillation (LS) counting for the gamma emitter 75Se has been developed. An expressly designed well-type LS vial and a 2,5-diphenyoxazole-1,4-bis(5-phenyl-2-oxazoyl)-benzene-xylene solution containing 35% tertrabutylzinn allow 75Se to be counted in a standard LS counter with counting efficiency up to 43.2%, much higher than that of conventional LS counting method. This external sample LS has a good count rate linearity and exhibits low background count rates. After in vivo labeling with [75Se]selenite, 75Se distributions and the Se-containing proteins present in tissues of male rat were investigated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, external-sample LS and gamma-detector. Eight Se-containing proteins or protein subunits were detected to be Se-containing proteins or protein subunits in arterial wall, and their apparent molecular masses (Mr) were 76.4, 67.0, 57.4, 30.3, 25.4, 22.7, 21.7, and 15.1 kDa, respectively. In addition, eight 75Se-labeled proteins (Mr: 66.8, 57.0, 43.1, 30.0, 24.8, 19.8, 18.0, and 14.8 kDa) were found in brain homogenates, and nine 75Se-labeled proteins (Mr: 117.0, 78.0, 66.6, 57.2, 43.0, 38.1, 25.0, 20.1, and 18.0 kDa) were detected in testis homogenates. Some of them should be new biologically important selenoproteins that have not been identified so far.

Radionuclide studies of articular cartilage in the early diagnosis of arthritis in the rabbit.

The compound Se-75 bis[beta-(N,N,N-trimethylamino-)ethyl]selenide diiodide (Se-75 BISTAES) has been synthesized and its biodistribution in rabbits studied. A high uptake of radioactivity is found in the knee cartilage. Good scans of the knee are obtained by nuclear scintigraphy at 15 minutes after the injection of Se-75 BISTAES. The results of an equilibrium dialysis study show that Se-75 BISTAES binds to chondroitin sulfate and the binding is directly proportional to the chondroitin concentration. It appears that Se-75 BISTAES or its derivative should have potential as an articular imaging agent.

Binding of tellurium to hepatocellular selenoproteins during incubation with inorganic tellurite: consequences for the activity of selenium-dependent glutathione peroxidase.

The metallic group XVIa elements selenium and tellurium possess remarkably similar chemical properties. However, unlike selenium, tellurium is not an essential micronutrient and, indeed, induces both acute and chronic toxicity in a variety of species. Despite this, very little is known of the molecular mechanisms of toxicity of tellurium, particularly with respect to potential chemical interactions with selenium-containing components in the cell. In this work we describe a novel interaction of inorganic tellurite with hepatocellular selenoproteins, particularly with selenium-dependent glutathione peroxidase. The accumulation of (121Te)-tellurite into cultured primary rat liver hepatocytes was shown to be much more rapid than that of (75Se)-selenite on a molar basis. Neither the uptake of (121Te)-tellurite nor of (75Se)-selenite was affected by a large molar excess of the unlabelled counterpart, respectively. Interestingly, separation of the hepatocellular proteins on continuous pH denaturing gels demonstrated clear binding of radiolabelled tellurium to a number of protein bands, including one at 23 and one at 58 kDa, which corresponded to proteins readily labelled in cells treated with (75Se)-selenite. The binding of (121Te) to these proteins was insensitive to reduction with mercaptoethanol and not affected by pre-treatment of the cells with cycloheximide. When purified selenium-dependent glutathione peroxidase was treated directly with (121Te)-tellurite, the protein became labelled in an analogous manner to that achieved in intact cells. This was not affected by coincubation of the enzyme with (121Te)-tellurite and one or both of its substrates. Additionally, incubation of the peroxidase with tellurite effectively inhibited its ability to catalyse glutathione-dependent reduction of hydrogen peroxide. These data suggest that inorganic tellurite delivers tellurium to the intracellular milieu in a form capable of binding to some intracellular selenoproteins and at least in the case of glutathione peroxidase, cause inhibition of catalytic activity. The nature of the binding seems not to be due to the insertion of tellurocysteine into the protein and the insensitivity to reductive cleavage with mercaptoethanol seems to preclude the formation of stable telluro-selenides in the proteins. These data may offer alternative explanations for the established toxicity of tellurium via disruption of selenoprotein function, particularly by the induction of intracellular oxidative stress by the inhibition of Se-dependent glutathione peroxidase.

[75-Se-labeled bile acid analog absorption in various gastrointestinal diseases using a whole body counter]. / Untersuchungen zur Resorption von 75Se-markiertem Gallensäureanalog bei verschiedenen gastrointestinalen Erkrankungen mit dem Ganzkörperzähler.

AIM: It is possible to detect disturbances of bile acid absorption using a whole body counter after administration of Se-75 labelled bile acid analogues. We scrutinized the benefit of a modification of the test method. METHODS: We investigated 77 patients with different forms of a gastrointestinal disease. After application of Se 75 homotaurocholic acid we measured patient-activity up to 7 days later including whole-body profile scans in the first 6 h. RESULTS: The fractional retention after 7 days was between 20 and 67%. In cases of impaired absorption it was below 12%. Patients with liver diseases and after cholecystectomy (without bile acid resorption disturbance) showed normal values. Patients with Crohn's disease of the ileum or with intestinal ileac by-pass or with colestyramine treatment or with disturbance of vitamin B12-absorption or with cystic fibrosis showed a disturbance of bile acid absorption. The normal whole-body half-life was more than 2.8 days. The 24 and 72 h values were 62 and 31% in cases with normal absorption. Smaller values are signs of bile acid malabsorption. Impulse rates measured with the whole body counter are of an order of magnitude that allows to reduce the usually administered dose of 37 kBq to 9.25 kBq. CONCLUSION: This is an efficient method to detect disturbances of bile acid absorption. The usually administered activity of 37 kBq can be reduced to 9.25 kBq.

Evaluation of radioselenium labeled selenomethionine, a potential tracer for brain protein synthesis by PET.

The blood-brain transfer, protein incorporation and metabolism of L-[75Se]selenomethionine (SeMet) of relatively high specific activity (> 400 GBq mmol) were studied in male Wistar rats. The highest uptake was found in the pancreas, followed by the tumor, kidney, liver, brain and muscle. In addition, plasma and brain samples of rats were analyzed for labeled fractions of free SeMet, metabolites, and SeMet bound to t-RNA and proteins. For example, free SeMet represented more than 80% of brain radioactivity at 1.5 min while it was less than 15% at 360 min. A concomitant increase was observed for protein bound SeMet in brain. A three-compartment model was applied to calculate the blood-brain transfer constant (K1 (0.15 +/- 0.070 mL g-1 min-1) and the rate constant of SeMet incorporation into proteins (k3 = 0.026 +/- 0.008 min-1). The apparent incorporation of methionine into proteins was estimated to be about 0.73 nmol g-1 min-1. From the studies it is concluded that the use of L-[75Se]selenomethionine may be appropriate to measure brain protein incorporation in humans with PET.

Age-dependent variation of selenium-75 biokinetics in rat.

Substantial levels of selenium-79 (79Se) in radioactive waste from the nuclear fuel cycle, may result in a significant collective dose commitment following release into the environment. Few data are available from which the effective dose equivalent among subgroups of the general population can be made. Accordingly, whole body retention and organ content were studied in neonate, adult and pregnant rat following oral contamination with 75Se. The results for whole-body retention conformed to a two-component exponential with terminal biological half-time of about 40, 30 and 20 days in adult male, neonate and pregnant rat, respectively. The highest concentrations of Se occurred in the liver, kidney, and testis. Influence of Se kinetics as a function of age and physiological development on dose estimates are discussed. Results were consistent with current dosimetric models but suggested that the testis should also be included.