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K Schümann

Publications and source records attributed to K Schümann.

At least 37 records · Page 2Linked to original sources
PubMed1997

Kinetic analysis of the intestinal iron absorption process in situ. The potential of vascularly autoperfused intestinal loops.

1 Blood sampling from mesenteric venules during absorption in situ is a useful tool to analyse intestinal absorption kinetics and prehepatic metabolism in different sections of the rat small intestine. By use of a micromanipulator, the method can be applied to the duodenum. This part of the small intestine shows the strongest adaptation of non-haem iron absorption to the demand for iron. 2 Iron absorption kinetics was linear in duodenal and jejunal segments. In iron-deficient animals, intestinal iron absorption capacity was increased in the duodenum, while simultaneously determined galactose absorption showed no change. 3 In situ perfusion and cannulation of mesenteric venules in duodenal segments are described. The use of a micromanipulator permits varying the blood volume collected by changing the vertical angle between the cannula and the mesenteric vessel. 4 Intestinal iron absorption rates remained close to constant when blood flow rates were varied by a factor of about ten. Plasma concentrations of absorbed iron vs mesenteric blood flow rates followed a hyperbolic function, as the plasma concentration of absorbed iron in mesenteric venules increased to the same extent as the blood flow decreased. 5 As the plasma transferrin concentration did not change over the experimental period, the concentration of absorbed iron in the mesenteric plasma exceeded the iron-binding capacity of plasma transferrin at low blood flow rates. This observation shows that enhancement of intestinal iron absorption does not require a corresponding increase in plasma iron-binding capacity in the intestinal tissue. 6 Vascularly perfused gut loops were also used to measure prehepatic metabolism, which may influence organotropism of carcinogenic metabolites. Therefore, this type of preparation is likely to find a variety of toxicological applications.

Animals↗
PubMed1997

Bioavailability of oral vitamins, minerals, and trace elements in perspective.

Bioavailability of orally administered vitamins, minerals, and trace elements is subject to a complex set of influences. Still, administrative regulation is necessary on how to quantify it. The most common approach to this problem is to determine the fraction of an oral dose that reaches the systemic circulation. For micronutrients, however, this approach has to consider the physiological plasma concentration as well as the mechanisms that regulate intestinal absorption and distribution of micronutrients between functional and storage compartments in response to the demand. The rate of exchange between these compartments has an impact on the delivery of such compounds into the plasma compartment as well as on the plasma clearance. Monitoring the area under the plasma concentration time curve after oral administration is an inadequate tool for bioavailability determination if there are substantial impacts of homeostatic mechanisms on the plasma concentration of a micronutrient. In nutritional science the term "bioavailability" encompasses the sum of impacts that may reduce or foster the metabolic utilisation of a nutrient. Bioavailability in this sense can be quantified by the rate by which deficiency symptoms are cured or by the weight gain during growth. both of these endpoints, again, are influenced by homeostatic mechanisms. To exemplify the scope of impacts on parameters that are commonly used to quantify the bioavailability of oral micronutrient preparations the basic traits of homeostatic regulation are summarised and compared for iron, magnesium, vitamin A, folic acid, and vitamin B12. The mechanisms that adapt absorption, distribution, and excretion of these five micronutrients to the demand differ to such an extent that no common approach can be derived to consider these impacts in bioavailability determination. In consequence, therefore, we recommend to define and regulate individual strategies for bioavailability testing for each micronutrient with regulated kinetics.

Administration, Oral↗
PubMed1996

A modified device for the differentiated study of intestinal transfer in isolated intestinal segments from mice and suckling rats in vitro.

An increasing number of mice with genetic variation of intestinal transfer properties is becoming available. A luminal perfusion system for small intestinal segments, therefore, was adapted for the use in mice and rat pups to investigate longitudinal differences in intestinal drug and toxin transfer and to explore the adaptation of transfer properties during maturation under standardized conditions in vitro. At present, cell cultures are inadequate for this goal. The perfusator consists of an upper reservoir and a lower moist chamber to accommodate the intestinal segment. The luminal perfusion fluid is oxygenized and circulated by a gas lift. It is directed through the segment by two three-way taps. For safe and easy decontamination of radioactive substrates, the system is made entirely of glass. To perfuse fragile segments from small animals such as mice and rat pups in vitro, the perfusion pressure had to be reduced to 15 cm H2O column. Therefore, the design of the perfusator was changed, and the gas lift and the three-way taps were moved to the side. With segments from adult rats, the modified perfusor yielded the same transfer data for 59Fe, glucose, and water as did the standard device. Experiments with proximal and distal segments from mice and rat pups showed a longitudinal pattern of adaptation during maturation as well as due to iron deficiency that was in accordance with expectations extrapolated from literature.

Aging↗
PubMed1996

State of iron repletion and cadmium tissue accumulation as a function of growth in young rats after oral cadmium exposure.

To check the hypothesis that adequate dietary iron supplementation reduces cadmium retention and cadmium-induced anaemia during fast growth, three different dietary iron concentrations (6 mg/kg = iron-deficient; 55 mg/kg = marginal iron supply; 180 mg/kg = luxurious iron supply) were offered to growing rats. Four groups of rats at different age (44 days approximately = 150 +/- 6 g, 49 days approximately = 180 +/- 3 g, 57 days approximately = 220 +/- 4 g, and 84 days approximately = 295 9 g) received a diet with 55 mg Fe/kg which is a marginal iron-supply during growth. Six animals in each age group were exposed to 10 mg Cd/l as CdCl2 in the drinking water for 1 week; six animals in each age group received no cadmium. In the youngest and oldest groups additional 6 animals were exposed to the same cadmium dose but received an iron-deficient (6 mg Fe/kg) and an iron-adequate diet (180 mg Fe/kg) together with corresponding controls. The state of iron repletion was monitored by the tissue iron content in liver, kidney, and duodenum as well as by the concentrations of haemoglobin, plasma iron and plasma transferrin. The youngest animals showed the highest percent weight increases. Cadmium administration influenced neither growth rates nor food and water intake. At a dietary iron content of 55 mg/kg, iron repletion was negatively correlated to growth while the cadmium content in liver and kidney showed a positive correlation. At fast growth, a dietary iron content of 6 mg/kg lead to iron-deficiency anaemia and high cadmium retention. At all dietary iron concentrations, cadmium retention as well as the cadmium-related reduction in haemoglobin concentration was significantly higher at fast growth. Adequate dietary iron supplementation reduced cadmium retention and cadmium-induced anaemia significantly. Thus, the delicate balance between iron supply and the increased iron demand during growth can be disturbed within one week by a daily cadmium intake as low as 0.7-1.3 mg Cd/kg body weight.

Administration, Oral↗
PubMed1994

Oral and subcutaneous administration of cadmium chloride and the distribution of metallothionein and cadmium along the villus-crypt axis in rat jejunum.

The route of Cd uptake influences the distribution of Cd, other metals, and metallothionein (MT). Although intestinal MT levels related to the tissue mass did not show proximodistal gradients after sc administration of CdCl2, orally administered high doses of CdCl2 increased mucosal MT levels longitudinally from the duodenum to the ileum. The gradient abolished when the mucosal MT level was related to the intestinal length. To further elucidate this finding, three groups of rats were studied: a control group, a group receiving dietary CdCl2, and a group receiving sc injections of CdCl2. The small intestine was removed after a 14-d treatment. Midjejunal segments were mounted in a cryomicrotome and cut transversally into five layers along the villus-crypt axis. Mucosal enzymes were measured to control these sections. Cd was measured by AAS and MT by RIA. Alkaline phosphatase and lactase activities exhibited the typical villus-crypt gradient. Mucosal MT levels paralleled those of Cd. Although Cd and MT concentrations were high at the tip of the villi and low in the crypts after oral administration, sc treatment reversed that profile. A molar Cd-MT ratio of approx 10 or 1 was reached after po or sc treatment, respectively. This demonstrates that only oral Cd may lead to an accumulation of Cd in the mucosal tissue fairly exceeding the binding capacity of small intestinal MT. The results show that different routes of Cd intake lead to a different MT-induction pattern in the intestinal wall and that longitudinal Cd and MT concentration gradients in the small intestine observed after high oral doses are a result of their high levels at the villus tips.

Administration, Oral↗
PubMed1993

[Therapy of iron deficiency. Diagnostic prerequisites--therapeutic procedures].

Iron is an essential trace element, and iron deficiency is common. Underlying causes must be carefully investigated (occult bleeding, carcinoma). Mild forms of iron deficiency may be due to rapid growth, an inappropriate diet, menstrual bleeding or pregnancy. As a rule, they can be corrected by dietary means. Pharmacological doses of iron may irritate the intestinal mucosa, limiting the size of the individual dose and impairing compliance. Overdosing can be fatal. The duration of medication depends upon the rapidity with which deficient hemoglobin iron and iron stores can be replenished. Failure of treatment may be due to a wrong diagnosis, persistent bleeding or disturbed absorption. Parenteral administration of iron should be reserved for patients in whom oral iron replacement fails.

Administration, Oral↗
PubMed1993

On the capacity of the rat intestine to excrete lithium ions at therapeutic and toxic plasma lithium concentrations.

Lithium (Li) excretion into the intestinal lumen was quantitated in rats in situ by use of a pendular perfusion technique. Male Sprague-Dawley rats were injected daily (7-10 days) i.p. with 1, 3, and 6 mmol LiCl per kg body weight (n = 9-12). Jejunal as well as ileal and colonic segments were perfused with isotonic saline containing 3H-PEG-4000. Perfusate samples were taken after 0, 5, 10, 20, and 60 min. At the highest dose toxic symptoms were observed. At 6 mmol Li per kg the plasma Li concentrations were higher than those linearly extrapolated from the lower-dose groups, which may be due to inappropriate renal excretion. The Li concentration in the perfusate increased linearly over time and was not significantly different between jejunal and colonic segments. The same ratio between the Li concentration in the plasma and in the luminal perfusate was observed in all groups. Intestinal Li excretion is not impaired by high plasma concentrations. The intestinal capacity to excrete Li is considerable: 45 cm of jejunum is able to excrete the intire plasma Li content in 30-40 min, when Li is not resupplemented from intracellular stores. The renal clearance of lithium (Li) decreases when toxic Li plasma concentrations are reached. Therefore, if it were possible to trap Li in the intestinal lumen, this excretion route might be of therapeutic interest in cases of Li intoxication with impaired renal Li-excretion.

Animals↗
PubMed1993

Influence of inorganic and organic arsenicals on intestinal transfer of nutrients.

The effects of organic (oxophenylarsine, PhAsO 2.5-50 mumol/l) and inorganic arsenicals (As2O3 2.5-250 mumol/l; As2O5 2.5-2500 mumol/l) on intestinal transfer of water, sodium, glucose and leucine was investigated in vitro using isolated jejunal segments of male Sprague Dawley rats. All three arsenicals decreased in a dose-dependent manner the transfer of water, sodium, glucose and leucine. At the highest concentrations investigated the amount absorbed was reduced to some 10-20% of the respective control values. For both glucose and leucine the concentration ratio between absorbate and perfusate was about 3.5-4 in controls. It decreased to about 2 for leucine and to near unity for glucose. As assessed from the concentration ratio between intestinal tissue and perfusate the arsenic compounds inhibited the uptake of glucose and leucine into the tissue. There was a marked difference with respect to the potency of arsenicals, PhAsO being about 10 times more potent than As2O3 which in turn was about 5 times more potent than As2O5.

Animals↗
PubMed1993

Influence of low luminal cadmium-concentrations on transfer of water and cadmium in the rat small intestine in vitro.

The sensitivity of the small intestinal water transfer for cadmium (Cd) exposure and its longitudinal gradient were investigated in luminally perfused intestinal segments in vitro and in vivo. Proximal segments accumulated Cd to a higher extent and, in addition, were more sensitive to Cd exposure than distal segments. In the proximal small intestine Cd impairs the intestinal water transfer at concentrations between 0.1 and 1.0 mumol/l in vitro and 4 mumol Cd/l in vivo. In vitro the Cd transfer from the intestinal tissue into the serosal absorbate declined in parallel to the reduction of the water transfer. In proximal but not in distal segments the declining water transfer corresponded to the decreases in glucose transfer in response to Cd exposure. According to literature the Cd effect on intestinal water transfer may be mediated by interaction of Cd with the Na-glucose co-carrier or by inhibition of the oxidative phosphorylation. The involvement of both mechanisms may differ along the small intestine.

Animals↗
PubMed1992

Endogenous intestinal metallothionein possibly contributes to the renal accumulation of cadmium.

At low levels of dietary cadmium chloride, cadmium accumulates directly in the kidneys and not in the liver. As dietary cadmium induces intestinal metallothionein (MT), intestinal CdMT complexes could be at least partly responsible for the renal accumulation of oral cadmium. For this to be possible, however, serosal release of mucosal CdMT would be required. To test this hypothesis, we perfused isolated rat small intestinal segments (Fisher-Parsons method) in an attempt to demonstrate the release of intestinal MT. After two weeks of feeding dietary cadmium chloride, intestinal MT was induced in amounts proportional to the dietary cadmium level. Subsequent in vitro perfusion of the small intestine revealed a concentration-dependent release of intestinal MT on the serosal side. When 109CdCl2 was present in the perfusion medium, 109Cd appeared on the serosal side mainly in the MT fraction. These results indicate that endogenous intestinal MT may deliver CdMT to the organism, thus possibly contributing to the renal accumulation of orally ingested cadmium.

Animals↗
PubMed1991

Influence of subchronic exposure to low dietary deoxynivalenol, a trichothecene mycotoxin, on intestinal absorption of nutrients in mice.

During a 6-wk feeding trial, effects of low dietary deoxynivalenol (DON; 0, 0.1, 1 and 10 ppm) on food consumption and weight gain were investigated in male mice. Food intake was similar in all four dietary groups. Weight gain in the group receiving 10 ppm DON was significantly (P less than 0.01) reduced. At the end of the feeding period, test animals were sacrificed and absorption of water, D-glucose, L-leucine, L-tryptophan, 5-methyltetrahydrofolic acid and iron was measured in isolated perfused jejunal segments in vitro. No effects were observed on absorption of water, leucine, tryptophan and iron. However, at a dietary DON concentration of 10 ppm, a slightly but significantly (P less than 0.05) reduced transfer of glucose was measured. Furthermore, transfer as well as tissue accumulation of 5-methyltetrahydrofolic acid in the jejunal segment were both significantly decreased up to 50%. Heavy metal and trace element content was determined in liver, kidney and small intestine. Manganese and molybdenum content in liver tissue was reduced with a DON concentration of 10 ppm in the diet. The findings indicate that subchronic ingestion of DON, in concentrations occurring in contaminated food and feed, results in an impairment of intestinal transfer and uptake of nutrients such as glucose and 5-methyltetrahydrofolic acid.

Animals↗
PubMed1991

Intestinal iron transfer after ileojejunal transposition.

Little is known on how longitudinal differences in intestinal iron absorption develop and to what extent distal segments can adapt to a more proximal location after surgical intervention. Therefore, 3 weeks after ileojejunal transposition in rats adaptational changes of intestinal iron transfer were measured together with those of glucose and water transfer, intestinal dry weight and villus surface. In vitro iron transfer (Fisher-Parsons technique) was significantly increased in transposed segments as compared to ileal controls, when related to intestinal length. Jejunal values were not reached, though, which was confirmed by corresponding in vivo results. Increases in intestinal mass which are known to be caused by villus hyperplasia were closely correlated to increases in iron transfer after ileojejunal transposition. Thus, the increased iron transfer might partly be due to an increased number of enterocytes. In addition, transposed enterocytes took up jejunal characteristics regarding the ratio between transferred iron and water quantities which significantly increased the serosal 59Fe concentration as compared to ileal segments. Similar changes were also observed for glucose. Therefore, the adaptation of intestinal 59Fe transfer after ileojejunal transposition seems to be part of a more general adaptation process, essential parts of which are likely to be located in the brush border.

Adaptation, Physiological↗
PubMed1990

Increased intestinal iron absorption in rats with normal hepatic iron stores. Kinetic aspects of the adaptative response to parenteral iron repletion in dietary iron deficiency.

Male Sprague-Dawley rats were fed an iron-deficient diet for 8 days. After this period, iron stores were repleted in three groups of animals by intravenous administration of iron dextran. In a second set of experiments, iron was administered in the same dose as Fe nitrilotriacetic acid complex. 12 h, 24 h and 48 h thereafter, the intestinal iron transfer in vitro and in vivo as well as the non-heme iron and ferritin content were determined in both the liver and the jejunal mucosa. In iron deficiency, intestinal iron transfer is increased to 230% of untreated controls, while non-heme iron and ferritin decreased to 20% and 10% in the liver and to 55% and 25% in the mucosa, respectively. 12 h and 24 h after parenteral administration of 0.1 mmol Fe/kg body weight iron transfer was as high as in iron deficiency, while liver iron stores were not significantly different from the untreated controls. In this situation, the close link between decreases in body iron stores and increases in iron transfer was temporarily dissociated. This can be related to the time lag between the incorporation of parenterally applied iron in the liver and in the jejunal mucosa. The data provide evidence for the hypothesis that the hepatic iron stores have no means of neural or hormonal communication with the small intestine in order to adapt iron transfer to their state of repletion on short notice. Intestinal iron transfer returned to control levels after 48 h.

Adaptation, Physiological↗
PubMed1990

[The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children].

There are differences between young and adult organisms regarding toxokinetic aspects and clinical manifestations of heavy metal intoxications. Chronically, toxic Cd intake causes a microcytotic hypochromic anemia in young rats at lower exposure levels and after shorter exposure periods than in adult animals. Cd absorption is increased by co-administration of milk and in conjunction with iron deficiency. After long exposure periods toxic Cd concentrations accumulate in the kidney cortex; this process starts very early in life. In 3-year-old children Cd concentrations in the kidney can reach up to one-third of those found in adults. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers. Toxic Pb concentrations can lead to Pb encephalopathia. A high percentage of surviving children have seizures and show signs of mental retardation. Anemia and reduced intelligence scores were recently observed in children after exposure to very low levels of Pb. Pb absorption is increased in children and after co-administration of milk. There are no definite proofs for carcinogenesis or mutagenesis after oral exposure to Cd, Hg, and Pb in man. Heavy metal concentrations were found in the same order of magnitude in commercial infant formulas and in breast milk. When infant formulas are reconstituted with contaminated tap water, however, Pb and Cd concentrations can be much higher. The average heavy metal uptake from such diets exceeds the provisional tolerable weekly intake levels set by the WHO for adults, calculated on the basis of an average food intake and a downscaled body weight. These considerations do not even provide for differences in absorption and distribution or for the increased sensitivity of children to heavy metal exposure. However, dilution effects for essential heavy metals were observed in fast-growing young children; this effect might be extrapolated to toxic metals. These theoretical considerations are compared with epidemiological evidence. A health statistic from Baltimore shows a decline of Pb intoxications in infants. This observation correlates with a simultaneous decline in exposure to Pb which was due, for example, to decreased use of lead dyes in house paints and the abolition of tin cans for infant food.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Retention of cadmium in cadmium-naive normal and iron-deficient rats as well as in cadmium-induced iron-deficient animals.

The retention of cadmium was investigated in cadmium-naive normal and iron-deficient rats in comparison to rats with cadmium-induced iron deficiency. Rats subchronically (4 weeks) exposed to dietary cadmium (28, 56, 112 ppm Cd and 28 ppm Fe) received a radioactively labeled dose of 2 mumol Cd/kg body wt; acutely (no cadmium exposure with diet) treated rats received doses between 1 and 8 mumol Cd/kg body wt. Two animals of each group received iron (1 mumol/kg as 59FeSO4 in order to monitor iron absorption in parallel. After a period of 4 weeks of feeding a cadmium-fortified diet, the test dose was administered and after a 2-weeks period 109Cd and of 59Fe retention was determined. The results showed in part an unexpected pattern of cadmium retention: subchronic feeding of cadmium induced iron deficiency. This implies an immediate interaction between the two metals with regard to intestinal transfer of iron. The retention of iron was increased in the Cd-induced anemia to the same extent as that in iron deficiency induced by iron restriction. Cadmium retention in iron deficiency induced by iron withdrawal also showed a marked increase, which implies that iron deficiency stimulates the intestinal transfer system for both metals in a similar way. Contrary to this effect, the cadmium retention in cadmium-induced iron deficiency was reduced to about 30% of control values. A self-induced aggravation of the body cadmium burden, as a consequence of the iron deficiency which is known to result from subchronic exposure to feeding of dietary cadmium, was thus excluded.

Anemia, Hypochromic↗
PubMed1990

Rat intestinal iron transfer capacity and the longitudinal distribution of its adaptation to iron deficiency.

The longitudinal gradient of intestinal iron transfer was investigated in normal and iron-deficient male Sprague-Dawley rats in vitro and in vivo. In normal rats in vitro iron transfer in the duodenum was approximately 3 times higher than in the jejunum and decreased in the ileum to approximately half the jejunal values. Compared to the controls in vitro iron transfer was increased 3-4 times in the duodenum and in the first jejunal segment and 2-3 times in the second jejunal segment. No significant adaptation to iron deficiency was found in the rest of the small intestine. Iron transfer rates showed the same longitudinal pattern when iron was chelated with nitrilotriacetic acid (NTA) or with ascorbate. The absorbed iron quantities, however, were approximately 5 times lower when Fe-ascorbate was used, which might be due to differences in bioavailability. Omission of Fe-NTA and Fe-ascorbate had no impact on the vitality of the segments. Glucose transfer was used as vitality criterion. It was not significantly different between corresponding iron-deficient and control segments. To control these results in vivo mesenteric blood was collected from duodenal and jejunal segments in situ. Corresponding to in vitro findings iron transfer was close to linear over the experimental period. In iron deficient duodenal segments iron transfer increased approximately 3 times as compared to controls while no adaptational changes were found in the distal jejunum. No significant longitudinal gradient was found in the mucosal content of ferritin and nonheme iron. Both parameters were decreased in iron deficiency by about half. The mucosal transferrin content showed no longitudinal gradient in control animals. In iron deficiency transferrin was significantly increased in the duodenum and in the three most proximal jejunal segments. The results indicate that in rats adaptation of iron absorption to the demand can only be expected in the duodenum and in the proximal 20 cm of the jejunum. Because this process shows a steep gradient in the proximal small intestine, studies on the adaptation of intestinal iron transfer to the demand should use short and well-defined segments in order to provide reproducible results.

Adaptation, Physiological↗