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Biomedical subjects

G Hunder

Publications and source records attributed to G Hunder.

At least 19 recordsLinked to original sources
PubMed2001

109Cd accumulation in the calcified parts of rat bones.

A recent epidemiological study showed an increased risk for bone fractures after chronic low-level cadmium exposure. This finding agrees with those of cadmium accumulation in rat bones after chronic oral exposure which reduced the mechanical strength of the bones. There are indications that ossicular cadmium uptake may be higher during growth and may contribute over proportion to life long cadmium accumulation in the skeleton. The present study investigates this hypothesis in 59 male Sprague-Dawley rats. 109Cd distribution showed no differences after intravenous (i.v.) administration of different doses (0.02-2.00 micromol 109Cd/kg body weight) and at different time points after injection (3 and 10 days). Iron-deficiency had no impact on 109Cd distribution, neither during growth nor in adult animals. Age, however, showed an impact on cadmium distribution. Hepatic 109Cd accumulation was significantly higher in adult rats while 109Cd distribution in the bones as well as 109Cd concentration in cortical and trabecular bone tissue was significantly higher during growth. No difference in 109Cd uptake was found between femur epiphysis and diaphysis after one-dose i.v. application, which is in contrast to earlier results after chronic oral cadmium administration to rats. This difference may be explained by a different saturation for cadmium uptake in these two bone sections. Cadmium exposure during growth, thus, seems to contribute considerably to cumulative ossicular cadmium accumulation over a lifetime and possibly to cadmium-derived bone fragility in advanced age.

Aging↗
PubMed2000

Use of gamma-spectrometry for simultaneous determination of 210Pb, 73As, 109Cd, 203Hg and 59Fe distribution and excretion in rats at low doses.

gamma-Spectrometry permits the identification and quantification of different gamma-isotopes in the same aliquot. To estimate the sensitivity and discriminative power of a comparably small and inexpensive 8% germanium detector, we determined the detection limits for simultaneously applied 210Pb, 73As, 109Cd, 203Hg and 59Fe. The concentration of Fe and of each of the four potential environmental contaminants was determined in aliquots from all organs and tissues 10 days after simultaneous i.v. administration (2 micromol/kg body weight) to adult and growing iron-deficient and iron-adequate rats. Relating these values to the total size of each organ permitted to derive a whole body distribution pattern for all five isotopes in each individual animal. Cumulative renal and faecal excretion values were determined during the 10 day distribution period to calculate the half-lives for both excretory pathways for all five isotopes simultaneously. Distribution and excretion values corresponded well to literature data. Extrapolation of the results showed that the detector would be sensitive enough to discriminate and quantify the five metals at human dietary exposure levels. The results recommend to use gamma-spectrometry to investigate kinetic aspects of interactions between toxic and essential trace metals, because the method reduces the number of required animals drastically.

Animals↗
PubMed1999

Longitudinal pattern of enzymatic and absorptive functions in the small intestine of rats after short-term exposure to dietary cadmium chloride.

In vitro and in situ findings suggest an impairment of digestive and absorptive functions in the small intestine by enteral cadmium salts. In the rat, diets with up to 1 mmol Cd/kg are well tolerated, however, so that the impairment might not be this drastic or compensated by adaptive changes. To elucidate whether small intestinal functions are altered, we studied the effect of dietary cadmium on the longitudinal pattern of mucosal enzymes and the in vitro uptake of methyl alpha-D-glucoside in the small intestine of female rats. Three groups of rats were employed, a control group and two groups receiving dietary CdCl2 either at 0.3 or 1.0 mmol Cd/kg of diet. Rats were killed after 1 week of feeding. The entire small intestine was removed, rinsed with ice-cold saline and divided into 12 segments of equal length. Mucosal scrapings from each segment were used to measure mucosal cadmium levels, sucrase, lactase, alkaline phosphatase, glycylleucine-hydrolase, and diamine oxidase activities. Sugar uptake was determined in vitro in all segments using everted rings tissue accumulation method. Although cadmium levels in the mucosa were high (>100 ng Cd/mg protein or >100 micromol Cd/kg WW) most enzyme activities were only slightly changed. When significant decreases in activity were detected, they were only observed in the proximal small intestine. Sugar uptake was also impaired only in proximal segments, the maximal transport capacity was reduced by approximately 20%. These findings suggest that cadmium even at dietary levels of 1 mmol/kg do not lead to a drastic impairment of digestive and absorptive functions in the small intestine and that in the rat presently observed, mostly proximal impairments are easily compensated by unaltered distal functions. Certainly, absorption of micronutrients, for which an impaired proximal function cannot be compensated, e.g. iron, might be critical in this respect.

Administration, Oral↗
PubMed1999

Species differences in arsenic-mediated renal copper accumulation: a comparison between rats, mice and guinea pigs.

1. Administration of arsenite leads to an accumulation of copper in the rat kidney. Owing to the high retention of arsenic in the erythrocytes, however, the rat is considered to possess special toxicokinetics of arsenic and is therefore considered less comparable with other species in this respect. 2. Therefore, we compared the effect of dietary arsenite in mice and guinea pigs with that in rats. Each species was divided into four groups of animals according to the diets fed which contained increasing concentrations of sodium arsenite (NaAsO2; 0, 10, 30 and 60 mg As/kg of diet). Animals were killed after 1, 2 and 3 weeks. Tissues were sampled and analyzed for arsenic and other trace metals (Cu, Fe, Zn and Mn). 3. Compared to controls with copper levels of about 10 microg Cu/g wet wt. in the renal cortex, dietary administration of arsenite up to 60 mg As/kg of diet for 3 weeks to rats increased cortical levels to 65 microg Cu/g wet wt. An increase of renal copper levels similar to that in rats, was only observed in guinea pigs but not in mice. Renal copper accumulation in guinea pigs was time- and concentration-dependent as in rats. Feeding a diet with 60 mg As/kg for 3 weeks increased cortical copper levels from about 6 - 40 microg Cu/g wet wt. Renal copper levels in mice as well as other trace metal levels in guinea pigs and mice were not essentially altered by dietary arsenite. 4. The study shows that the renal copper-arsenic interaction is not restricted to the rat. Since in rats and guinea pigs, but not in mice, arsenic accumulated in the kidney rather similarly, a common mechanism is suggestive. As it was previously shown in rats that only inorganic arsenic is involved in this interaction, a rapid conversion of the inorganic form into methylated metabolites as in mice may diminish the extent of the renal copper accumulation whereas the lack of, or a less efficient, methylation as in guinea pigs or rats increases it.

Animals↗
PubMed1998

New approaches for treatment of systemic lupus erythematosus.

Each of the new approaches to treating SLE offers some hope in the ongoing effort to respond effectively to the challenges of this debilitating and often lethal condition. Research is extremely active and promises to accelerate as more is learned.

Adjuvants, Immunologic↗
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

Are we ready to replace dimercaprol (BAL) as an arsenic antidote?

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulphonate sodium (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour. 2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication-especially with lipophilic organoarsenicals-may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular availability. 3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (= Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine. 4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL whenever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of-no-return is a limiting factor, BAL may still have a place as an arsenic antidote.

Animals↗
PubMed1996

Vasculitis: diagnosis and therapy.

Vasculitis comprises a broad group of syndromes characterized by inflammation and necrosis in the walls of blood vessels, resulting in narrowing or occlusion of the lumen. The distribution of blood vessel involvement varies considerably and serves as the basis for one classification of the vasculitic syndromes: large vessels (Takayasu arteritis, giant-cell arteritis); medium and small muscular arteries (polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, vasculitis in rheumatic diseases); and small vessels ("hypersensitivity" vasculitis, Henoch-Schonlein purpura, microscopic polyangiitis, cryoglobulinemia). The pathogenesis of most forms of vasculitis is only beginning to be understood, but is probably varied and complex. Because of the variability of vasculitides, there is no single, uniform method of diagnosis and treatment. However, a detailed history, careful physical examination, and appropriate laboratory tests are needed in all cases to determine the type of onset, course of illness, organ systems affected, and extent of involvement. Biopsy examination of involved tissues is nearly always essential for diagnosis, except in Takayasu arteritis, when aortography is usually indicated. In most cases of vasculitis, corticosteroid therapy is necessary. When the organ involvement is broader and more progressive (e.g., in cases of polyarteritis nodosa or Wegener's granulomatosis), a combination of cytotoxic drug and corticosteroids is often needed.

Drug Monitoring↗
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↗
PubMed1995

Effect of DMPS and various adsorbents on the arsenic excretion in guinea-pigs after injection with As2O3.

The present experiments were performed to test the possibility of interrupting the enterohepatic circulation of arsenic (As). Therefore the efficacy of adsorbents to bind As and/or As-DMPS adducts in vitro and their effect on the excretion of As into the feces and urine in vivo were investigated after injection of As2O3 and DMPS in guinea-pigs. The adsorbents bentonite, activated charcoal or colestyramine, respectively, were tested. Only slight binding of 73As (< 5% of the 73As dose) was observed to all adsorbents in vitro. After addition of DMPS, a good binding was found for 73As to colestyramine (50%) or activated charcoal (60%), respectively. However, the 73As-DMPS adduct was removed from the activated charcoal during washing. In the first in vivo experiment, male guinea-pigs (n = 4/group) received As2O3 [0.02 mmol As(III)/kg s.c. labelled with a tracer dose of 73As(III) (0.14 kBq/g)], 30 min later DMPS (0.1 mmol/kg i.p.) and by gastric tube (10 ml/kg body wt) either saline, bentonite (1 g/kg), activated charcoal (1 g/kg) or colestyramine (0.2 g/kg), respectively. Urine and feces were collected for 24 h. No increase in 73As excretion into the feces was observed after administration of DMPS and all adsorbents, compared to control animals. In the second in vivo experiment male guinea-pigs (n = 4/group) received the same As2O3 (+ 73As)- and DMPS dose. In addition, with a gastric tube (10 ml/kg) saline, colestyramine (0.2 g/kg), DMPS (0.1 mmol/kg), or the combination of DMPS (0.1 mmol/kg) + colestyramine (0.2 g/kg) were administered according to the scheme given in the following table. The amount of feces excreted did not differ between groups. Excretion of 73As within the feces during the first 12 h after As injection is shown in the following table (mean +/- SEM). The same amount of 73As (34% of the 73As dose) was excreted into the urine from animals in groups 4 and 5 during this time. Obviously, the combined oral administration of DMPS + colestyramine markedly enhanced fecal excretion of As mobilized by DMPS i.p. It is suggested that interruption of enterohepatic circulation of As may be a valuable adjunct in the treatment of As poisoning.

Animals↗
PubMed1994

Influence of glucocorticoids and activated charcoal on the lethality of rats after acute poisoning with T-2 toxin, diacetoxyscirpenol, or roridin A.

Lethal doses of the trichothecene mycotoxins T-2 toxin (1.5 mg/kg), diacetoxyscirpenol (DAS; 2.3 mg/kg) or roridin A (1.3 mg/kg) were intravenously administered to rats. When rats were treated with either activated charcoal (Superchar liquid, Norit A; 1 g/kg, po) or dexamethasone (8 mg/kg, iv) 30 min after poisoning with one of the trichothecenes, lethality was only marginally reduced. However, when the combination of activated charcoal (Superchar liquid or Norit A) and dexamethasone was administered, the survival rate of animals after 30 days was significantly enhanced by up to 50%. Comparison between 2 preparations of activated charcoal, Norit AR with a surface area of 1,000 m2/g and Superchar liquidR with a surface area of 3,000 m2/g, each in combination with dexamethasone, revealed no difference in their therapeutic efficacy. Prednisolone (60 mg/kg) was as effective as dexamethasone (8 mg/kg), each administered with activated charcoal, in preventing death in acute T-2 toxicosis.

Animals↗
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

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

Inhibition of intestinal glucose absorption in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Male Sprague-Dawley rats were injected with either 125 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg or vehicle (pair-fed and ad libitum-fed controls). Transfer of water, electrolytes and D-glucose as well as fats of a tracer dose of the non-metabolizable radioactive marker 3-O-methyl-D-[U-14C]glucose was studied in isolated perfused jejunal segments 1, 2, 7, and 21 d after treatment (TCDD-treated and pair-fed control rats) and after 26 d in ad libitum-fed controls. TCDD-treated rats demonstrated reduced feed consumption and loss of body weight. Active intestinal absorption of glucose was significantly inhibited 30 and 22% compared to pair-fed controls, respectively 2 and 7 d after TCDD treatment. After 21 d the inhibition (14%) was less significant. There were no differences in glucose transfer between severely starved pair-fed controls (body weights 370 +/- 26 g) and ad libitum-fed rats (body weights 512 +/- 15 g). Water absorption and transfer of sodium and calcium was not influenced by TCDD treatment. However, a significant increase of potassium transfer was observed in parallel with impaired glucose absorption. The uptake of 3-O-methylglucose into mucosal tissue was not impaired, whereas the transfer to the serosal side was significantly inhibited by 30-60% compared to pair-fed as well as ad libitum-fed animals from day 2 until the end of the experiment. These results suggest that TCDD is involved in an inhibition of glucose transport at the basolateral membrane.

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↗