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Biomedical subjects

J Aaseth

Publications and source records attributed to J Aaseth.

At least 55 records · Page 3Linked to original sources
PubMed1984

Haemolytic activity of copper as influenced by chelating agents, albumine and chromium.

The haemolytic activity of CuSO4 (0.3 mM) in vitro was reduced in the presence of albumine (5-20 g/l). The presence of D-penicillamine, triethylene tetramine or dimercaptosuccinic acid (0.3 mM) also reduced the copper-induced haemolysis, whereas 2,3-dimercaptopropane-1-sulphonate increased the cytolysis. N-ethylmaleimide (NEM) in appropriate concentrations (1 mM), as well as chromic chloride (0.3 mM), reduced the copper-induced haemolysis. Higher concentrations of NEM (2 mM) were ineffective. The results may provide helpful suggestions as regarding the clinical treatment of copper poisoning and Wilson's disease. The results may also be helpful for the understanding of the mechanisms of haemolysis associated with copper intoxication in vivo.

Adult↗
PubMed1983

Recent advance in the therapy of metal poisonings with chelating agents.

1 A survey is given of the use of chelating agents in the treatment of metal poisonings. 1 The complexing agents in established clinical use are the polyaminopolycarboxylic acid EDTA (ethylenediamine tetraacetate) and the thiols BAL (2, 3-dimercaptopropanol) and D-penicillamine. Desferrioxamine is useful in the treatment of iron overloading. 2 The theoretical foundation of the metal-ligand interaction and some general principles of value in the search for new metal antidotes are outlined. 3 Recent research has shown that 2, 3-dimercaptosuccinic acid (DMS) and 2, 3-dimercaptopropane-1-sulphonate (DMPS) are effective in mercury and arsenic poisonings. 4 DMS and DMPS are of significantly lower toxicity than BAL, and they can be administered orally or intravenously. 5 A particularly low toxicity of DMS is reported from clinical and experimental studies, and this agent may be useful against several metal poisonings including mercury, lead and gold.

Animals↗
PubMed1982

Organ distribution and cellular uptake of methyl mercury in the rat as influenced by the intra- and extracellular glutathione concentration.

Intravenous administration of CH3HgCl (4 mumol/Kg) premixed with glutathione or cysteine (8 mumole/kg) to female rats caused a rapid uptake of mercury in the kidney and a depressed content in the liver and blood as compared to CH3HgCl given alone. GSH depletion in the tissues, produced by injection of diethylmaleate, DEM (3.9 mmole/kg) did not influence the kidney uptake of mercury from administered (CH3Hg+-GSH, whereas the uptake of injected CH3HgCl was depressed. Both GSH and cysteine (8 mumole/kg) promoted the biliary excretion of methyl mercury. In suspensions of rat erythrocytes and isolated hepatocytes, additions of GSH reduced the cellular uptake of CH3Hg+ from the medium, whereas this was increased in the hepatocytes by adding cysteine or methionine. Cysteine addition slightly reduced the uptake of CH3Hg+ in the erythrocytes. GSH-depletion as obtained by DEM pretreatment of the cells, reduced the Ch3Hg+ uptake into hepatocytes by 40%, in contrast to only a negligible effect on the erythrocytes. Our results support previous reports that a physiological CH3Hg+-GSH-complexation takes place intracellularly, at least in liver cells. Our results are furthermore consistent with the assumption that biliary excreted CH3Hg+-GSH, which can be reabsorbed, only to a limited extent is taken up by the liver, whereas this GSH-complexation and reabsorption is of importance for the Ch3Hg+-uptake in the kidneys.

Animals↗
PubMed1982

The effect of chelating agents on vanadium distribution in the rat body and on uptake by human erythrocytes.

Pentavalent vanadium (V5) as Na48VO3 was given i.p. to male Wistar rats at a dose of 5 mumol/kg in order to study its organ distribution pattern. Two days after injection, kidneys reached a V level of about 28 nmol/g wet weight, followed in decreasing order by spleen, liver, bone, blood plasma, testis, lung, erythrocytes and brain in control rats. A similar distribution pattern was seen after injection of tetravalent vanadium (V4) given as 48VOSO4. Two chelators, desferrioxamine B (Desferal) or Ca-Na3-diethylene triamine pentaacetic acid (DTPA), were given i.p. 24 h after the vanadium injections to different groups of rats at two dosage levels, 30 and 100 mumol/kg. Desferal (30 mumol/kg) reduced the vanadium content of the kidney by 17%, of the liver by 0%, and of the lung by 7%. The corresponding figures for the effect of DTPA (30 mumol/kg) were 7%, plus 15%, and 0%, respectively. At 100 mumol/kg, Desferal reduced the same organ levels by 20%, 26%, and 25%, respectively, and DTPA by 9%, 18%, and 25%, respectively. Both chelators raised faecal excretion at the low level, and both urinary and faecal excretion at the high level. Spleen and bone seemed to bind vanadium to a higher degree than the other organs under examination. Human erythrocytes, when incubated with 48VOSO4 (V4) or Na48VO3 (V5), were found to accumulate nearly the double amount of V5 as compared to V4. Glutathione (GSH) which is the main reducing substance within the erythrocytes, reduced the uptake of V5 to the V4 level when incubated together with GSH before addition to the cell suspension. Pretreating the erythrocytes with diethyl-maleate (DEM) which blocks the reducing SH groups of intracellular GSH, also reduced the uptake of V5. This may indicate a GSH dependent reduction of V5 to V4 within the erythrocytes. Four chelators, among them Desferal and DTPA, were found to reduce the cellbound amount of vanadium, either by extracting vanadium as V4, or by inhibiting uptake by the red blood cells.

Animals↗
PubMed1982

Uptake of chromium by rat liver mitochondria.

Isolated rat liver mitochondria rapidly accumulate chromate (1.2 microM 51CrO4(2-)) to about 0.25-0.30 nmol Cr/mg protein. The relative uptake decreases with increasing chromate doses. Chromate uptake decreases when pH is raised from 7.0 to 7.5.N-ethylmaleimide (0.25 mM) and butylmalonate (5 mM) inhibit chromate uptake to 70% and 30% of control values, respectively, whereas mersalyl (40 nmol/mg protein) causes an inhibition of greater than 95%. Both sulphate and phosphate decrease mitochondrial chromate uptake, the former being more effective in lower doses (5 mM). These results indicate that transport of chromate is mediated both on the dicarboxylate and the phosphate carrier. The extensive mitochondrial chromium accumulation can be explained by trapping of chromium, probably by reduction of chromate to the trivalent form, within the mitochondria. Release of chromium after chromate loading was seen after 15 min. Added after chromate loading, mersalyl partly prevents this release. Trivalent chromium as 51CrCl3 is taken up to a much lower degree than hexavalent chromium as 51CrO4(2-). The presence of glutathione (5 mM) reduces the uptake both of 51Cr-III and 51Cr-VI, indicating extramitochondrial reduction of Cr-VI to Cr-III and subsequent binding to GSH.

Animals↗
PubMed1982

Serum selenium levels in liver diseases.

A possible pathogenetic role of selenium deficiency in alcoholic cirrhosis of the liver has previously been discussed. In the present study serum selenium was analyzed in 5 groups of liver diseases. The method used for selenium determination was electrothermal atomic absorption, after thermal stabilization of selenium compounds by addition of nickel nitrate. The selenium level of a reference group of healthy Norwegian adults (n = 40) was 1.53 +/- 0.25 mumol/l. The serum concentrations of selenium in patients suffering from alcoholic cirrhosis, chronic active hepatitis and chronic persistent hepatitis were lowered to 40-80 per cent of those of the reference group. In alcoholic cirrhosis and chronic active hepatitis the decreased serum selenium concentrations were significantly correlated to decreased levels of albumin and prealbumin.

Hepatitis, Chronic↗
PubMed1982

Uptake of 51Cr-chromate by human erythrocytes-a role of glutathione.

Hexavalent chromium (Cr-VI), as Na2CrO4 in an aqueous solution, was reduced rapidly ot the trivalent form (Cr-III) in the presence of glutathione, GSH (0.3-3.0 mM). Such GSH-dependent reduction Cr-VI can take place in the cytosolic space of Cr-VI-exposed cells, since GSH is found in reactive concentrations in this compartment. The reduction makes chromium essentially impermeable through the cell membrane, explaining the observation that Cr-VI, when added to red cell suspensions, is bound quantitatively intracellularly after a few hours. Diethylmaleate conjugation of the SH-group of the intracellular GSH preventing the oxidation to GSSG, lowered the chromium-uptake significantly, showing that reduced GSH plays a role for the chromium binding. In healthy red cells chromium is partially bound to haemoglobin and partially to small molecular weight substances, probably in the trivalent form. This intracellular chromium cannot be removed to the extracellular space by addition of chelating agents as long as the cell membrane is intact.

Chromates↗
PubMed1982

Biliary excretion of chromium in the rat: a role of glutathione.

The relative amount of chromium excreted in rat bile after injection of Cr-III is much less than after injection of Cr-VI, about 0.1% and from 6-8% during 5 hours respectively, for corresponding dose levels. The liver to bile ratio was 50-100 for Cr-III injection, for Cr-VI the ratio was 2-3. With doses up to 18 mumol Cr/kg, only Cr-III was found in bile even after injection of Cr-VI. Glutathione depletion of the liver with cyclohexene oxide decreased chromium excretion in bile. Such treatment also decreased the reduction of Cr-VI to Cr-III in the liver cell as only Cr-VI was found in bile. A different distribution of Cr-III in the liver dependent on whether derived from Cr-VI or taken up by the liver as such must be assumed. Taking into account the usual low penetration of biological membranes by Cr-III, a possible active transport mechanism or a specific diffusable Cr-III compound must be postulated.

Animals↗
PubMed1982

Controlled clinical trial of duodenal ulcer healing with antacid tablets.

The effect of an antacid tablet regimen (total acid-neutralizing capacity, 280 mmol/day) and placebo was studied in 75 patients with duodenal ulcer in a double-blind 4-week trial. The ulcer healed in 30 out of 37 (81%) patients treated with antacids as compared with 9 out of 38 (24%) patients treated with placebo (p less than 0.001). Ulcer symptoms in the antacid- and the placebo-treated groups did not differ significantly until the last week of treatment (p less than 0.01). Both constipation and diarrhoea were slightly more common in antacid- than in placebo-treated patients (NS). Serum concentration of aluminium increased significantly (p = 0.01), whereas serum concentrations of calcium, phosphorus, magnesium, iron, and total iron-binding capacity did not change during treatment. No other side effects of antacids were recorded. Thirty-eight patients with unhealed ulcer after cessation of the antacid/placebo treatment were treated openly with 150 mg ranitidine twice daily. The ulcer healed in 31 out of 37 (83%) patients (one drop-out) after 4 weeks' treatment, and only one patient remained with unhealed ulcer after 6 weeks' ranitidine treatment. No side effects due to ranitidine were recorded.

Adult↗