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Biomedical subjects

J Aaseth

Publications and source records attributed to J Aaseth.

At least 19 recordsLinked to original sources

Prophylactic iron supplementation in pregnant women in Norway.

In the present study 67 non-anaemic women were randomly allocated to either 100 mg or 15 mg iron daily at about the 10. week of pregnancy. At about week 18, 30 and 36 of pregnancy, as well as 6 weeks after delivery, hemoglobin and the serum concentrations of ferritin, vitamin B12, folates, Zn, Cu and Se were monitored. Dietary allowances of other minerals and vitamins are also increased in pregnancy, and the 15 mg iron tablet was enriched with Zn (10 mg), Cu (2 mg), Se (50 microg), vitamin B12 (3 microg), and folate (0.1 mg). Neither ferritin, nor Cu, Zn or Se concentrations differed statistically significantly between the treatment groups during pregnancy. Ferritin and Zn appeared to decrease approximately parallel to the hemodilution, whereas Cu concentrations increased from a non-pregnant reference mean of 18 micromol Cu/L to a maximum mean of nearly 33 micromol Cu/L during pregnancy. Se decreased concomitantly to about 1.0 micromol Se/L. Serum folate (around 15 micromol/L) was essentially unaffected by pregnancy in the group given multivitamin/mineral supplementation, whereas the mean concentration fell below 10 micromol/L in the group supplemented with 100 mg iron daily. Our results indicate that supplementation of 15 mg Fe daily during pregnancy results in a small reduction of hemoglobin. It is suggested that additional supplementation with folate might be of importance to maintain the serum folate concentration during pregnancy.

Adult↗

Thyroid hypofunction in Down's syndrome: is it related to oxidative stress?

Oxidative stress affecting the thyroxin biosynthesis might explain the proneness of patients with Down's syndrome (DS) (trisomia 21) to develop hypothyroidism. Thyroideal cells are exposed to endogenous H2O2 that acts as a cofactor for the iodination of thyroxin precursors. The gland has high levels of selenium-containing proteins, including peroxide-detoxicating enzyme proteins. The object of the present study was to explore the hypothesis of a role of an imbalance between toxic oxygen production and protective metalloenzymes during the development of thyroid hypofunction in DS patients. We analyzed serum levels of thyroid hormones and trace metals in 38 institutionalized adults with DS, using mentally retarded subjects matched for age, sex, and behavioral function as controls. The DS patients had significantly lower mean values of free thyroxin (fT4) and increased TSH (thyroid stimulating hormone), as compared to the controls. They had lower serum selenium than the controls. A positive correlation was observed between serum concentrations of fT4 and selenium in the DS patients (r = 0.393, p < 0.05). No significant differences were found between the fT4 or the TSH concentrations in the patients with and without circulating antithyroid autoantibodies. Our results support the suggestion that thyroid hypofunction in patients with Down's syndrome in some way is linked to the low serum levels of selenium found in these patients. It is suggested that selenium-containing proteins are involved in thyroid hormonal synthesis, by protecting biosynthetic processes against the toxicity of free oxygen radicals.

Adult↗

Long-term effect of fibre supplement and reduced energy intake on body weight and blood lipids in overweight subjects.

A weight-reducing potential has been ascribed to high dietary fibre intake. To investigate the practical reliability of this hypothesis, fifty-three moderately overweight females (BMI > 27.5 kg/m2) on reduced energy intake (1200 kcal/day) were treated for 24 weeks with a fibre supplement on a randomly, double-blind, placebo-controlled basis. The fibre was administered as an initial dose of 6 g and a maintenance dose of 4 g. Body weight and blood pressure were recorded weekly during the first 3 months and thereafter every second week. Blood samples were drawn at start and at end of the study. Initial body weights were 75.6 +/- 1.6 kg in the fibre group versus 75.5 +/- 1.6 kg in the placebo group. After treatment, mean weight loss in the fibre group was 8.0 kg versus 5.8 kg in the placebo group (p < 0.05). Systolic and diastolic blood pressures were significantly reduced in both groups without differences between the groups. Serum concentrations of cholesterol, triglycerides and uric acid were significantly reduced in the group with reduced energy intake, whereas no additional effect was observed when fibre was supplemented. Serum concentrations of potassium and sodium did not change significantly. The results suggest that a dietary fibre supplement in combination with a hypocaloric diet is of value as an adjunct in the management of overweight.

Adolescent↗

[Diphosphonates--pharmacology and clinical use].

Based upon recent research, bisphosphonates have now attained a ranking as the first alternative to oestrogen replacement therapy in women with postmenopausal osteoporosis. The efficacy of these drugs has been clearly documented in recent years, particularly as a result of extensive clinical trials with alendronate. The studies have also confirmed the favourable risk/benefit ratio. The specific affinity of bisphosphonates for bone tissue has been recognized for many years, and explains the diagnostic use of radio-labelled species in skeleton scintigraphy. Bisphosphonates deposited in bone tissue reverse the osteoporotic process by inhibiting osteoclastic bone resorption. This mechanism also explains their role as the treatment of choice in patients with Paget's disease and cancer induced hypercalcaemia. In addition, the same drugs are useful adjuvants in the treatment of patients with multiple myeloma or bone metastases to lessen the pain and risk of fracture. A possible role of bisphosphonates in the management of cancer patients without detectable bone metastases or patients with rheumatoid arthritis has been discussed, but further research is needed in these areas.

Diphosphonates↗

[Mercury exposure from dental amalgam. Risk assessment and clinical evaluation].

Inorganic mercury is absorbed in small amounts from dental amalgam fillings. Exposure can be calculated by measuring the level of mercury in the blood or urine (u-Hg). The average u-Hg in Norwegians is approximately 2-3 micrograms/g creatinine (approximately 1-2 nmol/mmol creatinine). Classic signs of mercury poisoning occur in a fraction of long-term exposed subjects with u-Hg > 100 micrograms/g creatinine (56 nmol/mmol creatinine). Subtle effects (e.g. enzymuria, altered selenium metabolism, and changes in tremor spectra) have been reported in humans at average levels of 20-35 micrograms/g creatinine (approximately 11-20 nmol/mmol creatinine). There is widespread concern about possible adverse effects of mercury from amalgam fillings. Data on exposure-response relationships make it less likely that low-level mercury exposure from amalgam fillings should cause symptoms or physical signs. Studies of the association between symptoms and amalgam fillings have been negative. Patients with symptoms allegedly caused by mercury from amalgam should undergo thorough medical examination. Based on the patient's symptoms and physical signs adequate time should be allowed for careful recording of medical history, physical examination and relevant laboratory tests.

Dental Amalgam↗

Rheumatoid arthritis and metal compounds--perspectives on the role of oxygen radical detoxification.

Rheumatoid arthritis (RA) is characterised by migration of activated phagocytes and other leukocytes into synovial and periarticular tissue. Activated oxygen species and other mediating substances from triggered phagocytes appear to exacerbate and perpetuate the rheumatoid condition. Iron excesses are capable of aggravating the arthritic inflammation, probably through their pro-oxidant potentials. In contrast, therapeutically given gold salts, through a lysosomal loading of the metal, inhibit the triggered cells, thereby reducing the toxic oxygen production. Pharmacological doses of zinc also may immobilise macrophages. Furthermore, the copper-zinc-containing enzyme SOD (superoxide dismutase) can act as a scavenger of toxic oxygen in the tissues. Therapeutic remission of RA has been obtained following intraarticular administration of SOD. Intramuscular administration of copper complexes has induced remission in about 60% of RA patients in open studies. Another drug, penicillamine, that protects cellular membranes against toxic oxygen in vitro, is presumed to act as an antirheumatic via the SOD mimetic activity of its copper complex. Thiomalate and other thiols may possess similar activities. Selenium compounds also may act as oxygen radical scavengers. A significant alleviation of articular pain and morning stiffness was obtained following selenium and vitamin E supplementation in a double-blind study on RA patients. The observations reviewed here indicate that metal compounds and other antioxidants can reduce the rheumatic inflammation by reducing the cellular production and/or concentration of toxic oxygen species.

Arthritis, Rheumatoid↗

Hemolytic activity of copper sulfate as influenced by epinephrine and chelating thiols.

AIM: To study the effects of epinephrine, homocysteine, and other complexing agents on the cytotoxicity of copper sulfate. METHODS: In vitro suspensions of human red cells incubated with cupric sulfate were used, and hemolysis was determined by extracellular hemoglobin. RESULTS: The hemolytic activity of CuSO4 (0.3 mmol.L-1) was enhanced by the presence of epinephrine and to a lesser extent by homocysteine, whereas D-penicillamine, succimer, and mercaptodextran reduced the copper-induced hemolysis. The latter 3 chelating thiols also reduced the copper-epinephrine-induced hemolysis. The plasma protein ceruloplasmin reduced markedly the copper-epinephrine-induced hemolysis, even upon concentrations < 20% of that of copper. Chromic chloride, as well, acted anti-hemolytically. CONCLUSION: The latter protectors may interact with the production or activity of toxic oxygen, while classical copper chelators sequester cupric ions from interaction with epinephrine or homocysteine.

Adult↗

[A fatal case of hereditary angioedema].

A 27 year old woman suffered from recurrent attacks of laryngeal oedema due to C1-inhibitor deficiency, and was treated with danazol and tranexamic acid. The trachea was intubated with great difficulty, twice on one occasion. Two and a half years later she was admitted to the Intensive Care Unit with dyspnoea and dysphagia. Tranexamic acid, corticosteroids, adrenaline (also inhalated), were administered intravenously, but dyspnoea progressed. During preparation for tracheostomy the patient suffered from sudden airway collapse. Attempts to ventilate by mask, puncture of the cricothyroid membrane and intubation were unsuccessful. A small tube was eventually inserted into the trachea after four minutes. The patient was then severely cyanotic with a pulse of thirty, and had dilated pupils. The next morning convulsions ensued and a CT scan showed cerebral oedema. In spite of treatment with pentothal, mannitol and hyperventilation she died. The authors advocate the use of intravenous infusion of C1-inhibitor concentrate, since traditional treatment is inadequate. Persons with hereditary angio-oedema should have a personal supply of C1-inhibitor at hand.

Adult↗

Thallium-201 as an agent for myocardial imaging studies.

The increasing use of thallium-201 (201Tl) in myocardial imaging studies during the last two decades, has justified a re-examination of the metabolism of this metal compound. It was found that about 4% of an injected dose was rapidly distributed to the healthy human myocardium, which is in agreement with previous reports. Apparent similarities exist between the transport of ionic thallium and potassium through cell membranes. Upon clinical use, myocardial perfusion scintigraphy is routinely carried out after i.v. administration of the agent. It is generally accepted that the rapid myocardial extraction of circulating 201Tl, during the initial 30 min. depends upon an unimpaired blood perfusion; whereas the prolonged uptake/redistribution during the next 3 h reflects myocardial viability. In the present paper, the reliability of 201Tl scintigraphy to disclose insufficient myocardial perfusion is illustrated by the examination of biological samples from patients, that were also studied by the classical coronary angiographic technique, the two methods showed an acceptable degree of agreement.

Heart↗

Uptake of chromate in human red blood cells and isolated rat liver cells: the role of the anion carrier.

The transport of [51Cr]chromate into human erythrocytes and isolated rat hepatocytes has been investigated. It was found that uptake in both cell types could be inhibited by the established anion carrier inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. The uptake was very fast, and in kinetic studies a very low Km was found for both cell types, indicating either a high affinity of chromate for the carrier, and/or, more probably, an efficient intracellular reduction and trapping of 51Cr. The transport capacity, however, was of the same magnitude as for physiological substrates, such as lactate and sulfate. The uptake was temperature dependent and the activation energy was of the same magnitude as that for the physiological substrates. The uptake could be partly inhibited by high levels (mmol l-1) of lactate, pyruvate or sulfate. The uptake rate was greatly increased at lower pH (6.0 versus 7.4) which could indicate transport of the HCrO4- form or an increased intracellular rate of CrVI reduction. The results showed efficient uptake of 51CrO4(2-) by erythrocytes and hepatocytes. They were consistent with a mechanism of uptake which involved the cell membrane anion-exchange carrier in the transport and trapping of 51Cr within the cell.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Hepatic retention of copper and selenium in primary sclerosing cholangitis.

BACKGROUND: Previous studies have suggested abnormal copper metabolism in patients with primary sclerosing cholangitis (PSC). In the present work the trace element metabolism was studied in a group of 32 patients with PSC. METHODS: Hepatic copper and selenium concentrations were determined with a sensitive electrothermal atomic absorption technique. Serum concentrations of copper and zinc were determined by conventional atomic absorption. RESULTS: For the patient group serum copper values (20.3 +/- 4.5 mumol/l) were higher than those for the control group (14 +/- 3 mumol/l), and average hepatic copper concentrations were greater by a factor of four. Serum selenium values were slightly lower, although the average hepatic selenium was significantly higher than in the healthy control group. Previous studies have discussed possible toxic effects of hepatocellular copper accumulation, which may be accompanied by formation of activated oxygen species and depletion of glutathione. In the present study, however, it could not be demonstrated that the concentration of the lipoperoxidation product, malonic dialdehyde, was higher than normal in blood. Furthermore, blood concentrations of glutathione and glutathione peroxidase were not abnormal. CONCLUSION: Although a protective effect of the raised selenium concentrations in the liver might be discussed, it is apparent that the copper accumulation in the liver cells described here did not induce detectable changes in the indices studied.

Adolescent↗

Dental amalgam and mercury.

The mercury concentrations in blood (HgB) and urine (HgU) samples, and in exhaled air (HgAir) were measured in 147 individuals from an urban Norwegian population, using cold vapour atomic absorption spectrometry. The study aimed to estimate the mercury exposure from the dental restorations, by correlating the data to the presence of amalgam restorations. Mean values were HgB = 24.8 nmol/l, HgU = 17.5 nmol/l and HgAir = 0.8 micrograms/m3. HgU correlated with HgAir, and both HgU and HgAir with the number of amalgam restorations, amalgam restored surfaces and amalgam restored occlusal surfaces. HgB showed poor correlation to HgU and HgAir and the presence of amalgam restorations. A differentiation of the mercury absorption due to exposure from dental amalgams and from the dietary intake, necessitates measurements of both organic and inorganic mercury in the plasma, and in the erythrocytes. The results suggest that individuals with many amalgam restorations, i.e., more than 36 restored surfaces, absorb 10-12 micrograms Hg/day.

Adolescent↗

High serum selenium concentrations in reindeer breeding Lappish men.

This study investigated the relationship of serum selenium to its dietary sources in a group of Lappish men and a control population. Lappish men had higher serum selenium concentrations than non-Lappish men (1.79 vs 1.58 mumol/1; p = 0.003). Serum selenium correlated positively with consumption of reindeer meat, age and cholesterol. In linear regression models, however, being Lappish was the most significant predictor of high serum selenium. Lappish men ate more reindeer meat (p = 0.001) and less fish (p = 0.013) than men in the control group. Consumption of reindeer meat was also correlated with higher serum cholesterol levels. We conclude that high serum selenium concentrations in Lappish men may be important since low mortality from cancer is reported in this group.

Adult↗

Selenium concentrations in the human thyroid gland.

Recently, we found that prediagnostic serum selenium concentration was significantly lower for cases developing thyroid cancer (n = 43) than for controls. We assumed that redistribution of serum selenium into the affected tissue took place in the prediagnostic period. The present study was carried out to determine the physiological concentration of selenium in the thyroid, since very few data are available in the literature. The concentrations of selenium in the thyroid (n = 45) and liver samples from Norwegians who had died because of acute illness or accidents were determined by hydride generation atomic absorption spectrometry. The mean selenium concentration was found to be 0.72 +/- 0.44 microgram/g in the thyroid and 0.45 +/- 0.11 microgram/g in the liver tissue. The surprisingly high concentration of selenium in apparently normal thyroids indicates that selenium has important functions in this organ. The remarkably broad range, together with the observation that no significant correlation exists between thyroid and liver concentrations, suggest that factors other than the selenium status are important determinants for the selenium concentration in the thyroid gland. This observation is consistent with our hypothesis that in carcinogenesis, prediagnostic processes influence the serum-/thyroid-ratio of selenium.

Adult↗

Mercaptodextran--a new copper chelator and scavenger of oxygen radicals.

The therapy of copper poisoning with mercaptodextran inhibits the copper-induced haemolysis, whereas 2,3- dimercaptopropanesulfonic acid (DMPS) may accelerate such haemolysis. Some aspects of the mechanisms of these effects were investigated. The possible generation of activated oxygen species during the interaction of Cu++ and chelating thiols was studied using a chemoluminiscent method detecting oxygen radicals. It was found that incubation of DMPS with copper ions or erythrocyte membranes was accompanied by generation of oxygen radicals. Mercaptodextran added to similar suspensions did not lead to oxygen radical production. And unlike DMPS, mercaptodextran acted as a scavenger of radicals generated by the xanthine oxidase/acetaldehyde system. The different ability of the chelating thiols to cope with free radicals may explain their different potentials to protect against copper-induced haemolysis. Our results also indicate that mercaptodextran may be a useful therapeutic agent in cases of haemolytic crisis in Wilson's disease.

Chelating Agents↗

The determination of copper in human liver biopsy specimens by cup-in-tube ETAAS.

A method for the direct determination of copper in human liver biopsy specimens is described. The addition of a mixed Mg-Pd nitrate modifier is shown effectively to delay the volatilization of copper both from aqueous standards and the powered NISTBovine Liver to an appearance time comparable with the solid biopsy specimens. Calibration against solid liver reference materials is preferable compared with aqueous copper standard solutions. A number of copper absorption lines provide a wide range of sensitivities; the less sensitive Cu-line 222.6 nm was found optimal in the determination of copper concentrations in the range of 20-200 mg/kg in liver biopsy specimens. The copper concentrations measured in liver biopsy specimens from patients suffering from sclerosing cholangitis were considerably higher than those reported for a group of healthy persons.

Animals↗