Copper Abstracts 3

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Studies on copper metabolism.  XX.  Enzyme activities and iron metabolism in copper and iron deficiencies.
            (Cartwright et al., 1957) Download
In copper deficiency, an increase in allantoin and a relatively greater increase in uric acid excretion were found. This resulted in a 2.5-fold increase in the ratio of uric acid to allantoin excreted. In the heart, both the concentration and the total cytochrome c as well as the total myoglobin were increased in copper-deficient animals. Copper deficiency resulted in a marked (200 per cent) increase in heart weight and a moderate increase in liver and kidney weight relative to body weight.

The effect of copper acetate on p-dimethylaminoazobenzene carcinogenesis in the rat.
            (Howell, 1958) Download
Experiments are described which show that copper acetate has a powerful retarding effect on hepatic tumour development in rats treated with DMAB. Thus, of 16 rats which survived treatment with copper acetate and DMAB for longer than 6 months, only one animal developed a tumour which was found after 18 months' treatment. This can be contrasted with a control group receiving DMAB alone, in which 8 rats all developed tumours in an average time of 85 months.

Serum copper levels in benign and malignant thyroid diseases.
            (Kosova et al., 2012) Download
OBJECTIVE:  To examine the changes in serum copper (Cu) levels in benign and malignant thyroid disease in humans. BACKGROUND:  Thyroid hormones influence the metabolism of trace elements including copper. METHODS:  47 papillary thyroid cancer and 43 benign multinodular goitre patients who underwent total thyroidectomy and 37 healthy control subjects were included into this study. All of the patients and controls were females. Serum Cu levels were detected with atomic absorption spectrophotometer. RESULTS:  In the papillary thyroid cancer group serum level of Cu was 131.61 ± 33.9 μg/dL before surgery and 120.81 ± 30.4 μg/dL after 20 days from surgery. In the benign group serum Cu level was 84.75 ± 12.1 μg/dL and 68.01 ± 9.4 μg/dL postoperatively.These results were compared to healthy control's value of 105.87 ± 10.68 μg/dL. In the papillary thyroid cancer group pre- and postoperative serum Cu level was significantly higher when compared to control group (p<0.05). Postoperative serum Cu level significantly decreased when compared to pre-operative level(p<0.05), in which, it was still higher than the control(p<0.05). In the benign group pre- and postoperative serum Cu level was significantly lower than in the control group (p<0.05).Postoperative serum Cu level significantly decreased when compared to pre-operative level in the benign group (p<0.05). CONCLUSION:  This is a pioneer study to examine serum Cu level in benign and malignant thyroid patients compared to controls. In our small groups serum Cu levels increased in malignant thyroid patients and decreased in the benign group (Tab. 1, Ref. 18).

Serum copper as a novel biomarker for resistance to thyroid hormone.
            (Mittag et al., 2012) Download
Thyroid hormone action is mediated by the thyroid hormone receptors TRα1 and TRβ. Defects in TRβ lead to RTH (resistance to thyroid hormone) β, a syndrome characterized by high levels of thyroid hormone and non-suppressed TSH (thyroid-stimulating hormone). However, a correct diagnosis of RTHβ patients is difficult as the clinical picture varies. A biochemical serum marker indicative of defects in TRβ signalling is needed and could simplify the diagnosis of RTHβ, in particular the differentiation to TSH-secreting pituitary adenomas, which present with clinically similar symptoms. In the present paper we show that serum copper levels are regulated by thyroid hormone, which stimulates the synthesis and the export of the hepatic copper-transport protein ceruloplasmin into the serum. This is accompanied by a concerted reduction in the mRNA levels of other copper-containing proteins such as metallothioneins 1 and 2 or superoxide dismutase 1. The induction of serum copper is abolished in genetically hyperthyroid mice lacking TRβ and human RTHβ patients, demonstrating an important role of TRβ for this process. Together with a previously reported TRα1 specific regulation of serum selenium, we show that the ratio of serum copper and selenium, which is largely independent of thyroid hormone levels, volume changes or sample degradation, can constitute a valuable novel biomarker for RTHβ. Moreover, it could also provide a suitable large-scale screening parameter to identify RTHα patients, which have not been identified to date.

Hypothesis: Shwachman's syndrome of exocrine pancreatic insufficiency may be caused by neonatal copper deficiency.
            (Paterson and Wormsley, 1988) Download
Shwachman's syndrome is, after cystic fibrosis, the most common cause of exocrine pancreatic insufficiency in childhood. The cause of the disorder is not known but we were struck by the fact that the histological appearances of pancreatic atrophy in this condition resemble those seen in experimental copper deficiency, in which the pancreatic acinar damage persists long after the copper deficiency is relieved. Other features of Shwachman's syndrome include neutropenia, anaemia and abnormalities of the ribs and of the metaphyses of long bones. All these findings have also been reported in children with copper deficiency during the 1st year of life. We suggest that some or all cases of Shwachman's syndrome are caused by a period of copper deficiency in early infancy.

Anti-tumour activities of copper chelates.
            (Takamiya, 1960) Download
Chelating agents have been shown to interfere with the utilization of metals by micro-organisms, robbing cells of their necessary metals1. Retardation of growth of a tumour (sarcoma 37) by the administration of two chelating agents, dipyridyl and O-phenanthroline, was observed by Leiter et al.2. Now, α-ketoglutaric acid oxime has been found to form its copper, iron, or nickel chelate at the physiological pH, and its antitumour activity in vitro was observed by the stained cell count method3.

 


References

Cartwright, GE, CJ Gubler, and MM Wintrobe (1957), ‘Studies on copper metabolism. XX. Enzyme activities and iron metabolism in copper and iron deficiencies.’, J Biol Chem, 224 (1), 533-46. PubMed: 13398428
Howell, JS (1958), ‘The effect of copper acetate on p-dimethylaminoazobenzene carcinogenesis in the rat.’, Br J Cancer, 12 (4), 594-608. PubMed: 13628889
Kosova, F, et al. (2012), ‘Serum copper levels in benign and malignant thyroid diseases.’, Bratisl Lek Listy, 113 (12), 718-20. PubMed: 23173630
Mittag, J, et al. (2012), ‘Serum copper as a novel biomarker for resistance to thyroid hormone.’, Biochem J, 443 (1), 103-9. PubMed: 22220593
Paterson, CR and KG Wormsley (1988), ‘Hypothesis: Shwachman’s syndrome of exocrine pancreatic insufficiency may be caused by neonatal copper deficiency.’, Ann Nutr Metab, 32 (3), 127-32. PubMed: 3190162
Takamiya, K (1960), ‘Anti-tumour activities of copper chelates.’, Nature, 185 190-91. PubMed: 13836648