A kinetic model of copper metabolism in lactating dairy cows

Buckley, W. T.

doi:10.4141/cjas91-017

Cited by 30 publications

(10 citation statements)

References 6 publications

(3 reference statements)

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“…The astrocytosis was combined with a vacuolisation of the neuropil localised predominantly in the white matter (figs. 4,5). In brain sections of control animals there were only small regions which showed an immunopositivity for MT-I/II.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 93%

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Zatta

Raso

Zambenedetti³

et al. 2005

CMLS, Cell. Mol. Life Sci.

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Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.

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Section: Histology and Immunohistochemistrymentioning

confidence: 93%

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Zatta

Raso

Zambenedetti³

et al. 2005

CMLS, Cell. Mol. Life Sci.

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“…Furthermore, the studies presented here and those presented previously (Buckley et al 1996) indicate that EX Cu represents a physiologically meaningful Cu fraction that is metabolized separately and distinctly from ceruloplasmin Cu. Although EX Cu has been recognized as the absorbed form of Cu (Gordon et al 1987) and its central role in Cu metabolism has been included in kinetic models of Cu metabolism (Buckley 1991;Turnlund 1998), its metabolism and potential diagnostic attributes are largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence presented earlier indicates that EX Cu determined by isotope dilution analysis is physiologically significant (Buckley et al 1996). Because of its central role in distribution of absorbed Cu, plasma EX Cu has been included as a compartment in kinetic models of Cu metabolism (Buckley 1991;Turnlund 1998). However, the significance of EX Cu in various physiological or disease states is not well understood.…”

Section: Introductionmentioning

confidence: 97%

Analytical variables affecting exchangeable copper determination in blood plasma

Buckley

Vanderpool²

2008

Biometals

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To resolve discrepancies observed in the determination of plasma exchangeable Cu (also called direct reacting Cu or loosely bound Cu) by several methods, plasma storage techniques and various aspects of a stable isotope dilution procedure for exchangeable Cu were evaluated. Results indicated that the exchangeable Cu fraction of plasma increased with storage at room temperature, at 5 degrees C and when subjected to repeated freeze/thaw cycles. Samples could be safely stored at -65 degrees C. Exchange between added 65Cu2+ and endogenous plasma Cu rapidly went to completion in the isotope dilution procedure. Analytical results were unaffected by shaking method, sample size or the presence of heparin. A small difference was observed between serum and plasma. The determination of exchangeable Cu did not vary over a period of 4 h when plasma was exposed to 1.6 x 10(-4)-M sodium diethyldithiocarbamate (used in the isotope dilution method) but steadily increased when exposed to 1.1 x 10(-2)-M sodium diethyldithiocarbamate, which suggested that tightly bound Cu (probably in ceruloplasmin) was exchanging with isotopic tracer at the higher concentration. Determination of exchangeable Cu was constant from pH 7.2-8.5 but increased substantially at higher pH. Complete recovery of natural Cu added to plasma was obtained. Studies in solution indicated that 65Cu2+ exchanged readily with albumin- and amino acid-bound Cu. Ultrafiltration of plasma yielded a Cu fraction about half that of the exchangeable Cu fraction. We conclude that the stable isotope dilution procedure for plasma exchangeable Cu yields reliable, physiologically meaningful results.

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“…In contrast to the other main minerals of nutritional interest, very few papers have been published that attempt to model Cu metabolism in man using stable isotopes, although work has been done using animal models (Buckley, 1991;Dunn et al 1991). These studies were used as the basis for the human model of Scott & Turnlund (1994a) in which five young men took part in a 90-d intervention trial.…”

Section: Studiesmentioning

confidence: 99%

Use of stable isotopes and mathematical modelling to investigate human mineral metabolism

Dainty

2001

nutr res rev

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Individuals have varying needs for minerals that are dependent, amongst other things, on their lifestyle, age and genetic makeup. Knowledge of exact individual nutritional requirements should lead to better health, increased quality of life and reduced need for expensive medical care. Bioavailability, nutrient-gene interactions and whole-body metabolism all need to be investigated further if we are to progress towards the goal of defining optimal health and nutritional status. The discussion which follows will critically review the latest developments in the area of metabolism for several of the minerals that are essential for human health: Ca, Zn, Cu and Se. Stable-isotope tracers and mathematical modelling are some of the tools being used to facilitate the greater understanding in uptake, utilisation and excretion of these minerals. Stable isotopes, administered in physiological doses, present little or no risk to volunteers and allow metabolic studies to be carried out in vulnerable population groups such as children and pregnant women. Intrinsic labelling of foodstuffs ensures that the tracer and the native mineral will behave similarly once inside the body. Advances in computing power and software dedicated to solving nutritional problems have made it possible for investigators to use mathematical modelling in their experimental work. Mineral metabolism is ideally suited to a form of modelling known as compartmental analysis, which allows rates of mineral transfer and sizes of mineral stores to be calculated accurately without the need for invasive sampling of body tissues. Stable isotopes: Mathematical modelling: Mineral metabolismNutrition Research Reviews (2001) , IntroductionMost minerals have several naturally-occurring stable isotopes, all with a fixed abundance. In order to follow the metabolism of a mineral, it is necessary to ingest it in an altered form so that it can be distinguished from the naturally-abundant mineral. The form of the ingested mineral can be altered by enriching one of the low-abundance isotopes. This so-called 'tracer' or 'label' is injected and/or taken orally and its appearance in the plasma, urine and faeces can be monitored over several days. The concept of a tracer is important in isotope work. A true tracer is one that does not perturb the system it is investigating. Only radioisotopes can be called true tracers, since they are administered in extremely small quantities. The term 'label' is more appropriate for stable isotopes, since they are usually given in quantities equivalent to the amount received in the normal diet. The word 'tracer' is, however, still used in some stable-isotope studies with the implicit understanding that it will almost certainly perturb the system under investigation. The underlying assumption in this type of work is that the label (or tracer) behaves in the same kinetic way as the naturally-abundant mineral (sometimes called the tracee), otherwise the use of labels to mimic the behaviour of the native mineral is invalid. There must be no discri...

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A kinetic model of copper metabolism in lactating dairy cows

Abstract: Buckley, w. T. 1991. A kinetic model of copper metabolism in lactating dairy cows. can. J-Anim' Sci. 7f: [155][156][157][158][159][160][161][162][163][164][165][166]

Cited by 30 publications

References 6 publications

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Analytical variables affecting exchangeable copper determination in blood plasma

Use of stable isotopes and mathematical modelling to investigate human mineral metabolism

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