Early cell transplantation in LEC rats modeling Wilson's disease eliminates hepatic copper with reversal of liver disease

2002 ◽  
Vol 122 (2) ◽  
pp. 438-447 ◽  
Author(s):  
Harmeet Malhi ◽  
Adil N. Irani ◽  
Irene Volenberg ◽  
Michael L. Schilsky ◽  
Sanjeev Gupta
Keyword(s):  
Liver Disease ◽  
Cell Transplantation ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Hepatic Copper ◽  
Lec Rats

Uneven hepatic copper distribution in Wilson's disease

1995 ◽  
Vol 22 (3) ◽  
pp. 303-308 ◽  
Author(s):  
Gavino Faa ◽  
Valeria Nurchi ◽  
Luigi Demelia ◽  
Rossano Ambu ◽  
Giuseppina Parodo ◽  
...  
Keyword(s):  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Hepatic Copper ◽  
Copper Distribution

A comparison of copper-loading disease in Bedlington terriers and Wilson's disease in humans

1982 ◽  
Vol 243 (3) ◽  
pp. G226-G230 ◽  
Author(s):  
L. C. Su ◽  
S. Ravanshad ◽  
C. A. Owen ◽  
J. T. McCall ◽  
P. E. Zollman ◽  
...  
Keyword(s):  
Copper Concentration ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Normal Brain ◽  
Glutamic Pyruvic Transaminase ◽  
Serum Glutamic Pyruvic Transaminase ◽  
Hepatic Copper ◽  
Erythrocyte Survival ◽  
Ceruloplasmin Activity

Eleven Bedlington terriers were found to have a mean hepatic copper concentration of 6,321 micrograms/g dry wt (normal, 200 micrograms/g dry wt) and renal copper concentration that was three or four times normal. Brain copper levels were normal in younger dogs, were elevated in two older dogs, and were 100 times normal in one dog that died of the disease. Increased concentrations of copper in the liver, kidney, and brain also characterize Wilson's disease. Erythrocyte survival was normal in three affected dogs, but serum glutamic-pyruvic transaminase levels were usually elevated. Unlike the hypoceruloplasminemia of patients with Wilson's disease, plasma ceruloplasmin activity was not only normal but was also slightly elevated in the terriers. Despite their normal or excessive ceruloplasmin, the Bedlington terriers could convert ionic 64Cu to radioceruloplasmin but did so only very slowly. These dogs accumulated significantly more 64Cu in their livers than normal, much like patients with Wilson's disease do before symptoms develop.

Inherited diseases of copper metabolism: Wilson’s disease and Menkes’ disease

2020 ◽  
pp. 2115-2120
Author(s):  
Michael L. Schilsky ◽  
Pramod K. Mistry
Keyword(s):  
Liver Disease ◽  
Fulminant Hepatic Failure ◽  
Hepatic Failure ◽  
Wilson’S Disease ◽  
Menkes Disease ◽  
Wilson's Disease ◽  
Copper Transport ◽  
Loss Of Function ◽  
Copper Excretion ◽  
P Type

Copper is an essential metal that is an important cofactor for many proteins and enzymes. Two related genetic defects in copper transport have been described, each with distinct phenotypes. Wilson’s disease—an uncommon disorder (1 in 30 000) caused by autosomal recessive loss-of-function mutations in a metal-transporting P-type ATPase (ATP7B) that result in defective copper excretion into bile and hence copper toxicity. Typical presentation is in the second and third decade of life with liver disease (ranging from asymptomatic to acute fulminant hepatic failure or chronic end-stage liver disease) or neurological or psychiatric disorder (dystonia, dysarthria, parkinsonian tremor, movement disorder, a spectrum of psychiatric ailments). While no single biochemical test or clinical finding is sufficient for establishing the diagnosis, typical findings include low serum ceruloplasmin, high urinary copper excretion, and elevated liver copper content. Corneal Kayser–Fleischer rings may be seen. Treatment is with copper chelating agents and zinc. Liver transplantation is required for fulminant hepatic failure and decompensated liver disease unresponsive to medical therapy. Menkes’ disease—a rare disorder (1 in 300 000) caused by X-linked loss-of-function mutations in a P-type ATPase homologous to ATP7B (ATP7A) that result in defective copper transport across intestine, placenta, and brain and hence cellular copper deficiency. Clinical presentation is in infancy with facial dimorphism, connective tissue disorder, hypopigmentation, abnormal hair, seizures, and failure to thrive, usually followed by death by age 3 years (although some variants with a milder phenotype result from milder mutations, e.g. occipital horn syndrome). Treatment, which is only effective when presymptomatic diagnosis is made in a sibling after florid presentation in a previous affected sibling, is with intravenous copper histidine.

Deletion of the Wilson's disease gene in hereditary hepatitis LEC rats

1995 ◽  
Vol 70 (1) ◽  
pp. 25-33
Author(s):  
Takao ONO ◽  
Risaku FUKUMOTO ◽  
Yasumitsu KONDOH ◽  
Michihiro C. YOSHIDA
Keyword(s):  
Wilson’S Disease ◽  
Disease Gene ◽  
Wilson's Disease ◽  
Lec Rats

scholarly journals Differences of Accumulated Heavy Metal Levels in End-Stage Liver Disease, Wilson’s Disease, and Other Etiologies

2021 ◽  
Vol 13 (3) ◽  
pp. 184-193
Author(s):  
Sinan Hatipoğlu ◽  
Abuzer Dirican ◽  
Mustafa Ateş ◽  
Muhammer Özgür Çevik ◽  
Önder Yumrutaş ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Liver Disease ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
End Stage Liver Disease ◽  
Metal Levels ◽  
End Stage

scholarly journals Zinc as a Drug for Wilson’s Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6614
Author(s):  
Pierpaolo Coni ◽  
Giuseppina Pichiri ◽  
Joanna Izabela Lachowicz ◽  
Alberto Ravarino ◽  
Francesca Ledda ◽  
...  
Keyword(s):  
Liver Disease ◽  
Zinc Deficiency ◽  
Alcoholic Liver Disease ◽  
Wilson’S Disease ◽  
Severe Disease ◽  
Copper Metabolism ◽  
Wilson's Disease ◽  
Aged People ◽  
Positive Effects ◽  
Zinc Levels

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson’s disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson’s disease. On the basis of the similarities, at histological level, between Wilson’s disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.

Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease

1988 ◽  
Vol 254 (2) ◽  
pp. E150-E154
Author(s):  
T. O. Carpenter ◽  
M. L. Pendrak ◽  
C. S. Anast
Keyword(s):  
Vitamin D ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Hepatic Copper ◽  
25 Hydroxyvitamin D ◽  
Potential Factor

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.

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