Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Though myocardial alterations are well recognized in haemochromatosis, little attention has been paid to the cardiac changes in Wilson's disease. To define the extent of myocardial degeneration in newly diagnosed or chronically treated Wilson's disease, we reviewed the autopsy findings in 9 cases with this condition. We compared our observations with those in 3 control cases, selected for comparable age and with liver disease having no known association with cardiac degeneration. Our results revealed cardiac hypertrophy in 5 out of 9 cases of Wilson's disease. There was evidence of interstitial and replacement fibrosis, intramyocardial small vessel sclerosis and focal inflammatory cell inflammation to a variable degree in all cases. One case had AV nodal degeneration, and a 15 year old boy had severe atherosclerosis of the left main coronary artery. Two patients died suddenly, presumably secondary to an arrhythmia; one of these patients had the most marked myocardial alterations. We could not correlate these changes specifically with the tissue levels of copper, treatment with D-penicillamine, or the presence of cirrhosis. We conclude that there are definite morphological abnormalities in the hearts of patients with Wilson's disease consistent with a cardiomyopathy. Though the myocardial changes were non-specific, the fact that 2 patients died suddenly, suggests the need for a prospective study of cardiac function in these patients in the future.
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PMID:The cardiomyopathy of Wilson's disease. Myocardial alterations in nine cases. 715 67

Accumulation of lipids and cholesterol by macrophages and subsequent transformation into foam cells are key features in development of atherosclerosis. Serum copper concentrations have been shown to be associated with cardiovascular disease. However, the mechanism behind the proatherogenic effect of copper is not clear. We used DNA microarrays to define the changes in gene expression profile in response to copper exposure of human macrophages. Expression monitoring by DNA microarray revealed 91 genes that were regulated. Copper increased the expression of seven cholesterogenic genes (3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase, IPP isomerase, squalene synthase, squalene epoxidase, methyl sterol oxidase, H105e3 mRNA and sterol-C5-desaturase) and low-density lipoprotein receptor (LDL-R), and decreased the expression of CD36 and lipid binding proteins. The expression of LDL-R and HMG CoA reductase was also investigated using real time PCR. The expression of both of these genes was increased after copper treatment of macrophages (P<0.01 and P<0.01, respectively). We conclude that copper activates cholesterogenic genes in macrophages, which may provide a mechanism for the association between copper and atherosclerosis. The effect of copper on cholesterogenic genes may also have implications for liver steatosis in early stages of Wilson's disease.
Atherosclerosis 2003 Jul
PMID:Copper induces the expression of cholesterogenic genes in human macrophages. 1286 Feb 52

Complete loss of function in the WRN: RecQ3 DNA/RNA helicase gene causes Werner Syndrome (WS). WS patients with genetic instability manifest an early onset of age-related diseases including diabetes mellitus (DM), osteoporosis, atherosclerosis, and malignancy as well as early death. In 1,420 patients, WS was reported to be associated with chromosomal abnormality syndrome and other genetic diseases including Klinefelter syndrome in 2 patients, retinitis pigmentosa in 3, Wilson's disease in 1, xeroderma pigmentosum in 3, and porokeratosis Mibelli in 1. These clinical findings may support the concept of genetic instability in WS.
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PMID:Syndrome-causing mutations in Werner syndrome. 2010 20

The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment affects nearly 2 billion subjects in the developing world. High phytate content of the cereal proteins consumed in the developing world, results in decreased availability of zinc for absorption. Zinc therapy has been very successful and life saving measure in patients with acrodermatitis enteropathica and Wilson's disease. Beneficial therapeutic responses of zinc supplementation have been ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis, leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in decreasing incidences of infection in elderly and patients with sickle cell disease. Zinc supplementation was effective in preventing blindness in 25% of the elderly with dry type of age related macular degeneration. Zinc supplementation in the elderly decreased oxidative stress and decreased generation of inflammatory cytokines. Zinc is an intracellular signaling molecule in monocytes, dendritic cells and macrophages and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an anti-inflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress and increase generation of inflammatory cytokines. Oxidative stress and chronic inflammation may play important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and auto-immune diseases. It is therefore, important that status of zinc is assessed and zinc deficiency corrected in these chronic diseases. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is warranted.
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PMID:Impact of the discovery of human zinc deficiency on health. 2015 May 99

The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson's disease, Alzheimer's disease, and other age-related diseases.
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PMID:Zinc and human health: an update. 2241 66

Metal-based drugs, also called "metallopharmaceuticals" or "metallodrugs", are examples of sophisticated compounds that have been used in inorganic medicinal chemistry as therapeutic agents for a long time. Few of them have shown substantially promising results and many of them have been used in different phases of clinical trials. The Mo-based metallodrugs were successfully applied in the past for treating conditions such as anemia or Wilson's disease. Moreover, Mo complexes are supposed to exert their effect by intercalation/ cleavage of DNA/RNA, arrest of the cell cycle, and alteration of cell membrane functions. However, in the current literature, there are no reliable and in-depth reviews about the hypothetical therapeutic applications of all of the known molybdenum complexes as metallopharmaceuticals/ metallodrugs. The main emphasis was on the in-depth review of the potential applications of Mo-based complexes in medicinal chemistry as metallopharmaceuticals in treating diseases such as cancer and tumors, Wilson's disease, diabetes mellitus, Huntington's disease, atherosclerosis, and anemia. It must be emphasized that today the development of innovative and new Mo-based metalo-pharmaceuticals is not rapid, and hence the aim of this paper was also to inspire colleagues working in the field of Mo compounds who are trying to find "signpost" for research. The authors hope that this article will increase interest and initiate the Renaissance of Mo-compounds among medicinal inorganic chemists. This paper is the first review article in the literature that refers to and emphasizes many different and complex aspects of possible applications and capabilities of Mo-based metallodrugs.
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PMID:Molybdenum Metallopharmaceuticals Candidate Compounds - The "Renaissance" of Molybdenum Metallodrugs? 2714 89

Wilson's disease is a rare autosomal recessive disease, caused by impaired secretion of copper into bile due to a defective function of the ATPase 7B enzyme. Clinical manifestation is predominantly hepatic and neurological. Wilson's disease is traditionally considered a disease of children and young adults. It rarely manifests after 40 years of age. In our case report, we present a 67-year-old female in whom Wilson's disease manifested as tremors of the upper extremities and chin that were originally assessed as part of cerebral atherosclerosis and Parkinson's disease. Only the histological finding of liver steatofibrosis, performed due to suspected metastatic changes of the liver, led in the context of neurological symptoms to correct diagnosis and successful treatment.
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PMID:Late-Onset Wilson's Disease. 3211 11