Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kayser-Fleischer rings are pigmented corneal rings at the limbus of the cornea in Descemet's membrane that have been deemed pathognomonic of Wilson's disease. However, we have observed four exceptions in patients with non-Wilsonian liver disease. Three patients had primary biliary cirrhosis and one patient had chronic aggressive hepatitis with cirrhosis. Pigmented corneal rings were seen only by slit-lamp examination. Hepatic, serum, and urinary copper and serum ceruloplasmin levels were significantly elevated in the patients with primary biliary cirrhosis. Radiocopper (64Cu or 67Cu) studies in patients with primary biliary cirrhosis showed plasma disappearance curves which allowed a clear distinction from Wilson's disease in that all three patients with primary biliary cirrhosis showed a secondary rise in radiocopper that presumably represented copper incorporation into ceruloplasmin. In one patient, in whom 64Cu in ceruloplasmin was studied specifically, incorporation was found to be normal.
 ...
PMID:Pigmented corneal rings in non-Wilsonian liver disease. 84 86

Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism which usually affects young people. Excess copper accumulates in the tissues, primarily in the liver, brain, and cornea. This copper deposition results in a wide range of hepatic and neurological symptoms, and may produce psychiatric illness. Hepatic involvement often occurs in childhood, while neurological deficits generally are detected at a later age. The disease is inherited in an autosomal recessive fashion. Ocular findings are of particular importance because the corneal copper deposition, forming the Kayser-Fleischer ring,is the only pathognomonic sign of the disease. The structure of the ring and the presence of copper have been well established. An anterior capsular deposition of copper in the lens results in a characteristic sunflower cataract in some of these patients. Other ocular abnormalities have been described but are much less common. The pathogenesis of the disease and the basic genetic defect remain obscure. It is clear that there is excess copper in the tissues, but the mechanism of its deposition is unknown. It is in some way associated with a failure to synthesize the serum copper protein ceruloplasmin normally. Another theory suggests that an abnormal protein with a high affinity for copper may bind the metal in the tissues. The diagnosis may be suggested by the clinical manifestations and confirmed by the presence of a Kayser-Fleischer ring. In the absence of these findings biochemical determinations are necessary. The most important of these are the serum ceruloplasmin, the urinary copper, and the hepatic copper concentration on biopsy. Treatment consists in the administration of the copper chelating agent, penicillamine, and the avoidance of a high copper intake. This usually results in marked clinical improvement if irreversible tissue damage has not occurred. Maintenance therapy for life is necessary in order to continue the negative copper balance. The detection and prophylactic treatment of asymptomatic individuals with the disease is especially important. Seven cases of Wilson's disease have been presented in order to illustrate many of the features which have been discussed, with emphasis on the ocular findings.
 ...
PMID:Wilson's disease (hepatolenticular degeneration). 102 89

A patient with primary biliary cirrhosis who had high hepatic, serum, and urine copper levels was found by slit-lamp biomicroscopy to have pigmented corneal rings similar to Kayser-Fleischer rings. Wilson's disease was excluded on the basis of the elevated serum ceruloplasmin and copper levels, the lack of neurological disease despite advanced liver disease, a negative family history, and the typical clinical features of primary biliary cirrhosis. Although the exact chemical nature of the corneal rings is unknown, the cornea may be another tissue associated with elevated tissue copper levels in primary biliary cirrhosis.
 ...
PMID:Pigmented corneal rings in a patient with primary biliary cirrhosis. 115 26

The authors describe the case of a 27-year-old female patient with Wilson's disease who during penicillinamine treatment became pregnant and was delivered of a healthy infant. The diagnosis of Wilson's disease was confirmed by the finding of a Kayser-Fleischer ring in the cornea and a concurrent serum ceruloplasmin concentration lower than 0.20 g/l. Unrecognized and untreated, the disease is associated with the development of organ complications which in the end prove fatal. On the other hand, early diagnosis and effective treatment throughout life can prevent liver and brain damage and thus enable the patient to live a normal life and women can have a healthy child.
 ...
PMID:[Wilson's disease and pregnancy]. 159 20

The pathophysiology, symptomatology, and treatment of Wilson's disease are reviewed, and new approaches to drug management are discussed. Wilson's disease is a rare, autosomal recessive disorder that occurs between the ages of 6 and 60 years. Disturbances in copper metabolism may result in the accumulation of excess copper in the liver, the basal ganglia of the brain (lenticular degeneration), the kidneys, the cornea (Kayser-Fleischer rings), and other tissues. The diagnosis of Wilson's disease is frequently overlooked; nonspecific symptoms and multisystem involvement may mimic other disease states, such as neurologic and psychiatric disorders, and hemolytic anemia. Screening tests for Wilson's disease include 24-hour urinary copper levels, serum ceruloplasmin and copper assays, radioactive uptake of 64Cu, and liver biopsy. Current methods of therapy include the use of a chelating agent--penicillamine or trientine--for initial rapid decoppering. Penicillamine therapy has been associated with many adverse reactions, including worsening of the neurologic symptoms of the patient. Zinc is a useful agent for maintenance therapy. Investigational studies exploring the use of ammonium tetrathiomolybdate for initial rapid decoppering have shown promising results. Unless it is recognized and treated, Wilson's disease can cause severe symptoms and, ultimately, death. Initial rapid decoppering with chelating agents, such as penicillamine and trientine, followed by lifelong maintenance therapy with zinc is the current method of treatment.
 ...
PMID:Pathophysiology and treatment of Wilson's disease. 179 20

The interstitial fluid of MTW9A and Walker carcinomas and their ethanol extract induced strong angiogenic response in the rabbit (New Zealand White) corneal test. The fluid collected in vivo was rich in E-type prostaglandins, and prostaglandin E1 (PGE1) in particular was strongly angiogenic at the lowest dose as compared with the angiogenic responses of prostaglandins E2, I2, and F2 alpha. Neoplastic fibroblasts also induced a strong angiogenic response, but in indomethacin-treated rabbits neovascularization failed to occur. Copper was concentrated in the cornea during PGE1-induced neovascularization, and copper-deficient rabbits were unable to mount an angiogenic response in the corneal test. Ceruloplasmin, the copper carrier of plasma, was found to be angiogenic at high doses. In indomethacin-treated rabbits, however, ceruloplasmin at the same high doses failed to induce angiogenesis. The experiments are interpreted to indicate that angiogenesis is the end result of a sequence of events, two of which are PGE1 production and copper mobilization in the tissue where neovascularization occurs.
 ...
PMID:Role of prostaglandin E1 and copper in angiogenesis. 618 Feb 7

The ability to induce new formation of capillaries in the cornea was tested for ceruloplasmin, the copper carrier of serum, for fragments of the ceruloplasmin molecule with and without copper, for heparin, and for glycyl-L-histidyl-L-lysine, bound or not bound to copper ions. Male or female 2- to 3-kg New Zealand White rabbits were used. These experiments were prompted by the previous observation of copper accumulation in the cornea during angiogenesis and by the inability of copper-deficient rabbits to mount an angiogenic response. The results showed that the three different molecules were all able to induce angiogenesis provided that they were bound to copper. Fragments of the ceruloplasmin molecule also induced angiogenesis but only when copper was bound to the peptides. The data are interpreted to indicate that copper ions are involved in the sequence of events leading to angiogenesis and that the carrier molecules may be of quite a different nature.
 ...
PMID:Ceruloplasmin, copper ions, and angiogenesis. 618 32

Rats were injected intraperitoneally with copper-lactate daily for over 160 days (total dose of 30 mg copper in each animal). At 120 to 160 days of copper administration, animals developed symptoms similar to those of Wilson's disease, i.e., kidney functional disturbances, proteinuria, aminoaciduria, decreased blood ceruloplasmin oxidase activity and increased urinary copper excretion. Cirrhosis was found in some animals. Tubular necrosis of the kidneys, liver fibrosis and tigrolysis of thalamic nerve cells were also found. Copper depositions were observed in liver parenchymal cells, renal tubular epithels, thalamus glia cells and on the Descemet's membrane of the cornea. The similarities between induced copper- intoxication in rats and Wilson's disease are discussed.
 ...
PMID:Laboratory and histological similarities between Wilson's disease and rats with copper toxicity. 645 May 19

There is little absolute data in the form of prospective studies in patients with specific illnesses who are on oral contraceptives (OCs). Consequently, the clinician must depend on well-founded empiric decisions in prescribing the pill for these patients. The basis for the decision should be a firm understanding of the pathophysiology and laboratory effects of OCs. This needs to be juxtaposed with an understanding of the efficacy and effects of the estrogen and progestational components of the birth control pill and their interactions with maintenance medications. Available evidence is reviewed for the following medical disorders: central nervous system disorders (depression, Wilson's disease, headaches, epilepsy, multiple sclerosis, and the eye); immunologic and connective tissue diseases; diseases of the endocrine system, the gastrointestinal system, the genitourinary system, the memopoietic system; and skin disorders. 7% of women on OCs have increased or newly reported depression. Whether these are primarily psychogenic or metabolically derived is yet to be definitively determined. Wilson's disease can be exacerbated by OCs because of increased plasma ceruloplasmin and increased absorption of copper from the gastrointestinal tract. Headaches can be either a vague or a specific symptom, such as migraines, but 1/3 of these patients will become worse on OCs. There is good evidence that the headaches are caused by falling estrogen levels. There is no good evidence that epilepsy, in general, becomes worse on OCs. OCs have relatively no effect on the longterm prognosis in multiple sclerosis. Increased corneal sensitivity has been observed with OC use, and this has usually presented an intolerance to the use of contact lenses. This is primarily the result of increased edema of the cornea and changing of its contour. By inference, OCs cause some basic universal changes in the immunologic system. OCs have been reported as a cause of a rare form of rheumatoid arthritis, but the Royal College reports a decrease in incidence of cell-mediated immunologic disease, specifically rheumatoid arthritis in its more familiar form. There is no evidence that OCs markedly influence thyroid disease, but they do markedly alter thyroid function testing. OCs do not produce a chronic addisonian state nor do they inhibit the ability of the adrenal-pituitary axis to respond to stress. OCs can be used in thyroid disease but with some caution in hypothyroid states. They should not be used in patients with Cushing's syndrome and are not recommended in patients with adenomas. In general, estrogen works as an irritant to the gastric mucosa, but there is no increase in peptic ulcer diseases associated with OC use, and the incidence of duodenal ulcer disease is decreased. The most striking liver disease seen with OCs is cholelithiasis. The incidence is increased 2-fold. OCs should not be prescribed for patients with chronic renal disease because of the vascular effects as well as the reported increased risk of urinary tract infection. The Royal College report has shown a decreased incidence of iron deficiency anemia in patients on OCs. Various skin changes have been reported in women using OCs. The most common of these is chloasma. In all the diseases studied thus far, the use of OCs has not precipitated a catastrophic change.
 ...
PMID:The use of birth control pills in women with medical disorders. 702 14

A 41-year-old woman presented with a 6-month history of gradually progressive postural instability and dysarthria associated with cerebellar and extrapyramidal signs. No Kayser-Fleischer (K-F) rings were observed on biomicroscopic examination of each cornea. The only evidence of hepatic dysfunction was a modest elevation of alanine-aminotransferase. The diagnosis of Wilson disease (WD) was based on low serum ceruloplasmin, abnormal serum copper and urinary copper excretion, and DNA marker segregation analysis. WD should be considered in the presence of characteristic neurologic and laboratory features, regardless of age at onset, evidence of hepatic dysfunction, or absence of K-F rings.
 ...
PMID:Neurologic presentation of Wilson disease without Kayser-Fleischer rings. 878 87


1 2 3 Next >>