Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma metallothionein concentration was evaluated in healthy subjects and in patients with several types of liver disorders. Plasma metallothionein concentrations in controls varied between 2.4 and 4.8 ng/ml. Patients with disorders associated with increased liver copper concentrations (i.e., primary biliary cirrhosis and primary sclerosing cholangitis) had significantly (both p less than 0.002) elevated plasma metallothionein concentrations (range = 1.8 to 52.2 ng/ml), and a considerable number of these were above the maximum control level (21 of 41 patients). In contrast, patients with liver disorders not associated with increased liver copper concentrations (alcoholic and cryptogenic cirrhosis, and acute viral and chronic active hepatitis) generally had normal plasma metallothionein concentrations and only a few were above the maximum control level (11 of 64 patients, maximum = 8.8 ng/ml). The metallothionein concentrations in plasma samples from patients in stage I or II primary biliary cirrhosis were within or slightly above the control range, whereas most patients in stage III had elevated levels (p less than 0.002), and almost all patients in stage IV had clearly elevated (p less than 0.0001) concentrations. In primary biliary cirrhosis the plasma metallothionein concentration tended to increase during the evolution of the disorder, and the concentration correlated significantly with the serum total bilirubin concentration. In conclusion, the plasma metallothionein concentration is significantly elevated in patients with primary biliary cirrhosis and in patients with primary sclerosing cholangitis. Although related to the histological stage of primary biliary cirrhosis, the measurement of plasma metallothionein concentrations contributes little to the diagnosis or the evaluation of the severity of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma metallothionein concentration in patients with liver disorders: special emphasis on the relation with primary biliary cirrhosis. 195 46

Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.
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PMID:Treatment of Wilson's disease with zinc. VI. Initial treatment studies. 259 53

The content of metallothionein (MT) was determined in the livers (MT-L) and the kidneys (MT-K) of 145 deceased persons. The individual values showed marked variations; average levels (arithmetic means +/- S.D.) were 154.9 +/- 151.4 mg/kg liver wet wt. and 160.5 +/- 150.4 mg/kg total kidney wet wt. In contrast to MT-L, MT-K increased with age up to a maximum around mid-life and decreased at higher ages. Neither the MT-L nor the MT-K depend on sex. The MT content significantly correlates with the macroscopic and histopathologic status of the liver. As compared to normal tissue, livers with fatty degeneration, cirrhosis and brown atrophy show MT-L values of 40%, 25% and 233% respectively. Low MT-L of 40% of the control values are also observed in individuals with a history of alcohol abuse. This decline preceded visible macroscopic pathological findings. MT-L also responds to the cause of death. At suicidal overdose of drugs the MT-L is lowered to 62% and at "mechanical" suicides it is increased to 137%. Whereas MT-K is essentially independent of the kidney status, it is significantly increased to approximately 190% in male smokers.
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PMID:Metallothionein in human liver and kidney: relationship to age, sex, diseases and tobacco and alcohol use. 298 Aug 22

Zinc is essential for many metabolic and enzymatic functions in man. Deficiency of zinc in man has now been recognized to occur not only as a result of nutritional factors, but also in various disease states, including malabsorption syndromes, acrodermatitis enteropathica, Crohn's disease, alcoholism and cirrhosis of the liver. The deficiency state in human subjects exists as a spectrum extending from mild to severe degree. The clinical manifestations of mild zinc deficiency include oligospermia, weight loss and hyperammonaemia. Moderate zinc deficiency is characterized clinically by growth retardation, hypogonadism in males, skin changes, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In severe zinc deficiency states, bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorders, weight loss, intercurrent infections, hypogonadism in males and, if unrecognized, death have been observed. Zinc is needed for the functions of over 100 enzymes. It is essential for DNA, RNA and protein synthesis and, as such, is important for cell division. Zinc is an inducer of mRNA of metallothionein, a protein which may have an important role in the regulation of intestinal zinc absorption. Zinc has a specific effect on testes in animals and man. Recent reports indicate that in human subjects thymopoietin may be zinc dependent and in animal studies somatomedin may be affected adversely due to dietary zinc restriction. Zinc plays an important role in the protection of cell membrane integrity and may be protective against free radical injury. Zinc is known to compete with cadmium, lead, copper, iron and calcium for similar binding sites. In the future, a potential use of zinc may be to alleviate toxic effects of cadmium and lead in human subjects. Recent evidence suggests that thymic-dependent lymphocytes (T cells are zinc dependent. T-helper and suppressor cells, T-effector cells and T-natural killer cells appear to be zinc dependent. Zinc is also essential for some of the neutrophil functions. Thus, it appears that zinc may play an important role in immunity. One may suggest that some of the clinical features of cirrhosis of the liver, such as testicular atrophy, loss of body hair, night blindness, poor wound healing, poor appetite, susceptibility to infections and enhanced sensitivity to drugs, may be related to conditioned deficiency of zinc, future studies are required to determine whether or not zinc supplementation is beneficial to these patients.
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PMID:The role of zinc in gastrointestinal and liver disease. 661 39

Iron is an essential element in all living cells because it serves machineries for biological oxidation including hemoglobin, cytochrome c oxidase, etc. Copper is also essential for mammalian life since copper is the prosthetic element of several life-essential enzymes. Although intracellular excessive iron and copper were usually sequestrated in ferritin and metallothionein molecules, accumulation of excess iron and copper may also cause severe tissue injury by including oxyradicals and lipid peroxidation and eventually bring about tissue fibrosis such as liver cirrhosis. Hemochromatosis and Wilson's disease are known as iron and copper accumulation disorders, respectively. In this chapter, we review the cirrhosis in hemochromatosis and Wilson's disease.
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PMID:[Liver cirrhosis in primary hemochromatosis and Wilson's disease]. 811 95

We previously demonstrated decreased metallothionein (MT) synthesis in cultured fibroblasts obtained from an American boy with findings typical of Indian Childhood Cirrhosis (ICC). We now report normal basal, copper-induced, and zinc-induced MT synthesis in the fibroblasts of two Indian boys and one Irish boy with typical ICC and one Indian boy with copper-associated childhood cirrhosis. This suggests that etiologies other than impaired MT production should be sought as the primary defect in these disorders.
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PMID:Normal metallothionein synthesis in fibroblasts obtained from children with Indian childhood cirrhosis or copper-associated childhood cirrhosis. 858 60

Iron and copper deposition were examined in patients with chronic active viral hepatitis (CAH) and posthepatitic liver cirrhosis (LC) by Berlin blue, rhodanine, or Victoria blue staining and X-ray microanalysis. Considerable iron or copper deposition was demonstrated in the peripheral zones of hepatic lobules in both CAH (53% of specimens) and LC (63% of specimens). Frozen sections taken from the 2 CAH surgical sections with iron depositions were examined by photoncounting image analysis, and superoxide liberation from the metal granules were demonstrated. In areas of metal deposition, vacuolation of liver cell nuclei, accumulation of lipofuscin, and induction of metallothionein (69% of rhodanine- or Victoria blue-positive specimens) were often demonstrated, whereas induction of ferritin was found only in 14% of Berlin blue-positive specimens. The PCNA index was significantly lower in areas of metal deposition than in the adjacent areas without metal deposition, indicating lowered proliferative capability in the former. These results indicate that cell-mediated immune mechanisms causing the disturbance of bile secretion and heavy metal deposition in the peripheral zones of hepatic lobules may be involved in the progression of viral hepatitis from its acute phase to CAH and finally to LC phase, resulting in piecemeal necrosis. However, cholangitis could not be demonstrated in the present study.
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PMID:Iron and copper deposition in chronic active hepatitis and liver cirrhosis; pathogenetic role in progressive liver cell damage. 863 Apr 40

A novel copper-binding protein was identified in the liver supernatant (100,000 x g) of Indian childhood cirrhosis (ICC), purified to apparent homogeneity and characterized [corrected]. Purified major copper-binding protein (MCuBP) is solely responsible for binding about 35% of the total supernatant copper. Elution profile of ICC liver supernatant on Sephadex G-75 column chromatography showed three peaks. About 60% of the total supernatant copper was resolved in peak II, whereas zinc content was insignificant in this peak. But peak II was almost missing in a gel elution profile of control liver supernatant. The control group included cases of various liver diseases viz. neonatal hepatitis, septicemia, and mixed nodular cirrhosis. Copper-binding proteins of peak II further purified on ion-exchange chromatography and elution profile showed that peak II was a MCuBP with high copper-binding capacity (10 g atoms/mol of native protein). SDS-PAGE of this protein also revealed the existence of a single band with molecular mass of about 50 kD. UV spectra of MCuBP showed the maximal absorbance at 254 nm. Unlike the classical metallothionein, the amino acid composition of MCuBP revealed the presence of aromatic amino acids and higher content of glutamic acid and aspartic acid followed by glycine and serine. The ratio (0.3) of basic amino acids to acidic amino acids strongly indicates that it is an acidic protein. The cysteine content in this protein was insignificant, which further corroborates the possibility that the acidic amino acids might be prominent candidates for binding copper. Thus, the 50-kD MCuBP apparently makes a major contribution to the total copper-binding activity in ICC liver cytosol and may play a significant role in hepatic intracellular copper accumulation.
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PMID:Identification of a novel copper-binding protein from the liver of Indian childhood cirrhosis: purification and physicochemical characterization [corrected]. 980 48

This study was undertaken in order to investigate the effect of zinc (Zn) administration on induction of Zn-binding metallothionein in rat liver with thioacetamide-induced cirrhosis, and the localization of metallothionein in the liver. Normal and cirrhotic rats received intraperitoneal injections with or without Zn. Subsequently, metal analyses, purification of metallothionein by gel filtration and immunohistochemical assessments of metallothionein were carried out. Although in Zn-injected cirrhotic rats, the Zn contents in the liver and plasma increased significantly depending upon the dose of Zn, the Zn contents in the liver and plasma of the cirrhotic rats were lower than those of normal rats after the same dose of Zn. The results of gel filtration also showed that the levels of Zn-metallothionein in the cirrhotic liver were reduced in comparison with those of the normal liver. By the immunohistochemical method, the presence of metallothionein in the parenchymal areas but not in the fibrotic areas of the cirrhotic liver was confirmed. These results suggested that the induced metallothionein was only located in the parenchymal areas. The metallothionein induced in the parenchymal areas was considered to play a role in protecting the parenchymal cells against the progression of fibrosis, because metallothionein has been thought to be involved in the cellular defense against oxidative stress.
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PMID:Distribution of zinc-binding metallothionein in cirrhotic liver of rats administered zinc. 1114 Aug 29

The aim of the present study was to investigate the time-course of changes in hepatic lipid peroxidation, cytochrome P450 and metallothionein concentrations, and superoxide dismutase and catalase activities in relation to the onset and development of cirrhosis in CCl4-treated rats. Further, the effects of oral zinc administration on these parameters were assessed. Cirrhosis was induced in 120 rats by intraperitoneal injections of CCl4 twice weekly over 9 weeks. Controls were 120 additional animals. Both groups were further subdivided to receive either a standard diet or one supplemented with zinc. Subsets of 10 animals each were euthanized at weeks 1, 2, 3, 5, 7 and 9 from the start of the study. Results indicated that zinc administration delayed the cirrhotic process and the increase in lipid peroxidation. These changes, consistently maintained during the first 5 weeks of the study, were associated with a significant decrease in the hepatic concentration of cytochrome P450 and an increase in the hepatic concentration of metallothioneins. Zinc supplementation did not produce any significant change in superoxide dismutase and catalase activities. These results suggest that cytochrome P450 and metallothioneins may play an important role in the hepato-protective effects of zinc against lipid peroxidation in experimental cirrhosis.
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PMID:The antioxidant and hepatoprotective effects of zinc are related to hepatic cytochrome P450 depression and metallothionein induction in rats with experimental cirrhosis. 1158 58


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