Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe acute liver failure is associated with high mortality. Improved respiratory and hemodynamic management together with intracranial pressure monitoring and aggressive treatment of cerebral edema have greatly improved patient care. However, many patients die despite optimal medical treatment, because of failure to arrest the progression of cerebral edema. This in turn result in brain stem herniation with rapid neurologic deterioration and death. Liver transplantation has emerged as the definitive treatment for patients with severe acute liver failure. Unfortunately approximately up to one half of the patients with this severe form of liver failure will die while awaiting liver transplantation. There is thus a clear need for a liver support system to provide a "bridge" to transplantation. Over the years, many "bridge" systems were introduced which promised effective support but had no wide clinical success. Because of our incomplete understanding of the pathophysiology of liver failure and development of cerebral edema, it was felt that use of isolated hepatocytes or ex vivo whole liver perfusion would provide both detoxifying and synthetic functions. Whole liver perfusion appears to be effective but cumbersome and costly because it would require each center, where patients are being treated, to maintain animal colonies for patient treatment. Therefore, cryopreserved isolated xenogeneic hepatocytes appear to be the best candidates for building a "bridge" system. In a preliminary clinical study, we have used a porcine hepatocyte-based liver support system (Bioartificial Liver: BAL) to treat patients with acute liver failure as well as patients with acute exacerbation of chronic liver disease. Patients in the first group, who were candidates for transplantation, were successfully bridged to a transplant with excellent survival. No obvious benefit from BAL treatments was seen in the second group. In this group patients where cerebral edema is not a major component of the clinical presentation, it is possible that long-term support will be needed with repeated treatments over several weeks to provide adequate synthetic and detoxifying liver function until the patients' livers recover. For such liver recovery to take place, these chronic patients will need to be treated earlier in the course of their disease when they still have some residual liver mass as well as regenerative capacity. Prospective controlled trials will be initiated as soon as the current phase I study is concluded in order to determine the efficacy of this system in both patient populations.
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PMID:Artificial hepatic support systems. 922 9

Copper is an essential trace element, which is an important catalyst for heme synthesis and iron absorption. Following zinc and iron, copper is the third most abundant trace element in the body. Copper is a noble metal, like silver and gold. Useful industrial properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability. Most of the metallic copper appears in electrical applications. Copper is a constituent of intrauterine contraceptive devices and the release of copper is necessary for their contraceptive effects. The average daily intake of copper in the US is about 1 mg Cu with the primary source being the diet. The bioavailability of copper from the diet is about 65-70% depending on a variety of factors including chemical form, interaction with other metals, and dietary components. The biological half-life of copper from the diet is 13-33 days with bilary excretion being the major route of elimination. Copper sulfate is a gastric irritant that produces erosion of the lining of the gastrointestinal tract. Chronic copper toxicity is rare and primarily affects the liver. Wilson's disease and Indian childhood cirrhosis are examples of severe chronic liver disease that results from the genetic predisposition to the hepatic accumulation of copper. The serum copper concentration ranges up to approximately 1.5 mg/L in healthy persons. Gastrointestinal symptoms occur at whole blood concentrations near 3 mg Cu/L. Chelating agents (CaNa2EDTA, BAL) are recommended in severe poisoning, but there are little pharmacokinetic data to evaluate the effectiveness of these agents.
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PMID:Copper. 1038 57