Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023890 (
cirrhosis
)
42,195
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Because it has been suggested that an accumulation of false neurochemical transmitters plays a part in the cardiovascular and neurological complications of
cirrhosis
it appeared worthwhile to study the level of monoamine oxidase in the liver and platelets of cirrhotic patients. In fact a decrease of such activities might explain the increase of false neurotransmitters observed in cirrhotic patients. Other enzyme were also tested: the plasma
benzylamine oxidase
activity and the liver mixed function oxidases. 13 cases of severe
cirrhosis
(B, C according to Child classification) and 10 cases of less severe
cirrhosis
(A according to Child classification) were studied in comparison to patients affected by cholelithiasis. A defect in the level of monoamine oxidase activity of platelets and liver was observed in some cirrhotic patients together with a decrease of the level of the liver mixed function oxidases.
...
PMID:Platelet monoamine oxidase, plasma benzylamine oxidase and liver mixed function oxidase in cirrhotic patients. 86 53
Plasma and platelet
benzylamine oxidase
activity was tested before and after portacaval shunt in patients with histologically-confirmed
cirrhosis of the liver
. The level of plasma
benzylamine oxidase
activity was always higher in cirrhotic patients than in control subjects and was unchanged by the surgical operation. Platelet
benzylamine oxidase
activity was lower in cirrhotic than in control patients before the surgical operation, and higher afterwards but it returned to the original value at 80 days after surgery.
...
PMID:Platelet monoamine oxidase and blood plasma benzylamine oxidase activity in cirrhotic patients. 712 73
SSAO
/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure,
liver cirrhosis
, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect,
SSAO
substrates are possibly capable of ameliorating metabolic changes in diabetes, while
SSAO
inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on
SSAO
/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.
...
PMID:Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target. 1869 Oct 41
Nonalcoholic fatty liver disease (NAFLD) encompasses a range of manifestations, including steatosis and
cirrhosis
. Progressive disease is characterized by hepatic leukocyte accumulation in the form of steatohepatitis. The adhesion molecule vascular adhesion protein-1 (VAP-1) is a membrane-bound
amine oxidase
that promotes leukocyte recruitment to the liver, and the soluble form (sVAP-1) accounts for most circulating monoamine oxidase activity, has insulin-like effects, and can initiate oxidative stress. Here, we determined that hepatic VAP-1 expression is increased in patients with chronic liver disease and that serum sVAP-1 levels are elevated in patients with NAFLD compared with those in control individuals. In 4 murine hepatic injury models, an absence or blockade of functional VAP-1 reduced inflammatory cell recruitment to the liver and attenuated fibrosis. Moreover, disease was reduced in animals expressing a catalytically inactive form of VAP-1, implicating enzyme activity in the disease pathogenesis. Within the liver, hepatic stromal cells expressed functional VAP-1, and evaluation of cultured cells revealed that sVAP-1 promotes leukocyte migration through catalytic generation of ROS, which depended on VAP-1 enzyme activity. VAP-1 enhanced stromal cell spreading and wound closure and modulated expression of profibrotic genes. Together, these results link the
amine oxidase
activity of VAP-1 with hepatic inflammation and fibrosis and suggest that targeting VAP-1 has therapeutic potential for NAFLD and other chronic fibrotic liver diseases.
...
PMID:Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis. 2556 18