Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells have been shown to play a role in many chronic inflammatory and fibrotic disorders. However, their possible contribution to the pathological changes that occur in liver cirrhosis is unknown. To explore this, we examined whether changes in hepatic mast cell number and mediator content were associated with fibrotic changes in experimental biliary cirrhosis. Rats were studied 7, 14, or 21 days after bile duct resection (BDR). Hepatic mast cells were identified by histochemical and immunohistochemical stains. Rat mast cell protease II (RMCP-II), a marker of mast cell degranulation, was measured in liver by enzyme-linked immunosorbent assay. Hepatic collagen deposition was assessed by Sirius Red F3BA staining. In day 21 BDR rats, there was a one- to twofold increase (P < .001) in the number of hepatic mast cells, but this was not observed in day 7 or 14 BDR rats. Mild fibrotic changes were noted in BDR rat livers as early as 7 days after induction of cholestasis. Significant expansion and organization of fibrous tissue had occurred in day 14 BDR rats which progressed to bridging fibrosis by day 21. Liver RMCP-II levels were decreased by 50 percent (P < .05) and mast cell degranulation was apparent as shown by histamine immunostaining. These results suggest that hepatic mast cell hyperplasia and degranulation occur during prolonged cholestasis in the rat. Although these changes do not correlate with the onset of hepatic fibrosis, they do occur at a time during which there is significant deposition and organization extracellular matrix elements. Hepatic mast cells, by releasing profibrogenic mediators, may contribute to fibrotic changes in biliary cirrhosis.
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PMID:Hepatic mucosal mast cell hyperplasia in rats with secondary biliary cirrhosis. 866 46

Recent research in neurophysiology of itch has indicated the existence of itch-dedicated nociceptor neurones. The perception of itch is regulated by tonically inhibitory descending neuronal pathways and nociceptor spinal neuronal circuits. There is at present no convincing evidence of an 'itch centre' in the brain. A classification of itch has been proposed, based on neurophysiological considerations, which stresses the importance of neurogenic and neuropathic itch, and assists in differential diagnosis and selection of treatment. However, more than one class of itch can occur concurrently in the same patient. The importance of cross- talk between dermal mast cells and nociceptor nerve terminals, involving cleavage of proteinase-activated receptor 2 by mast cell tryptase, is highlighted. The pruritus of cholestasis is mediated at least in part by opioid peptides synthesized by the liver, and elevated levels of these mediators are found in the plasma and skin of patients with itch due to cholestasis. The combined use of both mu-receptor antagonists and kappa-receptor agonists (anti-pruritic) is worth exploring.
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PMID:Itch: more than skin deep. 1537 26