Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overproduction of tumor necrosis factor (TNF-), interleukin-1beta (IL-1beta), and nitric oxide (NO) is believed to be detrimental during the progression of acute pancreatitis, yet little is known about the hepatic production of these mediators and their role in mediating pancreatitis-induced hepatic dysfunction. Rats were randomized to receive a single intraperitoneal injection of the macrophage-pacifying compound, CNI-1493 (1.0 mg/kg), or vehicle 1 hour before the induction of retrograde bile salt pancreatitis. Sham-operated animals served as controls. Animals were killed 18 hours later, with serum and livers harvested to determine the degree of hepatocellular injury and the induction of TNF-, IL-1beta, and inducible nitric oxide synthase (iNOS). In addition, serum TNF- and nitrites (end-product of NO breakdown) were determined in each group to assess the mechanism of action of CNI-1493. TNF-, IL-1beta, and iNOS gene expression (by reverse-transcription polymerase chain reaction) as well as aspartate transaminase (AST), alanine transaminase (ALT), and lactic dehydrogenase (LDH) (but not alkaline phosphatase [ALP]) increased following the development of pancreatitis (all P < .05). Macrophage pacification significantly prevented the induction of TNF- and IL-1beta mRNA (but not iNOS), resulting in lessened serum AST, ALT, and LDH (all P < .05). Serum TNF- protein and nitrites correlated with gene induction in that both were increased following the onset of pancreatitis, and TNF- protein production was significantly attenuated in animals receiving CNI-1493. Hepatocellular, but not bile duct, injury occurs during experimental pancreatitis that is associated with hepatic TNF-, IL-1beta, and iNOS mRNA gene induction, as well as TNF- protein and nitrite production. Preventing the production of TNF- and IL-1beta by macrophage pacification attenuates the hepatocellular damage, suggesting that these mediators play a role in pancreatitis-induced hepatic injury.
 ...
PMID:Macrophage pacification reduces rodent pancreatitis-induced hepatocellular injury through down-regulation of hepatic tumor necrosis factor alpha and interleukin-1beta. 979 13

The prolonged use of CNI has been associated with nephrotoxicity. MMF is a new immunosuppressive agent. In the present study, the consequences of introducing MMF and reduction of CNI in liver-transplant children were analysed. The present study included eight pediatric liver-transplant patients who had transplantation at least 5 yr previously, had stable graft function and had renal dysfunction as a probable side-effect of CNI therapy. CNI was replaced with MMF in all patients and serum creatinine, uric acid concentration, azotemia and creatinine clearance before and 6 months after study entry were measured. The patients were monitored closely for side-effects of MMF as well as graft function. Six months after study entry serum creatinine, uric acid concentration, azotemia and creatinine clearance improved in all the patients at the last follow-up. The aspartate aminotransferase and alanine aminotransferase concentrations were stable during the study period and did not observe any serum bilirubin increased as well. No side-effects were reported in patients on MMF. Only one patient reported temporary pruritus and nausea. The results indicate that renal dysfunction significantly improved when MMF therapy is started and CNI reduced. Furthermore present data suggest that the risk of acute allograft rejection is very low when the CNI desired reduction is achieved in not too short time and absolutely when the MPA levels are strictly monitored.
 ...
PMID:Mycophenolate mofetil in pediatric liver transplant patients with renal dysfunction: preliminary data. 1487 Aug 93