Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic pedicle clamping (HPC) is widely used to control intraoperative bleeding during hepatectomy; intermittent HPC is better tolerated but is associated with blood loss during each period of reperfusion. Recently, it has been shown that ischemic preconditioning (IP) reduces the ischemia-reperfusion damage for up to 30 minutes of continuous clamping in healthy liver. We evaluated the safety of IP for more prolonged periods of continuous clamping in 42 consecutive patients with healthy liver submitted to hepatectomy. IP was used in 21 patients (group A); mean +/- SD of liver ischemia was 54 +/- 19 minutes (range, 27-110; in 7 cases >60 minutes). In the other 21 patients, continuous clamping alone was used (Group B); liver ischemia lasted 36 +/- 14 minutes (range, 13-70; in 2 cases >60 minutes). Two patients in Group A (9.5%) and 3 in Group B (14.2%) received blood transfusions. In spite of the longer duration of ischemia (P=.001), patients with IP had lower aspartate aminotransferase (AST; P=.03) and alanine aminotransferase (ALT; P=not significant) at postoperative day 1, with a similar trend at postoperative day 3. This was reconfirmed by multiple regression analysis, which showed that although postoperative transaminases increased with increasing duration of ischemia and of the operation in both groups, the increases were significantly smaller (P<.001) with the use of preconditioning. In conclusion, the present study confirms that IP is safe and effective for liver resection in healthy liver and is also better tolerated than continuous clamping alone for prolonged periods of ischemia. This technique should be preferred to continuous clamping alone in healthy liver. Additional studies are needed to assess the role of IP in cirrhotic liver and to compare IP with intermittent clamping.
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PMID:Pedicle clamping with ischemic preconditioning in liver resection. 1476 40

Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10-15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16-49 minutes (mean, 31 +/- 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 +/- 336 U/L) than group 2 (322 +/- 162 U/L; P = 0.03). Mean INR was significantly higher in group 1 (1.8 +/- 0.2) vs. group 2 (1.5 +/- 0.2; P = 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 +/- 2.9 days) than group 2 (6.2 +/- 1.1 days; P = 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy.
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PMID:Intermittent inflow occlusion in living liver donors: impact on safety and remnant function. 1476 62

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.
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PMID:Marginal donors in liver transplantation. 1511 May 80

This article seeks to standardize an experimental model of liver ischemia-reperfusion in rats following hemorrhagic shock modulated by N-acetylcysteine (NAC). Twenty-seven adult Wistar rats were randomized into three groups: the HS-IR-Garm underwent hemorrhagic shock with selective hepatic ischemia followed by reperfusion; the HSIR + NAC-G, the same procedure plus NAC; and the control group, only venous catheterization. Blood was withdrawn for 10 minutes until MABP reached 35 mm Hg, which was maintained for 1 hour. The blood was then reinjected as required to maintain MABP at that level. Ringer's lactate solution was infused in a volume equivalent to three times the shed blood, over a period of 15 minutes. Half of the shed blood was reinfused over 5 minutes. HSIR + NAC-G received 150 mg/kg of NAC, during treatment of the shock, and again 10 minutes before reperfusion and continued for 30 minutes. Finally, both groups were subjected to 40 minutes of warm selective hepatic ischemia and reperfusion for 1 hour. Data were analyzed by nonparametric tests (P < or =.05). Liver enzyme levels were higher in HS-IR-G (DHL = 6094 +/- 1688, AST = 746 +/- 175, and ALT = 457 +/- 90) than in HSIR + NAC-G group (DHL = 2920 +/- 284, AST = 419 +/- 113, and ALT = 253 +/- 26). The values in the control group were lower than both experimental groups (DHL = 965 +/- 173, AST = 163 +/- 42, and ALT = 82 +/- 28). Our data showed that liver ischemia-reperfusion injury following hemorrhagic shock produces important hepatic damage and that NAC reduces injury in this rat model.
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PMID:Effects of N-acetylcysteine in hepatic ischemia-reperfusion injury during hemorrhagic shock. 1519 90

Murine total hepatic ischemia (THI) followed by reperfusion without shunting of the portal vein induces significant lethality in rodents due to intestinal congestion. Two methods have been promulgated to study THI and reperfusion in mice without intestinal congestion: subcutaneous splenic transposition which creates a portosystemic shunt via epigastric vessels, and a caudal shunt with 30% hepatectomy, which creates a portosystemic shunt via the small remnant of remaining caudal lobe. We compared outcome, inflammatory response and hepatic injury due to THI and reperfusion in these two models. Female C57BL/6 mice underwent ST, caudal shunt or no surgery prior to having 30 min of total hepatic ischemia followed by 60 min of reperfusion. Survival, surgical complications, serum AST/ALT and IL-6 were determined. Apoptotic and necrotic hepatocytes were identified by morphological criteria. Complication rates for the ST and caudal shunt procedures were 6.7 and 20%, respectively. Subsequent mortality rates following THI and 60 min reperfusion were 5.9 and 50% in mice with ST and caudal shunt, respectively. Both groups had elevated serum AST/ALT concentrations. However, in mice undergoing caudal shunt, AST/ALT levels were also significantly increased even without THI. The number of apoptotic hepatocytes after THI and reperfusion in mice following caudal shunt was significantly higher compared with those of ST (P<0.001). Both ST and caudal shunt can be used in models of THI and reperfusion to prevent significant lethality due to intestinal congestion. However, ST is a simple, safe and suitable model, whereas caudal shunt requires manipulation of the liver, and is associated with significant hepatic injury and morbidity.
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PMID:Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia. 1555 60

Liver graft function after transplantation is dependent on ischemia-reperfusion injury, toxicity of drugs (immunosuppression, antibiotics and other) and transplant rejection. Although routinely monitored with enzymatic tests (AST, ALT, GGT, ALP), bilirubin and coagulation parameters, differentiation between these pathologies is hardly possible without liver biopsy. Arginase (3.5.3.1) mostly exists in the liver and in trace amounts in extra-hepatic tissue. Thus, we hypothesized that activity of arginase could be a more specific test of liver function. Sera of 32 liver transplant recipients were tested for AST, ALT, ATIII, bilirubin and arginase. Samples were obtained daily in first 2 weeks after LTx and weekly afterwards. Correlation of arginase activity with other liver function markers was calculated. Serum arginase peaked at day 1 post LTx (mean 64,6+/-91 IU/L), and decreased more rapidly than other tests if good liver function was observed. The values showed strong and significant correlation with AST and ALT activities (Pearsons R 0,65 and 0,47 respectively). We conclude that activity of arginase in the serum is an exact test of liver function.
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PMID:Clinical significance of arginase after liver transplantation. 1575 50

Tissue damage after ischemia and reperfusion (I/R) is largely caused by the sequelae of neutrophil infiltration. This inflammatory process can be initiated as the result of stroke, coronary ischemia, trauma, and other related conditions. The infiltration of neutrophils is facilitated by the expression of adhesion molecules on the surface of endothelial cells. Particularly important are the selectin family of adhesion molecules at the onset of neutrophil-mediated injury. The aim of this study was to determine the role of selectin inhibition in the modulation of chemokine expression and Akt/MAPK signaling after liver I/R. In addition, we evaluated the optimal dose and time of administration of a small molecule selectin inhibitor, TBC-1269. Mice subjected to 90 min of partial (70-80%) hepatic ischemia followed by 3 h of reperfusion were divided into 15 groups (n = 4/group); sham, ischemic control, and 10, 20, and 40 mg/kg dose groups for the antiselectin molecule were studied at 3 times of drug administration: 1 h before reperfusion (but after ischemia), at the time of reperfusion, and at 15 min after reperfusion. The parameters measured after 3 h of reperfusion included liver function tests (ALT and AST), histopathology, and tissue myeloperoxidase (MPO). Chemokine expression (MIP-1alpha, MIP-1beta, MIP-2 and KC), Akt, MAPK (p44/p42), and RSK expressions were also measured in liver tissue by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. It was demonstrated that the small molecule multi-selectin inhibitor (TBC-1269) offered the most significant protection for the ischemic liver when given at 40 mg/kg at the time ofreperfusion. AST significantly differed between the control group and the group receiving 40 mg/kg at the time of reperfusion (p = .01). MPO levels in the liver tissue of the ischemic controls were significantly increased when compared to the levels of this enzyme in the TBC-1269 group at 40 mg/kg. Histological examination reflected the same results, with a significant difference (p = .02) between these same two groups. The chemokine profile also showed that the same treatment group had a downregulation of MIP-lalpha, MIP-1beta, MIP-2, and KC, as well as a lower expression of Akt, MAPK(p44/42), and RSK when compared to the control group. Thus, we demonstrated that the small molecule selectin inhibitor, TBC-1269, offered significant functional and structural protection of the ischemic liver when given at 40 mg/kg at the time of reperfusion. Lower doses and different times of administration did not show as prominent a drug effect. This selectin inhibition modulated the expression of Akt, MAPK (p44/42), and RSK, as well as MIP-1alpha, MIP-1beta, MIP-2, and KC chemokines. These alterations in cellular signaling and chemokine expression represent potential mechanisms or pathways of inflammatory response in I/R.
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PMID:Selectin inhibition modulates Akt/MAPK signaling and chemokine expression after liver ischemia-reperfusion. 1576 97

Ischemia-reperfusion injury (I/R-I), which is unavoidable in liver transplantation, impairs liver regeneration and predisposes to liver failure. The three major mitogen-activated protein-kinases (MAPKs): ERK, p38, and JNK, are critical in the transmission of signals triggered by proinflammatory cytokines, by stress, and by growth factors. JNK and p38alpha activation have been associated with apoptosis; p38beta with cell survival; and ERK with proliferation. Previous studies have demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. Female mice are protected to a much greater extent from I/R-I than male mice. We assessed the effects of 17beta-estradiol (17beta-E) on liver function, host survival, and cellular activation of MAPK in a murine model of I/R-I in reduced-size livers. C57BL/6 mice were subjected to 45 minutes of warm ischemia (70% of the liver mass). After reperfusion, the nonischemic lobes were excised. Vehicle, 17beta-E or the estrogen receptor antagonist ICI-182780, was delivered 1 hour before the injury. We evaluated AST and apoptosis as well as activation of JNK, p38, and ERK. Female mice showed a lower level of hepatocellular injury (AST = 445 +/- 82 IU/L) after I/R-I compared with male mice (AST = 1400 +/- 210). 17beta-E decreased the liver injury in male mice (AST = 522 +/- 77), an effect that was partially reversed by ICI-182,780 (910 +/- 92). A higher rate of apoptosis was observed in male animals given saline (enrichment factor = 7.22 +/- 0.8) versus those treated with 17beta-E (5.85 +/- 0.3, P < .05). A significant increase in liver regeneration, as assessed by the percentage of liver weight/body weight was demonstrated in females (184% +/- 24%) and male mice given 17beta-E (168% +/- 22%) compared with male mice given vehicle (9% +/- 4%). 17beta-E significantly down-regulated JNK and p38alpha activities, whereas I/R-I promoted p38beta and ERK activation. These results suggest that the cytoprotective effects of 17beta-E on I/R-I to reduced-size livers are associated with selective modulation of MAPK kinases.
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PMID:17beta-estradiol differentially activates mitogen-activated protein-kinases and improves survival following reperfusion injury of reduced-size liver in mice. 1580 58

Hyperbaric oxygen (HBO) therapy is an effective adjunct in treating ischemia-reperfusion (I/R) injury of brain, small intestine, testis, and crushing extremities. This study was designed to test the hypotheses that preconditioning the rats with HBO could protect the liver against subsequent I/R injury. Daily treatment with one-dose HBO (90 min, 2.5 ATA) was brought about for male Sprague Dawley rats for 1 to 3 days before an I/R injury of liver. Hepatic expression of heat-shock protein 70 (Hsp70), total concentration of glutathione (GSH), activity of catalase, superoxide dismutase (SOD), and serum AST and ALT were estimated before and after HBO, as well as after I/R injury. The results showed that activity of hepatic catalase was decreased by one dose, but not three doses, of HBO as compared with baseline data. However, hepatic Hsp70 expression fluctuated insignificantly. AST and ALT increase less in rats preconditioned with one-dose HBO as compared with those without HBO or with three-dose HBO. Our results showed preconditioning by one-dose HBO protects rat liver against subsequent ischemia-reperfusion injury.
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PMID:Preconditioned hyperbaric oxygenation protects the liver against ischemia-reperfusion injury in rats. 1596 20

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.
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PMID:Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration. 1621 53


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