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

Livers can be preserved only for a short period without jeopardizing the transplantation outcome. Heat shock proteins (HSPs) protect against ischemia and reperfusion injury. We studied whether their induction and, in particular, the induction of heme oxygenase 1 (HO-1), improves transplantation survival after an extended time of cold storage. Rats were subjected to heat preconditioning (42 degrees C for 20 minutes). Livers were harvested 24 hours later, preserved in cold University of Wisconsin solution for 44 hours, and transplanted in isogeneic rats (arterialized transplantation). HO-1 was specifically induced and inhibited by cobalt protoporphyrin and tin protoporphyrin, respectively. All animals receiving a graft without preconditioning and subjected to 44 hours of cold preservation died within 3 days, whereas 89% of rats who received a graft exposed to heat survived for 3 weeks (P =.0004). Preconditioning reduced serum aspartate transaminase (AST) and lactate dehydrogenase activities after reperfusion, improved bile flow, and decreased the histologic lesions of reperfusion injury. These significant effects of heat preconditioning were prevented by administration of tin protoporphyrin and could be reproduced by administration of cobalt protoporphyrin. In grafts without preconditioning, only a small fraction (<5%) of hepatocytes were positive with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay, and even less expressed activated caspase 3. Preconditioning tended to reduce the number of positive cells and to stimulate the expression of antiapoptotic Bcl-X(L). In conclusion, heat preconditioning and, specifically, overexpression of HO-1 improve posttransplantation survival and graft function after prolonged cold ischemia preservation. The mechanism underlying these beneficial effects does not appear to be prevention of apoptosis.
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PMID:Extended preservation of rat liver graft by induction of heme oxygenase-1. 1198 58

The role of NF-kappaB, the rapid-response transcription factor for multiple genes, in cold ischemia-reperfusion (I/R) injury was examined after syngeneic transplantation of liver grafts. Lewis rat recipients were killed 1-48 h after reperfusion of three different liver grafts: 1) uninfected control, 2) infected ex vivo with control adenoviral vector (AdEGFP), and 3) infected ex vivo with AdIkappaB. In uninfected control livers, NF-kappaB was activated biphasically at 1-3 and 12 h after reperfusion with aspartate transaminase (AST) levels of 4,244 +/- 691 IU/l. The first peak of NF-kappaB activation associated with an increase of mRNA for TNF-alpha, IL-1beta, and IL-10. AdEGFP transfection resulted in similar outcomes. Interestingly, AdIkappaB-transfected liver grafts suffered more severe I/R injury (AST >9,000 IU/l). Transfected IkappaB was detected in transplanted livers as early as 6 h, and this correlated with the abrogation of the second, but not the first, peak of NF-kappaB activation at 12-48 h and increased apoptosis. Thus inhibition of the second wave of NF-kappaB activation in IkappaB-transfected livers resulted in an increase of liver injury, suggesting that NF-kappaB may have a dual role during liver I/R injury.
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PMID:Role of NF-kappaB on liver cold ischemia-reperfusion injury. 1238 32

Kupffer cell depletion by gadolinium chloride (GdCl(3)) in rat livers has previously been proven to minimize hepatic ischemia/reperfusion injury after experimental liver transplantation (LTX). In the current study, we evaluated the effects of donor pretreatment with GdCl(3) on hepatic ischemia/reperfusion injury, macro- and microcirculation, and endotoxin clearance of the liver in a porcine model of experimental LTX. Two groups of 12 pigs were treated either with intravenous NaCl (0.9%; control) or GdCl(3) (20 mg/kg). Twenty-four hours after pretreatment, hepatic macrocirculation was quantified by Doppler flowmetry and liver parenchymous microcirculation by implanted thermodiffusion electrodes. The liver grafts were transplanted after 4-6 h of cold ischemia in University of Wisconsin (UW) solution. At 1 and 24 h after LTX, the perfusion values were re-evaluated and histology, biochemical (aspartate aminotransferase, AST) and functional parameters (partial thromboplastin time, prothrombin time, and bilirubin) were analyzed. Furthermore, endotoxin clearance of the liver was evaluated at all time points. In GdCl(3)-treated animals 80% of the Kupffer cells were destroyed, and 24 h after LTX ischemia/reperfusion injury in treated grafts was significantly lower in comparison to controls, as shown by histology, AST levels (741+/-490 U/l in controls vs 379+/-159 U/l in treated grafts, P<0.05), survival (67% vs 92%), and enhanced macro- (total transhepatic blood flow [THBF]=112+/-22 ml/min per 100 g in controls vs 157+/-45 ml/min per 100 g in treated grafts, P<or=0.05) and microcirculation (thermodiffusion [TD]=73+/-9 ml/min per 100 g in controls vs 90+/-16 ml/min per 100 g in treated grafts, P<or=0.05). Despite destruction of the macrophage system in the liver, the transhepatic endotoxin gradient of treated livers was enhanced before and 1 h after transplantation (58% in controls vs 85% in treated grafts, P<0.05). Destruction of Kupffer cells of donors by pretreatment with GdCl(3) in pigs is effective in preventing liver graft dys- and nonfunction after LTX. Pretreatment with GdCl(3) does not diminish but increase hepatic endotoxin clearance.
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PMID:Donor pretreatment with gadolinium chloride improves early graft function and survival after porcine liver transplantation. 1287 29

Utilization of hepatitis C seropositive kidney donors remains controversial. We examined the use of hepatitis C seropositive donors for renal transplantation. Data for creatinine, liver function tests, cold ischemia time, and graft and patient survival were analyzed from 20 hepatitis C seropositive recipients receiving cadaveric renal allografts from seropositive donors and were compared with 20 hepatitis C seropositive recipients receiving allografts from seronegative donors. Recipients receiving a kidney from a hepatitis C seropositive donor were on the waitlist for 9.9 +/- 1.8 months, compared with 17.8 +/- 3.3 months for those receiving a kidney from a seronegative donor (p < 0.05). There were no significant differences in graft or patient survival. Incidences of acute cellular rejection and acute tubular necrosis were similar. There were no significant differences in creatinine, alanine aminotransferase, alkaline phosphatase, or bilirubin values. While there was a significant difference in aspartate aminotransferase at 2 wk and 6 months, these differences were of questionable clinical importance. In conclusion, donor seropositivity for hepatitis C should not preclude renal transplantation into a hepatitis C seropositive recipient and utilization of these organs decreases waitlist time for hepatitis C seropositive recipients.
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PMID:Use of kidneys from hepatitis C seropositive donors shortens waitlist time but does not alter one-yr outcome. 1470 26

The plant Mentha piperita, or peppermint, is commonly used in the treatment of loss of appetite, common cold, bronchitis, sinusitis, fever, nausea and vomiting, and indigestion as a herbal agent. In this study, we aimed to investigate biochemical and histological effects of M. piperita Labiatae, growing in the Yenisar Bademli town of Isparta city, and Mentha spicata Labiatae, growing in the Anamas high plateau of the Yenisar Bademli town, on the rat liver tissue. Forty-eight male Wistar albino rats weighing 200-250 g were used for this study. Rats were divided into four groups of 12 animals: Group I received no herbal tea (control group); Group II received 20 g/L M. piperita tea; Group III received 20 g/L M. spicata tea; and Group IV received 40 g/L M. spicata tea. Herbal teas were prepared daily and provided at all times to the rats during 30 days as drinking water. Liver function tests, including aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) activities were measured. To evaluate liver antioxidant defences, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid reactive substance (TBARS) activities were determined in the homogenates of liver tissue. In addition, liver tissues were submitted for histopathologic examination. AST and ALT activities were increased in Group II, Group III and Group IV gradually when compared with the control group. The difference between Group II and the control group was not statistically significant (P > 0.016). Increases in AST and ALT activities of Group III and Group IV were statistically significant when compared with the control group. SOD, GSH-Px and CAT activities were increased in Group II when compared with the control group but the difference was not statistically significant (P > 0.016). However, SOD, GSH-Px activities and the TBARS level were significantly increased, and CAT activity was significantly decreased in Group III when compared with the control group. In Group IV, while SOD, GSH-Px and CAT activities were decreased, the TBARS level was increased as compared with the control group (P < 0.0016). Histopathological evaluation of experimental groups revealed a mild to severe degree of hepatic damage when compared to the control group. In Group II, there was only minimal hepatocytes degeneration. In Groups III and IV, there were granular or ballooning hepatocyte degeneration and necrosis, sinusoidal and central vein dilatation. It was concluded that lipid peroxidation and hepatic damage occurs after M. piperita and M. spicata administration in rat liver and the damage seems to be dose dependent.
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PMID:Investigation of biochemical and histopathological effects of Mentha piperita Labiatae and Mentha spicata Labiatae on liver tissue in rats. 1502 12

This review reports some results from our laboratory on the setting up of a psychrophilic expression system for the homologous/heterologous protein production in cold-adapted bacteria by using natural plasmids as cloning vectors. By screening some Antarctic bacteria for the presence of extrachromosomal elements, we identified three new plasmids, pMtBL from Pseudoalteromonas haloplanktis TAC125, and pTAUp and pTADw, from Psychrobacter sp. TA144. The latter autoreplicating elements were isolated, cloned, and fully sequenced and their molecular characterisation was carried out; however, we focused our attention on the small multicopy plasmid, pMtBL, from the Gram-negative P. haloplanktis TAC125 strain. This episome turned out to be an interesting extrachromosomal element, since it displays unique molecular features as its transcriptional inactivity. Being cryptic, the inheritance of pMtBL totally relied on the efficiency of its replication function. This function was bound to a region of about 850 bp, identified by an in vivo assay based on the possibility to efficiently mobilize plasmidic DNA from a mesophilic donor (Escherichia coli) to psychrophilic recipient by intergeneric conjugation. This information was instrumental in the construction of a shuttle vector, able to replicate either in E. coli or in several cold-adapted hosts (clone Q). Since the conversion of a cloning system into an expression vector requires the insertion of transcription and translation regulative sequences, the corresponding signals from the aspartate aminotransferase gene isolated from P. haloplanktis TAC125 were inserted, generating the pFF vector. To investigate the possibility of obtaining recombinant proteins in this cold-adapted host, we used the psychrophilic alpha-amylase from the Antarctic bacterium P. haloplanktis TAB23 (previously known as Alteromonas haloplanktis A23) as a model enzyme to be produced. Our results demonstrate that the cold-adapted enzyme was not only produced but also efficiently secreted by the recombinant PhTAC125 cells. The described expression system represents the first example of heterologous protein production based on a true cold-adapted replicon.
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PMID:Recombinant protein production in Antarctic Gram-negative bacteria. 1526 27

Prolonged cold ischemia time (CIT) during graft preservation and warm ischemia time (WIT) during rewarming time have been reported to cause postoperative graft dysfunction after orthotopic liver transplantation (OLT). However, the effects of both CIT and WIT in combination on patient and graft survivals are not yet defined. The aim of this study was to determine whether simultaneously prolonged CIT and WIT were associated with early graft outcomes after clinical OLT. For analysis of liver graft survival within 90 days of OLT and postoperative graft function, 186 consecutive OLT cases were divided into four groups as follows: group A, CIT < 12 hours and WIT < 45 minutes; group B, CIT > 12 hours and WIT < 45 minutes; group C, CIT < 12 hours and WIT > 45 minutes; and group D, CIT > 12 hours and WIT > 45 minutes. The graft loss rates were 5.4% in group A, 9.8% in group B, 11.1% in group C, and 42.9% in group D. The mean highest aspartate aminotransferase (AST) value after OLT in group D (3352.3 +/- 569.4 U/L) was significantly greater than those in groups A (1411.7 +/- 169.2 U/L) and B (1931.3 +/- 362.6 U/L). The simultaneously prolonged cold and warm ischemia times significantly caused hepatic allograft injury and failure, suggesting some cumulative effects of CIT and WIT on postoperative graft function.
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PMID:Synergistic effect of cold and warm ischemia time on postoperative graft function and outcome in human liver transplantation. 1551 10

Normothermic preservation has been shown to be advantageous in an experimental model of preservation of non-heart-beating donor (NHBD) livers, which have undergone significant warm ischemic injury. The logistics of clinical organ retrieval might dictate a period of cold preservation prior to warm perfusion. We have investigated the effects of a brief period of cold preservation on NHBD livers prior to normothermic preservation. Porcine livers were subjected to 60 minutes of warm ischaemia and then assigned to following groups: Group W (n = 5), normothermic preservation for 24 hours; and Group C (n = 6), cold preservation in University of Wisconsin solution for 1 hour followed by normothermic preservation for 23 hours (total preservation time, 24 hours). Synthetic function (bile production and factor V production) and cellular damage were compared on the ex vivo circuit during preservation. There was no significant difference in the synthetic function of the livers (bile production and factor V production). Markers of hepatocellular damage (alanine aminotransferase and aspartate aminotransferase release), sinusoidal endothelial cell dysfunction (hyaluronic acid), and Kupffer cell injury (beta-galactosidase) were significantly higher in Group C. The histology of the livers at the end of perfusion was similar. In conclusion, a brief-period cold preservation prior to normothermic perfusion maintains the synthetic function and metabolic activity but results in significant hepatocellular damage, sinusoidal endothelial cell dysfunction, and Kupffer cell injury. Transplant studies are required to establish whether livers treated in this way are viable for transplantation.
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PMID:Non-heart-beating donor porcine livers: the adverse effect of cooling. 1569 May 34

For experimental machine perfusion (MP) of the liver, the modified University of Wisconsin solution (UW-G) is most often used. In our search for an enriched MP preservation solution, Polysol was developed. Polysol is enriched with various amino acids, vitamins, and other nutrients for the liver metabolism. The aim of this study was to compare Polysol with UW-G for MP preservation of the liver. Rat livers were preserved during 24 hours with hypothermic MP using UW-G (n = 5) or Polysol (n = 5). Hepatocellular damage (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], alpha-glutathione-S-transferase [alpha-GST]) and bile production were measured during 60 minutes of reperfusion (37 degrees C) with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours of cold storage in UW (n = 5). MP using UW-G or Polysol showed less liver damage when compared with controls. Livers machine perfused with Polysol showed less enzyme release when compared to UW-G. Bile production was higher after MP using either UW-G or Polysol compared with controls. In conclusion, machine perfusion using Polysol results in better quality liver preservation than cold storage with UW and machine perfusion using UW-G.
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PMID:Improved rat liver preservation by hypothermic continuous machine perfusion using polysol, a new, enriched preservation solution. 1583 88

Relevant mechanisms of reperfusion injury after liver transplantation are most likely mediated by activated Kupffer cells. Recently, it has been demonstrated that taurine prevents Kupffer cell-activation in vitro. Thus, this study was designed to assess the effects of taurine after liver transplantation. Female Sprague-Dawley rats (210-240 g) were infused with taurine dissolved in normal saline, before organ harvest. Controls were infused with the same volume of normal saline without taurine. Following 4 hours of cold ischemia, liver transplantation was performed. Graft and animal survival, serum transaminases, liver histology, perfusion data of intravital microscopy, blood distribution at reperfusion, and both phagocytosis of Kupffer cells and expression of tumor necrosis factor alpha (TNF-alpha) to index cellular activation were investigated. For comparison, both, analysis of variance (ANOVA) and Fisher's exact test were used as appropriate. Results are presented as mean +/- SEM. Controls survived in 60% of cases. Taurine improved survival in a dose-dependent manner to 100% (P < 0.05). In controls, mean aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) serum levels increased to 3,260 +/- 814; 1,703 +/- 432; and 14,071 +/- 3,177 U/L, respectively, after transplantation. In contrast, these values were between 20 and 45% of control values after taurine (P < 0.05). Histology taken after transplantation confirmed the significant protective effects of taurine, including the reduction of TNF-alpha expression. Time until homogeneous reperfusion of the graft improved to 50% of control values (P < 0.05). Further, taurine significantly decreased both phagocytosis of latex beads by Kupffer cells and leukocyte-endothelial cell interaction. In parallel, flow velocity of red blood cells as well as acinar and sinusoidal perfusion improved (P < 0.05). In conclusion, these data show for the first time in vivo that taurine minimizes reperfusion injury after liver transplantation. Decreased leukocyte-endothelial cell interaction and improved microcirculation are the proposed mechanisms, which are most likely Kupffer cell-dependent.
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PMID:Taurine improves graft survival after experimental liver transplantation. 1603 74


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