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

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The quality of cold-stored donor livers slowly declines beyond approximately 12 h, although these organs may still be used for clinical transplantation. The aim of the present study was to improve the energetic status and viability of long-term-preserved livers by short-term gaseous oxygen insufflation prior to implantation of the organ using a technique that has already been shown to promote aerobic energy metabolism during hypothermia. Livers from ten male Wistar rats were isolated, rinsed blood-free. Five livers (group 1) were stored for 48 h at 4 degrees C in UW preservation solution, and five livers (group 2) were isolated and stored in the same manner for 47 h, and were then, during the last 60 min of the preservation period, connected to a persufflation device and gaseous oxygen was introduced into the organ via the inferior caval vein, with the liver still immersed in cold UW solution. This technique of endischemic gaseous oxygenation resulted in a significant normalization of vascular resistance upon isolated reperfusion in vitro and a reduction in hepatic efflux of alanine aminotransferase as well as glutamate dehydrogenase, which led to improved recovery of the reperfused grafts of group 2 as evidenced by an elevated energy charge potential at the end of the reperfusion period. In conclusion, the technique described seemed effective in enhancing the preoperative viability of marginal donor grafts.
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PMID:Endischemic oxygen persufflation to improve viability of marginally preserved donor livers. 966 26

Intracellular-type electrolyte solutions were introduced into organ preservation to prevent K+ efflux and Na+ and Cl- influx into cells and cell swelling during cold ischemia. We studied cation accumulation in the interstitial space by microdialysis, during rat liver cold storage and after flush-out with high-K+ and low-K+ solutions. The effect of Na+ and K+ on graft function and survival was studied in an isolated perfused liver model and an orthotopic transplantation model after rat liver storage in iso-osmolar high-K+ and low-K+ solutions. After 24 hours of cold ischemia [Na+]o dropped from 136 +/- 2 mmol/L to 91.8 +/- 1.1 mmol/L, and [K+]o increased from 5.9 +/- 0.1 mmol/L to 12.2 +/- 1.6 mmol/L (P < .001 vs. control). [Na+]o and [K+]o after flush-out did not equilibrate with [Na+]sol and [K+]sol after 24 hours of cold storage. Rat livers preserved in low-K+ solutions produced significantly more bile during isolated reperfusion and released less alanine transaminase, aspartate transaminase, and lactate dehydrogenase into the reperfusion medium than high-K+ solutions. Rat liver survival after 14 hours of preservation was higher in low-K+ solutions (13 of 13) than in high-K+ solutions (7 of 13). Those studies indicate that during cold storage of rat livers, transmembraneous Na+-K+ sodium-potassium exchange might not follow the 3:2 stochiometry of a sole sodium-potassium exchange via Na+-K+ sodium-potassium adenosine triphosphatase (ATPase), and that low-K+ solutions might improve graft function and survival after rat liver preservation.
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PMID:Interstitial accumulation of Na+ and K+ during flush-out and cold storage of rat livers: implications for graft survival. 979 18

The purpose of this paper was to assess the role of continuous warm blood cardioplegia in heart valve replacement in comparison with standard intermittent cold crystalloid cardioplegia. Twenty patients undergoing open heart valve replacement were divided arbitrarily into two groups in this study; Group I was given intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (10 patients) and Group II was given continuous administration of warm blood cardioplegia with normothermic CPB (10 patients). The groups were similar with respect to sex, age, body surface area and preoperative ventricular function. Bypass conditions as well as perioperative complications were evaluated in the respective groups. Peak values of the serum enzyme levels within 120 hours of postoperation including alanine transaminase, aspartate aminotransferase, lactate dehydrogenase (LDH) and its isoenzymes LDH1 + LDH2, phosphokinase (CK) and its isoenzyme CK-MB, superoxide dismutase, and malondialdehyde in the two groups were also assessed. Biopsies from the right atrium were obtained immediately before aortic cross clamp removal (ischemic period), and 30 minutes after cross clamp removal (reperfusion period). Myocardial structures were observed and scored. No significant intergroup differences were found in the bypass conditions except for the perfusion flow, systemic temperature and central venous pressure. There were no significant differences in the intergroup perioperative complications, either. Serum enzymes except CK which reached peak values in Group I appeared prior to or consistent with Group II. There were no significant intergroup differences in peak levels of the serum enzymes except CK (307.44 +/- 38.56 U/L vs. 466.29 +/- 52.03 U/L, p = 0.039 for CK). From the pathological assessment, the structural alterations were the most severe during the reperfusion period in group I. Myocardial damage showed more severely in reperfusion than in ischemia in both. Warm blood cardioplegic technique, raising potential hazards, is still a practical method for myocardial protection in open heart surgery, but might be less effective in protecting the tissues beyond myocardium.
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PMID:Benefits and pitfalls of warm blood cardioplegia in heart valve replacement: systemic protective effects. 981 3

We investigated the protective effect of urinary trypsin inhibitor (ulinastatin: UTI) in vitro, in relation to the neutrophil activity in hepatic ischemia/reperfusion (I/R) injury. The rat liver was removed and preserved in cold Ringer's lactate solution for 60 min, followed by 120 min of reperfusion with oxygenated perfusate. The rats were divided into four groups (n = 8 in each group). The livers were perfused with Krebs-Henseleit (K-H) solution containing no additives in group 1, 50,000 U/kg of UTI in group 2, 3.5 x 10(6) of neutrophils in group 3, and both neutrophils and UTI in group 4. In group 3, the AST and ALT levels were always higher than those in other three groups at any point evaluated (P < 0.01) and the LDH levels were observed to be significantly higher than those in other three groups at 0, 5, 10, 60, and 90 min after reperfusion (P < 0. 01). These increase were suppressed by additional pretreatment with UTI in group 4. The bile flow during reperfusion was significantly suppressed in group 3 compared to that of group 4, at both 30 (P < 0. 01) and 60 (P < 0.05) min after reperfusion. The MPO activity after reperfusion in group 3 also significantly increased compared to other three groups (P < 0.01). These data thus suggest that UTI ameliorated the ischemia/reperfusion injury in vitro by inhibiting of neutrophil accumulation in the postischemic liver.
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PMID:Protective effects of ulinastatin against ischemia-reperfusion injury. 1006 23

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level > 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL-6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.
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PMID:Correlation between von Willebrand factor levels and early graft function in clinical liver transplantation. 1008 31

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and alpha2-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and plasmin/alpha2-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
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PMID:Plasma proteolytic activity in liver transplant rejection. 1036 91

Initial poor graft function is associated with increased morbidity and graft loss after liver transplantation. Donor age is a risk factor for the development of initial poor function. The severity of ischemic damage on intraoperative postreperfusion (0Post) allograft biopsy specimens is predictive of subsequent initial poor function. This study was performed to assess whether donor age is a risk factor for the development of ischemic damage on 0Post biopsy specimens. The records of 94 liver transplantations were reviewed. 0Post biopsy specimens were obtained after complete allograft revascularization. The severity of ischemic damage was graded as follows: 0, none; 1, minimal; 2, mild; 3, moderate; and 4, severe. Grafts were defined as older when donor age was 50 years or older. Other independent variables examined included donor cause of death, length of hospital stay, acidosis, serum alanine aminotransferase level, graft cold ischemia time, and degree of steatosis. Older grafts were associated with higher grades of ischemic damage than younger grafts (2.3 +/- 1.0 v 1.3 +/- 1.1; P =.003). Univariate and multivariate analysis identified donor age of 50 years or older as the only significant predictive variable of the severity of ischemic damage. In 16 transplantations involving older grafts, there was no statistically significant association between the severity of ischemic damage and incidence of initial poor function and graft loss. The use of older liver grafts is associated with more extensive ischemic damage immediately after graft reperfusion. Whether this early lesion identifies among older graft recipients those at risk for a worst outcome remains to be determined.
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PMID:Use of older donor livers is associated with more extensive ischemic damage on intraoperative biopsies during liver transplantation. 1047 50

It is well known that endothelin-1(ET-1) is a factor involved in the pathogenesis of ischemia-reperfusion injury. This study was undertaken to investigate the optimal route (intravenous vs intraportal) for administering mixed endothelin receptor antagonist (TAK-044) in a liver transplantation. First, in a rat isolated liver cold-perfusion model, the pharmacodynamics of TAK-044 and endothelin-1 (ET) in the liver tissue and the systemic circulation after cold perfusion were compared in the different administration routes. Next, in a rat orthotopic transplantation model, we compared the hepatoprotective effect of TAK-044 among different administration routes. In each model, there were three groups: IV group, intravenous injection of TAK-044 (10mg/kg) immediately before cold perfusion or anhepatic phase; IP group, intraportal administration with cold perfusion solution or with reflush solution for the graft; control group, no treatment. In the cold perfusion model, liver tissue ET level increased to a similar extent after reperfusion in the three groups, and the plasma and liver tissue TAK-044 concentrations after reperfusion were highest in the IV group. However, the increase in plasma ET was also greatest, and therefore, the ratio of liver tissue to plasma TAK-044 was lower in the IV group compared with the IP group. In the transplantation model, elevation of plasma ET was significantly higher in the IV group. Leakage of serum alanine aminotransferase (ALT), sinusoidal narrowing, and cell swelling after grafting were significantly suppressed in the IP group. We conclude that intraportal administration before reperfusion offers more efficient accumulation of TAK-044 in the liver tissue, without harmful systemic elevation of ET, and achieves a hepatoprotective effect on the graft compared with intravenous administration.
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PMID:Optimal route of administration of mixed endothelin receptor antagonist (TAK-044) in liver transplantation. 1068 Jun 67

The shortage of organ donors has led to reconsideration for the use of non-heart-beating donors (NHBDs). However, graft injury caused by warm ischemia in livers from NHBDs strongly affects posttransplantation outcome. The aim of the present study is to investigate the role of adenosine A2 receptor with regard to hepatic viability after cold preservation of NHBD livers. Cardiac arrest was induced in Wistar rats by phrenotomy of the anesthetized nonheparinized animal. After 60 minutes, the livers were excised and flushed with 60 mL of histidine-tryptophan-ketoglutarate (HTK) and stored submerged in HTK at 4 degrees C for 24 hours. Reperfusion was performed in vitro after all livers were incubated at 22 degrees C in saline solution to account for the period of slow rewarming during surgical implantation in vivo. Addition of the selective A2-receptor agonist (CGS 21680; 30microg/100 mL) to the preservation solution resulted in a significant reduction to one quarter of the parenchymal enzyme release of alanine aminotransferase or lactate dehydrogenase on reperfusion and promoted a 2-fold increase in hepatic bile production. This salutory effect was accompanied by a significant increase (40%) in the activity ratio of protein kinase A (PKA) in the liver tissue and could be abrogated in large part by the PKA inhibitor, Rp-cAMPs. Stimulation of the adenosine A2 receptor during harvest and storage of the graft improves maintenance of tissue integrity in liver grafts. A major part of this effect, which may represent a promising approach for the use of NHBD grafts, seems to be mediated through activation of PKA.
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PMID:Adenosine A2 receptor stimulation protects the predamaged liver from cold preservation through activation of cyclic adenosine monophosphate-protein kinase A pathway. 1071 20

Celsior, a low viscosity and low potassium preservation solution, has recently been tested successfully in the cold preservation of heart, lung, kidney and small intestine. The purpose of the present study was to evaluate the potential of Celsior in the cold preservation of the liver. Livers were harvested from male Wistar rats and then flushed with either Celsior (CE), University of Wisconsin solution (UW) or histidine-tryptophan-alpha-ketoglutarate solution (HTK) and stored for 24 h at 4 degrees C in the respective solution. The reperfusion was performed in vitro using a recirculating model with oxygenated (95% O(2), 5% CO(2)) Krebs-Henseleit buffer at 37 degrees C. To simulate the slow rewarming during the surgical implantation in vivo, all livers were stored for 30 min at room temperature prior to reperfusion. After ischemic storage and also after reperfusion some samples were freeze-clamped for analysis of tissue metabolites while others were tested for structural and functional integrity by the isolated perfusion. CE vs. UW vs. HTK: Metabolic preservation of tissue ATP (micromol/g dry weight) during cold storage was best with Celsior (0. 46 +/- 0.17 vs. 0.26 +/- 0.03 vs. 0.35 +/- 0.07; p < 0.05 CE vs. UW), but upon reperfusion energetic recovery was comparable in the three groups (3.45 +/- 0.66 vs. 4.27 +/- 0.41 vs. 3.63 +/- 0.64 micromol/g/dry weight). There appeared to be structural integrity during reoxygenation irrespective of the used preservation solution with comparable values of parenchymal enzyme release (ALT: 575 +/- 82 vs. 547 +/- 106 vs. 593 +/- 38 mU/g/l), bile production (18.0 +/- 1.0 vs. 18.5 +/- 2.5 vs. 18.7 +/- 1.4 microl/g/ min), and the release of acid phosphatase, an indicator for activated Kupffer cells (89 +/- 13 vs. 90 +/- 5 vs. 123 +/- 21 mU/g/l) in this in vitro model. Vascular flow characteristics were approximated by the portal perfusion pressure, which tended to be elevated upon initial reperfusion in the UW group (8.4 +/- 0.6 mm Hg) compared to 6.6 +/- 1.0 and 7.3 +/- 0.4 mm Hg in Celsior and HTK, respectively. However, the pressure values decreased to the normal range even in the UW group with ongoing perfusion. The sensitivity of our model in detecting protective effects of the tested solution was confirmed by a negative control group of livers stored in Ringer's solution at 4 degrees C, yielding an impaired recovery which differed by one magnitude from the three other groups. Within the limits of an in vitro study it is concluded from these results that Celsior may become a suitable alternative for liver preservation and further studies including a transplantation in vivo are strongly encouraged.
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PMID:Experimental liver preservation with Celsior: a novel alternative to University of Wisconsin and histidine-tryptophan-alpha-ketoglutarate solutions? 1087 54


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