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)

Temporary occlusion of hepatic inflow is a useful maneuver to reduce hemorrhage from liver trauma and difficult hepatic resections. The liver can be protected with a hepatic protective solution before inflow occlusion, just as the stopped heart is protected by a cardioplegic solution during open heart surgery. Twenty dogs were divided into two groups. The portal inflow of group A was infused via the mesenteric venous branch with a hepatic protective solution composed of 250 mg of hydrocortisone, 15 mEq of KC1, 6 mL of 0.1 N HC1, 5 mL of 10% magnesium sulfate and 250 mg of dextrose in one liter of cold lactated Ringer's solution. Group B was infused with cold lactated Ringer's solution as a control. The hepatic artery and portal vein were isolated and then clamped for 30 minutes. The elevation of serum GOT and GPT after release of the clamps was significantly greater in group B, especially during the first 48 hours. The levels of alkaline phosphatase and total bilirubin were also higher in group B until the 7th day. The results liver biopsies 3 hours after release of the clamps revealed marked congestion and destruction of hepatocytes in group B. We conclude that liver perfusion with a hepatic protective solution before inflow occlusion results in less damage to liver tissue and less impairment of liver function. Such protection is important in liver surgery.
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PMID:Protection of liver ischemia due to inflow occlusion using prior perfusion with hepatic protective solution in dogs. 168 52

Intracellular enzyme activities can be greatly influenced by alterations of pH, and non-physiologic pH may inhibit cell metabolism. The study was undertaken to examine the influence of pH values in preservation solution on ischemic tolerance time of the liver. BDE rat livers were used. Livers were preserved for 20 min or 2 h in warm ischemia after an initial perfusion with Ringer's solution at pH 9.0, 7.4, and 6.0. The values of total adenine nucleotide (TAN) and energy reserve (ER) in the livers were determined at the end of the preservation. After 20 min of warm ischemia, TAN values at pH 9.0 and 7.4 fell to 2.727 +/- 0.255 and 2.410 +/- 0.164 mumol/g, respectively (normal values: 3.414 +/- 0.270 mumol/g) and ER values to 0.786 +/- 0.186 mumol/g at pH 9.0 and to 0.446 +/- 0.095 mumol/g at pH 7.4 (normal values: 2.962 +/- 0.214 mumol/g). A similar trend was also observed after 2 h of warm ischemia. The preservation with a solution at pH 6.0 did not present any difference as compared to that at pH 7.4. Four-hour preservation in cold ischemia with Ringer's solution at pH 9.0 rendered higher values of TAN (2.635 +/- 0.085 mumol/g) and ER (0.336 +/- 0.026 mumol/g) than those in preservation at pH 7.4. No significant difference between TAN and ER values was found when 4-h preservation at pH 7.4 and 6.0 was compared. In another group an intermittent liver perfusion at 1-h interval was performed with chilled Ringer's solution; afterwards GOT, GPT, beta-glucuronidase, and acid phosphatase values in the effluents were evaluated. All of these enzymes showed higher concentration in the effluent with solution at pH 7.4 than that at 9.0. These results suggested that better intracellular energy reserve and organ viability can be maintained by preservation with alkaline solution. Furthermore, ER values seemed to be an excellent indicator of the organ viability during preservation. These were also confirmed by orthotopic hepatic transplantation in pigs. Livers were successfully preserved with alkaline Ringer's solution for up to 12 h. However, without change of pH, livers could not be preserved for more than 4.5 h.
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PMID:[Prolongation of ischemic tolerance time of donor livers by alkaline preservation solutions]. 647 1

The new method of hyperthermochemotherapy by the isolated liver perfusion technique without oxygenation is developed using beagle dogs. In this study, we investigated the influence of this method on the liver and other organs. The isolated liver perfusion was performed at the rate of 75-100 ml/min through the portal vein for 30 min under the V-V bypass. Experimental groups were divided as following; Croup I (n = 5): The perfusate was lactate Ringer's solution without oxygenation and kept at 42 degrees C. Group II (n = 5), Mitomycin C (10 micrograms/ml) was added to the perfusate used in Group I. During the perfusion the liver temperature was kept at 41 degrees C. PH of the liver and AKBR returned quickly to preperfusion level after liver perfusion. In the both groups, GOT, GPT, ALP were elevated, and returned to normal range within 14 days, although GPT was significantly high until the 5th day in Group II compared with Group I. In the values of amylase, BUN and Cr., no remarkable changes were observed, and any histologic damage of the liver and other organs was not found on day 14. In conclusion, this new hyperthermochemotherapy system could be a simple and safe method, and should be applicable for clinical cases.
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PMID:[An experimental study of hyperthermochemotherapy without oxygenation by isolated liver perfusion]. 796 18

A previously well 24-year-old man complained of persistent epigastric pain after a session of intensive muscle building exercise especially of the abdominal muscles. The abdomen was diffusely tender without guarding. There was an increased concentration of bilirubin (64.7 mumol/l), GOT (117 U/l), GPT (529 U/l) and alkaline phosphatase (150 U/l). Ultrasound examination showed a widening of the choledochal duct to 11 mm without signs of gallstones. Endoscopic retrograde cholangiography additionally revealed contrast-medium extravasation from the left hepatic duct. Computed tomography, performed immediately afterwards, confirmed the extravasation, while liver and pancreas were unremarkable. Laparoscopy revealed a 5 mm tear in the left hepatic duct, close to the hepatic duct bifurcation with bile effusion into the peritoneal cavity. The latter was rinsed endoscopically with Ringer's solution and drains were placed in the omental bursa and subhepatically in the region of the bile leak. To relax the sphincter Oddi glycerol trinitrate was administered postoperatively, for the first five days 72 mg/24 h intravenously, then for nine days twice daily 20 mg by month. No more bile drained as early as the second postoperative day and the patient was free of symptoms 2 weeks later.
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PMID:[Spontaneous rupture of the left hepatic duct]. 845 9

The principal cause of primary non-function in orthotopic liver transplantation is thought to be preservation injury to the microvasculature. We, therefore, evaluated if effluent levels of hyaluronate, whose uptake is an endothelial cell marker, could predict early graft function and ultimate graft outcome in orthotopic liver transplantation. A total of 102 cases were studied in two phases. In the first phase, we attempted to determine if a correlation existed between effluent hyaluronate levels, early graft function and ultimate graft outcome. This phase of the study was also used to determine hypothetical cut-off values for hyaluronate which could discriminate between good and bad livers. Thirty-two livers orthotopically transplanted to randomly selected primary recipients were studied. After varying periods of static cold storage (4 degrees C) in University of Wisconsin solution, the livers were reinfused with cold (4 degrees C) lactated Ringer's solution. The first 50 ml of the reperfusion effluent was collected from the infrahepatic vena cava. Effluent samples were analyzed for hyaluronate. Linear regression analysis demonstrated a significant correlation between effluent hyaluronate levels and post-operative aspartate and alanine aminotransferase levels (p < 0.001 for both). Logistic regression demonstrated a highly significant correlation (p = 0.0056) between effluent hyaluronate levels and ultimate graft outcome. Generation of Receiver Characteristics Curves indicated that a level between 400 and 430 micrograms.l-1 could possibly discriminate between good livers and those at risk of early graft failure. The authenticity of this hyaluronate cut-off level was further confirmed in the second phase of the study where 70 consecutive primary crossmatch-negative transplants were performed. A highly significant difference was observed in peak aspartate and alanine aminotransferase levels in the first week (p < 0.0006 and p < 0.0005, respectively) between livers with effluent hyaluronate levels < or = 400 micrograms.l-1 and livers with hyaluronate levels higher than 400 micrograms.l-1. Logistic regression revealed a highly significant correlation between effluent hyaluronate levels and graft success (p = 0.0001). Since hyaluronate uptake by the microvascular endothelial cell is significantly greater than production, high hyaluronate effluent levels in failed livers would be due to decreased hyaluronate uptake by the injured microvascular endothelial cell. We therefore conclude that effluent hyaluronate levels may prove to be a reliable preoperative test to assess early graft function and outcome in clinical orthotopic liver transplantation.
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PMID:Hyaluronate levels in donor organ washout effluents: a simple and predictive parameter of graft viability. 886 78

Livers of male Wistar rats (250-300 g) were isolated and flushed with 10 ml of Ringer's solution and 10 ml of UW preservation solution. Then the organs were stored for 24 h at 4 degrees C in UW solution. Livers of Group 1 were rinsed with 10 ml of Ringer's solution and reperfused after hypothermic storage with oxygenated Krebs-Henseleit solution (95% O2; 5% CO2) in a nonrecirculating system at constant pressure (10 mmHg) and 37 degrees C. Livers of Group 2 were incubated for 30 min at 37 degrees C prior to reperfusion, in order to simulate rewarming of the organ upon surgical implantation. Livers of Group 3 were treated like Group 2, but taurine was admixed to the UW solution (1 mM). Livers of Group 1 showed little signs of a preservation/reperfusion injury, with low enzyme activities of the parenchymal ALT and endothelial purine nucleoside phosphorylase (PNP) in the postischemic rinse solution (ALT: 19.9 +/- 12.4; PNP: 3.3 +/- 0.4 U/liter), adequate portal flow values about 3 ml/g/min and high O2 uptake at the end of the experiment (VO2: 3.2 +/- 0.4 ml/100g/min). Livers of Group 2 exhibited nearly tenfold higher enzyme activities in the rinse solution (ALT: 247.0 +/- 94.7*; PNP: 29.5 +/- 17.0* U/l) and disturbed tissue perfusion with significantly reduced flow values of about 2 ml/g/min during the first 10 min of reperfusion. As a result, the recovery of O2 uptake was only 2.2 +/- 0.3 ml/100 g/min*. Addition of taurine (Group 3) resulted in a significant reduction of the enzyme loss (ALT: 96.2 +/- 50.0#; PNP:12.4 +/- 7.0# U/liter) and improved portal flow values and O2 uptake at the end of reperfusion (2.7 +/- 0.3 ml/100 g/min#). The results give evidence for the importance of the rewarming period after hypothermic storage, which is inevitable during implantation of the organ in vivo. Taurine seems to exert a protective effect, affecting both the vascular endothelium and parenchymal tissue (*p < 0.05 vs Group 1; # p < 0.05 vs Group 2).
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PMID:Taurine reduces experimental liver injury after cold ischemic preservation and a period of rewarming prior to reperfusion. 891 53

The objective of this study was to examine the effects of volume replacement with recombinant human serum albumin (rHSA), which was developed to reduce the consumption of human blood derivatives, on maintaining hepatic energy metabolism. Hemorrhagic shock with a mean blood pressure of 50 mmHg was induced within 20 min and maintained for 60 min by Wiggars' method in rabbits. Fluid resuscitation replacing two thirds of the blood withdrawn with plasma-derived 5% human serum albumin (pHSA; n = 7) or rHSA (n = 10), or replacing double the volume of blood withdrawn with lactated Ringer's solution (n = 7) was completed within 20 min, and observed for 120 min. No significant differences were observed in the blood pressures, blood gas analyses, blood counts, biochemical parameters (e.g., alanine aminotransferase, lactate dehydrogenase, creatine kinase, blood urea nitrogen, creatinine) or blood glucose levels among the three groups. There were also no significant differences in the parameters of hepatic energy metabolism such as blood pyruvate and lactate levels and their ratios, ketone body concentrations and their ratios, and hepatic tissue energy charge levels among the experimental groups. It is suggested that volume replacement with rHSA, like pHSA, is able to maintain hemodynamics and organ function in hemorrhagic shock, particularly hepatic energy metabolism.
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PMID:Effects of fluid resuscitation with recombinant human serum albumin solution on maintaining hepatic energy metabolism in hemorrhagic shock rabbits. 901 Sep 64

Our study was aimed at developing a reliable method of hyperthermic isolated liver perfusion (HILP) in pigs and at assessing its local and systemic side effects. HILP was performed via the hepatic artery and portal vein in 15 animals. The perfusate consisted of blood (200 ml), oxypolygelatine (500 ml), Ringer's solution (1000 ml), and trapped intrahepatic blood. HILP was carried out for 45 min at a mean perfusate inflow temperature of 41.2 degrees C. The mean portal flow and pressure were adjusted to 500 ml/min and 20-25 mm Hg; the mean arterial flow and pressure were 130 ml/min and 40-60 mm Hg, respectively. After 20 min of perfusion the mean temperature in the right and the left liver lobe were 40.8 degrees C and 40.3 degrees C and remained almost constant over the whole perfusion period. Liver enzymes (alanine aminotransferase and aspartate aminotransferase) and serum lactate levels showed slight increases after perfusion but normalized within 1 week. Histology of liver parenchyma showed only mild pathological changes, which were also reversible within 7 days. The presented method of HILP is a safe and reproducible technique for isolated hyperthermic liver perfusion. Based on this animal model, experimental HILP with different chemotherapeutic agents can be investigated in order to assess hepatic and systemic toxicity of this therapy.
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PMID:A porcine model for investigation of hyperthermic isolated liver perfusion. 989 14

Conventional resuscitation of hypovolemia due to hemorrhage has consisted of aggressive fluid administration. Recent studies have suggested that surgical control of bleeding before fluid resuscitation might improve early survival. The effects of limited resuscitation on organ function have not been assessed in these studies. We developed a model of moderate intraperitoneal hemorrhage designed to evaluate long-term end-organ function after various resuscitation protocols. Male Sprague-Dawley rats underwent ketamine anesthesia, followed by placement of femoral artery and vein lines. Intraperitoneal hemorrhage was induced by division of distal branches of the ileocolic artery and vein. After 5 minutes of bleeding, the animals were randomized to one of three resuscitation groups: Group 1 received no fluid resuscitation before surgical control of the hemorrhage; Group 2 received 0.5 mL of lactated Ringer's solution (LR) every 5 minutes for a mean arterial pressure (MAP) of less than 80 mm Hg; Group 3 received 2.0 mL of LR every 5 minutes for a MAP of less than 80 mm Hg. In all three groups, after 20 minutes, the bleeding was surgically controlled. All rats were then resuscitated with LR to a MAP of 80 mm Hg. The intravascular lines were removed, and the rats were allowed to recover from anesthesia and were returned to animal holding. On the 7th day, survivors were sacrificed, and their blood was assayed for hematocrit and serum levels of bilirubin, alanine aminotransferase, urea nitrogen, and creatinine. Kidneys, lungs, and liver were harvested for microscopic examination. Survival was lower in Group 2 than in the other groups (90%, 60%, and 100%, respectively; P = 0.04), but all deaths occurred within 3 hours of hemorrhage and were due to either hypovolemia or anesthetic complications. No histologic abnormalities were identified in the livers of the animals that survived, but pulmonary atelectasis and mild-to-moderate renal tubular necrosis were identified uniformly. No histologic differences could be discerned between the groups. Hematocrit and indices of liver and renal function were similar in all groups, and no animal developed organ dysfunction. In this model of moderate uncontrolled intraperitoneal hemorrhage, the volume of fluid resuscitation, or the absence of resuscitation, had an inconsistent effect of 7-day survival and did not influence function or histologic appearance of the liver, lungs, or kidneys 7 days after hemorrhage.
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PMID:Initial resuscitation volume in uncontrolled hemorrhage: effects on organ function. 1007 94

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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