[Objectives]To observe the effect of Shuanghuanglian oral solution on liver function in BABL/cJ mice in non-alcoholic steatohepatitis(NASH)model.[Methods]The BABL/cJ mice were randomly divided into three groups:a cont...[Objectives]To observe the effect of Shuanghuanglian oral solution on liver function in BABL/cJ mice in non-alcoholic steatohepatitis(NASH)model.[Methods]The BABL/cJ mice were randomly divided into three groups:a control group,a model group,and an experimental group.The experimental group was administered with 10%Shuanghuanglian oral solution at a dose of 0.1 mL/(10 g·d),while the control group and experimental group received an equivalent dosage of normal saline.All three groups were treated for a period of 28 d.The liver function of the mice in each group was examined after the treatment.[Results]The body mass,liver index,triacylglycerol(TG),total cholesterol(TC),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels were all significantly reduced compared to the model group(P<0.05).[Conclusions]Shuanghuanglian oral solution has a beneficial effect on liver function in BABL/cJ mice.展开更多
In order to study the effect of self-made liver preservation solution on liver preservation by comparing with UW solution and HC-A solution, the self-made liver preservation solution (SM) and perfusion solution were...In order to study the effect of self-made liver preservation solution on liver preservation by comparing with UW solution and HC-A solution, the self-made liver preservation solution (SM) and perfusion solution were prepared under the aseptic conditions. The isolated non-circulated perfusion rat liver model was established. According to the different preservation solutions, the rats were randomly divided into UW group, SM group and HC-A group. The three groups were divided into 6 subgroups according to the preservation duration (n=6 in each group). The transferase in liver perfusion solution and intercellular adhesion molecule-1 (ICAM-1) and nitric oxide (NO) in liver tissues were determined at 2, 8 and 24 h respectively. The results showed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had no significant difference between SM group and UW group, but significantly lower than in HC-A group. The levels of ICAM-1 and NO were increased simultaneously in SM group and UW group (P〉0.05), but there was significant difference as compared with HC-A group (P〈0.05). At the same time point, the level of ICAM-1 was higher in SM group than in UW group, but NO was lower. The preservation effect of SM solution is the same as UW solution, but better than HC-A solution.展开更多
To investigate the cold preservation effect of rat livers by modified storage method with self made HYD solution. Methods. The modified method was that the vascular bed of rat livers was expanded with an additional 20...To investigate the cold preservation effect of rat livers by modified storage method with self made HYD solution. Methods. The modified method was that the vascular bed of rat livers was expanded with an additional 20 to 40ml self made HYD solution/100g liver. After removing the liver, the extra HYD solution expressed as % liver weight was entrapped via portal infusion by tying off the supra and infra hepatic inferior vena cava. According to the amount of extra HYD solution, 40 rats were randomly divided into four groups including: control group with conventional storage method, 20% group, 30% group and 40% group. The preservation effect of modified storage method with that of conventional storage method by using isolated perfused rat liver model was compared. [WT5”BX] Results.[WT5”BZ] Bile production and all the indices of hepatic microcirculation including portal perfusion pressure, endothelin 1 in the effluent, trypan blue distribution time and histology in modified method groups were significantly superior to those in control group (P<0.05). The liver enzymes in 30% group were markedly lower than those in control group (P<0.05). The preservation effect of rat liver in 30% group was the best among the modified method groups. Conclusion. The modified cold storage method is effective and may have potential for clinical application for liver preservation.展开更多
BACKGROUND: A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end- stage liver disease. The increasing use of marginal...BACKGROUND: A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end- stage liver disease. The increasing use of marginal donors and non-heart beating donors as well as the establishment of a national organ allocation network call for better preservation. New preservation solutions like histidine- tryptophan-ketoglutarate (HTK) solution and Celsior solution have been introduced to liver preservation, and protective gene intervention and other modifications have also been investigated. In this article, we review recent advances in liver preservation solutions. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on liver preservation solution, biliary complication, protective gene and other related subjects. RESULTS: Although the high viscosity of the University of Wisconsin (UW) solution proved harmful to the hepatic microcirculation, three solutions showed equivalent preservation effects. When the cold ischemia time was short, there were no significant differences among the three solutions in the incidence of biliary complications. So far, modifications of preservation solutions have achieved great success. Several types of protective genes like A20, Bcl-2, Bcl-XL and HO-1 were reported to have definite liver protective effects. The addition of other substrates like TNF-α antibody, tacrolimus (FK506) and fructose-1, 6-bisphosphate (FBP) can also improve the preservation effect. However, addition of insulin to UW solution is harmful to the graft. CONCLUSIONS: In centers with highly-developed transplantation techniques, HTK and Celsior solutions are acceptable in liver preservation. Protective genemodification and addition of substrates like TNF-α antibody, FK506 and FBP are prominent approaches to improve liver preservation.展开更多
BACKGROUND: Percutaneous ethanol injection has been widely used as a non-surgical therapy for liver cancer, but it has some shortcomings such as local diffusion and une- qual permeation. This study was designed to obs...BACKGROUND: Percutaneous ethanol injection has been widely used as a non-surgical therapy for liver cancer, but it has some shortcomings such as local diffusion and une- qual permeation. This study was designed to observe the volume, controllability and completeness of necrosis after injection of low concentration sodium hydroxide in the normal liver parenchyma so as to assess its possibility in treatment of liver cancer instead of ethanol. METHODS: Twenty-seven New Zealand rabbits were di- vided randomly into 9 groups (Aa, Ab, Ac, Ba, Bb, Bc, Ca, Cb, and Cc) by a 3 × 3 (three-by-three) factorial de- sign, each consisting of 3 rabbits. Group A was given sodi- um hydroxide solution at a concentration of 5%, while B at 2.5% and C at 1% in liver parenchyma. Each group re- ceived three doses of the solution: a (0.2 ml), b (0.5 ml) and c (1.0 ml). Then another 3 rabbits as side-effect group were dropped with sodium hydroxide solution in their liver lobe space. Liver and renal function changes in all the rab- bits were compared after injection with pre-injection. RESULTS: All the lesions were localized. At the concentra- tion of 2.5% and 5%, the lesion volume increased with the dose increased from 0.2 ml to 1.0 ml (P < 0. 05). No sig- nificant differences were found in the lesion volume of the groups receiving the same dose but different concentration. Changes in liver and renal function were not significant 7 days after injection, compared with those before injection. CONCLUSIONS: 2.5% and 5% sodium hydroxide solution could control local complete necrosis in normal liver. With regard to safety, 2.5% alkali solution is considered promis- ing as a new agent for intratumoral injection therapy in- stead of ethanol.展开更多
AIM: To compare the preservation of non-heart- beating donor (NHBD) livers in cold histidine-trytophan- ketoglutarate (HTK) solution and extracorporeal liver perfusion (ECLP). METHODS: Livers harvested from health pig...AIM: To compare the preservation of non-heart- beating donor (NHBD) livers in cold histidine-trytophan- ketoglutarate (HTK) solution and extracorporeal liver perfusion (ECLP). METHODS: Livers harvested from health pigs were stored for 10 h in cold HTK solution (group A, n = 4) or perfused with oxygenated autologous blood at body temperature (group B, n = 4). Both groups were then tested on the circuit for 4 h. Bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of extracorporeal livers were tested in each group. Liver tissues from each group were examined at the end of reperfusion. RESULTS: At 1, 2, 3 and 4 h after reperfusion, bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of livers in group A were statistically different from those in group B (P < 0.05 or P < 0.01). CONCLUSION: ECLP is better than HTK solution to preserve NHBD livers. ECLP can assess the graft viabilitybefore liver transplantation.展开更多
AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Coch...AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31^(st), 2017. The inclusion criteria were comparative, randomized controlled trials(RCTs) for deceased donor liver(DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin(UW) solution or histidinetryptophan-ketoglutarate(HTK), Celsior(CS) and Institut Georges Lopez(IGL-1) solutions. Fifteen RCTs(1830 livers) were included; the primary outcomes were primary non-function(PNF) and one-year posttransplant graft survival(OGS-1). RESULTS All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1(RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1(RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSION Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.展开更多
AIM: To compare, in a pig the protective effect of UW liver transplantation model, with that of IGL-1, a highsodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply. METHODS: All liv...AIM: To compare, in a pig the protective effect of UW liver transplantation model, with that of IGL-1, a highsodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply. METHODS: All livers were harvested and grafted orthotopically according to standard techniques. The livers were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7) at 4℃. In a sham group (n = 4), the livers underwent a 60-min warm ischemia at 37℃. The hepatocellular injury was assessed in organ preservation solution washed out from the graft at the end of ischemic storage (before revascularization), and in serum 2 h after reperfusion and daily for up to 6 d. RESULTS: Livers preserved in IGL-1 solution released markedly less AST than that preserved in the UW solution before and after revascularization (P 〈 0.05). Besides, the activity of creatine kinase-BB, a marker of sinusoidal lining cells injury, was higher in the UW group than in the IGL-1 group (P 〈 0.05). Histological results showed less necrotic regions in livers preserved in IGL-1 solution; however, no difference was observed for inflammation. CONCLUSION: IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against preservation-reperfusion injuries.展开更多
BACKGROUND: A suitable perfusate is very important in reducing various problems in liver preservation, prolonging the time of organ preservation and enhancing the quality of donor tissue. University of Wisconsin (UW) ...BACKGROUND: A suitable perfusate is very important in reducing various problems in liver preservation, prolonging the time of organ preservation and enhancing the quality of donor tissue. University of Wisconsin (UW) solution is the most successful solution for preserving multiple organs at present, but it has many shortcomings. We set out to develop a new liver preservation solution (KYL solution) and study its effects on apoptosis in rat liver undergoing cold preservation. METHODS: Using non-circulated isolated perfused rat liver (IPRL), we randomly preserved Sprague-Dawley rat livers for 0, 4, 8, 16, 24, and 48 hours with KYL solution or UW solution. The effects were assessed by measuring the content of free radicals in Krebs-Henseleit solution and the intracellular calcium content of hepatocytes, assessing hepatocellular apoptosis and related-gene expression, and observing the morphological changes in liver. To evaluate the protection by KYL and UW solutions in rat liver perfusion and preservation, we chosed normal saline for negative comparison. RESULTS: The intracellular calcium content of the liver preserved in KYL solution was less than that preserved in UW solution. At every different period of preservation, the malonaldehyde and superoxide dismutase content in Krebs-Henseleit solution, the percentage of apoptotic cells and the expression patterns of apoptosis-related-genes were similar in livers preserved in KYL and UW solutions. Morphological changes in the two groups were almost the same. The variables in both groups were better than those of livers preserved in normal saline. Both KYL and UW solutions protected rat liver from ischemia-reperfusion injury. CONCLUSIONS: KYL solution is superior to UW solution in preventing calcium overload. More severe hepatocyte damage may appear in the KYL group than in the UW group and the effect of KYL solution on apoptosis in rat liver preservation is similar to that of UW solution.展开更多
[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury ...[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury model was established by intraperitoneal injection of 500 mg/kg of D-galactosamine. The ALT,AST,MDA,SOD and GSH-Px in serum,as well as serum TNF-α,IL-1β and IL-6 levels were measured,and liver tissue lesions were observed under microscope. [Results] CTDD can significantly reduce ALT,AST and MDA levels,increase SOD,GSH-Px activity,and significantly reduce serum TNF-α,IL-1β and IL-6 levels,and improve liver tissue lesions.[Conclusions]CTDD has a protective effect on D-galactosamine-induced acute liver injury in rats,and its mechanism may be related to inhibition of oxidative stress and inflammatory reaction.展开更多
AIM: To investigate whether amifostine contributes to the antioxidant and cytoprotective effects of histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions.
AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin col...AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.展开更多
Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion)...Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.展开更多
Since Dr. Thomas Starzl performed the first series of successful liver transplants(LTs), important advances have been made in immunosuppression, operative techniques, and postoperative care. In 1988, Belzer's grou...Since Dr. Thomas Starzl performed the first series of successful liver transplants(LTs), important advances have been made in immunosuppression, operative techniques, and postoperative care. In 1988, Belzer's group reported the first successful LT using the University of Wisconsin preservation solution(UW).Since then, UW has replaced EuroCollins solution and allowed prolonged and safer preservation of liver, kidney, and pancreas allografts, thus contributing to the improvement of transplant outcomes. Although UW is still considered the standard of care in the United States and in several countries worldwide, a recent meta-analysis revealed similar LT outcomes among UW, Celsior solution, and the Institut Georges Lopez-1 preservation solution, which were slightly superior to those obtained with histidine-tryptophan-ketoglutarate preservation solution.Dynamic preservation has been recently developed, and liver allografts are preserved mainly through the following methods: hypothermic machine perfusion, normothermic machine perfusion, and subnormothermic machine perfusion. Their use has the potential advantage of improving clinical results in LT involving extended criteria donor allografts. Although associated with increased costs, techniques employing machine perfusion of liver allografts have been considered clinically feasible. This editorial focuses on recent advances and future perspectives in liver allograft preservation.展开更多
文摘[Objectives]To observe the effect of Shuanghuanglian oral solution on liver function in BABL/cJ mice in non-alcoholic steatohepatitis(NASH)model.[Methods]The BABL/cJ mice were randomly divided into three groups:a control group,a model group,and an experimental group.The experimental group was administered with 10%Shuanghuanglian oral solution at a dose of 0.1 mL/(10 g·d),while the control group and experimental group received an equivalent dosage of normal saline.All three groups were treated for a period of 28 d.The liver function of the mice in each group was examined after the treatment.[Results]The body mass,liver index,triacylglycerol(TG),total cholesterol(TC),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels were all significantly reduced compared to the model group(P<0.05).[Conclusions]Shuanghuanglian oral solution has a beneficial effect on liver function in BABL/cJ mice.
文摘In order to study the effect of self-made liver preservation solution on liver preservation by comparing with UW solution and HC-A solution, the self-made liver preservation solution (SM) and perfusion solution were prepared under the aseptic conditions. The isolated non-circulated perfusion rat liver model was established. According to the different preservation solutions, the rats were randomly divided into UW group, SM group and HC-A group. The three groups were divided into 6 subgroups according to the preservation duration (n=6 in each group). The transferase in liver perfusion solution and intercellular adhesion molecule-1 (ICAM-1) and nitric oxide (NO) in liver tissues were determined at 2, 8 and 24 h respectively. The results showed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had no significant difference between SM group and UW group, but significantly lower than in HC-A group. The levels of ICAM-1 and NO were increased simultaneously in SM group and UW group (P〉0.05), but there was significant difference as compared with HC-A group (P〈0.05). At the same time point, the level of ICAM-1 was higher in SM group than in UW group, but NO was lower. The preservation effect of SM solution is the same as UW solution, but better than HC-A solution.
文摘To investigate the cold preservation effect of rat livers by modified storage method with self made HYD solution. Methods. The modified method was that the vascular bed of rat livers was expanded with an additional 20 to 40ml self made HYD solution/100g liver. After removing the liver, the extra HYD solution expressed as % liver weight was entrapped via portal infusion by tying off the supra and infra hepatic inferior vena cava. According to the amount of extra HYD solution, 40 rats were randomly divided into four groups including: control group with conventional storage method, 20% group, 30% group and 40% group. The preservation effect of modified storage method with that of conventional storage method by using isolated perfused rat liver model was compared. [WT5”BX] Results.[WT5”BZ] Bile production and all the indices of hepatic microcirculation including portal perfusion pressure, endothelin 1 in the effluent, trypan blue distribution time and histology in modified method groups were significantly superior to those in control group (P<0.05). The liver enzymes in 30% group were markedly lower than those in control group (P<0.05). The preservation effect of rat liver in 30% group was the best among the modified method groups. Conclusion. The modified cold storage method is effective and may have potential for clinical application for liver preservation.
基金This study was supported by grants from the National Basic Research Program (973) of China (No. 2003CB515506).Ethical approval: Not needed.
文摘BACKGROUND: A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end- stage liver disease. The increasing use of marginal donors and non-heart beating donors as well as the establishment of a national organ allocation network call for better preservation. New preservation solutions like histidine- tryptophan-ketoglutarate (HTK) solution and Celsior solution have been introduced to liver preservation, and protective gene intervention and other modifications have also been investigated. In this article, we review recent advances in liver preservation solutions. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on liver preservation solution, biliary complication, protective gene and other related subjects. RESULTS: Although the high viscosity of the University of Wisconsin (UW) solution proved harmful to the hepatic microcirculation, three solutions showed equivalent preservation effects. When the cold ischemia time was short, there were no significant differences among the three solutions in the incidence of biliary complications. So far, modifications of preservation solutions have achieved great success. Several types of protective genes like A20, Bcl-2, Bcl-XL and HO-1 were reported to have definite liver protective effects. The addition of other substrates like TNF-α antibody, tacrolimus (FK506) and fructose-1, 6-bisphosphate (FBP) can also improve the preservation effect. However, addition of insulin to UW solution is harmful to the graft. CONCLUSIONS: In centers with highly-developed transplantation techniques, HTK and Celsior solutions are acceptable in liver preservation. Protective genemodification and addition of substrates like TNF-α antibody, FK506 and FBP are prominent approaches to improve liver preservation.
文摘BACKGROUND: Percutaneous ethanol injection has been widely used as a non-surgical therapy for liver cancer, but it has some shortcomings such as local diffusion and une- qual permeation. This study was designed to observe the volume, controllability and completeness of necrosis after injection of low concentration sodium hydroxide in the normal liver parenchyma so as to assess its possibility in treatment of liver cancer instead of ethanol. METHODS: Twenty-seven New Zealand rabbits were di- vided randomly into 9 groups (Aa, Ab, Ac, Ba, Bb, Bc, Ca, Cb, and Cc) by a 3 × 3 (three-by-three) factorial de- sign, each consisting of 3 rabbits. Group A was given sodi- um hydroxide solution at a concentration of 5%, while B at 2.5% and C at 1% in liver parenchyma. Each group re- ceived three doses of the solution: a (0.2 ml), b (0.5 ml) and c (1.0 ml). Then another 3 rabbits as side-effect group were dropped with sodium hydroxide solution in their liver lobe space. Liver and renal function changes in all the rab- bits were compared after injection with pre-injection. RESULTS: All the lesions were localized. At the concentra- tion of 2.5% and 5%, the lesion volume increased with the dose increased from 0.2 ml to 1.0 ml (P < 0. 05). No sig- nificant differences were found in the lesion volume of the groups receiving the same dose but different concentration. Changes in liver and renal function were not significant 7 days after injection, compared with those before injection. CONCLUSIONS: 2.5% and 5% sodium hydroxide solution could control local complete necrosis in normal liver. With regard to safety, 2.5% alkali solution is considered promis- ing as a new agent for intratumoral injection therapy in- stead of ethanol.
基金The National High Technology Research and Development Program of China (863 Program), No. 2001AA216071Guangdong Health Bureau Scientific Funds, No. 2006345
文摘AIM: To compare the preservation of non-heart- beating donor (NHBD) livers in cold histidine-trytophan- ketoglutarate (HTK) solution and extracorporeal liver perfusion (ECLP). METHODS: Livers harvested from health pigs were stored for 10 h in cold HTK solution (group A, n = 4) or perfused with oxygenated autologous blood at body temperature (group B, n = 4). Both groups were then tested on the circuit for 4 h. Bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of extracorporeal livers were tested in each group. Liver tissues from each group were examined at the end of reperfusion. RESULTS: At 1, 2, 3 and 4 h after reperfusion, bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of livers in group A were statistically different from those in group B (P < 0.05 or P < 0.01). CONCLUSION: ECLP is better than HTK solution to preserve NHBD livers. ECLP can assess the graft viabilitybefore liver transplantation.
基金Supported by grants from the National Research Development and Innovation Office,NKFI K120232Hungarian Science Research Fund,No.GINOP 2.3.2-15-2016-00015 and No.EFOP-3.6.2-16-2017-00006New National Excellence Program of the Ministry of Human Capacities,No.UNKP-17-4
文摘AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31^(st), 2017. The inclusion criteria were comparative, randomized controlled trials(RCTs) for deceased donor liver(DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin(UW) solution or histidinetryptophan-ketoglutarate(HTK), Celsior(CS) and Institut Georges Lopez(IGL-1) solutions. Fifteen RCTs(1830 livers) were included; the primary outcomes were primary non-function(PNF) and one-year posttransplant graft survival(OGS-1). RESULTS All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1(RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1(RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSION Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.
文摘AIM: To compare, in a pig the protective effect of UW liver transplantation model, with that of IGL-1, a highsodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply. METHODS: All livers were harvested and grafted orthotopically according to standard techniques. The livers were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7) at 4℃. In a sham group (n = 4), the livers underwent a 60-min warm ischemia at 37℃. The hepatocellular injury was assessed in organ preservation solution washed out from the graft at the end of ischemic storage (before revascularization), and in serum 2 h after reperfusion and daily for up to 6 d. RESULTS: Livers preserved in IGL-1 solution released markedly less AST than that preserved in the UW solution before and after revascularization (P 〈 0.05). Besides, the activity of creatine kinase-BB, a marker of sinusoidal lining cells injury, was higher in the UW group than in the IGL-1 group (P 〈 0.05). Histological results showed less necrotic regions in livers preserved in IGL-1 solution; however, no difference was observed for inflammation. CONCLUSION: IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against preservation-reperfusion injuries.
文摘BACKGROUND: A suitable perfusate is very important in reducing various problems in liver preservation, prolonging the time of organ preservation and enhancing the quality of donor tissue. University of Wisconsin (UW) solution is the most successful solution for preserving multiple organs at present, but it has many shortcomings. We set out to develop a new liver preservation solution (KYL solution) and study its effects on apoptosis in rat liver undergoing cold preservation. METHODS: Using non-circulated isolated perfused rat liver (IPRL), we randomly preserved Sprague-Dawley rat livers for 0, 4, 8, 16, 24, and 48 hours with KYL solution or UW solution. The effects were assessed by measuring the content of free radicals in Krebs-Henseleit solution and the intracellular calcium content of hepatocytes, assessing hepatocellular apoptosis and related-gene expression, and observing the morphological changes in liver. To evaluate the protection by KYL and UW solutions in rat liver perfusion and preservation, we chosed normal saline for negative comparison. RESULTS: The intracellular calcium content of the liver preserved in KYL solution was less than that preserved in UW solution. At every different period of preservation, the malonaldehyde and superoxide dismutase content in Krebs-Henseleit solution, the percentage of apoptotic cells and the expression patterns of apoptosis-related-genes were similar in livers preserved in KYL and UW solutions. Morphological changes in the two groups were almost the same. The variables in both groups were better than those of livers preserved in normal saline. Both KYL and UW solutions protected rat liver from ischemia-reperfusion injury. CONCLUSIONS: KYL solution is superior to UW solution in preventing calcium overload. More severe hepatocyte damage may appear in the KYL group than in the UW group and the effect of KYL solution on apoptosis in rat liver preservation is similar to that of UW solution.
文摘[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury model was established by intraperitoneal injection of 500 mg/kg of D-galactosamine. The ALT,AST,MDA,SOD and GSH-Px in serum,as well as serum TNF-α,IL-1β and IL-6 levels were measured,and liver tissue lesions were observed under microscope. [Results] CTDD can significantly reduce ALT,AST and MDA levels,increase SOD,GSH-Px activity,and significantly reduce serum TNF-α,IL-1β and IL-6 levels,and improve liver tissue lesions.[Conclusions]CTDD has a protective effect on D-galactosamine-induced acute liver injury in rats,and its mechanism may be related to inhibition of oxidative stress and inflammatory reaction.
基金Supported by The Ministerio de Sanidad y Consumo No.PIO81988(Madrid,Spain)Eirini Pantazi wishes to thank the Agència de Gestiód’Ajuts Universitaris i de Recerca No.2012FI_B00382Mohamed Bejaoui thanks CSIC No.I-COOP05 for their fellowships
文摘AIM: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts.
文摘AIM: To investigate whether amifostine contributes to the antioxidant and cytoprotective effects of histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions.
基金Supported by National Science and Technology Major Project,No.2012ZX10002-017Natural Science Foundation of China for Innovative Research Group,No.81121002+4 种基金National Natural Science Foundation of China,No.81000137 and No.81470891The Qianjiang Talent Program of Zhejiang Province,China,No.2012R10045the Scientific Research Program for the Returned Overseas Chinese Scholars,Ministry of Health,China,No.J20112008National High Technology Research and Development Program of China for Young Scientists(863 Program),No.2015AA020923Ministry of Education,Zhejiang Province,China,No.Y201328095
文摘AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.
基金Supported by Fondo de Investigaciones Sanitarias,Ministerio de Economía y Competitividad(Madrid,Spain)No.PI15/00110
文摘Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.
文摘Since Dr. Thomas Starzl performed the first series of successful liver transplants(LTs), important advances have been made in immunosuppression, operative techniques, and postoperative care. In 1988, Belzer's group reported the first successful LT using the University of Wisconsin preservation solution(UW).Since then, UW has replaced EuroCollins solution and allowed prolonged and safer preservation of liver, kidney, and pancreas allografts, thus contributing to the improvement of transplant outcomes. Although UW is still considered the standard of care in the United States and in several countries worldwide, a recent meta-analysis revealed similar LT outcomes among UW, Celsior solution, and the Institut Georges Lopez-1 preservation solution, which were slightly superior to those obtained with histidine-tryptophan-ketoglutarate preservation solution.Dynamic preservation has been recently developed, and liver allografts are preserved mainly through the following methods: hypothermic machine perfusion, normothermic machine perfusion, and subnormothermic machine perfusion. Their use has the potential advantage of improving clinical results in LT involving extended criteria donor allografts. Although associated with increased costs, techniques employing machine perfusion of liver allografts have been considered clinically feasible. This editorial focuses on recent advances and future perspectives in liver allograft preservation.