AIM To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin(UW) and Institut Georges Lopez-1(IGL-1)solutions.METHODS Fatty liver grafts from male obese Z&#...AIM To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin(UW) and Institut Georges Lopez-1(IGL-1)solutions.METHODS Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 ℃and subjected to "ex vivo " normo-thermic perfusion(2 h; 37 ℃). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system(UPS: measured as chymotryptic-like activity and 20 S and 19 S proteasome), the prevention of liver injury(transaminases), mitochondrial injury(confocal microscopy) and inflammation markers(TNF 1 alpha, high mobility group box-1(HGMB-1) and PPAR gamma), and liver apoptosis(TUNEL assay, cytochrome c and caspase 3).RESULTS Profiles of free AA(alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW(P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity(measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury(AST/ALT) and mitochondrial damage(revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers(TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels. CONCLUSION Our comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis.展开更多
珍妮弗·洛佩兹(Jennifer Lopez)荣升人母后已很少出席公开场合。目前以照顾龙凤胎为乐的她,前阵子穿上时尚大师Oscar de la Renta设计的小洋装为《Elle》杂志拍照,她昔日以S曲线著称,如今却变得虎背熊腰,几乎撑坏名牌新装。珍妮弗&...珍妮弗·洛佩兹(Jennifer Lopez)荣升人母后已很少出席公开场合。目前以照顾龙凤胎为乐的她,前阵子穿上时尚大师Oscar de la Renta设计的小洋装为《Elle》杂志拍照,她昔日以S曲线著称,如今却变得虎背熊腰,几乎撑坏名牌新装。珍妮弗·洛佩兹2月生下龙凤胎,号称半年甩肉20多公斤,但洋装背后的拉链根本拉不上,造型师用了5个别针和肤色布料勉强固定。39岁的她每天勤做蒸汽浴3小时,但甩掉的是水非油,体重总是迅速回升,她憋足了劲节食,只吃柳橙与薄片成饼干也不见成效。友人向美国某杂志爆料,洛佩兹对目前的身材感到十分沮丧,她很怕魔鬼身材成为永远的回忆:"她痛恨赘肉缠身,想恢复产前的玲珑曲线。"可怜的JLo,抗拒不了意大利面的诱惑,数次大快朵颐,才使得自己肥肉缠身,昔日的性感不复存在,看来,女人还是少贪吃为妙。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
AIM: To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1) solution to protect fatty liver against cold ischemia reperfusion injury. METHO...AIM: To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1) solution to protect fatty liver against cold ischemia reperfusion injury. METHODS: Steatotic livers were preserved for 24 h in IGL-1 solution supplemented with or without IGF-1 and then perfused "ex vivo " for 2 h at 37℃. We examined the effects of IGF-1 on hepatic damage and function (transaminases, percentage of sulfobromophthalein clearance in bile and vascular resistance). We also studied other factors associated with the poor tolerance of fatty livers to cold ischemia reperfusion injury such as mitochondrial damage, oxidative stress, nitric oxide, tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinases.RESULTS: Steatotic livers preserved in IGL-1 solutionsupplemented with IGF-1 showed lower transaminase levels, increased bile clearance and a reduction in vascular resistance when compared to those preserved in IGL-1solution alone. These benefits are mediated by activation of AKT and constitutive endothelial nitric oxide synthase (eNOS), as well as the inhibition of inflammatory cytokines such as TNF-α. Mitochondrial damage and oxidative stress were also prevented.CONCLUSION: IGL-1 enrichment with IGF-1 increasedfatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.展开更多
In order to achieve the objectives of transparency and accountability,Mexican President Andres Manuel Lopez Obrador(AMLO)has offered a press conference every morning since he took office.This situation seemed to be a ...In order to achieve the objectives of transparency and accountability,Mexican President Andres Manuel Lopez Obrador(AMLO)has offered a press conference every morning since he took office.This situation seemed to be a transcendental change in the field of democratic dynamics and political communication in Mexico;however,not merely a means of communication,these conferences have instead become a method of government.Using postulates of Mimetic Theory,this essay analyzes AMLO’s conferences,showing how this daily practice has become propaganda for the regime.展开更多
基金Supported by Instituto de Salud Carlos III(ISCIII)through the FIS project PI12/0056,co-funded by FEDER from Regional Development European Funds(European Union)
文摘AIM To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin(UW) and Institut Georges Lopez-1(IGL-1)solutions.METHODS Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 ℃and subjected to "ex vivo " normo-thermic perfusion(2 h; 37 ℃). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system(UPS: measured as chymotryptic-like activity and 20 S and 19 S proteasome), the prevention of liver injury(transaminases), mitochondrial injury(confocal microscopy) and inflammation markers(TNF 1 alpha, high mobility group box-1(HGMB-1) and PPAR gamma), and liver apoptosis(TUNEL assay, cytochrome c and caspase 3).RESULTS Profiles of free AA(alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW(P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity(measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury(AST/ALT) and mitochondrial damage(revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers(TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels. CONCLUSION Our comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis.
文摘珍妮弗·洛佩兹(Jennifer Lopez)荣升人母后已很少出席公开场合。目前以照顾龙凤胎为乐的她,前阵子穿上时尚大师Oscar de la Renta设计的小洋装为《Elle》杂志拍照,她昔日以S曲线著称,如今却变得虎背熊腰,几乎撑坏名牌新装。珍妮弗·洛佩兹2月生下龙凤胎,号称半年甩肉20多公斤,但洋装背后的拉链根本拉不上,造型师用了5个别针和肤色布料勉强固定。39岁的她每天勤做蒸汽浴3小时,但甩掉的是水非油,体重总是迅速回升,她憋足了劲节食,只吃柳橙与薄片成饼干也不见成效。友人向美国某杂志爆料,洛佩兹对目前的身材感到十分沮丧,她很怕魔鬼身材成为永远的回忆:"她痛恨赘肉缠身,想恢复产前的玲珑曲线。"可怜的JLo,抗拒不了意大利面的诱惑,数次大快朵颐,才使得自己肥肉缠身,昔日的性感不复存在,看来,女人还是少贪吃为妙。
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.
基金Supported by The Ministry of Health and Consumption(PI081988),CIBER-ehd,Carlos Ⅲ Institute,Madrid,SpainMinistry of Foreign Affairs and International Cooperation(A/020255/08and A/02987/09)Mohamed Amine Zaouali is fellowship-holder from the Catalan Society of Transplantation
文摘AIM: To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1) solution to protect fatty liver against cold ischemia reperfusion injury. METHODS: Steatotic livers were preserved for 24 h in IGL-1 solution supplemented with or without IGF-1 and then perfused "ex vivo " for 2 h at 37℃. We examined the effects of IGF-1 on hepatic damage and function (transaminases, percentage of sulfobromophthalein clearance in bile and vascular resistance). We also studied other factors associated with the poor tolerance of fatty livers to cold ischemia reperfusion injury such as mitochondrial damage, oxidative stress, nitric oxide, tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinases.RESULTS: Steatotic livers preserved in IGL-1 solutionsupplemented with IGF-1 showed lower transaminase levels, increased bile clearance and a reduction in vascular resistance when compared to those preserved in IGL-1solution alone. These benefits are mediated by activation of AKT and constitutive endothelial nitric oxide synthase (eNOS), as well as the inhibition of inflammatory cytokines such as TNF-α. Mitochondrial damage and oxidative stress were also prevented.CONCLUSION: IGL-1 enrichment with IGF-1 increasedfatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.
文摘In order to achieve the objectives of transparency and accountability,Mexican President Andres Manuel Lopez Obrador(AMLO)has offered a press conference every morning since he took office.This situation seemed to be a transcendental change in the field of democratic dynamics and political communication in Mexico;however,not merely a means of communication,these conferences have instead become a method of government.Using postulates of Mimetic Theory,this essay analyzes AMLO’s conferences,showing how this daily practice has become propaganda for the regime.
