Sarcoidosis is a chronic multi-systemic granulomatous disease,and liver involvement frequently occurs.in most cases,no evidence of liver dysfunction is ob-served,and portal hypertension due to sarcoid liver diseases i...Sarcoidosis is a chronic multi-systemic granulomatous disease,and liver involvement frequently occurs.in most cases,no evidence of liver dysfunction is ob-served,and portal hypertension due to sarcoid liver diseases is a rareoccurrence.Moreover,no case of liver sarcoidosis has ever been reported with confirma-tion of the disease progression.Herein we describe a patient having hepatic sarcoidosis with severe portal hypertension and liver dysfunction.The diagnosis was histologically confirmed from granulomatous status to established liver cirrhosis over 10 years.A 46-year-old woman developed massive hematemesis due to the rupture of gastric cardial varices.She underwent emer-gency endoscopic injection sclerotherapy,and clear evi-dence of chronic hepatic failure.Twelve years ago,she was diagnosed as having sarcoidosis with respiratoryclinicalsymptoms.Liver biopsy revealed asymptomatic incidental granulomas without fibrosis development.After a couple of years,features of liver dysfunction were manifest and progressed.Ten years after the first biopsy,a second liver biopsy was performed,and well established dense fibrosis was revealed.Although significant liver dysfunction with portal hypertension is rarely seen in sarcoidosis,this case indicates that we have to consider the possibility that sarcoidosis may cause end-stage liver cirrhosis.展开更多
The expression and implication of vascular endothelial growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in residual hepatic tumor cells after lipiodol embolization were investi- gated. Two weeks after t...The expression and implication of vascular endothelial growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in residual hepatic tumor cells after lipiodol embolization were investi- gated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group （n=20） and lipiodol group （n=20）. For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using en- zyme-linked immunosorbent assay （ELISA）. A three-step immunohistochemieal technique （ABC） was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group （1.42~0.29 ng/mL） than in the control group （1.12~0.21 ng/mL） （P〈0.01）. Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group （62.13%~7.69%） than in the control group （53.16%~9.17%） （P〈0.05）. Similarly, the MMP-9 ex- pression in the residual ~mor cells was higher in the lipiodol group. The mRNA levels of VEGF （2.9313~2.4231） and MMP-9 （3.5721~1.6107） in the lipiodol group were significantly higher than those in the control group （1.5728~0.9453 and 1.7573~1.0641, respectively, P〈0.05）. Therefore, it was rea- sonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.展开更多
AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate...AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate as an index of IP,induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-α,assessed the results using an enzymatic-spectrophotometric method,transmission electron microscopy,immunohistochemistry,Western blotting and real-time quantitative polymerase chain reaction.The effect of the administration of antiTNF-α immunoglobulin G(IgG) antibody,before the administration of D-galactosamine/lipopolysaccharide,on TNF-α was also assessed.RESULTS:IP was significantly increased in the mouse model of FHF 6 h after injection(13.57 ± 1.70 mg/L,13.02 ± 1.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.001).Electron microscopic analysis revealed tight junction(TJ) disruptions,epithelial cell swelling,and atrophy of intestinal villi.Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models(occludin:0.57 ± 0.159 fold vs baseline,P = 0.000;claudin-1:0.3067 ± 0.1291 fold vs baseline,P = 0.003),as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein(occludin:0.61 ± 0.0473 fold vs baseline,P = 0.000;claudin-1:0.6633 ± 0.0328 fold vs baseline,P = 0.000).Prophylactic treatment with antiTNF-α IgG antibody prevented changes in IP(4.50 ± 0.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.791),intestinal tissue ultrastructure,and the mRNA levels of occludin and claudin-1 expression(occludin:0.8865 ± 0.0274 fold vs baseline,P = 0.505;claudin-1:0.85 ± 0.1437 fold vs baseline,P = 0.1),and in the protein levels(occludin:0.9467 ± 0.0285 fold vs baseline,P > 0.05;claudin-1:0.9533 ± 0.0186 fold vs baseline,P = 0.148).CONCLUSION:Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1,and destruction of the TJ in the colon,which were induced by TNF-α in FHF mice.展开更多
文摘Sarcoidosis is a chronic multi-systemic granulomatous disease,and liver involvement frequently occurs.in most cases,no evidence of liver dysfunction is ob-served,and portal hypertension due to sarcoid liver diseases is a rareoccurrence.Moreover,no case of liver sarcoidosis has ever been reported with confirma-tion of the disease progression.Herein we describe a patient having hepatic sarcoidosis with severe portal hypertension and liver dysfunction.The diagnosis was histologically confirmed from granulomatous status to established liver cirrhosis over 10 years.A 46-year-old woman developed massive hematemesis due to the rupture of gastric cardial varices.She underwent emer-gency endoscopic injection sclerotherapy,and clear evi-dence of chronic hepatic failure.Twelve years ago,she was diagnosed as having sarcoidosis with respiratoryclinicalsymptoms.Liver biopsy revealed asymptomatic incidental granulomas without fibrosis development.After a couple of years,features of liver dysfunction were manifest and progressed.Ten years after the first biopsy,a second liver biopsy was performed,and well established dense fibrosis was revealed.Although significant liver dysfunction with portal hypertension is rarely seen in sarcoidosis,this case indicates that we have to consider the possibility that sarcoidosis may cause end-stage liver cirrhosis.
基金supported by grants from the Natural Science Foundation of Shandong Province of China (No. Y2007C102)the Medical Science and Technology Development Foundation of Shandong Province of China (No. 2007H2071)
文摘The expression and implication of vascular endothelial growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in residual hepatic tumor cells after lipiodol embolization were investi- gated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group （n=20） and lipiodol group （n=20）. For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using en- zyme-linked immunosorbent assay （ELISA）. A three-step immunohistochemieal technique （ABC） was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group （1.42~0.29 ng/mL） than in the control group （1.12~0.21 ng/mL） （P〈0.01）. Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group （62.13%~7.69%） than in the control group （53.16%~9.17%） （P〈0.05）. Similarly, the MMP-9 ex- pression in the residual ~mor cells was higher in the lipiodol group. The mRNA levels of VEGF （2.9313~2.4231） and MMP-9 （3.5721~1.6107） in the lipiodol group were significantly higher than those in the control group （1.5728~0.9453 and 1.7573~1.0641, respectively, P〈0.05）. Therefore, it was rea- sonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.
基金Supported by National Ministry of Health of China,No.97100252
文摘AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate as an index of IP,induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-α,assessed the results using an enzymatic-spectrophotometric method,transmission electron microscopy,immunohistochemistry,Western blotting and real-time quantitative polymerase chain reaction.The effect of the administration of antiTNF-α immunoglobulin G(IgG) antibody,before the administration of D-galactosamine/lipopolysaccharide,on TNF-α was also assessed.RESULTS:IP was significantly increased in the mouse model of FHF 6 h after injection(13.57 ± 1.70 mg/L,13.02 ± 1.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.001).Electron microscopic analysis revealed tight junction(TJ) disruptions,epithelial cell swelling,and atrophy of intestinal villi.Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models(occludin:0.57 ± 0.159 fold vs baseline,P = 0.000;claudin-1:0.3067 ± 0.1291 fold vs baseline,P = 0.003),as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein(occludin:0.61 ± 0.0473 fold vs baseline,P = 0.000;claudin-1:0.6633 ± 0.0328 fold vs baseline,P = 0.000).Prophylactic treatment with antiTNF-α IgG antibody prevented changes in IP(4.50 ± 0.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.791),intestinal tissue ultrastructure,and the mRNA levels of occludin and claudin-1 expression(occludin:0.8865 ± 0.0274 fold vs baseline,P = 0.505;claudin-1:0.85 ± 0.1437 fold vs baseline,P = 0.1),and in the protein levels(occludin:0.9467 ± 0.0285 fold vs baseline,P > 0.05;claudin-1:0.9533 ± 0.0186 fold vs baseline,P = 0.148).CONCLUSION:Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1,and destruction of the TJ in the colon,which were induced by TNF-α in FHF mice.
