Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G contributed analyti...Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G contributed analytic tools; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C analyzed the data; Diamantis G and Scarpa M wrote the paper; all authors revised and approved the final version of the manuscript.展开更多
AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to...AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis.METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet,iron-supplemented diet, and sham-treated controls.Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured.RESULTS: Macroscopic damage was reduced in irondeprived groups and increased in iron-supplemented rats.Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats.CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.展开更多
AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included...AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS： TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients （P=0.05）. IL-1β was higher in cirrhosis patients （P=0.05）. A sig- nificant correlation was found between TNF-α and staging （P= 0.05） and between IL-1β levels and grading （P=0.04）. c-myc showed a significantly higher expression in cirrhosis patients （P=0.001）. Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients （P=0.05） and in HCV genotype 1 （P=0.03）. Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype （P=0.04） and grading （P=0.007）. Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype （P= 0.02）. CONCLUSION： In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.展开更多
AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxi...AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo , S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150 000/μL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFα, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150 000/μL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen. CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.展开更多
AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent mu...AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.展开更多
Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least...Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least 6cm associated with systemic toxicity. Methods: Overall, 15 patients had surgery for TM at our institutions over a 10- year period (1993- 2003). In contrast to other studies that used medical therapy as the first- line treatment for TM, in our experience all patients underwent surgery as soon as possible after diagnosis of TM (early surgery). Results: 14 patients underwent subtotal colect- omy with terminal ileostomy, while for 1 patient the surgical procedure consisted only in a decompressive cecostomy. Two major complications occurred consisting of 2 cases of multiple organ failure leading to death. No other major complications or deaths were reported. The overall mortality rate was therefore 13% (0% in patients < 65 years). Conclusion: This study shows that early surgery has the potential to represent a valid therapeutic strategy for patients with TM resulting in a small number of TM- related complications and deaths. Elderly patients seem to have a high risk of multiple organ dysfunction syndrome and postsurgical death.展开更多
文摘Diamantis G, Scarpa M, Castoro C, Ancona E and Battaglia G designed the research; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C performed the research; Castoro C, Ancona E and Battaglia G contributed analytic tools; Diamantis G, Scarpa M, Bocus P, Realdon S and Castoro C analyzed the data; Diamantis G and Scarpa M wrote the paper; all authors revised and approved the final version of the manuscript.
文摘AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis.METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet,iron-supplemented diet, and sham-treated controls.Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured.RESULTS: Macroscopic damage was reduced in irondeprived groups and increased in iron-supplemented rats.Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats.CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.
基金Supported by PRIN grants from the Italian Ministry of Science and Technology, No. 2003063143-006
文摘AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS： TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients （P=0.05）. IL-1β was higher in cirrhosis patients （P=0.05）. A sig- nificant correlation was found between TNF-α and staging （P= 0.05） and between IL-1β levels and grading （P=0.04）. c-myc showed a significantly higher expression in cirrhosis patients （P=0.001）. Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients （P=0.05） and in HCV genotype 1 （P=0.03）. Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype （P=0.04） and grading （P=0.007）. Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype （P= 0.02）. CONCLUSION： In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.
文摘AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo , S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150 000/μL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFα, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150 000/μL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen. CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.
文摘AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.
文摘Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least 6cm associated with systemic toxicity. Methods: Overall, 15 patients had surgery for TM at our institutions over a 10- year period (1993- 2003). In contrast to other studies that used medical therapy as the first- line treatment for TM, in our experience all patients underwent surgery as soon as possible after diagnosis of TM (early surgery). Results: 14 patients underwent subtotal colect- omy with terminal ileostomy, while for 1 patient the surgical procedure consisted only in a decompressive cecostomy. Two major complications occurred consisting of 2 cases of multiple organ failure leading to death. No other major complications or deaths were reported. The overall mortality rate was therefore 13% (0% in patients < 65 years). Conclusion: This study shows that early surgery has the potential to represent a valid therapeutic strategy for patients with TM resulting in a small number of TM- related complications and deaths. Elderly patients seem to have a high risk of multiple organ dysfunction syndrome and postsurgical death.
