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Research paper thumbnail of The Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat hepatic stellate cells

Journal of Hepatology, 1999

Research paper thumbnail of Fibrogenic effect of oxidative stress on rat hepatic stellate cells

Hepatology, 1998

Oxidative stress is associated with liver fibrosis and with hepatic stellate cell (HSC) activatio... more Oxidative stress is associated with liver fibrosis and with hepatic stellate cell (HSC) activation in vivo. However, it remains controversial whether oxidative stress contributes to HSC activation either directly or through a paracrine stimulation by damaged hepatocytes. A medium containing products released from cells undergoing oxidative stress was obtained after incubation of hepatocytes with (HCM/ Fe) or without (HCM) 0.1 mmol/L ferric nitrilotriacetate complex (FeNTA). Exposure of HSC to HCM/Fe for 24 hours significantly increased the number of proliferating HSC compared with HCM and to controls at all dilutions tested. The simultaneous coincubation of HSC with HCM/Fe and desferrioxamine (50 mol/L) did not reduce the observed increase in cell proliferation, thus excluding a role for eventually contaminating iron in HCM/Fe. HCM/Fe induced also a significant increase in collagen type I accumulation in HSC culture media. To study the cellular mechanism underlying HCM/Fe effects, we evaluated the activity of the Na ؉ /H ؉ exchanger, which plays a role in regulating HSC proliferation. The incubation of HSC for 24 hours with HCM/Fe significantly increased baseline intracellular pH (pHi) and Na ؉ /H ؉ exchanger activity, indicating a plausible role of this antiport in mediating cell response. In conclusion, hepatocytes undergoing oxidative stress release factors which are fibrogenic for HSC, thereby, confirming what has been only hypothesized in vivo. In addition, HSC proliferation is associated with changes in the Na ؉ /H ؉ exchanger activity, thus providing a useful target for the evaluation of inhibitors of this pathway for the treatment of hepatic fibrosis.

Research paper thumbnail of The antifibrotic effect of interferon-gamma is not related to modifications of t-lymphocytes pattern, but to a direct effect on lipocyte activation

Research paper thumbnail of Effects on gastric emptying, orocecal transit time (OCTT), gas production and abdominal symptoms of guar gum (GG), ispaghula (I) and mycrocristalline cellulose (MC) on healthy volunteers

Research paper thumbnail of Inhibition of the Na+/H+ exchanger reduces rat hepatic stellate cell activity and liver fibrosis: An in vitro and in vivo study

Research paper thumbnail of Supplementation of microcrystalline cellulose to a solid meal causes less symptoms than other dietary fibers. A study on dietary fibers physiological effects on human gut

Digestive and Liver Disease, 2000

Research paper thumbnail of 9 OP Early versus delayed cholecystectomy in acute lithiasic cholecystitis. A meta-analysis

Digestive and Liver Disease, 2002

Research paper thumbnail of 47 PS Functional dyspepsia and helicobacter pylori (HP): Is eradication clinically relevant? A meta-analysis on the natural history of gastritis and gastric and duodenal ulcers

Digestive and Liver Disease, 2002

Research paper thumbnail of 46 P Helicobacter pylori (HP) and functional dyspepsia: Eradication doesn't improve symptoms. A cumulative meta-analysis, updated to February 2002

Digestive and Liver Disease, 2002

Research paper thumbnail of Safety of eradication for Helicobacter pylori: How many patients stop a 7–15 days therapy for side effects? A meta-analysis of randomized trials for dyspepsia

Digestive and Liver Disease, 2001

Research paper thumbnail of Functional dyspepsia and helicobacter pylori (HP): Is eradication clinically relevant? a meta-analysis on the natural history of gastritis and gastric and duodenal ulcers

Digestive and Liver Disease, 2001

Backsmud and aim: To investiwte the incidence of retlux escphaxitis after Heliccbacter pylori (HP... more Backsmud and aim: To investiwte the incidence of retlux escphaxitis after Heliccbacter pylori (HP) &&&ion in patients witl~unccmplicated, Hp-associatedchronic gastritis during a lrmcntb follow up wricd. Material and methods: Afrer bistcdogically pmven Hp eradication, 113 pts (WF 61,52: &e-47*1 I; E gmup) without histological timI& of escphagitis (ES) at the time of emdication, were followed up for one year (I I*3 month), tbm reexamined by EGD-scopy with multiale bicosies. These data WETC conmated with those of 61 sex-and we-matched, Hp+ve, ~n&cd pts (contmls, C group) wit&t histclogical tindings of ES, endoscopically rpinvestigated after a similar follow-up paicd (12'4 month). Patients with atrcpbic gsstritis, pepric UlcSr, necplasia or pyloric stenosis have been excluded. Results: A biatal hernia (HH) ~8s found in 99 (57%) pts (64 E, 35 c: p=+.9). At the end of the follow up, ES was bistclcgically diagnosed in 28 (16%) pts (25 E, 3 C), with a greater incidence in eradicated pts (22% VI 5%; p=O.OW cdds ratio 5.49; 95%CL: 1.56-29.48). From pts of both gmup with H?I, bistcIogical tindings of ES were detect& in 25 (25%) pts (22 E, 3 C), with a significantly bigba incidence in eradicated pts (34% vs 6%; fl.01; cdds 5.59; 9WnCL.z I .46-31.22). No significant difference between gmups for incidence of ES was found in patients without HH (6% E vs 0% C, p=O.S). Conclusions: These results suggest that reflex cw&gitis may develop in some patients after Hp eradication for uncomplicated, Hp.associated chronic gastitis, probably because of an increased gastric acid secretion. The presence of a hiatal hernia may expose eradicated patients tc B higher nsk of developing escphagitis

Research paper thumbnail of Timing of Cholecystectomy for Acute Calculous Cholecystitis: A Meta-Analysis

American Journal of Gastroenterology, 2004

Research paper thumbnail of Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis

Hepatology, 1996

procollagen type I, fibronectin, and laminin in the DMN Interferon gamma (IFN-g) inhibits in vitr... more procollagen type I, fibronectin, and laminin in the DMN Interferon gamma (IFN-g) inhibits in vitro the activa-/ IFN-g group. Thus, this study indicates that IFN-g retion of hepatic stellate cells (HSC), the primary extracelduces extracellular matrix deposition in vivo by inhibilular matrix-producing cells in liver fibrosis. This study tion of HSC activation. (HEPATOLOGY 1996;23:1189-1199.) was undertaken to determine in vivo the effect of IFN-g in the rat model of liver fibrosis induced by dimethylnitrosamine (DMN), where HSC activation represents an Hepatic fibrosis is a common response to chronic liver early response to cell injury. Rats were killed after 1 or injury of variable origin (viral, metabolic, or toxic). Re-3 weeks of treatment with DMN, IFN-g, DMN / IFN-g, gardless of the etiologic factor, liver fibrosis is characor saline. Immunohistochemistry was used to identerized by increased production of extracellular matrix Address reprint requests to: Gianluca Svegliati Baroni, M.D., Department chondrocytes, 27 fetal rat bone, 28 and human dermal fi

Research paper thumbnail of The case of Helicobacter pylori and functional dyspepsia: The jury in the trial is still out. A 2000 cumulative meta-analysis, updated to May

Digestive and Liver Disease, 2000

Research paper thumbnail of 47 PS Functional dyspepsia and helicobacter pylori (HP): Is eradication clinically relevant? A meta-analysis on the natural history of gastritis and gastric and duodenal ulcers

Digestive and Liver Disease, 2002

deve~pmem ofthromb& erterial and venous diseases vitamin BI2, wth warnin 86 and folates, are cofa... more deve~pmem ofthromb& erterial and venous diseases vitamin BI2, wth warnin 86 and folates, are cofactors of the most important enzymes of Its metabolic pathway Their deficiency predispose to hyperhomocysteinemia In particular, since vitamin Bl2 absorption depends on the secretion of intrmsec factor by the pa&al cells, gestnc atrophy (GA) may &se a melabsorptive state of this vitemin To investigate If GA is a risk factor, we e vitamin B I2 malabsorption, for hyperhomocysteinemia Methods Twenty (20) dyspeptic out-petients (pts)were enrolled, 5 men and 15 women with mean age 55+4 IO pts with hystological signs of GA and IO without Blood samples were collected for measurement ofhomocvsteinemia and vitamin 812 Hyperhomosysteinemia was defined as fasting serum total homocysteme levels (> I2 wmoI/L) Vitamin BI2 deficiency was defined as concentrations 000 pgiml,. The other principal causes of gastrointestinal viteminic malabsorption were excluded in all pts Results Seven (7) out of IO patients pts wth GA (70%) showed hyperhomocysteinemia (mean value 16+6) wth respect to 2 patients in the control group (mean value 8+4) In all sublens with GA and hyperhomocysteinemia a vitamin 812 deficiency wes present (mean v&e 169+23), in the c&ml group no patients showed a vitaminic deficiency (mean value 357+27) The difference between groups were statistically significant @CO 05) Conclusion These preliminary study seem to suggest a mle of GA in development of hyperhomocysteinemie, due to an impairement ofvitamin 812 absorption. Since hyperhomocysteinemia is an indipendent risk factor for cardiovascular diseases, it is plausible to hypothesize a link between gastric atrophy and thrombotic pathologies 46 P HELiCOBACTERPYL.ORI @IF') AND FUNCTIONAL DYSPEPSIA ERADICATION DOESN'T IMPROVE SYMPTOMS A CUMULATIVE META-ANALYSIS. UPDATED TO FEBRUARY 2002 M KOCY L D'AMBROSIO, L GILI, M BIANCHI, A DEZI, L CAPURSO DEPT GASTROENTEROLOGY AND INTERNAL MEDICINE, SAN FILIPPO NERl HOSPITAL, ROME

Research paper thumbnail of The Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat hepatic stellate cells

Journal of Hepatology, 1999

Research paper thumbnail of Fibrogenic effect of oxidative stress on rat hepatic stellate cells

Hepatology, 1998

Oxidative stress is associated with liver fibrosis and with hepatic stellate cell (HSC) activatio... more Oxidative stress is associated with liver fibrosis and with hepatic stellate cell (HSC) activation in vivo. However, it remains controversial whether oxidative stress contributes to HSC activation either directly or through a paracrine stimulation by damaged hepatocytes. A medium containing products released from cells undergoing oxidative stress was obtained after incubation of hepatocytes with (HCM/ Fe) or without (HCM) 0.1 mmol/L ferric nitrilotriacetate complex (FeNTA). Exposure of HSC to HCM/Fe for 24 hours significantly increased the number of proliferating HSC compared with HCM and to controls at all dilutions tested. The simultaneous coincubation of HSC with HCM/Fe and desferrioxamine (50 mol/L) did not reduce the observed increase in cell proliferation, thus excluding a role for eventually contaminating iron in HCM/Fe. HCM/Fe induced also a significant increase in collagen type I accumulation in HSC culture media. To study the cellular mechanism underlying HCM/Fe effects, we evaluated the activity of the Na ؉ /H ؉ exchanger, which plays a role in regulating HSC proliferation. The incubation of HSC for 24 hours with HCM/Fe significantly increased baseline intracellular pH (pHi) and Na ؉ /H ؉ exchanger activity, indicating a plausible role of this antiport in mediating cell response. In conclusion, hepatocytes undergoing oxidative stress release factors which are fibrogenic for HSC, thereby, confirming what has been only hypothesized in vivo. In addition, HSC proliferation is associated with changes in the Na ؉ /H ؉ exchanger activity, thus providing a useful target for the evaluation of inhibitors of this pathway for the treatment of hepatic fibrosis.

Research paper thumbnail of The antifibrotic effect of interferon-gamma is not related to modifications of t-lymphocytes pattern, but to a direct effect on lipocyte activation

Research paper thumbnail of Effects on gastric emptying, orocecal transit time (OCTT), gas production and abdominal symptoms of guar gum (GG), ispaghula (I) and mycrocristalline cellulose (MC) on healthy volunteers

Research paper thumbnail of Inhibition of the Na+/H+ exchanger reduces rat hepatic stellate cell activity and liver fibrosis: An in vitro and in vivo study

Research paper thumbnail of Supplementation of microcrystalline cellulose to a solid meal causes less symptoms than other dietary fibers. A study on dietary fibers physiological effects on human gut

Digestive and Liver Disease, 2000

Research paper thumbnail of 9 OP Early versus delayed cholecystectomy in acute lithiasic cholecystitis. A meta-analysis

Digestive and Liver Disease, 2002

Research paper thumbnail of 47 PS Functional dyspepsia and helicobacter pylori (HP): Is eradication clinically relevant? A meta-analysis on the natural history of gastritis and gastric and duodenal ulcers

Digestive and Liver Disease, 2002

Research paper thumbnail of 46 P Helicobacter pylori (HP) and functional dyspepsia: Eradication doesn't improve symptoms. A cumulative meta-analysis, updated to February 2002

Digestive and Liver Disease, 2002

Research paper thumbnail of Safety of eradication for Helicobacter pylori: How many patients stop a 7–15 days therapy for side effects? A meta-analysis of randomized trials for dyspepsia

Digestive and Liver Disease, 2001

Research paper thumbnail of Functional dyspepsia and helicobacter pylori (HP): Is eradication clinically relevant? a meta-analysis on the natural history of gastritis and gastric and duodenal ulcers

Digestive and Liver Disease, 2001

Backsmud and aim: To investiwte the incidence of retlux escphaxitis after Heliccbacter pylori (HP... more Backsmud and aim: To investiwte the incidence of retlux escphaxitis after Heliccbacter pylori (HP) &&&ion in patients witl~unccmplicated, Hp-associatedchronic gastritis during a lrmcntb follow up wricd. Material and methods: Afrer bistcdogically pmven Hp eradication, 113 pts (WF 61,52: &e-47*1 I; E gmup) without histological timI& of escphagitis (ES) at the time of emdication, were followed up for one year (I I*3 month), tbm reexamined by EGD-scopy with multiale bicosies. These data WETC conmated with those of 61 sex-and we-matched, Hp+ve, ~n&cd pts (contmls, C group) wit&t histclogical tindings of ES, endoscopically rpinvestigated after a similar follow-up paicd (12'4 month). Patients with atrcpbic gsstritis, pepric UlcSr, necplasia or pyloric stenosis have been excluded. Results: A biatal hernia (HH) ~8s found in 99 (57%) pts (64 E, 35 c: p=+.9). At the end of the follow up, ES was bistclcgically diagnosed in 28 (16%) pts (25 E, 3 C), with a greater incidence in eradicated pts (22% VI 5%; p=O.OW cdds ratio 5.49; 95%CL: 1.56-29.48). From pts of both gmup with H?I, bistcIogical tindings of ES were detect& in 25 (25%) pts (22 E, 3 C), with a significantly bigba incidence in eradicated pts (34% vs 6%; fl.01; cdds 5.59; 9WnCL.z I .46-31.22). No significant difference between gmups for incidence of ES was found in patients without HH (6% E vs 0% C, p=O.S). Conclusions: These results suggest that reflex cw&gitis may develop in some patients after Hp eradication for uncomplicated, Hp.associated chronic gastitis, probably because of an increased gastric acid secretion. The presence of a hiatal hernia may expose eradicated patients tc B higher nsk of developing escphagitis

Research paper thumbnail of Timing of Cholecystectomy for Acute Calculous Cholecystitis: A Meta-Analysis

American Journal of Gastroenterology, 2004

Research paper thumbnail of Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis

Hepatology, 1996

procollagen type I, fibronectin, and laminin in the DMN Interferon gamma (IFN-g) inhibits in vitr... more procollagen type I, fibronectin, and laminin in the DMN Interferon gamma (IFN-g) inhibits in vitro the activa-/ IFN-g group. Thus, this study indicates that IFN-g retion of hepatic stellate cells (HSC), the primary extracelduces extracellular matrix deposition in vivo by inhibilular matrix-producing cells in liver fibrosis. This study tion of HSC activation. (HEPATOLOGY 1996;23:1189-1199.) was undertaken to determine in vivo the effect of IFN-g in the rat model of liver fibrosis induced by dimethylnitrosamine (DMN), where HSC activation represents an Hepatic fibrosis is a common response to chronic liver early response to cell injury. Rats were killed after 1 or injury of variable origin (viral, metabolic, or toxic). Re-3 weeks of treatment with DMN, IFN-g, DMN / IFN-g, gardless of the etiologic factor, liver fibrosis is characor saline. Immunohistochemistry was used to identerized by increased production of extracellular matrix Address reprint requests to: Gianluca Svegliati Baroni, M.D., Department chondrocytes, 27 fetal rat bone, 28 and human dermal fi

Research paper thumbnail of The case of Helicobacter pylori and functional dyspepsia: The jury in the trial is still out. A 2000 cumulative meta-analysis, updated to May

Digestive and Liver Disease, 2000

Research paper thumbnail of 47 PS Functional dyspepsia and helicobacter pylori (HP): Is eradication clinically relevant? A meta-analysis on the natural history of gastritis and gastric and duodenal ulcers

Digestive and Liver Disease, 2002

deve~pmem ofthromb& erterial and venous diseases vitamin BI2, wth warnin 86 and folates, are cofa... more deve~pmem ofthromb& erterial and venous diseases vitamin BI2, wth warnin 86 and folates, are cofactors of the most important enzymes of Its metabolic pathway Their deficiency predispose to hyperhomocysteinemia In particular, since vitamin Bl2 absorption depends on the secretion of intrmsec factor by the pa&al cells, gestnc atrophy (GA) may &se a melabsorptive state of this vitemin To investigate If GA is a risk factor, we e vitamin B I2 malabsorption, for hyperhomocysteinemia Methods Twenty (20) dyspeptic out-petients (pts)were enrolled, 5 men and 15 women with mean age 55+4 IO pts with hystological signs of GA and IO without Blood samples were collected for measurement ofhomocvsteinemia and vitamin 812 Hyperhomosysteinemia was defined as fasting serum total homocysteme levels (> I2 wmoI/L) Vitamin BI2 deficiency was defined as concentrations 000 pgiml,. The other principal causes of gastrointestinal viteminic malabsorption were excluded in all pts Results Seven (7) out of IO patients pts wth GA (70%) showed hyperhomocysteinemia (mean value 16+6) wth respect to 2 patients in the control group (mean value 8+4) In all sublens with GA and hyperhomocysteinemia a vitamin 812 deficiency wes present (mean v&e 169+23), in the c&ml group no patients showed a vitaminic deficiency (mean value 357+27) The difference between groups were statistically significant @CO 05) Conclusion These preliminary study seem to suggest a mle of GA in development of hyperhomocysteinemie, due to an impairement ofvitamin 812 absorption. Since hyperhomocysteinemia is an indipendent risk factor for cardiovascular diseases, it is plausible to hypothesize a link between gastric atrophy and thrombotic pathologies 46 P HELiCOBACTERPYL.ORI @IF') AND FUNCTIONAL DYSPEPSIA ERADICATION DOESN'T IMPROVE SYMPTOMS A CUMULATIVE META-ANALYSIS. UPDATED TO FEBRUARY 2002 M KOCY L D'AMBROSIO, L GILI, M BIANCHI, A DEZI, L CAPURSO DEPT GASTROENTEROLOGY AND INTERNAL MEDICINE, SAN FILIPPO NERl HOSPITAL, ROME