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Effect of oral zinc supplementation in animal model of Wilson disease
Category 8: Nutrition, metabolism, alcoholic liver disease, pharmacology ~2-7
EFFECT OF ORAL ZINC SUPPLEMENTATION IN ANIMAL MODEL OF WILSON DISEASE
V. Medici, P. Irato, R. D'Inca, G.C. Albergoni, A. Cecchetto, R. Cardin, G.C. Sturniolo. Surgical and Gastroenterological Sciences, University
199
and PUO (n = 2). E. coli, streptococci and pseudomonas were isolated. Mean hospital stay was 33 days. The concept of restoring the normal gut flora instead of eliminating potentially pathogenic bacilli decreased the rate of bacterial-infections after liver-transplantation.
of padua, Italy Background: Long-Evans Cinnamon (LEC) rat has a mutation homologous to the human Wilson disease (WD) gene leading to Cu induced hepatotoxicity. WD is effectively treated in humans by Zn administration which increases metaUothionein (MT) concentrations. Aims: To determine the effect of oral Zn treatment on antioxidant mechanisms, oxidative injury to DNA and hepatic damage in LEC rats. Matherial and Methods: 24 male LEC rats, 5 weeks of age, were treated for 1 (group A) or 2 weeks (group B) either with Zn Acetate (0.8 mg/Kg/day) by gavage (groups A and B) or standard diet (groups Ac and Bc). Liver, intestinal and kidney concentrations of MT, superoxide dismutase (SOD), catalase, Cu, Fe and Zn and liver OH8dG levels were determined. Liver damage was assessed histologically. Results: Liver MT were significantly higher in A than in Ac and returned to control values after 2 week treatment. Intestinal and renal MT concentrations were significantly increased in A and B vs Ac and Bc. Zn didn't have any affect on liver and kidney SOD and Catalase. Liver and kidney Fe and Cu were significantly lower in B than in the other groups. Intestinal Cu was significantly increased in A than in the other groups. Zn didn't affect intestinal Fe while a significant reduction was observed in the kidney in A and B compared to Ac and Bc. Zn was significantly increased in A and B in all sites. Liver OH8dG amount was significantly higher in A than in B. No change was observed in liver histology in any group. Conclusions: Short term Zn-treatment increases MT concentration and reduces OH8dG formation in liver. Our results support the role of Zn in the defence mechanisms against oxidant Cu-induced tissue injury probably by inducing MT synthesis and thus preventing intestinal Cu absorption.
- ~ EARLY ENTERAL SUPPLY OF LACTOBACILLI AND FIBRE VERSUS SBD - A PROSPECTIVE RANDOMISED TRIAL IN LIVER TRANSPLANT RECIPIENTS N. Rayes, M. Brammer, S. Hansen, A.R. Mueller, S. Serke, D. Seehofer, S. Bengmark, P. Neuhaus. Charit' Campus Virchow, General-, Visceral-
and Transplant-Surgery, Germany Translocation as an important source of bacterial infections following liver-transplantation can be decreased by SBD (selective-bowel-decontamination). Disadvantages are costs, elimination of protective gut-flora and minor effectiveness for grampositive-bacilli. A new concept tries to prevent translocation using lactobacilli and fibre. We conducted a randomised prospective trial comparing a) SBD plus conventional enteral-diet with b) a fibre- containing enteral-solution plus lactobacillus-plantarnm or c) placebo. 90 liver transplant-recipients have been enrolled. All received 2 litres of enteral nutrition via feeding-tube from POD-1 to POD-11 additionally to the normal diet. Urine and stool samples, swabs from the drainages, catheters and wounds were sent regularly for microbiological investigation. Group 1: Pts received SBD from POD-0 to POD-28. In this group 10/30 (33%) had infections: cholangitis (n = 4), UTI (n = 4), pneumonia (n = 3), wound infection (n = 1) and sepsis (n = 1). Serratia marcescens, enterococci, pseudomonas, xanthomonas and staphylococci were isolated from the specimen. Mean hospital stay was 38 days. Group 2: The enteral diet contained 1.5 g fibre/100 ml. Twice daily lactobacillus-plantarum was added. In this group 6/30 (20%) patients had infections: cholangitis (n = 3) and UTI (n = 3). E. coli, enterococci, streptococci and pseudomonas were isolated. Mean hospital stay was 33 days. Group 3: The same enteral solution was given as in group 2 but placebo (inactivated-lactobacilli) was added. The infection rate was 9/30 (30%): cholangitis (n = 4), UTI (n = 3)
--] EPIDEMIOLOGICAL STUDIES SUPPORTS AN OCCUPATIONAL ETIOLOGY FOR NONALCOHOLIC STEATOHEPATITIS AMONG PETROCHEMICAL WORKERS FROM BAHIA, BRAZIL F.M. Carvalho, A.M. Silvany-Neto, H.P. Cotrim, J.L.B. Mendes, J.E Gidi, E Guedes, R. Oliveira. Medicine, Universidade Federal da
Bahia, Brazil Four studies an oil refinery in the State of Bahia, Brazil, with approximately 2,000 workers, gathered 548 individuals with GGT, ALT or AST enzymes 10% above reference levels. A case-control study among 150 individuals, with GGT and ALT simultaneously elevated, and 150 controls, has estimated a risk of 7.3 for those working in production sectors, the effects of drinking, body mass index, medical antecedents of hepatitis and employment time being adequately controlled. A casecontrol study with 19 workers, with histopathological diagnostic of Nonalcoholic Steatohepatitis (NASH) and 19 controls, showed a risk estimation of 15.0 for those working in the production sectors. Eightynine out of the 150 cases occurred from 1992 to 1994, with a sharp peak in 1993; 88 of them came from production sectors. The prevalence of hepatic alterations (simultaneous GGT and ALT elevation) in a sample of 692 workers from the refinery was 15.0% and 3.8% in a sample of 377 workers from the administrative office, at Salvador City. Within the refinery, workers from the production sector were also mostly affected. Similar studies were carried out among workers from a pollution control enterprise which treats industrial residues from most of the 53 industries from the Petrochemical Pole of Camaqari City, Bahia. Simultaneous GGT and ALT elevation was present in 13.7% of work force, those from production sectors being more affected than those from the administrative one: 15.7 versus 9.1%, respectively. Results support the hypothesis of an occupational etiology for hepatic liver disease, including NASH, in these populations.
~']
CHRONIC HEPATITIS C AND ALCOHOL-INDUCED OXIDATIVE STRESS
S. Morelli l, C. Rigarnonti 1, E. Maduli 1, S. Andorno 1, R. Rolla 2, M. Vidali 2, R. Boldorini 3, M. Sartori i E. Albano 2. 1 Clinica Medica
Generale; 2Dipartimento di Scienze Mediche; 3Anatomia Patologica University del Piemonte Orientale A. Avogadro, Novara, Italy Alcohol and HCV infection are both responsible for liver damage. Our aim is to investigate whether oxidative stress induced by alcohol is involved in worsening liver fibrosis in patients with chronic hepatits C. Eighty-nine consecutive patients biopsied for chronic hepatitis C were divided according to alcohol intake (35 with no alcohol intake, 34 with intake of 140 g of alcohol/week for women and 350 g/week for men, 20 with higher intake). They were compared to twentyfour healthy controls and 15 BBV and HCV negative patients with ALD. As markers of oxidative stress we evaluated serum antibodies against human albumin adducts with malonildiaidehyde- acetaldehyde (HSA-MAA), lipid hydroperoxide (HSA-LOOH) and oxidised cardiolipin (Ox-CL), using ELISA. HCV positive patients with high alcohol intake had Ishak's staging scores higher than those with low alcohol intake or no alcohol intake (P = 0.007). As compared to the other groups, ALD patients showed a statistically significant (p < 0.001) increase in the titres of the antibodies tested. Moreover, the test for trend applied to the HCV positive patients, showed a significant increase in antibodies against HSA-LOOH (p = 0.003) and Ox-CL (p = 0.02) with rising alcohol intake. Even low or moderate alcohol intake promotes liver fibrosis
EFFECT OF ORAL ZINC SUPPLEMENTATION IN ANIMAL MODEL OF WILSON DISEASE
V. Medici, P. Irato, R. D'Inca, G.C. Albergoni, A. Cecchetto, R. Cardin, G.C. Sturniolo. Surgical and Gastroenterological Sciences, University
199
and PUO (n = 2). E. coli, streptococci and pseudomonas were isolated. Mean hospital stay was 33 days. The concept of restoring the normal gut flora instead of eliminating potentially pathogenic bacilli decreased the rate of bacterial-infections after liver-transplantation.
of padua, Italy Background: Long-Evans Cinnamon (LEC) rat has a mutation homologous to the human Wilson disease (WD) gene leading to Cu induced hepatotoxicity. WD is effectively treated in humans by Zn administration which increases metaUothionein (MT) concentrations. Aims: To determine the effect of oral Zn treatment on antioxidant mechanisms, oxidative injury to DNA and hepatic damage in LEC rats. Matherial and Methods: 24 male LEC rats, 5 weeks of age, were treated for 1 (group A) or 2 weeks (group B) either with Zn Acetate (0.8 mg/Kg/day) by gavage (groups A and B) or standard diet (groups Ac and Bc). Liver, intestinal and kidney concentrations of MT, superoxide dismutase (SOD), catalase, Cu, Fe and Zn and liver OH8dG levels were determined. Liver damage was assessed histologically. Results: Liver MT were significantly higher in A than in Ac and returned to control values after 2 week treatment. Intestinal and renal MT concentrations were significantly increased in A and B vs Ac and Bc. Zn didn't have any affect on liver and kidney SOD and Catalase. Liver and kidney Fe and Cu were significantly lower in B than in the other groups. Intestinal Cu was significantly increased in A than in the other groups. Zn didn't affect intestinal Fe while a significant reduction was observed in the kidney in A and B compared to Ac and Bc. Zn was significantly increased in A and B in all sites. Liver OH8dG amount was significantly higher in A than in B. No change was observed in liver histology in any group. Conclusions: Short term Zn-treatment increases MT concentration and reduces OH8dG formation in liver. Our results support the role of Zn in the defence mechanisms against oxidant Cu-induced tissue injury probably by inducing MT synthesis and thus preventing intestinal Cu absorption.
- ~ EARLY ENTERAL SUPPLY OF LACTOBACILLI AND FIBRE VERSUS SBD - A PROSPECTIVE RANDOMISED TRIAL IN LIVER TRANSPLANT RECIPIENTS N. Rayes, M. Brammer, S. Hansen, A.R. Mueller, S. Serke, D. Seehofer, S. Bengmark, P. Neuhaus. Charit' Campus Virchow, General-, Visceral-
and Transplant-Surgery, Germany Translocation as an important source of bacterial infections following liver-transplantation can be decreased by SBD (selective-bowel-decontamination). Disadvantages are costs, elimination of protective gut-flora and minor effectiveness for grampositive-bacilli. A new concept tries to prevent translocation using lactobacilli and fibre. We conducted a randomised prospective trial comparing a) SBD plus conventional enteral-diet with b) a fibre- containing enteral-solution plus lactobacillus-plantarnm or c) placebo. 90 liver transplant-recipients have been enrolled. All received 2 litres of enteral nutrition via feeding-tube from POD-1 to POD-11 additionally to the normal diet. Urine and stool samples, swabs from the drainages, catheters and wounds were sent regularly for microbiological investigation. Group 1: Pts received SBD from POD-0 to POD-28. In this group 10/30 (33%) had infections: cholangitis (n = 4), UTI (n = 4), pneumonia (n = 3), wound infection (n = 1) and sepsis (n = 1). Serratia marcescens, enterococci, pseudomonas, xanthomonas and staphylococci were isolated from the specimen. Mean hospital stay was 38 days. Group 2: The enteral diet contained 1.5 g fibre/100 ml. Twice daily lactobacillus-plantarum was added. In this group 6/30 (20%) patients had infections: cholangitis (n = 3) and UTI (n = 3). E. coli, enterococci, streptococci and pseudomonas were isolated. Mean hospital stay was 33 days. Group 3: The same enteral solution was given as in group 2 but placebo (inactivated-lactobacilli) was added. The infection rate was 9/30 (30%): cholangitis (n = 4), UTI (n = 3)
--] EPIDEMIOLOGICAL STUDIES SUPPORTS AN OCCUPATIONAL ETIOLOGY FOR NONALCOHOLIC STEATOHEPATITIS AMONG PETROCHEMICAL WORKERS FROM BAHIA, BRAZIL F.M. Carvalho, A.M. Silvany-Neto, H.P. Cotrim, J.L.B. Mendes, J.E Gidi, E Guedes, R. Oliveira. Medicine, Universidade Federal da
Bahia, Brazil Four studies an oil refinery in the State of Bahia, Brazil, with approximately 2,000 workers, gathered 548 individuals with GGT, ALT or AST enzymes 10% above reference levels. A case-control study among 150 individuals, with GGT and ALT simultaneously elevated, and 150 controls, has estimated a risk of 7.3 for those working in production sectors, the effects of drinking, body mass index, medical antecedents of hepatitis and employment time being adequately controlled. A casecontrol study with 19 workers, with histopathological diagnostic of Nonalcoholic Steatohepatitis (NASH) and 19 controls, showed a risk estimation of 15.0 for those working in the production sectors. Eightynine out of the 150 cases occurred from 1992 to 1994, with a sharp peak in 1993; 88 of them came from production sectors. The prevalence of hepatic alterations (simultaneous GGT and ALT elevation) in a sample of 692 workers from the refinery was 15.0% and 3.8% in a sample of 377 workers from the administrative office, at Salvador City. Within the refinery, workers from the production sector were also mostly affected. Similar studies were carried out among workers from a pollution control enterprise which treats industrial residues from most of the 53 industries from the Petrochemical Pole of Camaqari City, Bahia. Simultaneous GGT and ALT elevation was present in 13.7% of work force, those from production sectors being more affected than those from the administrative one: 15.7 versus 9.1%, respectively. Results support the hypothesis of an occupational etiology for hepatic liver disease, including NASH, in these populations.
~']
CHRONIC HEPATITIS C AND ALCOHOL-INDUCED OXIDATIVE STRESS
S. Morelli l, C. Rigarnonti 1, E. Maduli 1, S. Andorno 1, R. Rolla 2, M. Vidali 2, R. Boldorini 3, M. Sartori i E. Albano 2. 1 Clinica Medica
Generale; 2Dipartimento di Scienze Mediche; 3Anatomia Patologica University del Piemonte Orientale A. Avogadro, Novara, Italy Alcohol and HCV infection are both responsible for liver damage. Our aim is to investigate whether oxidative stress induced by alcohol is involved in worsening liver fibrosis in patients with chronic hepatits C. Eighty-nine consecutive patients biopsied for chronic hepatitis C were divided according to alcohol intake (35 with no alcohol intake, 34 with intake of 140 g of alcohol/week for women and 350 g/week for men, 20 with higher intake). They were compared to twentyfour healthy controls and 15 BBV and HCV negative patients with ALD. As markers of oxidative stress we evaluated serum antibodies against human albumin adducts with malonildiaidehyde- acetaldehyde (HSA-MAA), lipid hydroperoxide (HSA-LOOH) and oxidised cardiolipin (Ox-CL), using ELISA. HCV positive patients with high alcohol intake had Ishak's staging scores higher than those with low alcohol intake or no alcohol intake (P = 0.007). As compared to the other groups, ALD patients showed a statistically significant (p < 0.001) increase in the titres of the antibodies tested. Moreover, the test for trend applied to the HCV positive patients, showed a significant increase in antibodies against HSA-LOOH (p = 0.003) and Ox-CL (p = 0.02) with rising alcohol intake. Even low or moderate alcohol intake promotes liver fibrosis