乙型肝炎肝硬化患者血清铁和铁蛋白水平与脂质过氧化损伤的相关性研究

目的探讨乙型肝炎肝硬化患者血清铁（SI）、铁蛋白（FE）水平与脂质过氧化损伤的关系。方法选择61例不同Child-Pugh分级的乙型肝炎肝硬化患者,采用采用比色法检测SI,放射免疫法检测FE,黄嘌呤氧化酶法检测超氧化物歧化酶（SOD）和硫代巴比妥酸法检测丙二醛（MDA）。结果乙型肝炎肝硬化患者血清SI和FE水平均明显高于对照组;SI、FE、MDA水平依Child-Pugh分级而呈上升趋势,而SOD水平则依次降低;SI和FE水平与MDA水平均呈正相关（r=0.562,P〈0.01;r=0.535,P〈0.01）,与SOD水平均呈负相关（r=-0.429,P〈0.01;r=-0.422,P〈0.01）。结论乙型肝炎肝硬化患者血清SI和FE水平与脂质过氧化损伤有相关性,过重铁负荷加重了肝细胞损害。     

Ferroportin (Q248H) mutations in African families with dietary iron overload

BACKGROUND: Dietary iron overload found in sub-Saharan Africa might be caused by an interaction between dietary iron and an iron-loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. METHODS: Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of iron overload and inflammation. RESULTS: We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. CONCLUSIONS: The present study of 19 families with African iron overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations.     

Relationship between serum ferritin,alcohol intake,and social status in 2235 Danish men and women

 The objective was to examine the relationships between serum ferritin, alcohol intake, and socioeconomic factors (school education, occupational education, occupation, income, marital status, cohabitation status, housing, social class) in a population survey performed in Copenhagen County during 1982–1984. The participants were selected at random from the census register and comprised 2235 healthy Danish individuals, non-blood donors (1044 men, 1191 women) in cohorts being 30, 40, 50, and 60 years old. The participants gave a detailed social and medical history and had a clinical examination including blood samples. In all age-groups, men had significantly higher serum ferritin and alcohol intake than women. In men, there was no relationship between serum ferritin and social class. Significant relationships were observed between ferritin and occupation (unemployed and self-employed men had higher ferritin than those with other occupations) and ferritin and income (in younger men, ferritin displayed a steady increase with income). None of the social variables were related to the prevalence of iron deficiency or iron overload. Alcohol intake was related to occupation and income, but not to social class. In women, none of the social variables showed any significant relationship to ferritin levels or iron overload. The prevalence of small iron stores (serum ferritin ≤30 μg/l) was lower and the intake of alcohol was higher in women from high social classes. In both men and women, serum ferritin displayed highly significant positive correlations with alcohol intake. Likewise, the prevalence of iron overload (serum ferritin >90th percentile) was closely correlated to alcohol intake. In conclusion, socioeconomic factors per se had a minor influence on serum ferritin levels and iron status in Danes. The distinct association between alcohol intake and serum ferritin levels should be considered in future iron status surveys. Received: 24 July 1995 / Accepted: 13 December 1995     

Erythrocyte and plasma ferritin in normal subjects,blood donors and iron deficiency anemia patients

Summary Ferritin concentration has been determined with an immunoradiometric assay in plasma and washed sedimented erythrocytes after hypotonic lysis. There was a gradual decrease of plasma ferritin in the sequence normal males, normal females, blood donors and patients with iron deficiency anemia. Erythrocyte ferritin remained unchanged in normal males and females and in blood donors, but dropped significantly in the anemic patients. Correspondingly, the ratio of erythrocyte to plasma ferritin rose from less than 2 in healthy males up to 8 in persons with iron deficiency.Little, if any effect on plasma and erythrocyte ferritin was observed in 12 male and female volunteers when taking iron for 4 weeks. In 2 patients with iron deficiency anemia the blood counts were normalized within 2–3 months during oral iron substitution, accompanied by a drastic increase of the erythrocyte ferritin concentration to values far above normal. In contrast, the plasma ferritin concentration remained below normal.Thus, in iron deficiency erythrocyte ferritin is synthesized with priority in the presence of iron and, in addition to plasma ferritin, appears to be a useful parameter of the iron status.     

Effects of alcohol consumption on iron metabolism in mice with hemochromatosis mutations

Background: Alcoholic liver disease is associated with increased hepatic iron accumulation. The liver-derived peptide hepcidin is the central regulator of iron homeostasis and recent animal studies have demonstrated that exposure to alcohol reduces hepcidin expression. This down-regulation of hepcidin in vivo implies that disturbed iron sensing may contribute to the hepatosiderosis seen in alcoholic liver disease. Alcohol intake is also a major factor in expression of the hemochromatosis phenotype in patients homozygous for the C282Y mutation of the HFE gene. Methods: To assess the effect of alcohol in mice with iron overload, alcohol was administered to mice with disrupted Hfe and IL-6 genes and Tfr2 mutant mice and their respective 129x1/SvJ, C57BL/6J, and AKR/J wild-type congenic strains. Iron absorption, serum iron levels, and hepcidin expression levels were then measured in these mice compared with water-treated control mice. Results: Alcohol was shown to have a strain-specific effect in 129x1/SvJ mice, with treated 129x1/SvJ mice showing a significant increase in iron absorption, serum iron levels, and a corresponding decrease in hepcidin expression. C57BL/6J and AKR/J strain mice showed no effect from alcohol treatment. 129x1/SvJ mice heterozygous or homozygous for the Hfe knockout had a diminished response to alcohol. All 3 strains were shown to have high blood alcohol levels. Conclusions: The effect of alcohol on iron homeostasis is dependent on the genetic background in mice. In an alcohol-susceptible strain, mutation of the Hfe gene diminished the response of the measured iron indices to alcohol treatment. This indicates that either maximal suppression of hepcidin levels had already occurred as a result of the Hfe mutation or that Hfe was a component of the pathway utilized by EtOH in suppressing hepcidin production and increasing iron absorption.     

Iron stores in 1359, 30- to 60-year-old Danish women: Evaluation by serum ferritin and hemoglobin

Summary Iron status, including serum (S-)ferritin and hemoglobin (Hb), was assessed in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years. S-ferritin levels were similar in 30- and 40-year-old women; they displayed a significant increase in 50-year-old women and a further significant increase in 60-year-old women. In the 30- and 40-year-old women, median S-ferritin was 38g/l, 5–95 percentile 6–135g/l; 17.2% had values < 15,g/l (i.e., depleted iron stores), 22.7% values from 15 to 30g/l (i.e., small iron stores), and 60.1% values > 30g/l (i.e., replete iron stores). In the 50-year-old women, median S-ferritin was 54g/l, 5–95 percentile 10–164g/l; 10.3% had values < 15g/l, 16.5% values from 15 to 30g/l, and 73.2% values > 30g/l. For the 60-year-old women, median S-ferritin was 84g/l, 5–95 percentile 25–249g/l; 1.6% had values < 15g/l, 8.6% values from 15 to 30g/l, and 89.8% values > 30g/l. Blood donors (n=180) had lower S-ferritin than nondonors in all age-groups (p<0.001). In the entire series, Hb levels were similar in 30- and 40-year-old women, median 137 g/l (8.5 mmol/l), 5–95 percentile 121–152 g/1 (7.5–9.4 mmol/l), and higher in 50- and 60-year-old women, median 140 g/l (8.7 mmol/l), 5–95 percentile 123-158 g/l (7.6–9.8 mmol/l) (p<0.0001). Hb values < 121 g/l (7.5 mmol/l) were observed in 3.8% of the women. Women with S-ferritin < 15 g/l (n=161) had lower Hb, median 134 g/l (8.3 mmol/l), than those with S-ferritin > 15 g/l, median 139 g/l (8.6 mmol/l) (p<0.001). Iron deficiency anemia (S-ferritin < 15 g/l and Hb < 121 g/l) was seen in 2.3% of 30- and 40-year-old women, and in 1.1% of 50- and 60-year-old women.     

Regulatory failure of serum prohepcidin levels in patients with hepatitis C

BACKGROUND/AIMS: Elevated serum ferritin and hepatic iron concentrations are frequently observed in chronic hepatitis C (CHC), which may be related to hepcidin. Because the role of hepcidin in CHC patients remains unknown, we aimed in this study to generate some information about hepcidin in CHC. METHODS: To determine whether serum hepcidin correlates with markers of iron status in patients with viral hepatitis, we measured serum prohepcidin levels in patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and in healthy controls. RESULTS: Serum prohepcidin and ferritin levels were negatively correlated (r=-0.182, P=0.037) in HCV patients and positively correlated in HBV patients and in healthy controls. The total iron scores in liver specimens from HCV patients were also negatively correlated (r=-0.403, P=0.013). Serum prohepcidin levels in patients with liver cirrhosis (LC) were significantly lower than in patients with chronic hepatitis (CH). In both CH and LC patients, serum prohepcidin levels were significantly lower in HCV patients than in HBV patients. CONCLUSION: Failure of homeostatic regulation of serum prohepcidin concentrations may be induced by HCV infection, resulting in elevation of serum ferritin levels, which leads to the progression of liver injury by iron overload in CHC patients.     

Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes

Ferritin heavy chain (FHC) protein was significantly reduced in murine failing hearts following left coronary ligation or thoracic transverse aortic constriction. The mRNA expression of FHC was not significantly altered in failing hearts, compared to that in control sham-operated hearts. Prussian blue staining revealed spotty iron depositions in myocardial infarct failing hearts. Oxidative stress was enhanced in the myocardial infarct failing hearts, as evidenced by increases in 4-hydroxy-2-nonenal and 8-hydroxy-2′-deoxyguanosine immunoreactivity. To clarify the functional significance of FHC downregulation in hearts, we infected rat neonatal cardiomyocytes with adenoviral vector expressing short hairpin RNA targeted to FHC (Ad-FHC-RNAi). The downregulation of FHC induced a reduction in the viability of cardiomyocytes. The relative number of iron deposition-, 4-hydroxy-2-nonenal- or 8-hydroxy-2′-deoxyguanosine-positive cardiomyocytes was significantly higher in Ad-FHC-RNAi-infected cardiomyocytes than in control vector-infected cardiomyocytes. Treatment of Ad-FHC-RNAi-infected cardiomyocytes with desferrioxamine, an iron chelator, significantly reduced the number of iron, 4-hydroxy-2-nonenal or 8-hydroxy-2′-deoxyguanosine-positive cells, and increased viability. In addition, treatment with N-acetyl cysteine, an antioxidant, significantly reduced the number of 4-hydroxy-2-nonenal- or 8-hydroxy-2′-deoxyguanosine-positive cells. Reduced viability in Ad-FHC-RNAi-infected cardiomyocytes was significantly improved with N-acetyl cysteine treatment. These findings indicate that excessive free iron and the resultant enhanced oxidative stress caused by downregulation of FHC lead to cardiomyocyte death. The decrease in FHC expression in failing hearts may play an important role in the pathogenesis of heart failure.     

Ascorbic-acid-mediated iron release from cellular ferritin and its relation to the formation of DNA strand breaks in neuroblastoma cells

Ascorbic acid at pharmacologically attainable concentrations effectively inhibited the growth of the catecholamine-positive neuroblastoma cell line SK-N-SH; it inhibited LS cells to a smaller extent and catecholamine-negative SK-N-LO cell growth least effectively. In all three cell lines high concentrations of H₂O₂ were found. Since ascorbic acid was shown to release iron from ferritin in vitro and to keep it in the reduced state, we suggested that it acted as a pro-oxidant in ferritin-rich neuroblastoma cells in the presence of H₂O₂ and Fe²⁺ (Fenton reaction), implying iron release from cellular ferritin. We show here that iron could be mobilized from cellular ferritin by 1 mM ascorbic acid in iron-59-preloaded SK-N-SH and LS cells, but not in SK-N-LO cells. In agreement with these results, DNA strand break formation by ascorbate was only observed in SK-N-SH and LS cells. In SK-N-LO cells, DNA strand breaks could be induced by a combination of 1 mM ascorbic acid and 100 M H₂O₂. Since cell-damaging effects caused by chemotherapy further facilitate iron release from ferritin, we conclude that ascorbate could be a powerful enhancer of some cytostatic drugs in neuroblastoma therapy.Abbreviations ECL enhanced chemoluminescence - MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - PBS phosphatebuffered saline Supported by the Deutsche Krebshilfe, grant W54/89/Ni4     

Relation between bone marrow hemosiderin iron,serum iron status markers,and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease

Summary Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18–84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18–90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p=0.03). Correlations were found between marrow iron and histochemical liver iron (rho=0.38,p=0.0001) as well as chemical liver iron (rho=0.33,p=0.01). Marrow iron was correlated to S-ferritin (rho=0.53,p=0.0001), mean red cell volume (rho=0.34,p=0.003), and S-transferrin (rho=–0.24,p=0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p=0.001) and controls (p=0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p=0.01). Correlations were found between marrow iron and ferritin (rho=0.64,p=0.0001), transferrin saturation (rho=0.56,p= 0.001), transferrin (rho=–0.53,p=0.001), S-iron (rho= 0.37,p=0.01), and hemoglobin in women (rho= 0.38,p=0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.     

The influence of blood donation on iron stores assessed by serum ferritin and hemoglobin in a population survey of 1359 Danish women

Summary The general impact of blood donation on iron status was studied in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal; 180 (13%) were blood donors. Iron stores were assessed by serum (S-)ferritin and hemoglobin (Hb). Hb levels were not significantly different in donors: mean 137±10 (SD) g/l (8.5±0.6 mmol/l) compared with nondonors, 139±11 g/l (8.6±0.7 mmol/l). Values < 121 g/l (7.5 mmol/l) were observed in 3.3% of donors vs 3.8% of nondonors. Correlations between S-ferritin and Hb were without practical relevance:r _s=0.29,p<0.0001 in donors vsr _s=0.22, p<0.0001 in nondonors. Blood donation had a profound influence on iron status, especially in the premenopausal women population. Donors had lower S-ferritin than nondonors in all age-groups and in pre- and postmenopausal groups (p<0.001 in all groups). Premenopausal donors had a median S-ferritin of 31g/l vs 39g/l in nondonors, postmenopausal donors of 47g/l vs 72g/l in nondonors. S-ferritin values < 15g/l (i.e., depleted iron stores) were observed in 31.7% of premenopausal donors vs 15.2% of nondonors, and in 7.0% of postmenopausal donors vs 2.9% of nondonors. Iron deficiency anemia (i.e., S-ferritin < 15g/l and Hb < 121 g/l) was seen in 2.8% of donors vs 1.5% of nondonors. Donors using oral contraceptives had higher S-ferritin, median 33g/l compared with nonusers, 22g/l, and a lower frequency of depleted iron stores, 29% vs 39%. Ideally, the frequency of phlebotomy should be adjusted according to S-ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with predonation values 124–125 g/l should be allowed to undergo phlebotomy.This study was supported by grants from the Health Insurance Foundation (H 11-23-89); the Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands, and Greenland (no. 46-83); the Research Foundation of Danish Voluntary Blood Donors; the Danish National Board of Health; and Hässle A/S, DK-2620 Albertslund     

Association of smoking, alcohol drinking and dietary factors with esophageal cancer in high- and low-risk areas of Jiangsu Province, China

AIM: To study the main environmental and lifestyle factors that account for the regional differences in esophageal cancer (EC) risk in low- and high-risk areas of Jiangsu Province, China. METHODS: Since 2003, a population-based case-control study has been conducted simultaneously in low-risk (Ganyu County) and high-risk (Dafeng County) areas of Jiangsu Province, China. Using identical protocols and pre-tested standardized questionnaire, following written informed consent, eligible subjects were inquired about their detail information on potential determinants of EC, including demographic information, socio-economic status, living conditions, disease history, family cancer history, smoking, alcohol drinking, dietary habits, frequency, amount of food intake, etc. Conditional logistic regression with maximum likelihood estimation was used to obtain Odds ratio (OR) and 95 % confidence interval (95% CI), after adjustment for potential confounders. RESULTS: In the preliminary analysis of the ongoing study, we recruited 291 pairs of cases and controls in Dafeng and 240 pairs of cases and controls in Ganyu, respectively. In both low-risk and high-risk areas, EC was inversely associated with socio-economic status, such as level of education, past economic status and body mass index. However, this disease was more frequent among those who had a family history of cancer or encountered misfortune in the past 10 years. EC was also more frequent among smokers, alcohol drinkers and fast eaters. Furthermore, there was a geographic variation of the associations between smoking, alcohol drinking and EC risk despite the similar prevalence of these risk factors in both low-risk and high-risk areas. The dose-response relationship of smoking and smoking related variables, such as age of the first smoking, duration and amount were apparent only in high-risk areas. On the contrary, a dose-response relationship on the effect of alcohol drinking on EC was observed only in low-risk areas. CONCLUSION: The environmental risk factors, together with genetic factors and gene-environmental interactions might be the main reason for this high-risk gradient in Jiangsu Province, China.     

Alcohol effects on cerebral blood flow in subjects with low and high responses to alcohol

Background: Although there are multiple indications that alcohol can alter many physiological brain functions, including cerebral blood flow (CBF), studies of the latter have generally used small‐ or modest‐sized samples. Few investigations have yet evaluated how CBF changes after alcohol relate to subsets of subjects with elevated alcoholism risks, such as those with lower levels of response (LR) to alcohol. This study used arterial spin labeling (ASL) after alcohol administration to evaluate a large sample of healthy young men and women with low and high alcohol responses, and, thus, varying risks for alcohol use disorders (AUD). Methods: Healthy young adult social drinkers with low and high LR (N = 88, 50% women) matched on demography and drinking histories were imaged with whole‐brain resting ASL ～1 hour after ingesting ～3 drinks of ethanol and after a placebo beverage (i.e., 178 ASL sessions). The relationships of CBF changes from placebo to alcohol for subjects with low and high LR were evaluated. Results: CBF increased after alcohol when compared to placebo in 5 frontal brain regions. Despite identical blood alcohol concentrations, these increases with alcohol were less prominent in individuals who required more drinks to experience alcohol‐related effects (i.e., had a lower LR to alcohol). The LR group differences remained significant after covarying for recent drinking quantities. Conclusions: The results confirm that alcohol intake is associated with acute increases in CBF, particularly in frontal regions. Less intense CBF changes were seen in subjects with a genetically influenced characteristic, a low LR to alcohol, that relates to the future risk of heavy drinking and alcohol problems.     

Iron status markers,serum ferritin and hemoglobin in 1359 Danish women in relation to menstruation,hormonal contraception,parity, and postmenopausal hormone treatment

Summary Iron status was assessed by measuring serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 1359 nonpregnant Danish women, in age cohorts of 30,40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Median age for menarche was 14 years, for menopause (artificial and natural) 48 years. Premenopausal women had lower S-ferritin (median 37g/l) than postmenopausal women (median 71g/l;p<0.0001). Of the premenopausal women, 17.7% had S-ferritin < 15g/l (i.e., depleted iron stores), and 23.1% S-ferritin of 15–30g/l (i.e., small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Hb values in premenopausal women were mean 137±10 (SD) g/l (8.5±0.6 mmol/l) vs. 140±10 g/l (8.7±0.6 mmol/l) in postmenopausal women (p<0.0001); 4.1% of pre- and 3.3% of postmenopausal women had values < 121 g/l (7.5 mmol/l). Iron deficiency anemia (i.e., S-ferritin < 15g/l and Hb < 121 g/l) was found in 2.6% of pre- and 0.36% of postmenopausal women. Premenopausal multipara had lower S-ferritin than nulli- and unipara (p<0.04). The use of oral contraceptives had a marked influence on iron stores; premenopausal women taking the pill had higher S-ferritin and a lower frequency of depleted iron reserves than nonusers (p<0.01). Postmenopausal estrogen treatment had no influence on S-ferritin or Hb.     

HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women

BACKGROUND AND AIM: Hereditary hemochromatosis (HH) is a disorder characterized by inappropriately high intestinal iron absorption. In populations of Northern European descent, HH is most commonly caused by mutations (C282Y/H63D) in the HFE gene. METHODS AND RESULTS: We investigated the effects of dietary heme iron intake and HFE mutations on serum ferritin concentrations in a population-based random sample of 1611 women aged >50 years using analysis of covariance (ANCOVA). Higher heme iron intake was associated with significantly higher serum ferritin concentrations (P(trend) < 0.001). Also, women with the compound or C282Y homozygous genotype had significantly higher serum ferritin concentrations (geometric mean 115.2 microg/L (95% CI 81.4-162.9 microg/L) than women carrying normal alleles (geometric mean 76.6 microg/L (95% CI 72.5-80.9 microg/L). We observed the highest serum ferritin concentrations among postmenopausal women who are compound heterozygous or C282Y homozygous, and who consume relatively high amounts of heme iron (geometric mean 183.9 microg/L (95% CI 97.2-347.8 microg/L). CONCLUSIONS: Even when there are currently no clinical signs, women with the compound or C282Y homozygous genotype may still be at risk for developing iron overload sometime after menopause.     

Hepatic iron concentration does not predict response to standard and pegylated-IFN/ribavirin therapy in patients with chronic hepatitis C

BACKGROUND/AIMS: Iron overload is common among patients with chronic hepatitis C (CHC). In this study the role of hepatic iron concentration (HIC) and serum iron parameters was assessed to determine response to standard and pegylated interferon (IFN)/ribavirin combination therapy in patients with CHC. METHODS: Liver biopsies were obtained from 169 IFN-na?ve patients (m=115, f=54, age: 40.8+/-10.7) with CHC. 140 patients were treated with standard IFN/ribavirin, 29 patients with pegylated-IFN/ribavirin. Biopsy specimens were evaluated according to the DiBisceglie scoring system and iron grading. HIC was determined by atomic absorption spectroscopy. Ferritin and transferrin saturation and presence of HFE-C282Y and H63D gene mutations were determined at baseline. RESULTS: Nonresponders to combination therapy had higher serum ferritin levels at baseline (p<0.01). There was no difference of HIC, transferrin saturation levels, and the HFE-mutation status between responders and nonresponders. Logistic regression analysis revealed serum ferritin as an independent predictor of response. HIC correlated with the DiBisceglie score (r=0.352, p<0.001), iron grading (r=0.352, p<0.001) and serum ferritin (r=0.335, P<0.001). CONCLUSIONS: Pretreatment liver iron concentration does not predict response to combination therapy in patients with CHC. In contrast, high baseline serum ferritin levels are predictors of poor response to antiviral therapy.     

Iron status in 358 apparently healthy 80-year-old Danish men and women: relation to food composition and dietary and supplemental iron intake

In Denmark, the intake of dietary iron has decreased since 1987, when the mandatory iron fortification of flour (30 mg carbonyl iron/kg) was stopped. Since there have been no studies of iron status in elderly Danes after the abolishment of iron fortification, there is a need to assess actual iron status in the elderly population. The objective was to evaluate iron status and the relationship with food composition and dietary and supplemental iron intake in an elderly population in Copenhagen County. Participants in this health examination survey were 358 subjects (171 men, 187 women) 80 years of age from a 1914 cohort study. Blood samples included serum ferritin and hemoglobin (Hb). A dietary survey was performed in 232 subjects (120 men, 112 women) using a dietary history method. Median serum ferritin was 100 g/l in men and 78 g/l in women (p<0.001). Ferritin concentrations <16 g/l (i.e., depleted iron stores) were found in three men (2%) and in ten women (5%). Median Hb was 140 g/l in men and 131 g/l in women (p<0.001). Three subjects (0.84%) had iron deficiency anemia (i.e., ferritin <13 g/l and Hb <5th percentile for iron-replete subjects (121 g/l in men, 114 g/l in women). Ferritin concentrations >300 g/l (i.e., iron overload) were found in 15 (9%) men and in 5 (3%) women. Median dietary iron intake was higher in men (8.7 mg/day) than in women (7.3 mg/day) (p<0.001). Serum ferritin was positively correlated to dietary intake of iron, meat, and alcohol and to body mass index in men. Serum ferritin displayed a negative correlation to the consumption of tea. The use of vitamin-mineral supplements containing iron had no influence on iron status. Dietary intake of iron and/or the bioavailability of dietary iron were adequate to maintain a favorable iron status in 80-year-old subjects displaying a low prevalence of iron deficiency and a moderate prevalence of iron overload.     

fMRI differences between subjects with low and high responses to alcohol during a stop signal task

Background: A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. Methods: Forty‐nine drinking but not yet alcoholic matched pairs of 18‐ to 25‐year‐old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event‐related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. Results: Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level–dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition‐related activation after alcohol compared with placebo. Conclusions: This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life‐threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.     

Iron overload and cofactors with special reference to alcohol, hepatitis C virus infection and steatosis/insulin resistance

There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species (ROS) produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore,hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported.Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload,which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.