Relationship of blood trace elements to liver damage, nutritional status, and oxidative stress in chronic nonalcoholic liver disease

Trace elements are involved in chronic liver diseases because these elements may have a direct hepatic toxicity or may be decreased as a consequence of the impaired liver function, particularly in patients with alcoholic cirrhosis and/or malnutrition. In this study, we determined plasma and erythrocytes trace elements in 50 inpatients with nonalcoholic chronic liver disease (11 with biopsy-proven chronic hepatitis, 39 with cirrhosis [16 in stage A according to Child-Pugh criteria, 23 Child B+C]), and in a control group of 10 healthy subjects by the proton induced x-ray emission method. The relationship between trace element concentration and the extent of liver damage, the nutritional status (by anthropometric evaluations), and various blood markers of oxidative stress--reduced glutathione, total lipoperoxides and malonyldialdehyde--was investigated. We found that cirrhotics had a significant decrease of Fe, Zn, Se, and GSH levels in the plasma and of GSH and Se in the erythrocytes with respect to the control and chronic hepatitis groups. GSH levels were related to the degree of liver damage; a significant direct correlation was observed among Se, Zn, and GSH plasma values and between GSH and Se in the erythrocytes. The trace element decrease was, on the contrary, independent of the degree of liver function impairment and only partially affected by the nutritional status. Data indicate that liver cirrhosis, even if not alcohol related, induces a decrease of Se and Zn and that, in these patients, an oxidative stress is present, as documented by the significant correlation between Se and GSH. The plasma Br level was higher in cirrhotics with respect to the control and chronic hepatitis groups.     

Serum levels of trace elements in Egyptian patients with chronic hepatitis C under interferon therapy

The relationships between chronic liver diseases and trace heavy metal contents in blood are debatable and have not been understood clearly. The present study was designed to determine the interaction of IFN α-2b with some trace elements as (Cu, Fe, Mn and Zn) in patients with chronic hepatitis C, and study the effect of this interaction on the response to therapy. This study was performed on 42 patients having positive HCV-Ab & HCV-RNA by PCR and treated with interferon and ribavirin. Besides, 20 healthy subjects served as control. ALT and trace elements were determined before and after treatment with IFN-α 2b. The results showed that the levels of Zinc and Manganese in hepatitis C virus (HCV) infected patients’ were decreased compared to healthy group and this decrement became more after treatment. While the levels of Iron and Copper increased compared to healthy group and these increment became more after treatment. Serum ALT levels in the patients after treatment was statistically significant decrease (p < 0.05) when compared to its level before treatment.Conclusion: Our findings imply that the levels of trace elements (manganese, iron, copper, zinc, and Cu: Zn ratios) might serve as biochemical parameters with a predictive value for the responsiveness of patients to interferon/ribavirin therapy as there were changes in the levels of some trace elements (Zn and Mn) between responder and non-responder patients. So trace element abnormalities may reflect the condition of liver dysfunction.     

Prognostic Value of Blood Zinc, Iron, and Copper Levels in Critically Ill Children with Pediatric Risk of Mortality Score III

We aimed to explore the association of blood Zn, Fe, and Cu concentrations and changes in the pediatric risk of mortality (PRISM) score in critically ill children, to predict prognosis. We included 31 children (22 boys and 9 girls, 1 month to 5 years old), who had been admitted to the intensive care unit of our hospital and who were critically ill according to PRISM score of III. Another 20 children (12 boys, 8 girls, 3 months to 5 years old) who were brought to the hospital for a health checkup were included as controls. We recorded clinical data, time in the intensive care unit, prognosis, and PRISM III score for critically ill children. Blood Cu, Zn, and Fe values were measured by inductively coupled plasma atomic emission spectrophotometry. Zn and Fe levels were significantly lower in patients than in controls (all p?<?0.05). Cu levels differed between patients and controls, but not significantly (p?>?0.05). In ill children, blood Zn and Fe concentrations were inversely correlated with PRISM III score (Zn: r?=??0.36; Fe: r?=??0.50, both p?<?0.05), with no significant correlation of blood Cu level and PRISM III score (r?=??0.13, p?>?0.05). Serious illness in children may lead to decreased Zn and Fe blood concentrations. Zn and Fe supplements may be beneficial for critically ill children.     

Protective role of intraperitoneally administered vitamin E and selenium on the antioxidative defense mechanisms in rats with diabetes induced by streptozotocin

The aim of this work was to determine the protective effects of intraperitoneally administered vitamin E and selenium (as Na₂SeO₃, Se) on the lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and vitamin E levels, glutathione peroxidase (GSH-Px), reduced glutathione (GSH) activities in the plasma, red blood cell (RBC), liver, and muscle of rats with streptozotocin-induced diabetes. Fifty adult male Wistar rats were used and all rats were randomly divided into five groups. The first group was used as a control and the second group as a diabetic control. A placebo was given to first and second groups by injection. The third group was intraperitoneally administered with vitamin E (20 mg over 24 h), the fourth group with Se (0.3 mg over 24 h), and the fifth group with vitamin E and Se combination (COM) (20 mg vitamin E + 0.3 mg Se over 24 h). This administration was done for 25 days and the TBARS, vitamin E, GSH-Px, GSH levels in the plasma, RBC, liver, and muscle samples were determined. The vitamin E level in the plasma and liver was significantly (p < 0.05) higher in the control than in the diabetic control group. Also, the TBARS levels in the RBC, liver, and muscle were significantly (p < 0.05) lower in the control than in the diabetic control group. However, GSH-Px and GSH activities in RBC, liver, and muscle were not statistically different between the control and the diabetic control groups. The vitamin E levels in plasma and liver (p < 0.01 and p < 0.001) and GSH-Px activities (p < 0.01, p < 0.001) in RBC were significantly higher in vitamin E, Se, and COM groups than in both control and diabetic control groups. However, the TBARS levels of RBC, muscle, and liver in vitamin E and Se administered groups were significantly (p < 0.05-p < 0.001, respectively) decreased. These results indicate that intraperitoneally administered vitamin E and Se have significant protective effects on the blood, liver, and muscle against oxidative damage of diabetes. The abstract of this study was presented in Physiological Research 48(Suppl. 1), S99 (1999).     

Essential trace elements selenium, zinc, copper, and iron concentrations and their related acute-phase proteins in patients with vivax malaria

The aim of the present study is to evaluate the status of plasma essential trace elements selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) concentrations and their related acute-phase proteins, ceruloplasmin (Cp), ferritin, transferrin (Tf), and albumin levels in patients with vivax malaria. Plasma Cu and Zn concentrations were determined by atomic absorption spectrometry (AAS). Se concentrations were determined by graphite furnace AAS. Fe, Cp, Tf, and albumin levels were determined by colorimetric methods. Plasma Se, Fe, and albumin levels were found to be significantly lower (p<0.01, p<0.001, and p<0.05, respectively) and Cu, Cp, and ferritin levels and Cu/Zn ratios were significantly higher (p<0.001, p<0.001, p<0.001, and p<0.05, respectively) in patients when compared with those of healthy subjects. Plasma, Tf, and Zn levels were not found to be significantly different (p>0.05) in patients and controls. There were positive important correlations between Cu and Cp (r=0.908, p<0.001), Zn and albumin (r=0.633, p<0.001), and negative correlations between Fe and ferritin content (r=−0.521, p<0.05) and Fe and Tf (r=−0.616, p<0.01) in the patients group. Our findings demonstrated that plasma essential trace elements Se, Cu, and Fe change, but these changes might be dependent on acute-phase proteins, which were regulated as a part of defense strategies of the organism, induced by hormonelike substances.     

Oxidative Stress EPR Measurement in Human Liver by Radical-probe Technique. Correlation with Etiology,Histology and Cell Proliferation

The role of reactive oxygen species (ROS) in liver disease is controversial. This mostly reflects the difficulties to quantify ROS in vivo, particularly in humans. We aimed to measure the presence of ROS in diseased human liver and identify possible relations between ROS levels and etiology, histology and hepatocyte proliferation. Liver biopsy specimens from 102 individuals: 18 healthy controls and 84 patients (42 HCV chronic hepatitis (CHC), 19 HBV chronic hepatitis (CHB), 7 PBC, 4 PSC, 4 HCV relapsing hepatitis after liver transplantation, 3 autoimmune hepatitis, 3 hepatocellular carcinoma, 2 alcoholic hepatitis) underwent analysis by radical-probe electron paramagnetic resonance (EPR). ROS in patients (median=5 &#50 10 &#109 6 mmol/mg) were higher than in controls (median=3 &#50 10 &#109 11 mmol/mg) ( p <0.001). Progressively increasing levels of ROS were recorded passing from control values to CHB (median=4 &#50 10 &#109 7 mmol/mg), CHC (median=3 &#50 10 &#109 6 mmol/mg) and PBC (median=2 &#50 10 &#109 5 mmol/mg), the differences being significant ( p <0.001). ROS in CHC positively correlated with histological disease activity ( r =0.92; p <0.001). No correlation was found between ROS and hepatocyte proliferation rate, presence/degree of steatosis, serum ferritin levels and aminotransferases. ROS overproduction in liver appears to be a common thread linking different pathologic conditions and seems to be influenced by diseases' etiologies.     

Erdosteine modulates radiocontrast‐induced hepatotoxicity in rat

It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)‐induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM‐induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH‐Px) values and histological evaluation. Twenty‐one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for 1 day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor‐driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH‐Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media‐induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system. Copyright © 2009 John Wiley & Sons, Ltd.     

Intracellular glutathione deficiency is associated with enhanced nuclear factor-κB activation in older noninsulin dependent diabetic patients

Diabetes mellitus may be associated with intracellular glutathione (GSH) deficiency. Since in vivo studies have shown that plasma intracellular GSH plays a key role in regulating the activation of nuclear factor κB (NF-κB), we have investigated the relationship between intracellular thiols (GSH, homocysteine, cysteine and cysteinyglycine) and NF-κB activity in the peripheral blood mononuclear cells (PBMC) of 63 elderly non-insulin dependent diabetes mellitus (NIDDM) patients (28 microalbuminurics and 35 normoalbuminurics) and 30 healthy age- and sex-matched subjects. In addition, we have measured plasma concentrations of these thiol compounds, serum concentrations of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (sVCAM-1), that are partly dependent on the NF-κB activation, as well as the serum levels of thiobarbituric acid reacting substances (TBARS), as index of lipid peroxidation. Diabetic patients with microalbuminuria (MAB) and normoalbuminuria had NF-κB activity 2.1- and 1.5-fold greater, respectively, than the control group. As compared to normoalbuminuric patients, patients with MAB had significantly higher levels of glycemia, plasma homocysteine, and serum concentrations of TBARS, IL-6 and sVCAM-1 (in all cases, p < 0.01), and significantly lower GSH content in the PBMC (p < 0.05). The intracellular GSH in PBMC correlated with NF-κB activation (r = -0.82; p < 0.0001), serum TBARS (r = -0.60; p < 0.001), and with fasting glycemia (r = -0.56; p < 0.001) in patients with MAB, whereas a weaker association between GSH levels in PBMC and NF-κB activation (r = -0.504, p < 0.001) was seen in patients without MAB. These results suggest that the decrease of intracellular GSH content in elderly NIDDM patients with MAB is strongly associated with enhanced NF-κB activation, which could contribute to the development of increased glomerular capillary permeability and its rapid progression.     

Plasma paroaoxonase activities, lipoprotein oxidation, and trace element interaction in asthmatic patients

Paraoxonase (PON1) protects low and high-density lipoproteins (LDL and HDL) against oxidation induced by reactive oxygen species formation facilitated by iron (Fe) and copper (Cu) ions. Plasma PON1, arylesterase, oxidized LDL (Ox-LDL), Cu, Fe, thiobarbituric acid-reactive substances (TBARS), lipid, lipoprotein, and apolipoprotein profile in bronchial asthma were determined and the relations among these parameters in different steps of asthma were interpreted. A total of 58 individuals, 30 asthmatics and 28 controls, were included into the scope of this study. Plasma PON1, arylesterase, and TBARS levels were measured spectrophotometrically. Determination of plasma oxidized LDL, Cu, and Fe levels were performed by enzyme-linked immunosorbent assay, atomic absorption spectrophotometry, and the automated TPTZ method, respectively. Apo-A-1 and Apo-B levels were determined immunoturbidometrically. Plasma total cholesterol, triglyceride, and HDL cholesterol levels were enzymatically determined. Plasma LDL levels were estimated using the Fridewald formula. The average plasma PON1 and arylesterase activities in the group of patients were lower than those of the individuals in the control group, but there was no statistically significant difference found between them (p>0.05). No significant difference was found in plasma Apo-A-1, Apo-B, total cholesterol, triglyceride, HDL, and LDL concentrations between the control and patient groups (p>0.05). Plasma oxidized LDL (p<0.05), Cu (p<0.01), Fe (p<0.01), and TBARS (p<0.001) levels in patients with asthma were found to be significantly higher than for the control group. Increases in Cu, Fe, lipid peroxidation, and oxidized LDL levels supported by relative decreases in PON1 activities observed in asthmatic patients might be introduced as the striking findings as well as the possible potential indicators of this airway disease, the prevalence of which has increased dramatically over recent decades.     

Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus

The present investigation evaluates the changes in the levels of antioxidant enzymes, lipid peroxidation (LPO), and protein carbonyl content (PCC) in brain mitochondria following thiamine deficiency (TD). The study was carried out on Mus musculus allocated into three groups, namely control and thiamine-deficient group for 8 (TD 8) and 10 (TD 10) days. The LPO was measured in terms of reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. A significant increase in the TBARS (p?<?0.0001) and PCC (p?<?0.001) levels in group II (TD 8) and group III (TD 10) animals was observed in comparison to controls. The GSH levels were found to be reduced in both the treated groups compared to the control. A significant reduction in the activities of SOD was also observed in group II (p?<?0.01) and group III (p?<?0.0001) animals in comparison to the control. Enzymatic activities of CAT (p?<?0.001) and GPx (p?<?0.05) were found to be significantly reduced in group III (TD 10) in comparison to the control. In conclusion, reduction in the activities of antioxidant enzymes as well as an increase in LPO and PCC following TD implies oxidative stress in brain mitochondria that may further leads to neurodegeneration.     

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.     

Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown. To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH). C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro. In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.     

Serum Levels of Trace Elements and Heavy Metals in Patients with Acute Hemorrhagic Stroke

Trace elements are essential components of biological structures, but alternatively, they can be toxic at concentrations beyond those necessary for their biological functions. Changes in the concentration of essential trace elements and heavy metals may affect acute hemorrhagic stroke. The aim of this study was to measure serum levels of essential trace elements [iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), and magnesium (Mg)] and heavy metals [cobalt (Co), cadmium (Cd), and lead (Pb)] in patients with acute hemorrhagic stroke. Twenty-six patients with acute hemorrhagic stroke and 29 healthy controls were enrolled. Atomic absorption spectrophotometry (UNICAM-929) was used to measure serum Fe, Cu, Pb, Cd, Zn, Co, Mn and Mg concentrations. Serum Cd, Pb and Fe levels were significantly higher in patients with acute hemorrhagic stroke than controls (p < 0.001), while serum Cu, Zn, Mg and Mn levels were significantly lower (all p < 0.001). However, there was no significant difference between the groups with respect to serum Co levels (p > 0.05). We first demonstrate increased Cd, Pb, and Fe levels; and decreased Cu, Zn, Mg, and Mn levels in patients with acute hemorrhagic stroke. These findings may have diagnostic and prognostic value for acute hemorrhagic stroke. Further studies are required to elucidate the roles of trace elements and heavy metals in patients with acute hemorrhagic stroke.     

Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis

In recent years, a great number of studies have investigated the possible role of trace elements in the etiology and pathogenesis of rheumatoid arthritis (RA) and osteoartritis (OA). We studied synovial fluid and plasma concentrations of selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) in patients with RA and OA and compared them with sex- and age-matched healthy subjects. Plasma albumin levels were measured as an index of nutritional status. Plasma Se, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry and Fe concentrations were determined by the colorimetric method. Although plasma and synovial fluid Se concentration were found to be significantly lower (p<0.05, and p<0.05, respectively), Cu concentrations were significantly higher in patients with RA than those of healthy subjects and OA (p<0.05 and p<0.05, respectively). There were no significant differences in plasma and synovial fluid Zn concentrations and albumin levels among three groups (p>0.05). On the other hand, synovial fluid Cu and Fe concentrations were significantly higher in patients with OA than those of healthy subjects (p<0.05). There was a significantly positive correlation between synovial fluid Se−Cu values and Zn−Fe values in patients with RA. Our results showed that synovial fluid and plasma trace element concentrations, excluding Zn, change in inflammatory RA, but not in OA. These alterations in trace element concentrations in inflammatory Ra might be a result on the changes of the immunoregulatory cytokines.     

Increased urinary excretion of bile alcohol glucuronides in patients with primary biliary cirrhosis

The bile alcohol glucuronides in urine of 12 patients with primary biliary cirrhosis (PBC), 10 patients with chronic active hepatitis (CAH), and 6 healthy volunteers were analyzed by capillary gas-liquid chromatography-mass spectrometry. In all subjects studied, the major urinary bile alcohol was found to be 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol (C26 pentol). In PBC patients, the excretion of C26 pentol (main isomer) was significantly increased above values observed in healthy volunteers (mean +/- SD = 5.2 +/- 3.5 mumol/24 h, range 1.0-13.4; versus 0.6 +/- 0.3, range 0.4-1.0). In addition, PBC patients excreted increased amounts of other bile alcohols such as isomers of C26 pentol, pentahydroxylated C27 bile alcohols (5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol) and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol) and a hexahydroxylated C26 bile alcohol (27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol). In CAH patients, the excretion of the C26 pentol main isomer ranged from 0.3 to 2.0 mumol/24 h (mean +/- SD = 0.7 +/- 0.5) and did not significantly differ from that in healthy volunteers. Moreover, the bile alcohol profile was comparable to those found in healthy volunteers and PBC patients. These findings show that total urinary bile alcohol glucuronide excretion is significantly increased in primary biliary cirrhosis. A PBC-specific urinary bile alcohol profile, however, does not exist.     

Estimation of Copper and Iron Burden in Biological Samples of Various Stages of Hepatitis C and Liver Cirrhosis Patients

There is accumulative evidence that the metabolism of iron (Fe) and copper (Cu) is altered in human due to infections, indicating that both elements have roles in pathogenesis and progress of viral diseases. In the present study, the correlation of Cu and Fe was evaluate in biological samples (serum and scalp hair) of hepatitis C (hepatitis C virus (HCV)) patients of both genders at different stages. For comparative study, the scalp hair and serum samples of healthy individuals of same age group (30–50 years) and socioeconomic status were collected. The biological samples were analyzed for Fe and Cu by atomic absorption spectroscopy after microwave-assisted acid digestion. The validity and accuracy of methodology were checked by certified reference materials of same matrixes. The levels of Cu and Fe in biological samples were enhanced in hepatic disorder patients, including acute (after diagnosis test, anti-HCV sero-positive) hepatic fibrosis and liver cirrhosis as compared to healthy referents. The difference was significant (p?<?0.01) in the case of liver cirrhotic patients. It was observed that the data of Cu and Fe in referents and patients of both genders had normal distributions. The inter-elemental correlation (r) among Cu vs Fe in serum and scalp hair samples of referents and patients were not significant in both genders (p?>?0.1) except in the first stage of HCV (p?<?0.1). It was concluded that the increase of Cu and Fe content in human body seems to contribute to the development of cirrhosis in patients with viral hepatitis C.     

Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia

A number of essential trace elements play a major role in various metabolic pathways. Selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) are essential trace elements that have been studied in many diseases, including autoimmune, neurological, and psychiatric disorders. However, the findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied these elements in patients with a DSM-IV diagnosis of schizophrenia and compared them with sex- and age-matched healthy controls. Plasma Cu concentrations were significantly higher (p<0.01) and Mn and Fe concentrations were lower (p<0.05 and p<0.05, respectively) in schizophrenic patients than in controls. Se and Zn concentrations and protein levels did not differ between patients and healthy controls. These observations suggest that alterations in essential trace elements Mn, Cu, and Fe may play a role in the pathogenesis of schizophrenia. However, findings from trace element levels in schizophrenia show a variety of results that are difficult to interpret.     

Glutathione protection against dive-associated ischemia/reperfusion in ringed seal tissues

Ischemia/reperfusion is a potentially hazardous condition that increases reactive oxygen species (ROS) production and oxidative damage. Seals of the phocid family experience repetitive episodes of ischemia/reperfusion during and after a dive as a consequence of preferential distribution of blood flow to the central nervous system and reduction or elimination of perfusion in most vascular beds. Previous studies showed that ROS production is higher in ringed seal than in domestic pig tissues as a direct consequence of the ischemia/reperfusion associated with the diving response; however, oxidative damage is not related to this high ROS production. Apparently, antioxidant enzyme activities participate in the antioxidant protection in ringed seal tissues. In the present study we addressed the potential antioxidant protection of the glutathione system against dive-induced ischemia/reperfusion in ringed seal tissues. Total glutathione (GSH-Eq = GSH + 2GSSG), glutathione (GSH) and glutathione disulfide (GSSG), the ratio GSSG:GSH-Eq, the activities of the enzymes glutathione disulfide reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), as well as lipid peroxidation (TBARS) and carbonyl proteins, were measured in ringed seal and domestic pig heart, kidney, liver, lung and muscle samples. In heart, kidney, lung and muscle GSH-Eq and GSH content was higher in seal than in pig (p < 0.05). GSSG content was higher in seal than in pig heart kidney, liver and muscle (p < 0.05). GR and G6PDH activities were higher in all seal than in pig tissues (p < 0.05). GSSG:GSH-Eq ratio was higher in pig than in seal heart, and lung (p < 0.05). TBARS content was higher in pig than in seal lung (p < 0.05). Higher content of carbonyl proteins was present in pig than in seal heart, kidney, liver and muscle (p < 0.05). These results suggest that the glutathione levels and the activity of enzymes involved in its recycling are efficient mechanisms that ameliorate protein and lipid oxidative damage and protect ringed seal tissues against dive-induced ischemia/reperfusion.     

Plasma Levels of Trace Elements Have an Implication on Interferon Treatment of Children with Chronic Hepatitis B Infection

This study evaluated the plasma levels of trace elements in children with chronic hepatitis B virus (HBV) infection and assessed whether they can be a factor that affects the response to interferon alpha (IFN-α) treatment. The study included 35 cases (ten girls, 25 boys) aged 3–13 years with chronic HBV infection and the control group. Plasma levels of copper (Cu), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) were measured before IFN-α treatment and biochemical, virological, and histopathologic response to treatment were assessed. Children were followed for at least 15 months. Although plasma Cu levels showed no difference between the groups, Mn, Mo, Se, and Zn levels were significantly lower in the study group before treatment. Fourteen cases (40%) showed biochemical response; 17 (48.6%) showed virological response; 16 (47.6%) showed histopathologic response, and ten (28.6%) showed response according to all three parameters. Plasma Cu and Mn levels of patients with triple response showed no difference; but Mo, Se, and Zn levels were significantly lower (p?<?0.001) in the study group. No difference was observed between responders and nonresponders (p?>?0.05). Plasma levels of Mn, Mo, Se, and Zn are lower in children with chronic HBV infection compared to healthy children. The pretreatment levels of these elements did not show difference between responders and nonresponders to IFN-α.     

Antibodies to hepatocyte membrane antigens in chronic liver disease: detection by immunofluorescence after Bouin's fixation

Using a modified indirect immunofluorescent (IF) technique in which cryostat tissue sections were fixed in Bouin's solution for ten minutes prior to reaction with sera under test, we have looked for antibodies to the hepatocyte membrane (HMA) in the sera of patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). Samples were tested initially in parallel on unfixed and Bouin's-fixed rat composite blocks (kidney, stomach, liver) at a titer of 1:100 and those found to be positive were diluted further and reexamined. Conventional unfixed sections of rat composite block showed no liver membrane immunofluorescence although antinuclear (ANA), mitochondrial (AMA), and smooth muscle antibodies (SMA) were detected as anticipated. By contrast, prior Bouin's fixation abolished most of the fluorescence due to ANA, AMA and SMA but resulted in brilliant fluorescence of rat hepatocyte membranes in eleven of twelve patients with CAH (93%) and all ten patients with PBC. Only one of 22 normals (5%), one of 20 with collagen-vascular diseases (5%), and one of seven with nonimmunologic liver disease (14%) were positive for this hepatocyte membrane antibody. Bouin's fixation prior to IF is a simple technique which appears to alter the hepatocyte membrane so that HMA become detectable. The strong association of HMA with CAH and PBC suggests that this test might be of value and may contribute towards a further understanding of the pathogenesis of these conditions.