Biomedical subjects

O Niemelä

Publications and source records attributed to O Niemelä.

At least 19 recordsLinked to original sources

PubMed2005

Biomarkers of alcohol consumption in patients classified according to the degree of liver disease severity.

OBJECTIVE: In the search for optimal biomarkers of excessive drinking, only a few studies have been conducted to compare the relationships between ethanol consumption, liver status, and various laboratory markers of ethanol-induced diseases. MATERIAL AND METHODS: Concentrations of carbohydrate-deficient transferrin (%CDT and CDTect methods), serum sialic acid (SA), gamma-glutamyl transferase (gamma-GT), aspartate aminotransferase (ASAT), mean corpuscular volume (MCV), and a marker of fibrogenesis (PIIINP) were studied in 102 alcoholics with (n=59) or without (n=43) alcoholic liver disease. Controls were 34 healthy volunteers who were either social drinkers or abstainers. RESULTS: Although concentrations of all markers were significantly higher in the alcoholic patients than in the healthy controls, their diagnostic characteristics showed a considerable degree of variation. The %CDT, SA, and MCV showed the strongest correlations with the amount of recent alcohol intake. The presence of liver pathology notably influenced the results of CDTect, GT, ASAT, and PIIINP. In ROC analyses, the highest rates of diagnostic accuracy for detecting hazardous drinking were reached with GT (0.94), CDT (0.86), and SA (0.85), followed by MCV (0.79) and ASAT (0.77). Upon abstinence, the estimated times for normalization varied between 10 days (CDTect) and 25 days (GT). CONCLUSIONS: Our data suggest distinct differences in the clinical characteristics of biological markers of ethanol consumption. While the overall accuracy of CDT and GT appear to be highest in the detection of problem drinking, serum SA and PIIINP measurements are of further value when the effects of liver pathology and ethanol drinking need to be differentiated.

Adult↗

PubMed2002

99m Tc-ciprofloxacin (Infecton) imaging in the diagnosis of knee prosthesis infections.

The purpose of this study was to evaluate the usefulness of 99mTc labelled ciprofloxacin imaging in detecting the presence of infection in patients with symptomatic knee prostheses. Among 16 randomly selected patients of whom seven had infection based on clinical and microbiological findings and nine did not, 99mTc-ciprofloxacin images were obtained at 1, 4 and 24h after the injection of the tracer. While there was some diffuse non-specific accumulation of 99mTc-ciprofloxacin in large synovial joints and in prosthetic knee joints, the infected knee prostheses were found to show more intensive focal uptake, which also extended outside the synovial cavity. The infection related uptake remained visible in the 24h images, whereas non-specific uptake had a fading tendency at this time point. 99mTc-ciprofloxacin imaging showed diagnostic sensitivity of 86% and a specificity of 78% for correctly classifying the presence of infection. The data indicate that 99mTc-ciprofloxacin imaging may be used in the diagnosis of knee prosthesis infections. Infection-related uptake remains visible in the 24h images and is typically found also outside the synovial cavity, which should be noted in the evaluation of the images.

Aged↗

PubMed2002

Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with extended imaging time.

The purpose of this study was to compare the utility of 99mTc labelled ciprofloxacin (Infecton) imaging with the 99mTc white blood cell and three-phase bone imaging procedures for identifying hip prosthesis infection. We studied 30 symptomatic patients in whom infection was confirmed in eight and excluded in 22 cases based on clinical and microbiological findings. 99mTc ciprofloxacin images were obtained at 1, 4 and 24 h after the injection of the tracer, and the data were compared to those obtained from 99mTc leukocyte and three-phase bone imaging. The 99mTc ciprofloxacin imaging correctly identified all true infections. In 13 (59%) of the non-infected patients, non-specific uptake of 99mTc ciprofloxacin was found in the 1-h and 4-h images, which disappeared, however, in the 24-h images. When the early and late 99mTc ciprofloxacin images were compared, the specificity was found to improve from 41% to 95%, positive predictive value from 38% to 89%, and the diagnostic accuracy from 57% to 97%. The accuracy of the conventional 99mTc leukocyte imaging was 90%. Dynamic bone imaging also yielded abnormal findings in all the infected patients although also in 23% of the non-infected patients. Current data indicate that 99mTc ciprofloxacin is a useful method for confirming hip prosthesis infection. The diagnostic efficiency of this method is improved when the imaging time is extended to 24 h post-injection of the tracer.

Adult↗

PubMed2001

Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury.

Generation of oxygen free radicals and reactive aldehydes as a result of excessive ethanol consumption has been well established. Recent studies in human alcoholics and in experimental animal models have indicated that acetaldehyde, the first metabolite of ethanol, and the aldehydic products of lipid peroxidation can bind to proteins in tissues forming stable adducts. The demonstration of such adducts in zone 3 hepatocytes in alcoholics with an early phase of histological liver damage indicates that adduct formation may have an important role in the sequence of events leading to alcoholic liver disease. There may be interference with cellular functions, stimulation of fibrogenesis, and immunological responses. Autoantibodies towards distinct types of adducts have been shown to be associated with the severity of liver disease in alcoholic patients. High fat diet and/or iron supplementation combined with ethanol may increase the amount of aldehyde-derived epitopes and promote fibrogenesis in the liver. Recently, ethanol-derived protein modifications have also been found from other tissues exposed to ethanol and acetaldehyde, including rat brain after lifelong ethanol administration, pancreas, and rat muscle. Elevated adduct levels also occur in erythrocytes of alcoholics, which may be related to ethanol-induced morphological aberrations in hematopoiesis.

Acetaldehyde↗

PubMed2001

Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic accuracy in the detection of hip replacement infections.

Although the diagnosis of hip prosthesis infection is clinically important, X-ray studies, blood chemistry and synovial fluid aspiration may be unreliable for this purpose. The aim of this study was to evaluate whether extending the time for technetium-99m labelled leucocyte imaging to 24 h post injection improves the accuracy of diagnosis of hip replacement infections. We studied 64 symptomatic patients with hip prostheses. The presence of infections was verified by intraoperative bacterial cultures, and infection was excluded either by negative operative findings or by follow-up for at least 1 year. Leucocyte imaging was done with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocytes at 2-4 h (routine images) and at 24 h (late images) after the injection of the leucocytes. In addition, bone imaging was carried out with 99mTc-hydroxydiphosphonate (HDP) at the arterial, soft tissue and metabolic phases. A standardised method was used to compare leucocyte images with bone metabolic images. In this material, there were six confirmed infections. All the bone imaging methods had a sensitivity of 100% in detecting prosthesis infections whereas the specificity varied from only 2% to 82%. Routine leucocyte imaging was less sensitive (50% vs 83%) and less specific (90% vs 100%) than late leucocyte imaging. All tests had a high negative predictive value for excluding infection (95%-100%). However, both bone (10%-38%) and routine leucocyte imaging (33%) showed a poor positive predictive value (PPV), whereas late leucocyte imaging had a PPV of 100% and a diagnostic accuracy of 98%. We conclude that late leucocyte imaging improves the specificity of diagnosis of infected hip prostheses. This type of imaging procedure should be combined with three-phase bone scintigraphy in studies of patients with painful joint replacement.

Adult↗

PubMed2001

Serum IgG and IgE antibodies against mold-derived antigens in patients with symptoms of hypersensitivity.

BACKGROUND: Exposure to mold in water-damaged buildings has been suggested to be responsible for various health problems such as hypersensitivity and upper respiratory tract diseases. However, only little information is available on possible diagnostic tools for examining mold-associated health problems. METHODS: We used recently developed immunofluorometric IgG and IgE assays (UniCAP) to examine serum IgG and IgE antibodies against mold-derived allergens from 70 mold-exposed individuals with (n = 55) or without (n = 15) symptoms of sensitization. Controls were healthy individuals (n = 31) without any history of such exposure. RESULTS: The IgG titers exceeded the upper normal limits of control individuals (mean +/- 2 S.D.) in 35% of symptomatic men and in 25% of women. The IgG titers were usually higher in women than in men (P < 0.05) showing no significant association with the severity of symptoms. During follow-up of eight mold-exposed subjects for 9-12 months the IgG titers remained relatively constant. Elevated anti-mold IgEs were found in six (11%) of the exposed subjects who were all symptomatic. CONCLUSIONS: Measurements of anti-mold IgGs may help to confirm exposure in patients with hypersensitivity symptoms and evidence of mold growth in living or working environment. Some exposed symptomatic patients present IgE-mediated responses. Combined measurements of IgGs and IgEs may prove to be of value in the comprehensive assessment and treatment of such patients.

Adolescent↗

PubMed2001

HFE mutations do not account for transfusional iron overload in patients with acute myeloid leukemia.

BACKGROUND: Hereditary hemochromatosis (HH) is a HFE gene-linked disorder affecting 1 of 200 to 400 persons in white populations. It has been proposed that patients with a hematologic malignancy who are receiving frequent RBC transfusions should be screened for HFE mutations. This would identify C282Y homozygotes, who have a high risk of developing severe iron overload. STUDY DESIGN AND METHODS: DNA samples from 128 controls and 23 adult long-term survivors of acute myeloid leukemia (AML) treated at the Oulu University Hospital (Oulu, Finland) from 1987 to 2000 were examined for the presence of the C282Y and H63D mutations in HFE. All the patients were severely iron-overloaded, as determined from high serum ferritin values and/or increased storage iron in bone marrow. Phlebotomies were performed in five patients because of the symptoms of iron overload. DNA extracted from the blood was used to amplify HFE gene fragments by the PCR method, after which the amplification products were digested with restriction endonucleases SnaB I and Bcl I, and the restriction fragments were analyzed on agarose gels. RESULTS: No chromosomes with the C282Y mutation were found among the AML patients, and 5 patients (21.7%) were heterozygous for the H63D mutation. In the control group, 13 persons (10.2%) were heterozygous for the C282Y mutation and 26 (20.3%) for the H63D mutation, including 3 C282Y/H63D double heterozygotes. CONCLUSION: HFE mutations do not account for the harmful iron overload that develops in AML patients who receive large quantities of RBC concentrates after intensive chemotherapy.

Acute Disease↗

PubMed2001

Molecular aspects of iron absorption and HFE expression.

Hereditary hemochromatosis, a disease of iron overload, occurs in about 1 in 200-400 Caucasians. The gene mutated in this disorder is termed HFE. The product of this gene, HFE protein, is homologous to major histocompatibility complex class I proteins, but HFE does not present peptides to T cells. Based on recent structural, biochemical, and cell biological studies, transferrin receptor (TfR) is a ligand for HFE. This association directly links HFE protein to the TfR-mediated regulation of iron homeostasis. Although evidence is accumulating that binding of HFE to TfR is critical for the effects of HFE, the final pieces in the HFE puzzle have not been established. This review focuses on recent advances in HFE research and presents a hypothetical model of HFE function.

Absorption↗

PubMed2001

Improved method for detecting knee replacement infections based on extended combined 99mTc-white blood cell/bone imaging.

The purpose of this study was to evaluate whether an extension of the imaging time to 24 h post-injection improves the diagnostic accuracy of technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) leucocyte imaging in detecting knee replacement infections. Thirty patients were studied, with infection confirmed in eight (27%) and excluded in 22 on the basis of clinical and microbiological findings. Leucocyte imaging was carried out at 2-4 h (routine images) and at 24 h (late images) post-injection. For comparison, bone imaging with technetium-99m-hydroxydiphosphonate (99mTc-HDP) was carried out at arterial, soft tissue and metabolic phases. Late leucocyte imaging was found to be more sensitive (100% vs. 87.5%) and more specific (82% vs. 77%) than routine leucocyte imaging in detecting infections. All the bone imaging methods showed a sensitivity of 100%, whereas the specificity varied from only 5% to 23%. All procedures had high negative predictive values (NPVs) (94 to 100%) for excluding infection. However, the positive predictive value (PPV) was only 28 to 32% for bone imaging and 58% for routine leucocyte imaging, whereas late leucocyte imaging showed a PPV of 67% and a diagnostic accuracy of 87%. The data indicate that late leucocyte imaging may be superior to routine leucocyte imaging for examining patients with symptomatic knee replacements.

Aged↗

PubMed2001

Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities.

BACKGROUND: Although alcohol abuse is known to cause a wide array of adverse effects on blood cell formation, the molecular mechanisms by which alcohol exerts its toxic actions remain poorly defined. We examine here the formation of acetaldehyde-derived protein modifications in erythrocytes and in their bone marrow precursors using antibodies specifically recognizing acetaldehyde-modified epitopes in proteins independently of the nature of the carrier protein. MATERIALS AND METHODS: We studied 138 consecutive adult patients undergoing bone marrow aspiration due to macrocytosis (MCV values above 99 fL). Assessment included complete blood counts, morphologic review, assessment of alcohol consumption, and biochemical and immunocytochemical assays for acetaldehyde adducts. RESULTS: There were 68 patients (49%) with a history of excessive alcohol consumption, 28 (20%) of whom were patients with severe dependence. The blood smears prepared from the alcoholic patients with macrocytosis also contained stomatocytes and knizocytes. Bone marrow aspirates from 12 alcoholic patients showed vacuolization of pronormoblasts and the presence of ring sideroblasts was noted in 8 cases. In immunocytochemical analyses of the peripheral blood erythrocytes, acetaldehyde-derived epitopes were found to occur both on the cell membrane and inside the erythrocytes. Bone marrow aspirates also showed positive staining for acetaldehyde adducts in the erythropoietic cells in 8 of 11 (73%) consecutive alcoholic patients. Separation of the erythrocyte proteins from the samples of alcoholics on HPLC-chromatography revealed the formation of fast-eluting hemoglobin fractions, which also reacted with antibodies against acetaldehyde adducts. CONCLUSIONS: Current data suggest that acetaldehyde-erythrocyte adducts are formed in vivo in blood and bone marrow of patients with excessive alcohol consumption. This may contribute to the generation of the erythrocyte abnormalities, which are frequently observed in alcoholic patients.

Acetaldehyde↗

PubMed2001

Assays for acetaldehyde-derived adducts in blood proteins based on antibodies against acetaldehyde/lipoprotein condensates.

BACKGROUND: Acetaldehyde-derived protein condensates (adducts) have been suggested as promising biological markers of alcohol abuse because they represent actual metabolites of ethanol. However, the detection of such condensates in vivo has been hampered by a lack of sensitive and specific methods. METHODS: To develop new approaches for the detection of acetaldehyde adducts, we have raised antibodies against condensates with acetaldehyde and lipoproteins, which have previously been shown to be readily modified by acetaldehyde in vitro. The characteristics of these antibodies were compared with those raised against bovine serum albumin/acetaldehyde adduct and against other types of lipoprotein modifications, as induced by malondialdehyde, oxidation, and acetylation. RESULTS: The antibodies raised against low-density lipoprotein (LDL)/acetaldehyde, very low density lipoprotein (VLDL)/acetaldehyde, and bovine serum albumin/acetaldehyde all reacted with protein adducts generated at physiologically relevant concentrations of acetaldehyde in vitro, whereas the antibodies raised against malondialdehyde/LDL, oxidized LDL, or acetylated LDL were not found to cross-react with the acetaldehyde-derived adducts. In assays for acetaldehyde adducts from erythrocyte and serum proteins of patients with excessive ethanol consumption (n = 32) and healthy control individuals (n = 22), the antibody prepared against the acetaldehyde/VLDL condensate was found to provide the most effective detection of acetaldehyde adducts in vivo. CONCLUSIONS: Current data indicate that acetaldehyde generates immunogenic adducts with lipoproteins in vivo. Antibodies raised against the VLDL/acetaldehyde may provide a basis for new diagnostic assays to examine excessive alcohol consumption.

Acetaldehyde↗

PubMed2000

Cytochromes P450 2A6, 2E1, and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases.

BACKGROUND/AIMS: Interaction between CYP2E1, ethanol metabolites, and enhanced lipid peroxidation is linked to the pathogenesis of alcoholic liver disease. This study was conducted to compare the expression of various cytochrome enzymes and the appearance of aldehyde adducts in humans. METHODS: Acetaldehyde- and lipid peroxidation-derived protein adducts and CYP2A6, 2E1, and 3A4/5 were examined immunohistochemically from liver specimens of 12 alcohol abusers with either mild (n=7) or severe (n=5) liver disease, and from nine non-drinking patients with non-alcoholic steatosis (n=4), or hepatitis (n=5). RESULTS: Ethanol-inducible CYP2E1 was present in all alcoholic livers. While CYP2A6 in zone 3 hepatocytes was also abundant in the alcoholic patients with various degrees of liver disease, CYP3A415 was most prominent in alcoholic cirrhosis. The sites of CYP2E1 and CYP2A6 immunoreactivity co-localized with fatty deposits, and with the sites of acetaldehyde and lipid peroxidation-derived protein adducts. The CYP enzymes were also abundant in the centrilobular hepatocytes of patients with fatty liver due to obesity or diabetes. CONCLUSIONS: Alcohol-induced liver damage is associated with a generalized induction of CYP2A6, CYP2E1 and CYP3A4 and generation of acetaldehyde and lipid peroxidation-derived protein-aldehyde adducts. However, CYP induction also occurred in patients with non-alcoholic steatosis.

Acetaldehyde↗

PubMed2000

Covalent adducts of proteins with acetaldehyde in the liver as a result of acetaldehyde administration in drinking water.

BACKGROUND/AIMS: Acetaldehyde, the first metabolic product of ethanol, has been suggested to be responsible for several adverse effects of ethanol through its ability to form covalent adducts with proteins and cellular constituents. It has recently been suggested that acetaldehyde derived from microbial ethanol oxidation in the gut could also contribute to the effects of ethanol in the liver. The present work aimed to examine whether modification of proteins by acetaldehyde occurs in rat liver as a result of acetaldehyde administration in drinking water. METHODS: Rats were fed with either 0.7% acetaldehyde (n=10) or water (n=10) for 11 weeks. At the end of the feeding period, liver specimens were processed for immunohistochemistry for protein adducts with acetaldehyde and for hepatic cell type-specific protein markers. RESULTS: Mild fatty change was found in the liver of the acetaldehyde-treated animals but not in the control animals. Immunohistochemical stainings for acetaldehyde adducts revealed intensive positive staining for acetaldehyde adducts in eight (80%) of the animals fed with acetaldehyde. The adducts were predominantly perivenular, although positive staining also occurred along the sinusoids and in the periportal area. Double immunofluorescence staining experiments revealed that hepatocytes were the primary targets of acetaldehyde adduct deposition, although stellate cells and Kupffer cells also showed weak positive reactions. CONCLUSIONS: The present data indicate that acetaldehyde-protein adducts are formed in the liver of animals following acetaldehyde administration in drinking water, which may contribute to the hepatotoxicity of extrahepatic acetaldehyde. These findings should be implicated in studies on the extrahepatic pathways of ethanol oxidation.

Acetaldehyde↗

PubMed2000

Mean cell volume and gamma-glutamyl transferase are superior to carbohydrate-deficient transferrin and hemoglobin-acetaldehyde adducts in the follow-up of pregnant women with alcohol abuse.

BACKGROUND AND OBJECTIVE: To compare the usefulness of carbohydrate-deficient transferrin (CDT), the ratio of CDT to total transferrin, and hemoglobin-acetaldehyde adducts with mean cell volume (MCV) and gamma-glutamyl transferase (GGT) in the follow-up of alcohol abuse during pregnancy. METHODS: Forty-four pregnant drug and alcohol abusing female patients attending a special outpatient clinic were followed from the 8th to 24th gestational week onwards. A population of sixty-two healthy pregnant women was recruited to assess the effect of gestation on the markers. RESULTS: Eight of thirteen heavy drinking (> or =8 drinks/week) patients delivered infants with fetal alcohol effects (FAE). MCV and GGT were higher among heavy drinking patients than in moderately drinking (<8 drinks/week) patients (92+/-4 vs 90+/-3 fl and 31+/-34 vs 16+/-10 U/ L, respectively), and in patients delivering infants with FAE compared with patients delivering healthy infants (95+/-3 vs 90+/-3 fl and 34+/-26 vs 15+/-10 U/L, respectively). Hemoglobin-acetaldehyde adducts, CDT, and the ratio of CDT to total transferrin were neither associated with the reported level of alcohol consumption nor with the occurrence of FAE. In the receiver operating characteristics analysis MCV was found to be superior to CDT and the adducts, and GGT superior to the adducts, in identifying heavy drinking and in predicting FAE. In the control population, both CDT and total transferrin were found to rise during pregnancy, whereas the ratio of CDT to total transferrin was found to decline. The upper reference range of 33 U/L for CDT was considerably higher than that of non-pregnant women (26 U/L). CONCLUSION: MCV and GGT appear to be the most efficient laboratory markers for detecting excessive alcohol consumption and the adverse effects of alcohol on the fetus.

Acetaldehyde↗

PubMed2000

Autoimmune responses against oxidant stress and acetaldehyde-derived epitopes in human alcohol consumers.

BACKGROUND: Studies in experimental animals have indicated that chronic ethanol ingestion triggers the formation of antibodies directed against proteins modified with reactive metabolites of ethanol and products of lipid peroxidation. However, the nature and prevalence of such antibodies have not been compared previously in alcoholic patients. METHODS: Autoantibodies against adducts with acetaldehyde- (AA), malondialdehyde- (MDA), and oxidized epitopes (Ox) were examined from sera of 54 alcohol consumers with (n = 28) or without (n = 26) liver disease, and from 20 nondrinking controls. RESULTS: Anti-AA-adduct IgA and IgG antibodies were elevated in 64% and 31% of patients with biopsy-proven alcoholic liver disease (ALD, n = 28), respectively. The IgA titers were significantly higher than those from nondrinking controls (p < 0.001), or heavy drinkers without significant liver disease (p < 0.001). Anti-MDA adduct titers (IgG) were elevated in 70% of the ALD patients. These titers were significantly higher (p < 0.001) than those from nondrinking controls, or heavy drinkers without liver disease. Antibodies (IgG) against Ox epitopes occurred in 43% of ALD patients, and the titers also were significantly higher (p < 0.05) than those from nondrinking controls. The anti-AA and anti-MDA adduct titers in ALD patients correlated significantly with the combined clinical and laboratory index (CCLI) of liver disease severity (r(s) = 0.449, p < 0.05; r(s) = 0.566, p < 0.01, respectively), the highest prevalences of anti-AA-adducts (73%) and anti-MDA-adducts (76%) occurring in ALD patients with cirrhosis. CONCLUSIONS: The present results indicated that autoantibodies against several distinct types of protein modifications are generated in ALD patients showing an association with the severity of liver disease.

Acetaldehyde↗

PubMed1999

Aldehyde-protein adducts in the liver as a result of ethanol-induced oxidative stress.

A number of systems that generate oxygen free radicals and reactive aldehydic species are activated by excessive ethanol consumption. Recent studies from human alcoholics and from experimental animals have indicated that acetaldehyde and aldehydic products of lipid peroxidation, which are generated in such processes, can bind to proteins forming stable adducts. Adduct formation may lead to several adverse consequences, such as interference with protein function, stimulation of fibrogenesis, and induction of immune responses. The presence of protein adducts in the centrilobular region of the liver in alcohol abusers with an early phase of histological liver damage indicates that adduct formation is one of the key events in the pathogenesis of alcoholic liver disease. Dietary supplementation with fat and/or iron strikingly increases the amount of aldehyde-derived epitopes in the liver together with promotion of fibrogenesis.

Aldehydes↗

PubMed1999

Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs.

To assess possible links between ethanol-induced oxidant stress, expression of hepatic cytochrome P450 (CYP) enzymes, and sex steroid status, we used immunohistochemical methods to compare the generation of protein adducts of acetaldehyde (AA), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) with the amounts of CYP2E1, CYP2A, and CYP3A in the livers of castrated and noncastrated male micropigs fed ethanol for 12 months. In castrated micropigs, ethanol feeding resulted in accumulation of fat, hepatocellular necrosis, inflammation, and centrilobular fibrosis, whereas only minimal histopathology was observed in their noncastrated counterparts. CYP2A and CYP3A were more prominent in the castrated animals than in the noncastrated micropigs. Ethanol feeding increased the hepatic content of all CYP forms. The most significant increases occurred in CYP2E1 and CYP3A in the noncastrated animals and in CYP2E1 and CYP2A in the castrated animals. Ethanol-fed castrated animals also showed the greatest abundance of perivenular adducts of AA, MDA, and HNE. In the noncastrated ethanol-fed micropigs a low expression of each CYP form was associated with scant evidence of aldehyde-protein adducts. Significant correlations emerged between the levels of different CYP forms, protein adducts, and plasma levels of sex steroids. The present findings indicate that the generation of protein-aldehyde adducts is associated with the induction of several cytochrome enzymes in a sex steroid-dependent manner. It appears that the premature, juvenile, metabolic phenotype, as induced by castration, favors liver damage. The present findings should be implicated in studies on the gender differences on the adverse effects of ethanol in the liver.

Aldehydes↗

PubMed1999

Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury.

Studies in experimental animals have indicated that enhanced lipid peroxidation may play a role in the hepatic injury produced by iron overload or by excessive alcohol consumption. The aim of this study was to compare the formation of lipid peroxidation-derived aldehydes in the liver of patients with hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were classified as having HH based on hepatic iron index or human leukocyte antigen identity with a known proband. All patients were homozygous for the Cys282Tyr mutation. In addition, 8 patients with alcoholic liver disease were examined, 2 of whom also had hemochromatosis. For comparison, 17 patients with liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondialdehyde and 4-hydroxynonenal. Both malondialdehyde- and 4-hydroxynonenal-protein adducts were found from liver specimens of patients with HH and alcohol abuse in more abundant amounts than from patients in a control group. In alcoholics the adducts were primarily in zone 3, whereas in hemochromatosis staining had an acinar zone 1 predominance, which followed the localization of iron. The most abundant amounts of protein adducts were noted in patients with alcohol abuse plus iron overload. The data support the concept that both chronic alcohol use and iron overload induce hepatic lipid peroxidation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.

Adult↗