Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

Science.gov (United States)

Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

2018-01-01

Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

International Nuclear Information System (INIS)

Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

2006-01-01

Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

Hepatic iron content is independently associated with serum hepcidin levels in subjects with obesity.

Science.gov (United States)

Moreno-Navarrete, José María; Moreno, María; Puig, Josep; Blasco, Gerard; Ortega, Francisco; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel

2017-10-01

Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed. Serum hepcidin, ferritin and hepatic iron content (HIC) were significantly increased in participants with obesity. Age- and gender-adjusted serum hepcidin was positively correlated with BMI, hsCRP, ferritin and HIC. In addition, age- and gender-adjusted serum hepcidin was positively correlated with ferritin and HIC in both non-obese and obese participants. In multivariate regression analysis, hepatic iron content (p obesity. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Serum ferritin

International Nuclear Information System (INIS)

Rochna Viola, E.M.; Diaz de Domingo, N.B.; Lazarowski, A.

1981-01-01

Serum ferritin (SF) concentration as determined by the immunoradiometric method allows the direct measurement of a fraction of the body ferritin pool. In normal subjects, SF is an excellent index of body iron stores. In certain conditions associated with increased ferritin synthesis (such as liver disease, inflammation, malignancy, chronic disorders, ineffective erythropoiesis, or during ferrotherapy), SF may not accurately reflect body iron stores. In hyposideremic anemias SF concentration permits to differentiate those due to iron deficiency from those due to chronic disorders. With a good assay quality, subnormal SF levels are incontrovertible in the diagnosis of iron deficiency. SF determination has been investigated as possible tumor marker. When performed in combination with the alpha-fetoprotein assay, SF enhances the specificity of serodiagnosis of hepatoma. SF results must be interpreted bearing in mind the possible participation of circumstances that i) modify the body iron stores and ii) lead to increased ferritin synthesis. (author) [es

Concentration-dependent sedimentation properties of ferritin: implications for estimation of iron contents of serum ferritins

International Nuclear Information System (INIS)

Niitsu, Y.; Adachi, C.; Takahashi, F.; Goto, Y.; Kohgo, Y.; Urushizaki, I.; Listowsky, I.

1985-01-01

Serum ferritins from various sources sedimented at lower densities than tissue ferritins in sucrose gradient centrifugation systems. The sedimentation patterns of ferritins, however, were shown to be dependent on the concentration of the protein; as the concentration decreased the protein appeared to sediment at lower densities. Thus, at the low concentration levels usually used for analysis of serum ferritin, tissue ferritins also sedimented in the same lower density regions. Iron labeling experiments indicated that the sedimentation changes upon dilution were not due to release of iron or was there any indication that the protein dissociated into subunits. The anomalous sedimentation behavior of serum ferritin should therefore not be interpreted in terms of its iron content. The disclosure that serum ferritins may have full complements of iron is counter to the prevalent view that serum ferritins are low iron forms and has potential implications with regard to the sources and possible function of this protein in the circulation

Serum ferritin in patients with cancer: determination with antibodies to HeLa cell and spleen ferritin

International Nuclear Information System (INIS)

Jones, B.M.; Worwood, M.; Jacobs, A.

1980-01-01

Some malignant tissues and cell lines contain acidic isoferritins and it has been suggested that the assay of such isoferritins in serum may be of value in the diagnosis of malignancy. This paper describes a radioimmunoassay for acidic ferritin purified from HeLa cells. Examination of purified heart, kidney, liver and spleen ferritin showed that the assay was highly specific for acidic isoferritins. Ferritin concentrations have been measured with antibodies to HeLa cell and spleen ferritin in extracts of normal and tumour tissue. Although the tumours contained more HeLa type ferritin than the corresponding normal tissue the HeLa/spleen type ferritin ratio was low. HeLa-type ferritin concentrations have been compared with values obtained with anti-spleen ferritin in over 1000 sera from normal subjects and patients with cancer and leukaemia. HeLa-type ferritin was not detected (<2 μg/l) in most normal sera. Concentrations of up to 53 μg/l were found in sera from patients with malignant disease but the HeLa/spleen type ferritin ratio was always very low. There appears to be little application for antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of cancer. (Auth.)

Multiple post-transcriptional regulatory mechanisms in ferritin gene expression

International Nuclear Information System (INIS)

Mattia, E.; Den Blaauwen, J.; Van Renswoude, J.; Ashwell, G.

1989-01-01

The authors have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. They show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. They conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. They propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H-and L-subunit mRNAs

Serum Ferritin in Patients With Cirrhosis is Associated With Markers of Liver Insufficiency and Circulatory Dysfunction, but Not of Portal Hypertension.

Science.gov (United States)

Ripoll, Cristina; Keitel, Felix; Hollenbach, Marcus; Greinert, Robin; Zipprich, Alexander

2015-10-01

Iron overload is an increasingly recognized phenomenon in nonhemochromatosis cirrhosis. To evaluate the relationship between iron overload and liver insufficiency and portal hypertension. Cirrhotics with hepatic hemodynamic and ferritin measurement (within 30 d) were included. Exclusion criteria were malignancy (except hepatocellular carcinoma Milan-in), severe chronic obstructive pulmonary disease, acute events in the previous 2 weeks, immunosuppression, transjugular intrahepatic portosystemic shunt or portal vein thrombosis, and end-stage renal disease. Patients were followed-up until death or liver transplant. Univariate and multivariate analysis were used. Fifty-one patients were included (male 61%; median age 57 y; interquartile range, 47 to 66 y); Child-Pugh A 11/B 25/C 15). A positive correlation was observed between ferritin and markers of inflammation (C-reactive protein: r=0.273, P=0.06 and aspartate aminotransferase: r=0.302, P=0.035). No correlation between ferritin and hepatic venous pressure gradient was seen. Negative correlations were observed between ferritin and circulatory dysfunction (mean arterial pressure: r=-0.360, P=0.014 and serum sodium: r=-0.419, P=0.002). In contrast, associations to markers of liver failure such as international normalized ratio (r=0.333, P=0.005), bilirubin (r=0.378, P=0.007), albumin (r=-0.265, P=0.082), model for end-stage liver disease (r=0.293, P=0.041), and Child-Pugh score (r=0.392, P=0.009) were observed. No differences in survival according to ferritin was detected. In patients with cirrhosis, serum ferritin levels are associated with markers of liver insufficiency, inflammation, and circulatory dysfunction but not portal hypertension.

Multilayer Ferritin Array for Bionanobattery

Science.gov (United States)

Chu, Sang-Hyon (Inventor); Choi, Sang H. (Inventor); Kim, Jae-Woo (Inventor); Lillehei, Peter T. (Inventor); Park, Yeonjoon (Inventor); King, Glen C. (Inventor); Elliott, James R., Jr. (Inventor)

2009-01-01

A thin-film electrode for a bio-nanobattery is produced by consecutively depositing arrays of a ferritin protein on a substrate, employing a spin self-assembly procedure. By this procedure, a first ferritin layer is first formed on the substrate, followed by building a second, oppositely-charged ferritin layer on the top of the first ferritin layer to form a bilayer structure. Oppositely-charged ferritin layers are subsequently deposited on top of each other until a desired number of bilayer structures is produced. An ordered, uniform, stable and robust, thin-film electrode material of enhanced packing density is presented, which provides optimal charge density for the bio-nanobattery.

Theories about evolutionary origins of human hepatitis B virus in primates and humans

Directory of Open Access Journals (Sweden)

Breno Frederico de Carvalho Dominguez Souza

2014-09-01

Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

IRON, ZINC, AND FERRITIN ACCUMULATION IN COMMON BEANS

DEFF Research Database (Denmark)

Urbanski, Dorian Fabian; Sørensen, Kirsten; Jurkiewicz, Anna Malgorzata

Iron and zinc malnutrition are major threats to human health and development around the world. The World Health Organization states that over two billion people are affected by iron deficiency. In particular children and pregnant women in developing countries are affected by iron deficiency...... in mature seeds, but the ferritin protein was suggested to be the major iron storing protein in legumes [1]. Both iron and zinc localization, as well as speciation, can have an impact on their nutritional availability. We will present detailed information about iron, zinc, and ferritin distribution...

Quantitating Iron in Serum Ferritin by Use of ICP-MS

Science.gov (United States)

Smith, Scott M.; Gillman, Patricia L.

2003-01-01

A laboratory method has been devised to enable measurement of the concentration of iron bound in ferritin from small samples of blood (serum). Derived partly from a prior method that depends on large samples of blood, this method involves the use of an inductively-coupled-plasma mass spectrometer (ICP-MS). Ferritin is a complex of iron with the protein apoferritin. Heretofore, measurements of the concentration of serum ferritin (as distinguished from direct measurements of the concentration of iron in serum ferritin) have been used to assess iron stores in humans. Low levels of serum ferritin could indicate the first stage of iron depletion. High levels of serum ferritin could indicate high levels of iron (for example, in connection with hereditary hemochromatosis an iron-overload illness that is characterized by progressive organ damage and can be fatal). However, the picture is complicated: A high level of serum ferritin could also indicate stress and/or inflammation instead of (or in addition to) iron overload, and low serum iron concentration could indicate inflammation rather than iron deficiency. Only when concentrations of both serum iron and serum ferritin increase and decrease together can the patient s iron status be assessed accurately. Hence, in enabling accurate measurement of the iron content of serum ferritin, the present method can improve the diagnosis of the patient s iron status. The prior method of measuring the concentration of iron involves the use of an atomic-absorption spectrophotometer with a graphite furnace. The present method incorporates a modified version of the sample- preparation process of the prior method. First, ferritin is isolated; more specifically, it is immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose beads. The ferritin is then separated from other iron-containing proteins and free iron by a series of centrifugation and wash steps. Next, the ferritin is digested with nitric acid

Study of manganese binding to the ferroxidase centre of human H-type ferritin.

Science.gov (United States)

Ardini, Matteo; Howes, Barry D; Fiorillo, Annarita; Falvo, Elisabetta; Sottini, Silvia; Rovai, Donella; Lantieri, Marco; Ilari, Andrea; Gatteschi, Dante; Spina, Gabriele; Chiancone, Emilia; Stefanini, Simonetta; Fittipaldi, Maria

2018-05-01

Ferritins are ubiquitous and conserved proteins endowed with enzymatic ferroxidase activity, that oxidize Fe(II) ions at the dimetal ferroxidase centre to form a mineralized Fe(III) oxide core deposited within the apo-protein shell. Herein, the in vitro formation of a heterodimetal cofactor constituted by Fe and Mn ions has been investigated in human H ferritin (hHFt). Namely, Mn and Fe binding at the hHFt ferroxidase centre and its effects on Fe(II) oxidation have been investigated by UV-Vis ferroxidation kinetics, fluorimetric titrations, multifrequency EPR, and preliminary Mössbauer spectroscopy. Our results show that in hHFt, both Fe(II) and Mn(II) bind the ferroxidase centre forming a Fe-Mn cofactor. Moreover, molecular oxygen seems to favour Mn(II) binding and increases the ferroxidation activity of the Mn-loaded protein. The data suggest that Mn influences the Fe binding and the efficiency of the ferroxidation reaction. The higher efficiency of the Mn-Fe heterometallic centre may have a physiological relevance in specific cell types (i.e. glia cells), where the concentration of Mn is the same order of magnitude as iron. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

Energy Technology Data Exchange (ETDEWEB)

Eid, Rawan [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Boucher, Eric [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Gharib, Nada [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Khoury, Chamel [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Arab, Nagla T.T. [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Murray, Alistair [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Young, Paul G. [Department of Biology, Queen' s University, Kingston, Ontario (Canada); Mandato, Craig A. [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Greenwood, Michael T., E-mail: michael.greenwood@rmc.ca [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada)

2016-03-01

Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast. �

Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Eid, Rawan; Boucher, Eric; Gharib, Nada; Khoury, Chamel; Arab, Nagla T.T.; Murray, Alistair; Young, Paul G.; Mandato, Craig A.; Greenwood, Michael T.

2016-01-01

Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast. �

Theories about evolutionary origins of human hepatitis B virus in primates and humans.

Science.gov (United States)

Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix; Lima, Renato Santos de; Rosário, Mila de Oliveira Hughes Veiga do; Netto, Eduardo Martins

2014-01-01

The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate

Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency ...

African Journals Online (AJOL)

Background: The epidemiology of viral hepatitis and Human immunodeficiency virus (HIV) during pregnancy is of great importance for health planners and program managers. However, few published data on viral hepatitis and HIV are available in Sudan especially during pregnancy. Objectives: The current study was ...

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Abraham Rosas-Arellano

2016-02-01

Full Text Available Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH and Ferritin 2 Light Chain Homolog (Fer2LCH are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

Science.gov (United States)

Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

2008-08-01

Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

Oscillations in serum ferritin associated with antiviral therapy in chronic hepatitis C Oscilaciones de la ferritina sérica asociadas al tratamiento antiviral en la hepatitis crónica por virus C

Directory of Open Access Journals (Sweden)

J. M. Ladero

2009-01-01

Full Text Available Background: hyperferritinemia is often found in patients with chronic hepatitis C (CHC and is predictive of poorer response to antiviral therapy. Objective: to investigate changes in ferritinemia during and after antiviral therapy. Patients and methods: serum ferritin levels were measured in 262 CHC patients (163 males, mean age 48.5 years ± 10.1 before and during antiviral therapy, and six months post-treatment in all 154 patients whit undetectable serum HCV-RNA after therapy completion. Results: baseline serum ferritin was higher in patients with primary therapeutic failure than in those reaching sustained viral response (330 ± 291 ng/mL vs. 211 ± 192 ng/mL, p = 0.002. Serum ferritin transiently increased during therapy from baseline (257 ± 242 ng/mL vs. 875 ± 630 ng/mL, p Antecedentes: la hiperferritinemia es frecuente en los enfermos con hepatitis crónica C (HCC y reduce las probabilidades de respuesta al tratamiento antiviral. Objetivo: investigar las variaciones de la ferritina sérica durante y después del tratamiento y su relación con la respuesta al mismo. Pacientes y métodos: la ferritina sérica se ha medido en 262 enfermos con HCC (163 hombres, edad media 48,5 años ± 10,1 antes y durante el tratamiento antiviral, y a los 6 meses de finalizado en los 154 enfermos con viremia indetectable al final del tratamiento. Resultados: la ferritina sérica basal era más alta en enfermos con fracaso terapéutico primario que en los que consiguieron respuesta viral sostenida (RVS (330 ± 291 ng/ml vs. 211 ± 192 ng/ml, p = 0,002. La ferritina sérica aumentó transitoriamente durante el tratamiento (257 ± 242 ng/ml vs. 875 ± 630 ng/ml, p < 0,001. La ferritina sérica descendió a valores inferiores a los basales seis meses después de finalizado el tratamiento en los pacientes con RVS (117 ± 102 ng/ml vs. 211± 192 ng/ml, p < 0,001 y, en menor grado, en los que sufrieron recidiva viral (217 ± 174 ng/ml vs. 257 ± 221 ng/m, p = 0

Serum ferritin in recurrent oral ulceration

International Nuclear Information System (INIS)

Challacombe, S.J.; Scully, C.; Keevil, B.; Lehner, T.

1983-01-01

A sensitive radio-assay for ferritin was developed and used to examine serum ferritin levels in 105 patients with recurrent oral ulceration (ROU), 41 patients with Behcet's syndrome (BS), 42 with other ulcerative oral lesions, 35 patients with non-ulcerative oral lesions and in 78 controls. Ferritin levels increased with age and were significantly higher in males than females. The mean ferritin concentrations in male patients with ROU, BS or with other oral ulcers were significantly reduced in comparison with controls, and in female patients were significantly reduced in those with major aphthous ulcers. The prevalence of low serum ferritin levels was about 8% in patients with ROU, 15% in BS and 9.5% in patients with other ulcerative oral lesions, compared with less than 3% in patients with non-ulcerative oral disorders and in controls. Most of the iron-deficient patients were female. Serum ferritin levels did not directly correlate with serum iron levels and may be a more accurate indicator of iron deficiency. Furthermore, serum ferritin can distinguish between patients with true iron deficiency and those with secondary sideropenia. It is suggested that in a small number of patients, oral ulceration may be a presenting sign of iron deficiency, and that in a further small proportion of patients, ROU already present will be exacerbated by concurrent iron deficiency. Both groups will show a therapeutic response to correction of the iron deficiency. The results suggest that serum ferritin levels are a useful part of the haematological investigatons in patients with ROU. (author)

Prevalence of hepatitis B surface antigen, hepatitis C and Human ...

African Journals Online (AJOL)

Objective: Human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C viruses (HCV) are major causes of mortality and morbidity worldwide. They are also among the commonest transfusiontransmissible infectious agents. Students of higher institutions are often used as voluntary unpaid donors by many ...

Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

Energy Technology Data Exchange (ETDEWEB)

Balejcikova, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Strbak, Oliver [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Baciak, Ladislav [Faculty of Chemical and Food Technology STU, Radlinskeho 9, 812 37 Bratislava (Slovakia); Kovac, Jozef [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Masarova, Marta; Krafcik, Andrej; Frollo, Ivan [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Dobrota, Dusan [Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Kopcansky, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia)

2017-04-01

Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation. - Highlights: • MRI is the sensitive technique for detecting iron-based aggregates. • Reconstructed Ferritin is suitable model system of iron-related disorders. • MRI allow distinguish of native ferritin from reconstructed ferritin. • MRI could be useful for diagnostics of diseases associated with iron accumulation.

A Protein-Based Ferritin Bio-Nanobattery

Directory of Open Access Journals (Sweden)

Gerald D. Watt

2012-01-01

Full Text Available Nanostructured materials are increasingly important for the construction of electrochemical energy storage devices that will meet the needs of portable nanodevices. Here we describe the development of a nanoenergy storage system based on inorganic mineral phases contained in ferritin proteins. The electrochemical cell consists of an anode containing ~2000 iron atoms as Fe(OH2 in the hollow protein interior of ferritin and a cathode containing ~2000 of Co(OH3 in a separate ferritin molecule. The achieved initial voltage output from a combination of Fe2+- and Co3+-ferritins adsorbed on gold electrodes was ~500 mV, while a combination of Fe2+- and Co3+-ferritins immobilized on gold produced a voltage of 350–405 mV. When fully discharged, Fe(OH3 and Co(OH2 are the products of a single electron transfer per metal atom from anode to cathode. The spent components can be regenerated by chemical or electrochemical methods restoring battery function. The properties of ferritins are presented and their unique characteristics are described, which have led to the development of a functional bio-nanobattery.

Oxidative modification of ferritin induced by methylglyoxal

Directory of Open Access Journals (Sweden)

Sung Ho An

2012-03-01

Full Text Available Methylglyoxal (MG was identified as an intermediate innon-enzymatic glycation and increased levels were reported inpatients with diabetes. In this study, we evaluated the effects ofMG on the modification of ferritin. When ferritin wasincubated with MG, covalent crosslinking of the proteinincreased in a time- and MG dose-dependent manner.Reactive oxygen species (ROS scavengers, N-acetyl-L-cysteineand thiourea suppressed the MG-mediated ferritinmodification. The formation of dityrosine was observed inMG-mediated ferritin aggregates and ROS scavengers inhibitedthe formation of dityrosine. During the reaction betweenferritin and MG, the generation of ROS was increased as afunction of incubation time. These results suggest that ROSmay play a role in the modification of ferritin by MG. Thereaction between ferritin and MG led to the release of ironions from the protein. Ferritin exposure to MG resulted in aloss of arginine, histidine and lysine residues. It was assumedthat oxidative damage to ferritin caused by MG may induce anincrease in the iron content in cells, which is deleterious tocells. This mechanism, in part, may provide an explanation orthe deterioration of organs under diabetic conditions. [BMBreports 2012; 45(3: 147-152

Distinguishing ferritin from apoferritin using magnetic force microscopy

International Nuclear Information System (INIS)

Nocera, Tanya M; Zeng, Yuzhi; Agarwal, Gunjan

2014-01-01

Estimating the amount of iron-replete ferritin versus iron-deficient apoferritin proteins is important in biomedical and nanotechnology applications. This work introduces a simple and novel approach to quantify ferritin by using magnetic force microscopy (MFM). We demonstrate how high magnetic moment probes enhance the magnitude of MFM signal, thus enabling accurate quantitative estimation of ferritin content in ferritin/apoferritin mixtures in vitro. We envisage MFM could be adapted to accurately determine ferritin content in protein mixtures or in small aliquots of clinical samples. (fast track communication)

Distinguishing ferritin from apoferritin using magnetic force microscopy

Science.gov (United States)

Nocera, Tanya M.; Zeng, Yuzhi; Agarwal, Gunjan

2014-11-01

Estimating the amount of iron-replete ferritin versus iron-deficient apoferritin proteins is important in biomedical and nanotechnology applications. This work introduces a simple and novel approach to quantify ferritin by using magnetic force microscopy (MFM). We demonstrate how high magnetic moment probes enhance the magnitude of MFM signal, thus enabling accurate quantitative estimation of ferritin content in ferritin/apoferritin mixtures in vitro. We envisage MFM could be adapted to accurately determine ferritin content in protein mixtures or in small aliquots of clinical samples.

Magnetism in plant and mammalian ferritin

International Nuclear Information System (INIS)

Bauminger, E.R.; Nowik, I.

1989-01-01

A rich variety of magnetic phenomena is observed in Moessbauer studies of ferritin. Depending on the amount of iron in the horse spleen ferritin core, a paramagnetic relaxation spectrum, or quadrupole split doublet or a magnetically split sextet showing superparamagnetism, are obtained at 4.1 K. Moessbauer studies of the recently prepared iron loaded concanavalin A yield hyperfine parameters identical to those found previously in mammalian ferritin, yet show the existence of larger iron aggregates. Due to the larger particle size it is possible to follow the magnetic hyperfine field and to obtain the magnetic ordering temperature as 240 K. This is exactly the Neel temperature of ferrihydrite, thus establishing that this is indeed the iron compound in the ferritin core. (orig.)

Ferritin as a photocatalyst and scaffold for gold nanoparticle synthesis

Energy Technology Data Exchange (ETDEWEB)

Keyes, Jeremiah D.; Hilton, Robert J. [Brigham Young University, Department of Chemistry and Biochemistry (United States); Farrer, Jeffrey [Brigham Young University, Department of Physics and Astronomy (United States); Watt, Richard K., E-mail: rwatt@chem.byu.edu [Brigham Young University, Department of Chemistry and Biochemistry (United States)

2011-06-15

The ferrihydrite mineral core of ferritin is a semi-conductor capable of catalyzing oxidation/reduction reactions. This report shows that ferritin can photoreduce AuCl{sub 4}{sup -} to form gold nanoparticles (AuNPs). An important goal was to identify innocent reaction conditions that prevented formation of AuNPs unless the sample was illuminated in the presence of ferritin. TRIS buffer satisfied this requirement and produced AuNPs with spherical morphology with diameters of 5.7 {+-} 1.6 nm and a surface plasmon resonance (SPR) peak at 530 nm. Size-exclusion chromatography of the AuNP-ferritin reaction mixture produced two fractions containing both ferritin and AuNPs. TEM analysis of the fraction close to where native ferritin normally elutes showed that AuNPs form inside ferritin. The other peak eluted at a volume indicating a particle size much larger than ferritin. TEM analysis revealed AuNPs adjacent to ferritin molecules suggesting that a dimeric ferritin-AuNP species forms. We propose that the ferritin protein shell acts as a nucleation site for AuNP formation leading to the AuNP-ferritin dimeric species. Ferrihydrite nanoparticles ({approx}10 nm diameter) were unable to produce soluble AuNPs under identical conditions unless apo ferritin was present indicating that the ferritin protein shell was essential for stabilizing AuNPs in aqueous solution.

Maxi- and mini-ferritins: minerals and protein nanocages.

Science.gov (United States)

Bevers, Loes E; Theil, Elizabeth C

2011-01-01

Ferritins synthesize ferric oxide biominerals and are central to all life for concentrating iron and protection against oxidative stress from the ferrous and oxidant chemistry. The ferritin protein nanocages and biomineral synthesis are discussed in terms of wide biological distribution of the maxi-ferritins (24 subunit ± heme) and mini-ferritins (Dps) (12 subunit), conservations of the iron/oxygen catalytic sites in the protein cages, mineral formation (step i. Fe(II) entry and binding, step ii. O(2) or H(2)O(2) binding and formation of transition intermediates, step iii. release of differric oxo mineral precursors from active sites, step iv. nucleation and mineralization) properties of the minerals, and protein control of mineral dissolution and release of Fe(II). Pores in ferritin protein cages control iron entry for mineralization and iron exit after mineral dissolution. The relationship between phosphate or the presence of catalytically inactive subunits (animal L subunits) and ferritin iron mineral disorder is developed based on new information about contributions of ferritin protein cage structure to nucleation in protein cage subunit channels that exit close enough to those of other subunits and exiting mineral nuclei to facilitate bulk mineral formation. How and where protons move in and out of the protein during mineral synthesis and dissolution, how ferritin cage assembly with 12 or 24 subunits is encoded in the widely divergent ferritin amino acid sequences, and what is the role of the protein in synthesis of the bulk mineral are all described as problems requiring new approaches in future investigations of ferritin biominerals.

The optimum functionalization of carbon nanotube/ferritin composites

International Nuclear Information System (INIS)

Lee, Ji Won; Shin, Kwang Min; Kim, Seon Jeong; Lynam, Carol; Spinks, Geoffrey M; Wallace, Gordon G

2008-01-01

We fabricated a covalently linked composite composed of functionalized single-walled carbon nanotubes (f-SWNT) and ferritin protein as nanoparticles. The various f-SWNTs were prepared using an acid treatment of purified SWNT for different functionalization times (30, 60, 120 and 180 min), and ferritin was immobilized on each of the f-SWNT by covalent immobilization. The specific capacitance of the f-SWNT and the electrochemical activity of the f-SWNT/ferritin composites showed a Gaussian distribution. From the electrochemical analysis, the ferritin composite with functionalized SWNT for 60 min showed the highest capacitance and electrochemical activity than other f-SWNT/ferritin composites. This result suggests the optimum value for the best performance of the electrochemical properties of f-SWNT/ferritin composites was found for a potential bioapplication

Sequence analysis of dolphin ferritin H and L subunits and possible iron-dependent translational control of dolphin ferritin gene

Directory of Open Access Journals (Sweden)

Sasaki Yukako

2008-10-01

Full Text Available Abstract Background Iron-storage protein, ferritin plays a central role in iron metabolism. Ferritin has dual function to store iron and segregate iron for protection of iron-catalyzed reactive oxygen species. Tissue ferritin is composed of two kinds of subunits (H: heavy chain or heart-type subunit; L: light chain or liver-type subunit. Ferritin gene expression is controlled at translational level in iron-dependent manner or at transcriptional level in iron-independent manner. However, sequencing analysis of marine mammalian ferritin subunits has not yet been performed fully. The purpose of this study is to reveal cDNA-derived amino acid sequences of cetacean ferritin H and L subunits, and demonstrate the possibility of expression of these subunits, especially H subunit, by iron. Methods Sequence analyses of cetacean ferritin H and L subunits were performed by direct sequencing of polymerase chain reaction (PCR fragments from cDNAs generated via reverse transcription-PCR of leukocyte total RNA prepared from blood samples of six different dolphin species (Pseudorca crassidens, Lagenorhynchus obliquidens, Grampus griseus, Globicephala macrorhynchus, Tursiops truncatus, and Delphinapterus leucas. The putative iron-responsive element sequence in the 5'-untranslated region of the six different dolphin species was revealed by direct sequencing of PCR fragments obtained using leukocyte genomic DNA. Results Dolphin H and L subunits consist of 182 and 174 amino acids, respectively, and amino acid sequence identities of ferritin subunits among these dolphins are highly conserved (H: 99–100%, (99→98 ; L: 98–100%. The conserved 28 bp IRE sequence was located -144 bp upstream from the initiation codon in the six different dolphin species. Conclusion These results indicate that six different dolphin species have conserved ferritin sequences, and suggest that these genes are iron-dependently expressed.

Investigation and management of a raised serum ferritin.

Science.gov (United States)

Cullis, Jonathan O; Fitzsimons, Edward J; Griffiths, William Jh; Tsochatzis, Emmanouil; Thomas, D Wayne

2018-05-01

Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline. © 2018 John Wiley & Sons Ltd.

Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans

NARCIS (Netherlands)

ter Horst, Kasper W.; Gilijamse, Pim W.; Versteeg, Ruth I.; Ackermans, Mariette T.; Nederveen, Aart J.; la Fleur, Susanne E.; Romijn, Johannes A.; Nieuwdorp, Max; Zhang, Dongyan; Samuel, Varman T.; Vatner, Daniel F.; Petersen, Kitt F.; Shulman, Gerald I.; Serlie, Mireille J.

2017-01-01

Hepatic lipid accumulation has been implicated in the development of insulin resistance, but translational evidence in humans is limited. We investigated the relationship between liver fat and tissue-specific insulin sensitivity in 133 obese subjects. Although the presence of hepatic steatosis in

Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.

Science.gov (United States)

Lenzhofer, Markus; Schroedl, Falk; Trost, Andrea; Kaser-Eichberger, Alexandra; Wiedemann, Helmut; Strohmaier, Clemens; Hohensinn, Melchior; Strasser, Michael; Muckenthaler, Martina U; Grabner, Guenther; Aigner, Elmar; Reitsamer, Herbert A

2015-04-01

Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens. During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed. Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene. In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.

Ferritin-Templated Quantum-Dots for Quantum Logic Gates

Science.gov (United States)

Choi, Sang H.; Kim, Jae-Woo; Chu, Sang-Hyon; Park, Yeonjoon; King, Glen C.; Lillehei, Peter T.; Kim, Seon-Jeong; Elliott, James R.

2005-01-01

Quantum logic gates (QLGs) or other logic systems are based on quantum-dots (QD) with a stringent requirement of size uniformity. The QD are widely known building units for QLGs. The size control of QD is a critical issue in quantum-dot fabrication. The work presented here offers a new method to develop quantum-dots using a bio-template, called ferritin, that ensures QD production in uniform size of nano-scale proportion. The bio-template for uniform yield of QD is based on a ferritin protein that allows reconstitution of core material through the reduction and chelation processes. One of the biggest challenges for developing QLG is the requirement of ordered and uniform size of QD for arrays on a substrate with nanometer precision. The QD development by bio-template includes the electrochemical/chemical reconsitution of ferritins with different core materials, such as iron, cobalt, manganese, platinum, and nickel. The other bio-template method used in our laboratory is dendrimers, precisely defined chemical structures. With ferritin-templated QD, we fabricated the heptagonshaped patterned array via direct nano manipulation of the ferritin molecules with a tip of atomic force microscope (AFM). We also designed various nanofabrication methods of QD arrays using a wide range manipulation techniques. The precise control of the ferritin-templated QD for a patterned arrangement are offered by various methods, such as a site-specific immobilization of thiolated ferritins through local oxidation using the AFM tip, ferritin arrays induced by gold nanoparticle manipulation, thiolated ferritin positioning by shaving method, etc. In the signal measurements, the current-voltage curve is obtained by measuring the current through the ferritin, between the tip and the substrate for potential sweeping or at constant potential. The measured resistance near zero bias was 1.8 teraohm for single holoferritin and 5.7 teraohm for single apoferritin, respectively.

Ferritin gene transcription is regulated by iron in soybean cell cultures.

Science.gov (United States)

Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

1991-09-15

Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron.

The effects of variations in the specificities of the antibody components on a two-site immunoradiometric assay for ferritin

International Nuclear Information System (INIS)

Cowan, S.I.; Stagg, B.H.; Niemann, E.

1977-01-01

Variations in the sub-unit antigenic structure of ferritins derived from various human tissues are reflected in the differing specificities of antisera raised against these ferritin preparations. In this study it was shown that antibody specificity played an important role in determining the sensitivity and overall binding of labelled antibody in a two-site immunoradiometric assay for ferritin. Homologous assay systems, in which solid phase and radiolabelled antibodies were of similar specificities, were generally less sensitive and showed lower binding than heterologous assay systems, in which solid phase and labelled antibodies were of different specificities. The source of the ferritin which was used as assay standard also played an important part in determining the sensitivity and overall binding in homologous antibody systems, spleen ferritin standards yielding assays superior to those obtained with placenta or liver ferritin standards. However, these differences between standards were not seen in a heterologous system employing solid phase antibodies directed against liver ferritin and labelled antibodies directed against placenta ferritin. The nature of the ferritin used to prepare immunoadsorbant for the purification of antibodies prior to radioiodination also affected the assay characteristics; antibodies prepared on spleen ferritin immunoadsorbant being more reactive than antibodies prepared on placenta ferritin immunoadsorbant, which in turn were more reactive then antibodies prepared on liver ferritin immunoadsorbant. (orig.) [de

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women.

Science.gov (United States)

Lao, Terence T; Tse, Ka-Yu; Chan, Louis Y; Tam, Kar-Fai; Ho, Lai-Fong

2003-11-01

To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.

Red cell ferritin and iron stores in chronic granulocytic leukemia

International Nuclear Information System (INIS)

Cermak, J.; Neuwirth, J.; Voglova, J.; Brabec, V.; Chrobak, L.

1994-01-01

Basic red cell ferritin was investigated in 28 patients with different phases of chronic granulocytic leukemia (GCL). Red cell ferritin was significantly decreased in remission after busulphan treatment and significantly elevated in the blast crisis as compared to healthy controls. Bone marrow stainable iron was decreased or absent in 86% of patients in the initial phase at the time of diagnosis and in 92% of those in remission. Red cell ferritin correlated with serum ferritin, however, serum ferritin level remained above normal range during all phases of the disease. A negative correlation between red cell ferritin and hemoglobin (Hb) (r = -0.605, p < 0.001) suggested that red cell ferritin level reflected the rate of iron utilization for heme synthesis. Decrease red cell iron observed in the remission may be explained by regression of dyserythropoiesis and by restoration of normal Hb synthesis after busulphan treatment. A progressive dyserythropoiesis in the blast crisis may lead to an increased red cell ferritin level. (author)

Methodological approaches to disinfection of human hepatitis B virus.

OpenAIRE

Prince, D L; Prince, H N; Thraenhart, O; Muchmore, E; Bonder, E; Pugh, J

1993-01-01

Three commercial disinfectants (two quaternary formulations and one phenolic) were tested against human hepatitis B virus (HHBV). The treated virus was assayed for infectivity by the chimpanzee assay and for morphological alteration by the Morphological Alteration and Disintegration Test. The same agents were tested against duck hepatitis B virus in a duck hepatocyte infectivity assay. It is apparent that human and duck hepatitis viruses were relatively susceptible to disinfection, becoming n...

[Hepatitis: a longstanding companion in human history].

Science.gov (United States)

Craxi, Lucia

2012-03-01

Hepatitis has gone along with human history since its origins, due to its prompt identifiability linked to jaundice as a symptom. Written evidence of outbreaks of epidemic jaundice can be tracked back a few millenniums before Christ. Unavoidable confusion arises due to the overlap of different sources possibly linked to different aetiologies, identified over time as epidemic jaundice (HAV or HEV hepatitis?) and serum hepatitis (HBV or HCV hepatitis?). The journey that brought to recognize viruses as the main cause of jaundice was long and started midway during the last century, when the infectious hypothesis, which had taken place step by step, was finally confirmed by epidemiological investigations of an outbreak occurring in the US army in 1942, after a yellow fever immunization campaign. Further research identified two clinically different types of hepatitis, called for the first time hepatitis A and hepatitis B.

Ferritin nanocontainers that self-direct in synthetic polymer systems

Science.gov (United States)

Sengonul, Merih C.

Currently, there are many approaches to introduce functionality into synthetic polymers. Among these, for example, are copolymerization, grafting, and blending methods. However, modifications made by such methods also change the thermodynamics and rheological properties of the polymer system of interest, and each new modification often requires a costly reoptimization of polymer processing. Such a reoptimalization would not be necessary if new functionality could be introduced via a container whose external surface is chemically and physically tuned to interact with the parent polymer. The contents of the container could then be changed without changing other important properties of the parent polymer. In this context this thesis project explores an innovative nanocontainer platform which can be introduced into phase-separating homopolymer blends. Ferritin is a naturally existing nanocontainer that can be used synthetically to package and selectively transport functional moieties to a particular phase that is either in the bulk or on the surface of a homopolymer blend system. The principal focus of this work centers on modifying the surface of wild ferritin to: (1) render modified ferritin soluble in a non-aqueous solvent; and (2) impart it with self-directing properties when exposed to a homopolymer blend surface or incorporated into the bulk of a homopolymer blend. Wild ferritin is water soluble, and this research project successfully modified wild ferritin by grafting either amine-functional poly(ethylene glycol) (PEG) or short-chain alkanes to carbodiimide activated carboxylate groups on ferritin's surface. Such modified ferritin is soluble in dichloromethane (DCM). Modification was confirmed by ion-exchange chromatography, zeta-potential measurements, and electrospray mass spectroscopy. FT-IR was used to quantify the extent of PEGylation of the reaction products through area ratios of the -C-O-C asymmetric stretching vibration of the grafted PEG chains to the

Iron induction of ferritin synthesis in soybean cell suspensions.

Science.gov (United States)

Proudhon, D; Briat, J F; Lescure, A M

1989-06-01

In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes.

Reduced ferritin levels in individuals with non-O blood group

DEFF Research Database (Denmark)

Rigas, Andreas S; Berkfors, Adam A; Pedersen, Ole B

2017-01-01

stores expressed as ferritin levels. STUDY DESIGN AND METHODS: Ferritin levels were measured at least once for 30,595 Danish Blood Donor Study participants. Linear regression analyses were performed with the ABO blood group as explanatory variable and adjusted for age, number of donations 3 years before......BACKGROUND: Genomewide association studies have reported alleles in the ABO locus to be associated with ferritin levels. These studies warrant the investigation of a possible association between the ABO blood group and ferritin levels. We aimed to explore if ABO blood group is associated with iron...... blood group was associated with a ferritin level of less than 15 ng/mL. RESULTS: Non-O blood group donors had lower ferritin levels than blood group O donors, regardless of sex. Accordingly, risk of ferritin level of less than 15 ng/mL was increased for individuals with non-O blood group compared with O...

Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization

Science.gov (United States)

Buisson, Christophe; Daou, Nadine; Kallassy, Mireille; Lereclus, Didier; Arosio, Paolo; Bou-Abdallah, Fadi; Nielsen Le Roux, Christina

2014-01-01

In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis. PMID:24550730

Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization.

Directory of Open Access Journals (Sweden)

Diego Segond

2014-02-01

Full Text Available In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis.

Self-Assembly in the Ferritin Nano-Cage Protein Superfamily

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Yu Zhang

2011-08-01

Full Text Available Protein self-assembly, through specific, high affinity, and geometrically constraining protein-protein interactions, can control and lead to complex cellular nano-structures. Establishing an understanding of the underlying principles that govern protein self-assembly is not only essential to appreciate the fundamental biological functions of these structures, but could also provide a basis for their enhancement for nano-material applications. The ferritins are a superfamily of well studied proteins that self-assemble into hollow cage-like structures which are ubiquitously found in both prokaryotes and eukaryotes. Structural studies have revealed that many members of the ferritin family can self-assemble into nano-cages of two types. Maxi-ferritins form hollow spheres with octahedral symmetry composed of twenty-four monomers. Mini-ferritins, on the other hand, are tetrahedrally symmetric, hollow assemblies composed of twelve monomers. This review will focus on the structure of members of the ferritin superfamily, the mechanism of ferritin self-assembly and the structure-function relations of these proteins.

Hepatic tuberculosis presenting with extreme hyperferritinemia masquerading as adult-onset Still’s disease: a case report

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Manoj Edirisooriya

2012-07-01

Full Text Available Abstract Introduction Isolated hepatic tuberculosis is an uncommon manifestation of one of the most common infections worldwide, caused by Mycobacterium tuberculosis. Extremely high serum ferritin, which is regarded as a marker of adult onset Still’s disease, has not been observed in patients with tuberculosis of the liver. We report a case of hepatic tuberculosis who presented with clinical criteria of adult-onset Still’s disease and extreme hyperferritinemia, which posed a diagnostic confusion. Case presentation Our patient was a 48-year-old Sri Lankan man who presented with fever, polyarthralgia and a generalized skin rash of three months duration. He had marked constitutional symptoms, oral ulcers, hair loss, anemia and hepatomegaly. Laboratory investigations disclosed an inflammatory syndrome, evidence of hepatic dysfunction, bone marrow suppression and a raised serum ferritin level of 34,674 ng/ml. A rapidly deteriorating course of illness prompted treatment based on a presumptive diagnosis of adult-onset Still’s disease until liver histology was available. The patient died of sepsis followed by multi-organ dysfunction. Later, the liver histology revealed tuberculosis. Conclusion Extrapulmonary tuberculosis, although well known to present with peculiar manifestations, has not been reported to be associated with extremely high levels of serum ferritin in immunocompetent individuals. Isolated hepatic tuberculosis presenting with clinical criteria of adult-onset Still’s disease is remarkable. Since tuberculosis remains a potentially curable disease, an awareness of its’ protean manifestations is essential.

Hepatic cholesterol ester hydrolase in human liver disease.

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Simon, J B; Poon, R W

1978-09-01

Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

Re-purification of labelled ferritin antigen with HPLC

International Nuclear Information System (INIS)

Zhang Haoyi; Jin Lichun

2002-01-01

Objective: To improve the quality of long-term stored labelled ferritin antigen with HPLC. Methods: The antigen was analyzed and purified with HPLC and again analyzed with RIA afterwards. Results: Ferritin antigen underwent significant polymerization after long-term (aggregation) storage. After re-purification with HPLC, its immuno-activity and labelled specific radioactivity were both significantly improved. Conclusion: Quality of stored ferritin RIA kit could be greatly improved after re-purification with HPLC

Compounds which mediate Gallium-67 transfer from lactoferrin to ferritin

International Nuclear Information System (INIS)

Weiner, R.E.; Schreiber, G.J.; Hoffer, P.B.; Bushberg, J.T.

1985-01-01

The influence of various low molecular weight compounds on the transfer of 67 Ga from human lactoferrin (LF) to horse spleen ferritin (HoFE) has been examined in vitro. When LF/sup */ 67 Ga complex was placed in competition with HoFE using a dialysis system the initial transfer rate (TR) of 67 Ga to HoFE was slow and continuous. In the presence of 1 mM pyrophosphate (PP/sub i/) ascorbate and adenosine triphosphate (ATP), the TR was dramatically enhanced. This effect was concentration sensitive since reduction of the ATP to 0.1 mM eliminated the enhancement. Although PP/sub i/ and ascorbate ions yielded larger TR's, ATP was more effective in the promotion of 67 Ga transfer to HoFE. When the LF/HoFE concentration ratio was decreased, in the presence of ATP, the transfer of 67 Ga was significantly increased. These results suggest that ferritin present intracellularly could remove and retain 67 Ga entering the cell in the form of a LF/sub */ 67 Ga complex. Moreover, increased synthesis of ferritin and cytosolic phosphate compounds would appear to enhance this process

Permanganate-based synthesis of manganese oxide nanoparticles in ferritin

Science.gov (United States)

Olsen, Cameron R.; Smith, Trevor J.; Embley, Jacob S.; Maxfield, Jake H.; Hansen, Kameron R.; Peterson, J. Ryan; Henrichsen, Andrew M.; Erickson, Stephen D.; Buck, David C.; Colton, John S.; Watt, Richard K.

2017-05-01

This paper investigates the comproportionation reaction of MnII with {{{{MnO}}}4}- as a route for manganese oxide nanoparticle synthesis in the protein ferritin. We report that {{{{MnO}}}4}- serves as the electron acceptor and reacts with MnII in the presence of apoferritin to form manganese oxide cores inside the protein shell. Manganese loading into ferritin was studied under acidic, neutral, and basic conditions and the ratios of MnII and permanganate were varied at each pH. The manganese-containing ferritin samples were characterized by transmission electron microscopy, UV/Vis absorption, and by measuring the band gap energies for each sample. Manganese cores were deposited inside ferritin under both the acidic and basic conditions. All resulting manganese ferritin samples were found to be indirect band gap materials with band gap energies ranging from 1.01 to 1.34 eV. An increased UV/Vis absorption around 370 nm was observed for samples formed under acidic conditions, suggestive of MnO2 formation inside ferritin.

Octopus microvasculature: permeability to ferritin and carbon.

Science.gov (United States)

Browning, J

1979-01-01

The permeability of Octopus microvasculature was investigated by intravascular injection of carbon and ferritin. Vessels were tight to carbon while ferritin penetrated the pericyte junction, and was found extravascularly 1-2 min after its introduction. Vesicles occurred rarely in pericytes; fenestrae were absent. The discontinuous endothelial layer did not consitute a permeability barrier. The basement membrane, although retarding the movement of ferritin, was permeable to it; carbon did not penetrate the basement membrane. Evidence indicated that ferritin, and thus similarly sized and smaller water soluble materials, traverse the pericyte junction as a result of bulk fluid flow. Comparisons are made with the convective (or junctional) and slower, diffusive (or vesicular) passage of materials known to occur across the endothelium of continuous capillaries in mammals. Previous macrophysiological determinations concerning the permeability of Octopus vessels are questioned in view of these findings. Possible reasons for some major structural differences in the microcirculatory systems of cephalopods and vertebrates are briefly discussed.

Loop electrostatics modulates the intersubunit interactions in ferritin.

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Bernacchioni, Caterina; Ghini, Veronica; Pozzi, Cecilia; Di Pisa, Flavio; Theil, Elizabeth C; Turano, Paola

2014-11-21

Functional ferritins are 24-mer nanocages that self-assemble with extended contacts between pairs of 4-helix bundle subunits coupled in an antiparallel fashion along the C2 axes. The largest intersubunit interaction surface in the ferritin nanocage involves helices, but contacts also occur between groups of three residues midway in the long, solvent-exposed L-loops of facing subunits. The anchor points between intersubunit L-loop pairs are the salt bridges between the symmetry-related, conserved residues Asp80 and Lys82. The resulting quaternary structure of the cage is highly soluble and thermostable. Substitution of negatively charged Asp80 with a positively charged Lys in homopolymeric M ferritin introduces electrostatic repulsions that inhibit the oligomerization of the ferritin subunits. D80K ferritin was present in inclusion bodies under standard overexpressing conditions in E. coli, contrasting with the wild type protein. Small amounts of fully functional D80K nanocages formed when expression was slowed. The more positively charged surface results in a different solubility profile and D80K crystallized in a crystal form with a low density packing. The 3D structure of D80K variant is the same as wild type except for the side chain orientations of Lys80 and facing Lys82. When three contiguous Lys groups are introduced in D80KI81K ferritin variant the nanocage assembly is further inhibited leading to lower solubility and reduced thermal stability. Here, we demonstrate that the electrostatic pairing at the center of the L-loops has a specific kinetic role in the self-assembly of ferritin nanocages.

Hepatitis B, C and Human Immunodeficiency Virus (HIV) Co ...

African Journals Online (AJOL)

TNHJOURNALPH

BACKGROUND. Nigeria which has one of the world's highest burden of children living with. Sickle cell anaemia is also endemic for hepatitis B, C and the Human immunodeficiency virus (HIV). This study set out to determine the prevalence of. Hepatitis B surface antigen (HBsAg), antibodies to Hepatitis C Virus (HCV) and.

Serum ferritin and stomach cancer risk among A-bomb survivors

International Nuclear Information System (INIS)

Akiba, Suminori; Neriishi, Kazuo; Blot, W.J.; Kabuto, Michinori; Stevens, R.G.; Kato, Hiroo; Land, C.E.

1990-02-01

Using stored serum samples collected from 1970-72 and/or from 1977-79, serum ferritin, transferrin, and ceruloplasmin levels were immunologically determined for 233 stomach cancer and 84 lung cancer cases diagnosed from 1973-83 and for 385 matched controls from a fixed population of Hiroshima and Nagasaki atomic bomb survivors. Elevated stomach cancer risk was associated with low serum ferritin levels, with more than a threefold excess among those in the lowest quintile as compared to the highest ferritin quintile. The average serum ferritin concentration was 8% lower in the stomach cancer cases than in the controls. Risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels five or more years before cancer diagnosis. Low ferritin combined with achlorhydria, diagnosed about 10 years before the blood collection and up to 25 years before cancer diagnosis, was an exceptionally strong marker of increased stomach cancer risk. No effect of transferrin or ceruloplasmin independent of ferritin was observed on gastric cancer risk. Lung cancer risk was not related to these three serum proteins. (author)

Four stages of hepatic hematopoiesis in human embryos and fetuses.

Science.gov (United States)

Fanni, D; Angotzi, F; Lai, F; Gerosa, C; Senes, G; Fanos, V; Faa, G

2018-03-01

The liver is a major hematopoietic organ during embryonic and fetal development in humans. Its hematopoietic activity starts during the first weeks of gestation and continues until birth. During this period the liver is colonized by undifferentiated hematopoietic stem cells (HSCs) that gradually differentiate and once mature, enter the circulatory system through the hepatic sinusoids, this process is called hepatic hematopoiesis. The morphology of hepatic hematopoiesis, has been studied in humans through the years, and led to a characterization of all the cell types that make up these phenomena. Studies on murine models also helped to describe the extent of hepatic hematopoiesis at different gestational ages. Using this knowledge, we attempted to describe how hepatic hematopoiesis morphologically evolves as gestation progresses, in human embryos and fetuses. Thus, we observed a total of 32 tissue specimens obtained from the livers of embryos and fetuses at different gestational ages. Basing our observations on the four stages of liver hematopoiesis identified by Sasaki and Sonoda in mice, we also described four consecutive stages of liver hematopoiesis in humans, which resulted to be highly similar to those described in murine models.

Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis

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Sandawana William Majoni

2017-01-01

Full Text Available Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT as measures of iron status and ferritin and C-reactive protein (CRP as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years on maintenance haemodialysis (>3 months from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9 years. 1244 (79.3% were Indigenous. 44.2% (n=693 were male. Indigenous patients were younger (mean age [52.3 (11.1 versus 57.4 (15.2, p<0.001] and had higher CRP [14.7 mg/l (7–35 versus 5.9 mg/l (1.9–17.5, p<0.001], higher median serum ferritin [1069 µg/l (668–1522 versus 794.9 µg/l (558.5–1252.0, p<0.001], but similar transferrin saturation [26% (19–37 versus 28% (20–38, p=0.516]. We observed a small positive correlation between ferritin and TSAT (r2=0.11, p<0.001, no correlation between ferritin and CRP (r2 = 0.001, p<0.001, and positive association between high serum ferritin and TSAT (p<0.001, Indigenous ethnicity (p<0.001, urea reduction ratio (p=0.001, and gender (p<0.001 after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation.

First comparative characterization of three distinct ferritin subunits from a teleost: Evidence for immune-responsive mRNA expression and iron depriving activity of seahorse (Hippocampus abdominalis) ferritins.

Science.gov (United States)

Oh, Minyoung; Umasuthan, Navaneethaiyer; Elvitigala, Don Anushka Sandaruwan; Wan, Qiang; Jo, Eunyoung; Ko, Jiyeon; Noh, Gyeong Eon; Shin, Sangok; Rho, Sum; Lee, Jehee

2016-02-01

Ferritins play an indispensable role in iron homeostasis through their iron-withholding function in living beings. In the current study, cDNA sequences of three distinct ferritin subunits, including a ferritin H, a ferritin M, and a ferritin L, were identified from big belly seahorse, Hippocampus abdominalis, and molecularly characterized. Complete coding sequences (CDS) of seahorse ferritin H (HaFerH), ferritin M (HaFerM), and ferritin L (HaFerL) subunits were comprised of 531, 528, and 522 base pairs (bp), respectively, which encode polypeptides of 177, 176, and 174 amino acids, respectively, with molecular masses of ∼20-21 kDa. Our in silico analyses demonstrate that these three ferritin subunits exhibit the typical characteristics of ferritin superfamily members including iron regulatory elements, domain signatures, and reactive centers. The coding sequences of HaFerH, M, and L were cloned and the corresponding proteins were overexpressed in a bacterial system. Recombinantly expressed HaFer proteins demonstrated detectable in vivo iron sequestrating (ferroxidase) activity, consistent with their putative iron binding capability. Quantification of the basal expression of these three HaFer sequences in selected tissues demonstrated a gene-specific ubiquitous spatial distribution pattern, with abundance of mRNA in HaFerM in the liver and predominant expression of HaFerH and HaFerL in blood. Interestingly, the basal expression of all three ferritin genes was found to be significantly modulated against pathogenic stress mounted by lipopolysaccharides (LPS), poly I:C, Streptococcus iniae, and Edwardsiella tarda. Collectively, our findings suggest that the three HaFer subunits may be involved in iron (II) homeostasis in big belly seahorse and that they are important in its host defense mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

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B.G. Nath

2013-08-01

Full Text Available The present study investigated 37 serum samples of non-human primates in Assam State Zoo and the Department of Forest and Environment, Govt. of Assam for seroprevalence of hepatitis A virus infection during the period from December, 2007 to November, 2009. Four serum samples were also collected from animal keepers of the zoo to investigate transmission of the disease to the attendants working with these primates. Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV to detect hepatitis A virus antibody in serum samples. Ten (27.21% of the non-human primate samples and three (75% human samples had detectable anti-hepatitis A virus antibodies. Living status of the non-human primates (Free living was a high potential risk for hepatitis A virus infection. Seroprevalence of hepatitis A virus infection had significant difference between free living non-human primates and captive non-human primates (P less than 0.05. No significant difference (p=0.86 was seen between male and female non-human primates

Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging.

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Wahidiyat, Pustika Amalia; Liauw, Felix; Sekarsari, Damayanti; Putriasih, Siti Ayu; Berdoukas, Vasili; Pennell, Dudley J

2017-09-01

Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy. This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy. The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r = -0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r = 0.37) was found between liver iron concentration (LIC) and serum ferritin. The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels. This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.

Iron and ADHD: Time to Move beyond Serum Ferritin Levels

Science.gov (United States)

Donfrancesco, Renato; Parisi, Pasquale; Vanacore, Nicola; Martines, Francesca; Sargentini, Vittorio; Cortese, Samuele

2013-01-01

Objective: (a) To compare serum ferritin levels in a sample of stimulant-naive children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. Method: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with…

The iron content and ferritin contribution in fresh, dried, and toasted nori, Pyropia yezoensis.

Science.gov (United States)

Masuda, Taro; Yamamoto, Ami; Toyohara, Haruhiko

2015-01-01

Iron is one of the essential trace elements for humans. In this study, the iron contents in fresh, dried, and toasted nori (Pyropia yezoensis) were analyzed. The mean iron content of fresh, dried, and toasted nori were 19.0, 22.6, and 26.2 mg/100 g (dry weight), respectively. These values were superior to other food of plant origin. Furthermore, most of the iron in nori was maintained during processing, such as washing, drying, and toasting. Then, the form of iron in fresh, dried, and toasted nori was analyzed. As a result, an iron storage protein ferritin contributed to iron storage in raw and dried nori, although the precise rate of its contribution is yet to be determined, while ferritin protein cage was degraded in the toasted nori. It is the first report that verified the ferritin contribution to iron storage in such edible macroalgae with commercial importance.

Helicobacter pylori infection and serum ferritin

DEFF Research Database (Denmark)

Berg, Gabriele; Bode, G; Blettner, M

2001-01-01

OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin...... in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot. RESULTS: In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study...... were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 microg/dl among H. pylori-infected compared with 63.8 microg/dl among uninfected persons. A multiple linear regression model with log...

Variability of human hepatic UDP-glucuronosyltransferase activity

NARCIS (Netherlands)

Little, JM; Lester, R; Kuipers, F; Vonk, R; Mackenzie, PI; Drake, RR; Frame, L; Radominska-Pandya, A

1999-01-01

The availability of a unique series of liver samples from human subjects, both control patients (9) and those with liver disease (6; biliary atresia (2), retransplant, chronic tyrosinemia type I, tyrosinemia, Wilson's disease) allowed us to characterize human hepatic UDP-glucuronosyltransferases

Ultrasensitive Nanoimmunosensor by coupling non-covalent functionalized graphene oxide platform and numerous ferritin labels on carbon nanotubes.

Science.gov (United States)

Akter, Rashida; Jeong, Bongjin; Choi, Jong-Soon; Rahman, Md Aminur

2016-06-15

An ultrasensitive electrochemical nanostructured immunosensor for a breast cancer biomarker carbohydrate antigen 15-3 (CA 15-3) was fabricated using non-covalent functionalized graphene oxides (GO/Py-COOH) as sensor probe and multiwalled carbon nanotube (MWCNTs)-supported numerous ferritin as labels. The immunosensor was constructed by immobilizing a monoclonal anti-CA 15-3 antibody on the GO modified cysteamine (Cys) self-assembled monolayer (SAM) on an Au electrode (Au/Cys) through the amide bond formation between the carboxylic acid groups of GO/Py-COOH and amine groups of anti-CA 15-3. Secondary antibody conjugated MWCNT-supported ferritin labels (Ab2-MWCNT-Ferritin) were prepared through the amide bond formation between amine groups of Ab2 and ferritin and carboxylic acid groups of MWCNTs. The detection of CA 15-3 was based on the enhanced bioelectrocatalytic reduction of hydrogen peroxide mediated by hydroquinone (HQ) at the GO/Py-COOH-based sensor probe. The GO/Py-COOH-based sensor probe and Ab2-MWCNT-Ferritin labels were characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscope (SEM), transmission electron microscope (TEM), and x-ray photoelectron spectroscopy (XPS) techniques. Using differential pulse voltammetry (DPV) technique, CA 15-3 can be selectively detected as low as 0.01 ± 0.07 U/mL in human serum samples. Additionally, the proposed CA 15-3 immunosensor showed excellent selectivity and better stability in human serum samples, which demonstrated that the proposed immunosensor has potentials in proteomic researches and diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Estimation of Hepatitis B Virus, Hepatitis C Virus, and Different Clinical Parameters in the Thalassemic Population of Capital Twin Cities of Pakistan

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Umar Saeed

2015-01-01

Full Text Available Hepatitis B and C are serious public health problems worldwide. Thalassemia patients are dependent on blood transfusions throughout their life and are at high risk of viral infections. The aim of this study was to estimate the prevalence of hepatitis B/C infections and different clinical parameters in multitransfused thalassemia population. In this study, 262 multitransfused β-thalassemia patients were enrolled from the capital twin cities of Pakistan. The presence of hepatitis B virus (HBV/hepatitis C virus (HCV, alanine aminotransferase (ALT level, serum creatinine, serum ferritin, hepatomegaly, splenomegaly, and splenectomy were analyzed. The overall prevalence of HBV and HCV was 3.08% and 55.73%, respectively, with 100% of patients older than 20 years had HCV infection. The ALT levels among HBV- and HCV-positive thalassemia patients were 92.62 ± 41.57 U/L and 98 ± 63.65 U/L, respectively; creatinine values observed were 0.4 ± 0.35 mg/dL (for HBV and 0.39 ± 0.24 mg/dL (for HCV, while serum ferritin levels were 6865.87 ± 1649.13 ng/dL (for HBV and 5445.95 ± 3059.28 ng/dL (for HCV. A total of 74.8% and 82.20% of HBV- and HCV-positive patients had hepatomegaly with an average increase in liver size of 4.17 and 4.33 cm, respectively. Splenomegaly was observed in 64.9% and 67.12% of HBV- and HCV-positive patients with an average increase in spleen size of 4 and 4.46 cm, respectively. Splenectomy was observed among 14.50% and 15.75% of HBV- and HCV-infected thalassemia patients. There is a strong need to properly screen blood before transfusions to reduce the future load of viral hepatitis from Pakistan.

Prevalence of human immunodeficiency virus, hepatitis C virus ...

African Journals Online (AJOL)

Background. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis remain major infections around the world. In Angola, about 166 000 individuals are living with HIV, representing a prevalence of 1.98% in adults between 15 and 49 years of age. In a 2003 study in Luanda, 4.5% ...

Ferritin protein imaging and detection by magnetic force microscopy.

Science.gov (United States)

Hsieh, Chiung-Wen; Zheng, Bin; Hsieh, Shuchen

2010-03-14

Magnetic force microscopy was used to image and detect ferritin proteins and the strength of the magnetic signal is discussed, revealing a large workable lift height between the magnetic tip and the ferritin sample.

Ferritin gene organization: differences between plants and animals suggest possible kingdom-specific selective constraints.

Science.gov (United States)

Proudhon, D; Wei, J; Briat, J; Theil, E C

1996-03-01

Ferritin, a protein widespread in nature, concentrates iron approximately 10(11)-10(12)-fold above the solubility within a spherical shell of 24 subunits; it derives in plants and animals from a common ancestor (based on sequence) but displays a cytoplasmic location in animals compared to the plastid in contemporary plants. Ferritin gene regulation in plants and animals is altered by development, hormones, and excess iron; iron signals target DNA in plants but mRNA in animals. Evolution has thus conserved the two end points of ferritin gene expression, the physiological signals and the protein structure, while allowing some divergence of the genetic mechanisms. Comparison of ferritin gene organization in plants and animals, made possible by the cloning of a dicot (soybean) ferritin gene presented here and the recent cloning of two monocot (maize) ferritin genes, shows evolutionary divergence in ferritin gene organization between plants and animals but conservation among plants or among animals; divergence in the genetic mechanism for iron regulation is reflected by the absence in all three plant genes of the IRE, a highly conserved, noncoding sequence in vertebrate animal ferritin mRNA. In plant ferritin genes, the number of introns (n = 7) is higher than in animals (n = 3). Second, no intron positions are conserved when ferritin genes of plants and animals are compared, although all ferritin gene introns are in the coding region; within kingdoms, the intron positions in ferritin genes are conserved. Finally, secondary protein structure has no apparent relationship to intron/exon boundaries in plant ferritin genes, whereas in animal ferritin genes the correspondence is high. The structural differences in introns/exons among phylogenetically related ferritin coding sequences and the high conservation of the gene structure within plant or animal kingdoms of the gene structure within plant or animal kingdoms suggest that kingdom-specific functional constraints may

Atomic absorption assessment of mineral iron quantity in ferritin

International Nuclear Information System (INIS)

Marinova, M.; Vladimirova, L.

2009-01-01

Possibilities for quantitative determination of the number of iron atoms in the mineral core of ferritin by atomic absorption spectroscopy (AAS) are investigated in the work. Different measurements with AAS show an iron content from 1000 up to 4500 atoms per molecule ferritin. This motivated us to investigate the amount of iron in the Horse Spleen Ferritin with atomic absorption spectroscopy under application of the Bulgarian standard BDS EN 14082/2003 Foodstuffs - Determination of trace elements - Determination of lead, cadmium, zinc, copper, iron and chromium by atomic absorption spectrometry (AAS) after dry ashing. The obtained results give approx. 1800 atoms per molecule Ferritin. It is in accordance with previous results, published by leading researchers. The investigation of the iron content with AAS under the use of the Bulgarian standard is a good opportunity to study many other objects of biological interest. (authors)

The use of non-human primates as animal models for the study of hepatitis viruses

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C.L. Vitral

1998-08-01

Full Text Available Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.

Variability of ferritin measurements in chronic kidney disease; implications for iron management.

Science.gov (United States)

Ford, Bradley A; Coyne, Daniel W; Eby, Charles S; Scott, Mitchell G

2009-01-01

Serum ferritin levels are a proxy measure of iron stores; and existing guidelines for managing anemia in hemodialysis patients suggest that serum ferritin concentrations should be maintained at >200 ng/ml. The KDOQI recommendations further state there is insufficient evidence advocating routine intravenous iron when ferritin levels exceed 500 ng/ml. Here we determined the interassay differences and short-term intraindividual variability of serum ferritin measurements in patients on chronic hemodialysis to illustrate how these variances may affect treatment decisions. Intermethod variations of up to 150 ng/ml were found comparing six commonly used ferritin assays that evaluated thirteen pools of serum from hemodialysis and nonhemodialysis patients. The intraindividual variability for ferritin in 60 stable hemodialysis patients ranged between 2-62% measured over an initial two-week period and from 3-52% when factored over a six-week period. Our results suggests that single serum ferritin values should not be used to guide clinical decisions regarding treatment of chronic hemodialysis patients with intravenous iron due to significant analytical and intraindividual variability.

Magnetic model for a horse-spleen ferritin with a three-phase core structure

Energy Technology Data Exchange (ETDEWEB)

Jung, J.H.; Eom, T.W. [Quantum Photonic Science Research Center, Department of Physics and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Y.P., E-mail: yplee@hanyang.ac.kr [Quantum Photonic Science Research Center, Department of Physics and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Rhee, J.Y. [Department of Physics, Sungkyunkwan University, Suwon (Korea, Republic of); Choi, E.H. [Kwangwoon University, Seoul (Korea, Republic of)

2011-12-15

The increasing interests in magnetic nanoparticles has prompted research on ferritin, which is naturally a well-defined iron-storage protein in most living organisms. However, the exact magnetic behavior of ferritin is not well understood, because the crystal structures of ferritin and ferrihydrite, its major component, are not fully understood. Briefly, we discuss the previous magnetization models of ferritin and ferrihydrite and we present a new model ({Sigma}3L) of the initial magnetization of ferritin, considering its different phases. The new model includes three Langevin-function terms, which represent three different magnetic moments provided by the likely hydroxide and oxide mineral phases in ferritin. Compared to previous models, our simple model fits the experimental data 12 times better in terms of the sum of least squares. The magnetic independence of each component supports the multi-phase compositional model of the mineral core of horse-spleen ferritin. This {Sigma}3L model gives a quantization of the amounts of the different phases within horse-spleen ferritins that matches other published experimental data: 60-80% ferrihydrite, 15-25% maghemite/magnetite, and 1-10% hematite. - Highlights: > We present a new model ({Sigma}3L) of the initial magnetization of ferritin, considering its different phases. > New model includes three Langevin-function terms, which represent three different magnetic moments provided by ferritin phases. > Compared to previous models, our simple model fits the experimental data 12 times better in terms of the sum of least square. > The magnetic independence of each component supports that ferritin and ferrihydrite are composed of different phases.

Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

DEFF Research Database (Denmark)

Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany

2010-01-01

Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

Science.gov (United States)

Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

1984-04-10

Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study.

Directory of Open Access Journals (Sweden)

Shaoxia Xu

Full Text Available The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health.Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010-2011. Positive human immunodeficiency virus tests were confirmed via western blotting.Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively than in women (4.45% and 0.021%, respectively. The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%, Emergency (1.71%, and Dermatology and Sexually Transmitted Diseases (1.12% departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60-70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients.During 2010-2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with

The diagnostic value of pleural effusion ferritin and the ratio of it to serum ferritin in differentiating exudates from transudates

International Nuclear Information System (INIS)

Yang Liu; Liu Junfeng; Yu Jiuru; Ju Ping; Ke Caiming

2003-01-01

To explore the diagnostic value of measuring the level of ferritin in pleural and peritoneal effusion for differentiating exudates from transudates, 128 effusion samples were initially detected for differentiating exudates from transudates by traditional method and Light's criteria. Ferritin in the effusions and serum ferritin were detected simultaneously, and the ratio of effusion ferritin (P Ft ) to serum ferritin (S Ft ) was counted. Based on the clinical data, the samples were divided into four groups and P Ft and P Ft /S Ft were compared. At the same time, the sensitivity and specificity of P Ft and P Ft /S Ft in differentiating exudates from transudates were compared with traditional method and Light's criteria. The results showed that in the groups of tuberculous pleurisy, non-tuberculous, benign pleurisy, and malignant tumor, the concentration of Ft in the effusions was significantly higher than that in the group of congestive heart failure and cirrhosis; and the Ft in exudates was significantly higher than that in transudates (P 0.05). If the cut-off value was set up for Ft in the effusion as 100 μg/L and P Ft /S Ft ratio as 0.5, respectively, the differentiating sensitivity and specificity were 94.2% and 87.0%, respectively. Conclusion was that the concentration of P Ft and P Ft /S Ft in exudates are higher than 100 μg/L and 0.5, respectively. On the contrary, they are lower than the cut-off level in transudates. P Ft and P Ft /S Ft have high sensitivity and high specificity in differentiating exudates from transudates, and have great diagnostic value

Estimation of serum ferritin for normal subject living in Khartoum area

International Nuclear Information System (INIS)

Eltayeb, E.A; Khangi, F.A.; Satti, G.M.; Abu Salab, A.

2003-01-01

This study was conducted with a main objective; the estimation of serum ferritin level in normal subjects in Khartoum area.To fulfil this objective, two hundred and sixty symptoms-free subjects were included in the study, 103 males with 15 to 45 years. serum ferritin was determined by radioimmunoassay (RIA). It was found that the mean concentration of males' serum ferritin was much higher than that of the females' (p<0.001). (Author)

Total and cause-specific mortality by moderately and markedly increased ferritin concentrations

DEFF Research Database (Denmark)

Ellervik, Christina; Marott, Jacob Louis; Tybjærg-Hansen, Anne

2014-01-01

. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10(-22)), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400-599 μg/L, 76 years at 200-399 μg/L, and 79 years at ferritin

Iron release from ferritin and lipid peroxidation by radiolytically generated reducing radicals

International Nuclear Information System (INIS)

Reif, D.W.; Schubert, J.; Aust, S.D.

1988-01-01

Iron is involved in the formation of oxidants capable of damaging membranes, protein, and DNA. Using 137 Cs gamma radiation, we investigated the release of iron from ferritin and concomitant lipid peroxidation by radiolytically generated reducing radicals, superoxide and the carbon dioxide anion radical. Both radicals released iron from ferritin with similar efficiencies and iron mobilization from ferritin required an iron chelator. Radiolytically generated superoxide anion resulted in peroxidation of phospholipid liposomes as measured by malondialdehyde formation only when ferritin was included as an iron source and the released iron was found to be chelated by the phospholipid liposomes

The clinical utility of serum ferritin levels in patients with malignant tumors treated by radiotherapy

International Nuclear Information System (INIS)

Mitsuhashi, Norio; Okazaki, Atsushi; Hayakawa, Kazushige; Nakano, Takashi; Yamanaka, Mikio

1983-01-01

The serum levels of ferritin in 394 patients, including 339 patients with various malignant tumors and 23 with various non-malignant diseases, and 32 healthy subjects were determined. The normal levels of ferritin were 82.7 +- 42.3 ng/ml for males and 42.0 +- 36.9 ng/ml for females. The positive ratio of serum ferritin level was 28% in patients with malignant tumors and 22% in patients with non-malignant diseases. The usefulness of serum ferritin assay in screening for malignant tumors appeared to be limited. High serum levels of ferritin were found in patients with malignant lymphoma (positive ratio: 42%), pulmonary cancer (38%) and esophageal cancer (37%). According to the histological types, epidermoid cancer appeared to produce a higher serum level of ferritin than adenocarcinoma in patients with pulmonary cancer. It was interesting that malignant lymphoma had a high serum level of ferritin in spite of its low serum level of CEA. Carcinoma of the digestive tracts except for esophagus was considered to have a normal serum ferritin level in spite of the advanced stage. There was no close relationship between serum ferritin levels and CEA levels in patients with pulmonary cancer and breast cancer. Serum CEA assay was more useful for detection of tumors than serum ferritin assay in patients with breast cancer. Serum ferritin levels in patients with good prognosis decreased following radiation therapy, but those in patients with poor prognosis elevated or unchanged in spite of therapy. Therefore, serial ferritin determinations may be useful for evaluation of radiotherapy and assessment of prognosis. (J.P.N.)

Time-resolved immunofluorometric assay of serum ferritin

Energy Technology Data Exchange (ETDEWEB)

Yan, Yao [China Inst. of Atomic Energy, Beijing (China)

2007-06-15

This assay is a solid phase, two-site fluoroimmunometric assay based on the direct sandwish technique. Standards or samples containing ferritin are first reacted with immobilized anti-ferritin antibodies. Then the europium-lablled antibodies are reacted with the bound antigen. The range of this assay is 2-1000 ng/mL. The analytical sentivity is better than 0.05 ng/mL. The intra-assay variation and inter-assay variation are both below 5%; This kit was compared with Wallac DELFIA kit. The correlation is r=0.96. (authors)

Characterization of ferritin core on redox reactions as a nanocomposite for electron transfer

International Nuclear Information System (INIS)

Shin, Kwang Min; Watt, Richard K.; Watt, Gerald D.; Choi, Sang H.; Kim, Hyug-Han; Kim, Sun I.; Kim, Seon Jeong

2010-01-01

The kinetics of the change in mass related to the release from and deposition onto the cavities of a ferritin in the SWCNT nanocomposite by electrochemical redox reactions, and the effects of the SWCNT on the kinetics of the variation in mass of the ferritin nanocomposite were characterized using an electrochemical quartz crystal microbalance. The change in mass of reconstituted ferritin in the SWCNT nanocomposite shows reversible variation and stability of the ferritin/SWCNT nanocomposite on redox reactions was confirmed by using a coreless apoferritin and a Fe 2+ chelating agent. The ferritin/SWCNT nanocomposite is a good candidate for applications based on electron transfer, such as biosensor, biobatteries and electrodes for biofuel cell.

Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

Science.gov (United States)

Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

2015-09-01

The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

Blood Transfusion, Serum Ferritin, and Iron in Hemodialysis Patients in Africa

Science.gov (United States)

Kouegnigan Rerambiah, Leonard; Essola Rerambiah, Laurence; Mbourou Etomba, Armel; Mouguiama, Rose Marlène; Issanga, Phanie Brunelle; Biyoghe, Axel Sydney; Batchilili, Batchelili; Akone Assembe, Sylvestre; Djoba Siawaya, Joel Fleury

2015-01-01

Background and Objectives. There is no data analyzing the outcome of blood transfusions and oral iron therapy in patients with kidneys failure in sub-Saharan Africa. The present study aimed to fill that gap and assess the value of ferritin in the diagnosis of iron overload and deficiency. Design. From January to February 2012, we prospectively studied 85 hemodialysis patients (78% of males and 22% of females aged 20 to 79 years) attending the Gabonese National Hemodialysis Centre. Results. Correlation studies showed (a) a strong positive linear relationship between the number of blood transfusions and high serum ferritin in hemodialysis patient (Spearman r : 0.74; P value: 0.0001); (b) a weak association between the number of blood transfusions and serum iron concentrations (Spearman r : 0.32; P value: 0.04); (c) a weak association between serum ferritin and serum iron (Spearman r : 0.32; P value: 0.003). Also, the strength of agreement beyond chance between the levels of ferritin and iron in the serum was poor (κ = 0.14). The prevalence of iron overload was 10.6%, whereas the prevalence of iron deficiency was 2.3%, comparing (1) patients with a maximum of one transfusion not on iron therapy; (2) patients with a maximum of one transfusion on iron therapy; (3) polytransfused patients not on iron therapy; and (4) polytransfused patients on oral iron therapy. The “Kruskal-Wallis test” showed that ferritin levels varied significantly between the groups (P value: 0.0001). Conclusion. Serum ferritin is not reliable as a marker of iron overload. For patients undergoing regular transfusion we recommend routine serum ferritin measurement and yearly measurement of LIC. PMID:25685597

Study of the rhizobacterium Azospirillum brasilense Sp245 using Mössbauer spectroscopy with a high velocity resolution: Implication for the analysis of ferritin-like iron cores

Science.gov (United States)

Alenkina, I. V.; Oshtrakh, M. I.; Tugarova, A. V.; Biró, B.; Semionkin, V. A.; Kamnev, A. A.

2014-09-01

The results of a comparative study of two samples of the rhizobacterium Azospirillum brasilense (strain Sp245) prepared in different conditions and of human liver ferritin using Mössbauer spectroscopy with a high velocity resolution demonstrated the presence of ferritin-like iron (i.e. iron similar to that found in ferritin-like proteins) in the bacterium. Mössbauer spectra of these samples were fitted in two ways: as a rough approximation using a one quadrupole doublet fit (the homogeneous iron core model) and using a superposition of quadrupole doublets (the heterogeneous iron core model). Both results demonstrated differences in the Mössbauer parameters for mammalian ferritin and for bacterial ferritin-like iron. Moreover, some differences in the Mössbauer parameters were observed between the two samples of A. brasilense Sp245 related to the differences in their preparation conditions.

Human Placenta Extract Therapy for Feline Hepatic Lipidosis

OpenAIRE

2018-01-01

Feline hepatic lipidosis (HL), the most common hepatobiliary disease in cats, is characterized by the accumulation of excessive triglycerides (TGs) in more than 80% of hepatocytes. Forced oral feeding is recommended as the only therapy for this disease but the prognosis is often poor. As human placenta extract (Laennec) has been used to improve hepatic metabolism, we investigated the efficacy of this drug for the treatment of cats with HL. Ten cats diagnosed with HL in this study were treated...

Role of Serum Uric Acid and Ferritin in the Development and Progression of NAFLD

Directory of Open Access Journals (Sweden)

Rosa Lombardi

2016-04-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD, tightly linked to the metabolic syndrome (MS, has emerged as a leading cause of chronic liver disease worldwide. Since it is potentially progressive towards non-alcoholic steatohepatitis (NASH and hepatic fibrosis, up to cirrhosis and its associated complications, the need for predictive factors of NAFLD and of its advanced forms is mandatory. Despite the current “gold standard” for the assessment of liver damage in NAFLD being liver biopsy, in recent years, several non-invasive tools have been designed as alternatives to histology, of which fibroscan seems the most promising. Among the different serum markers considered, serum uric acid (SUA and ferritin have emerged as possible predictors of severity of liver damage in NAFLD. In fact, as widely described in this review, they share common pathogenetic pathways and are both associated with hepatic steatosis and MS, thus suggesting a likely synergistic action. Nevertheless, the power of these serum markers seems to be too low if considered alone, suggesting that they should be included in a wider perspective together with other metabolic and biochemical parameters in order to predict liver damage.

Tribbles-1: a novel regulator of hepatic lipid metabolism in humans.

Science.gov (United States)

Bauer, Robert C; Yenilmez, Batuhan O; Rader, Daniel J

2015-10-01

The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target. © 2015 Authors; published by Portland Press Limited.

MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

Energy Technology Data Exchange (ETDEWEB)

Walsh, Edward G., E-mail: edward_walsh@brown.edu [Brown University, Department of Neuroscience (United States); Mills, David R. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Lim, Sierin; Sana, Barindra [Nanyang Technological University, Division of Bioengineering (Singapore); Brilliant, Kate E. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Park, William K. C. [Rhode Island Hospital, Department of Diagnostic Imaging (United States)

2013-01-15

A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r{sub 1} and r{sub 2}. The r{sub 1} and r{sub 2} values of the uniformly distributed modified ferritin were significantly higher (r{sub 1} = 1,290 mM{sup -1} s{sup -1} and r{sub 2} = 5,740 mM{sup -1} s{sup -1}) than values observed for wild-type ferritin (e.g., horse spleen, r{sub 1} = 0.674 mM{sup -1} s{sup -1}, r{sub 2} = 95.54 mM{sup -1} s{sup -1}). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T{sub 2} contrast with negligible T{sub 1} effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

Comparative study of the iron cores in human liver ferritin, its pharmaceutical models and ferritin in chicken liver and spleen tissues using Moessbauer spectroscopy with a high velocity resolution

Energy Technology Data Exchange (ETDEWEB)

Alenkina, I.V.; Semionkin, V.A. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Faculty of Experimental Physics, Ural Federal University, Ekaterinburg (Russian Federation); Oshtrakh, M.I. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Klepova, Yu.V.; Sadovnikov, N.V. [Faculty of Physiology and Biotechnology, Ural State Agricultural Academy, Ekaterinburg, (Russian Federation); Dubiel, S.M. [Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow (Poland)

2011-07-01

Full text: Application of the Moessbauer spectroscopy with a high velocity resolution (4096 channels) for a study of iron-containing biological species is of great interest. Improving the velocity resolution allows to reveal small variations in the electronic structure of iron, and to obtain hyperfine parameters with smaller instrumental (systematic) errors in comparison with measurements performed in 512 channels or less. It also allows a more reliable fitting of complex Moessbauer spectra. In the present study the Moessbauer spectroscopy with the high velocity resolution was used for a comparative analysis of ferritin and its pharmaceutically important models as well as iron storage proteins in a chicken liver and a spleen. The ferritin, an iron storage protein, consists of a nanosized polynuclear iron core formed by a ferrihydrite surrounded by a protein shell. Iron-polysaccharide complexes contain {beta}-FeOOH iron cores coated with various polysaccharides. The Moessbauer spectra of the ferritin and commercial products Imferon, MaltoferR and Ferrum Lek as well as those of the chicken liver and spleen tissues were measured with the high velocity resolution at 295 and 90 K. They were fitted using two models: (1) with a homogeneous iron core (an approximation using one quadrupole doublet), and (2) with a heterogeneous iron core (an approximation using several quadrupole doublets). The model (1) can be used as the first approximation fit to visualize small variations in the hyperfine parameters. Using this model, differences in the Moessbauer hyperfine parameters were obtained in both 295 and 90 K Moessbauer spectra. However, this model was considered as a rough approximation because the measured Moessbauer spectra had non-Lorentzian line shapes. Therefore, the spectra of the ferritin, Imferon, MaltoferR and Ferrum Lek as well as those of the liver and spleen tissues were fitted again using the model (2) in which a different number of the quadrupole doublets was

Wheat ferritins: Improving the iron content of the wheat grain

DEFF Research Database (Denmark)

Borg, Søren; Brinch-Pedersen, Henrik; Tauris, Birgitte

2012-01-01

The characterization of the full complement of wheat ferritins show that the modern hexaploid wheat genome contains two ferritin genes, TaFer1 and TaFer2, each represented by three homeoalleles and placed on chromosome 5 and 4, respectively. The two genes are differentially regulated and expresse...

Ferritin-iron increases killing of Chinese hamster ovary cells by X-irradiation

International Nuclear Information System (INIS)

Nelson, J.M.; Stevens, R.G.

1992-01-01

Stationary-phase Chinese hamster ovary cells were cultured in medium containing ferritin (∼19% iron by weight) added at concentrations ranging from 0 to 128 μg/ml. One set of cultures was unirradiated, another set exposed to 4.0 Gy of X-ray. Clonogenic cell survival was assessed in each set of cultures. In the absence of added ferritin, 4.0 Gy killed approximately 50% of the cells. In the absence of radiation, ferritin was not toxic at less than 48 μg/ml; above 48 μg/ml, toxicity increased with concentration. Apoferritin was not toxic at any concentration tested (up to 1000 μg/ml). Although 32 μg/ml ferritin, reflecting only a 3-6 fold increase in iron concentration over normal serum, was not toxic, it reduced survival of X-irradiated cells by an additional 75%. These results indicate that a sublethal concentration of ferritin can be a potent radiosensitizer. (Author)

MRI of the liver and the pituitary gland in patients with {beta}-thalassemia major: Does hepatic siderosis predict pituitary iron deposition?

Energy Technology Data Exchange (ETDEWEB)

Argyropoulou, Maria I.; Efremidis, Stavros C. [Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Kiortsis, Dimitrios N. [Laboratory of Physiology, Medical School, University of Ioannina, 45110 Ioannina (Greece)

2003-01-01

Our objective was to study, in thalassemic patients, if hepatic siderosis evaluated by MRI could predict the pituitary iron overload. In 36 thalassemic patients (age range 6-44 years, mean age 21.7 years) the liver/fat ratio (L/F), the pituitary/fat ratio (P/F), the liver and pituitary T2 relaxation times were evaluated, by using a multiecho spin-echo sequence. Serum ferritin levels were measured and an extensive endocrine evaluation was performed. The L/F, the P/F and pituitary T2 showed a good correlation with serum ferritin (r=-0.55, r=-0.55 and r=-0.53, respectively; p<0.01). Liver T2 did not show significant correlation with serum ferritin. The variability of L/F explained only the 10.8% of the variability of pituitary T2 and of the P/F. When ferritin was added to the model it predicted only the 26.85% and the 30.8% of the variability of pituitary T2 and of the P/F, respectively. The P/F and pituitary T2 were lower in patients with hypogonadotropic hypogonadism (group 1) compared with those without pituitary dysfunction (group 2). No significant differences of L/F were found between the two groups. Hepatic iron overload evaluated by MR is a poor predictor of pituitary siderosis. The MR studies of the pituitary gland might be necessary to evaluate the pituitary iron overload. (orig.)

Increased ferritin levels in patients with anorexia nervosa: impact of weight gain.

Science.gov (United States)

Wanby, P; Berglund, J; Brudin, L; Hedberg, D; Carlsson, M

2016-09-01

A few recent studies have found elevated ferritin levels in patients with anorexia nervosa (AN), indicating ferritin as a potential biomarker of disease severity. The purpose of this study was to study how body mass index (BMI) and changes in BMI affect plasma ferritin concentrations in Swedish patients with eating disorders. In a retrospective computer search from 2009 to 2014, 662 patients with an eating disorder were identified from more than 200,000 individuals with electronic medical records. Three hundred and eighty-nine patients (374 females and 15 males) were found to have at least one p-ferritin value with a corresponding BMI value. Patients with AN were compared to a combined group consisting of patients with bulimia nervosa (BN) and patients with an eating disorder not otherwise specified (EDNOS). Patients with AN had lower BMI compared to the combined group of patients with other eating disorders (BMI = 16.5 ± 1.5, n = 77 vs. 21.0 ± 4.7, n = 312, p < 0.001). Patients with AN also had higher plasma ferritin levels (median 42 μg/L (range 3.3-310) vs. 31 μg/L (range 2.8-280); p < 0.001). As BMI increased in patients with AN, ferritin levels decreased (from a median of 40 μg/L (7-400) to 26 (4-170), n = 47; p < 0.001). Measuring ferritin in patients with AN could be valuable in monitoring improvements of nutritional status, but the full clinical value of following ferritin in individual patients has yet to be determined. The study also shows how research can benefit from electronically captured clinical data using electronic health records.

Ferritin levels and risk of heart failure-the Atherosclerosis Risk in Communities Study.

Science.gov (United States)

Silvestre, Odilson M; Gonçalves, Alexandra; Nadruz, Wilson; Claggett, Brian; Couper, David; Eckfeldt, John H; Pankow, James S; Anker, Stefan D; Solomon, Scott D

2017-03-01

Severe iron overload is associated with cardiac damage, while iron deficiency has been related to worse outcomes in subjects with heart failure (HF). This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a community-based cohort. We examined 1063 participants who were free of heart failure from the Atherosclerosis Risk in Communities (ARIC) Study in whom ferritin serum levels were measured at baseline (1987-1989). The participants (mean age 52.7 ± 5.5 years, 62% women), were categorized in low (200 ng/mL in women and >300 ng/mL in men; n = 247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF. After 21 ± 4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared with participants with normal ferritin levels, participants with low ferritin levels had a higher risk of HF [hazard ratio (HR) = 2.24, 95% confidence interval (CI) 1.15-4.35; P = 0.02] as did those with high ferritin levels (HR = 1.81, 95% CI 1.01-3.25; P = 0.04), after adjusting for potential confounders. Notably, low ferritin levels remained associated with incident HF even after excluding subjects with anaemia (HR = 2.28, 95% CI 1.11-4.68; P = 0.03). Derangements in iron metabolism, either low or high ferritin serum levels, were associated with higher risk of incident HF in a general population, even without concurrent anaemia. These findings suggest that iron imbalance might play a role in the development of HF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Purification and characterisation of ferritin from the Baltic blue mussel Mytilus trossulus

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Potrykus Joanna

2009-12-01

Full Text Available Baltic blue mussels Mytilus trossulus were collected from the Gulf of Gdańsk (southern Baltic Sea in order to isolate ferritin from its soft tissues, as well as to purify and characterise this protein.     Proteins were isolated from the inner organs of M. trossulus (hepatopancreas, gills and soft tissue residue by thermal denaturation(70°C and acidification (pH 4.5 of the homogenates, followed by ammonium sulphate ((NH42SO4 fractionation.The ferritin was then separated by ultracentrifugation (100 000 × g, 120 min.. The protein content in thepurified homogenates was determined by the Lowry method using bovine serum albumin(BSA and horse spleen ferritin (HSF as standards. PAGE-SDS and Western blotting analysis permitted identification of ferritinin the purified preparations. Additionally, the purified homogenates and mussel soft tissue were analysed for their heavy metal contents(especially cadmium and iron in a Video 11 E atomic absorption spectrophotometer, following wet digestion of the samples (HNO3/HClO4.     The electrophoregrams showed that the inner organs of M. trossulus contained ferritin, which, like plant ferritin, is characterised by thepresence of subunits in the electrophoregram in the 26.6-28.0 kDa range. The highest ferritin content was recorded in the hepatopancreas,followed by the gills and the soft tissue residue. With regard to the sampling stations, the highest content of ferritin wasnoted in the animals sampled off Sopot (station D3, and in those collected by a diver off Jastarnia (W1 and Gdynia (W4. Ferritinisolated from the inner organs of mussels collected from these stations also contained the largest quantities of heavy metals(Cd and Fe. Ferritin isolated from the inner organs of mussels collected by a diver from wrecks - sites where the concentrationsof iron and other trace metals in the sea water are high - contained higher quantities of heavy metals (Cd and Fe than the ferritinisolated from the inner organs

Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults.

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Jeong Min Seong

Full Text Available The present study was conducted to assess the gender difference in the relationship between serum ferritin and 25-hydroxyvitamin D [25(OHD] in Korean adults.A total of 5,147 adults (2,162 men, 1,563 premenopausal women, and 1,422 postmenopausal women aged ≥ 20 years from the Korean National Health and Nutrition Examination Survey (KNHANES data (2012 were analyzed. A covariance test adjusted for covariates was performed for serum ferritin levels in relation to vitamin D status (vitamin D deficiency, 25(OHD < 10.0 ng/mL; vitamin D insufficiency, 25(OHD ≥ 10.0, < 20.0 ng/mL; vitamin D sufficiency, 25(OHD ≥ 20.0 ng/mL.The key study results were as follows: First, in men, in terms of serum ferritin levels by serum 25(OHD level after adjusting for age, smoking, alcohol drinking, regular exercise, SBP, DBP, WM. TC, TGs, HDL-C, FPG, Hb, Hct, MCV, and Fe, serum ferritin levels were inversely increased with the increasing of serum 25(OHD level (P = 0.012. Second, in premenopausal women, after adjusting for related variables, serum ferritin levels were increased with the increasing of serum 25(OHD level (P = 0.003. Third, in postmenopausal women, after adjusting for related variables, serum ferritin levels were not significantly increased with the increasing of serum 25(OHD level (P = 0.456.Serum 25(OHD level was inversely associated with the serum ferritin levels in men, but was positively associated with the serum ferritin levels in premenopausal women, and was not associated with the serum ferritin levels in postmenopausal women.

Increased serum ferritin levels are independently related to incidence of prediabetes in adult populations.

Science.gov (United States)

Meng, G; Yang, H; Bao, X; Zhang, Q; Liu, L; Wu, H; Du, H; Xia, Y; Shi, H; Guo, X; Liu, X; Li, C; Su, Q; Gu, Y; Fang, L; Yu, F; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Wu, Y; Niu, K

2017-04-01

To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. This prospective cohort study (n=7380) with a mean follow-up of 3.07 years (range: 1-7, 95% CI: 3.03-3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90-1.40), 1.20 (0.97-1.48), 1.41 (1.14-1.73) and 1.73 (1.41-2.11); and for women, 1.00, 1.01 (0.74-1.38), 0.68 (0.48-0.96), 0.84 (0.61-1.15) and 1.07 (0.80-1.45), respectively. Similar results were also observed for mean ferritin levels. Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels. Copyright © 2016. Published by Elsevier Masson SAS.

Ferritin and iron levels in children with autistic disorder.

Science.gov (United States)

Hergüner, Sabri; Keleşoğlu, Fatih Mehmet; Tanıdır, Cansaran; Cöpür, Mazlum

2012-01-01

Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.

Liver volume in thalassaemia major: relationship with body weight, serum ferritin, and liver function

Energy Technology Data Exchange (ETDEWEB)

Chan Yuleung; Law Manyee; Howard, Robert [Chinese University of Hong Kong, Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Hong Kong (China); Li Chikong; Chik Kiwai [Chinese University of Hong Kong, Department of Paediatrics, Prince of Wales Hospital, Hong Kong (China)

2005-02-01

It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in {beta}-thalassaemia major patients, who frequently have iron overload and hepatitis. The hypothesis is that liver volume in children and adolescents suffering from {beta}-thalassaemia major is affected by ferritin level and liver function. Thirty-five {beta}-thalassaemia major patients aged 7-18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. Body weight explained 65 and 86% of the change in liver volume in {beta}-thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P<0.001) in thalassaemia major patients than in control subjects. There was a significant correlation between ALT level and liver volume/kilogram body weight (r=0.55, P=0.001). Patients with elevated ALT had significantly higher liver volume/kilogram body weight (mean 42.9{+-}12 cm{sup 3}/kg) than control subjects (mean 23.4{+-}3.6 cm{sup 3}/kg) and patients with normal ALT levels (mean 27.4{+-}3.6 cm{sup 3}/kg). Body weight is the most important single factor for liver-volume changes in thalassaemia major patients, but elevated ALT also has a significant role. Direct liver volume measurement for chelation dose adjustment may be advantageous in patients with elevated ALT. (orig.)

Ferritin associates with marginal band microtubules

Czech Academy of Sciences Publication Activity Database

Infante, A. A.; Infante, D.; Chan, M. C.; How, P.-Ch.; Kutschera, W.; Linhartová, Irena; Müllner, E. V.; Wiche, G.; Propst, F.

2007-01-01

Roč. 313, č. 8 (2007), s. 1602-1614 ISSN 0014-4827 Institutional research plan: CEZ:AV0Z50200510 Keywords : erythrocyte * platelet * ferritin Subject RIV: EE - Microbiology, Virology Impact factor: 3.695, year: 2007

Human Interferon Alpha2a as Anti Hepatitis B and C

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Ratih A. Ningrum

2017-12-01

Full Text Available Hepatitis is an inflammation of the liver mainly caused by hepatitis viruses. There are 5 different types of hepatitis based on the infecting virus; A, B, C, D and E. Hepatitis B and C are chronic diseases that potentially develop into hepatocarcinoma and cirrhosis on unappropriate treatments. World Health Organization (WHO stated that currently 350 million people worldwide are living with chronic hepatitis B and 150 million people are living with Hepatitis C. The mortality rate in the world due to hepatitis is about 1.5 million people per year. The human interferon alpha2a (hIFNα2a is a therapeutic protein used as therapeutic protein for hepatitis B and C. This review discusses the hepatitis B (HBV and C (HCV viruses, mechanisms of hIFNα2a as antivirus through signal transduction pathway and improvement of hIFNα2a properties by protein modification. The application of recombinant hIFNα2a (rhIFNα2a in the treatment of hepatitis B and C that recommended by European Association for The Study of Liver (EASL and the viral resistance mechanism are also included. The status of hepatitis B and C and the development of rhIFNα2a is also described as well.

Phosphate and arsenate removal efficiency by thermostable ferritin enzyme from Pyrococcus furiosus using radioisotopes

KAUST Repository

Sevcenco, Ana-Maria

2015-03-13

Oxo-anion binding properties of the thermostable enzyme ferritin from Pyrococcus furiosus were characterized with radiography. Radioisotopes 32P and 76As present as oxoanions were used to measure the extent and the rate of their absorption by the ferritin. Thermostable ferritin proved to be an excellent system for rapid phosphate and arsenate removal from aqueous solutions down to residual concentrations at the picomolar level. These very low concentrations make thermostable ferritin a potential tool to considerably mitigate industrial biofouling by phosphate limitation or to remove arsenate from drinking water.

Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions.

Science.gov (United States)

Lescure, A M; Massenet, O; Briat, J F

1990-11-15

Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron.

Effect of RBC concentrate transfusions on serum ferritin content in children with acute leukaemia.

Science.gov (United States)

Bebeshko, V G; Bruslova, E M; Tsvietkova, N M; Iatsemirskii, S M; Puchkareva, T I; Gonchar, L A; Krukovska, V V; Zelinska, A V; Mishchenko, L P

2013-01-01

To study the serum ferritin levels in children with acute leukemia, depending on the number of transfusions of RBC concentrate and period of disease. We studied the red blood count, serum iron and ferritin levels in 54 patients with acute leukemia before chemotherapy, at the time of a standardized treatment protocol, and after transfusions of RBC concentrates. In the debute of acute leukemia just before treatment lauch the serum ferritin in 81.5% of children was 2.3-2.5 higher than normal. The need for transfusion of RBC concentrates was higher under serum ferritin level exceeding 500 ng/mL. The association was established between ferritin content and age of the children, variant of acute leukemia and period of the disease. The level of serum ferritin can be used as a marker of ferrokinetic status for timely diagnosis of iron overload in children with acute leukemias and for application of treatment-and-prophylactic actions. Bebeshko V. G., Bruslova K. M., Cvjetkova N. M., Jacemyrskyj S. M., Pushkarova T. I., Gonchar L. O., Krukovska V. V., Zelinska A. V., Mishhenko L. P., 2013.

Role of Bacterioferritin & Ferritin in M. tuberculosis Pathogenesis and Drug Resistance: A Future Perspective by Interactomic Approach

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Divakar Sharma

2017-06-01

Full Text Available Tuberculosis is caused by Mycobacterium tuberculosis, one of the most successful and deadliest human pathogen. Aminoglycosides resistance leads to emergence of extremely drug resistant strains of M. tuberculosis. Iron is crucial for the biological functions of the cells. Iron assimilation, storage and their utilization is not only involved in pathogenesis but also in emergence of drug resistance strains. We previously reported that iron storing proteins (bacterioferritin and ferritin were found to be overexpressed in aminoglycosides resistant isolates. In this study we performed the STRING analysis of bacterioferritin & ferritin proteins and predicted their interactive partners [ferrochelatase (hemH, Rv1877 (hypothetical protein/probable conserved integral membrane protein, uroporphyrinogen decarboxylase (hemE trigger factor (tig, transcriptional regulatory protein (MT3948, hypothetical protein (MT1928, glnA3 (glutamine synthetase, molecular chaperone GroEL (groEL1 & hsp65, and hypothetical protein (MT3947]. We suggested that interactive partners of bacterioferritin and ferritin are directly or indirectly involved in M. tuberculosis growth, homeostasis, iron assimilation, virulence, resistance, and stresses.

A case report of spontaneous mutation (C33>U) in the iron-responsive element of L-ferritin causing hyperferritinemia-cataract syndrome.

LENUS (Irish Health Repository)

Cao, Wei

2010-01-15

The hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disorder characterized by juvenile-onset cataracts and elevated serum ferritin levels. It is caused by mutation in the iron response element (IRE) within the 5\\'UTR of L-ferritin gene. The mutation results in a loss of post-transcriptional negative feedback exerted by the interaction between iron regulatory proteins 1, 2 (IRP1 and IRP2) and IRE, which leads to uncontrolled expression of L-ferritin. In this paper, we describe the molecular pathogenesis of non-hereditary hyperferritinemia cataract syndrome (non-H-HCS) in a patient with typical HHCS ocular lens morphology and high ferritin levels without obvious family history. Initial sequencing of the full-length L-ferritin cloned from genomic DNA demonstrated a mutation (C33>T) in the IRE of the affected patient but not in her unaffected family members. The mutation (C\\/T heterozygote) was also detected in cDNA derived from her blood mononuclear cells. Structure-prediction-modeling indicates that this mutation would significantly alter the secondary structure of the IRE, resulting in a loss of the interaction between IRP and IRE. By using IRP1\\/IRP2-human IgG1 Fc fusion proteins, we established a novel in vitro report system (modified ELISA) to verify impaired IRE\\/IRP binding. Both the C33>U and A40G mutations (the first identified mutation for HHCS) showed a dramatically decreased binding to IRP1\\/IRP2 protein, compared to the normal IRE RNA. Surprisingly, a decrease in L-ferritin mRNA levels was observed in the affected patient compared to controls suggesting a mechanism of transcriptional negative feedback by high intracellular L-ferritin protein levels not described heretofore. Taken together, spontaneous mutation in the IRE of L-ferritin may cause non-H-HCS by the same mechanism as HHCS. In addition, under abnormal circumstances, the protein level of L-ferritin may be principally controlled by post

Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0 Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins.

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Stephanie K Venn-Watson

Full Text Available Similar to humans, bottlenose dolphins (Tursiops truncatus can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A and lower (n = 19, Group B mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001 and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0 compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001. Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B's diet, had C17:0 (41 and 67 mg/100g, respectively. When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg, C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g; nonfat dairy products had no detectable C17:0. We hypothesize that humans' movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome.

Hepatic differentiation potential of commercially available human mesenchymal stem cells.

Science.gov (United States)

Ong, Shin-Yeu; Dai, Hui; Leong, Kam W

2006-12-01

The ready availability and low immunogenicity of commercially available mesenchymal stem cells (MSC) render them a potential cell source for the development of therapeutic products. With cell source a major bottleneck in hepatic tissue engineering, we investigated whether commercially available human MSC (hMSC) can transdifferentiate into the hepatic lineage. Based on previous studies that find rapid gain of hepatic genes in bone marrow-derived stem cells cocultured with liver tissue, we used a similar approach to drive hepatic differentiation by coculturing the hMSC with rat livers treated or untreated with gadolinium chloride (GdCl(3)). After a 24-hour coculture period with liver tissue injured by GdCl(3) in a Transwell configuration, approximately 34% of the cells differentiated into albumin-expressing cells. Cocultured cells were subsequently maintained with growth factors to complete the hepatic differentiation. Cocultured cells expressed more hepatic gene markers, and had higher metabolic functions and P450 activity than cells that were only differentiated with growth factors. In conclusion, commercially available hMSC do show hepatic differentiation potential, and a liver microenvironment in culture can provide potent cues to accelerate and deepen the differentiation. The ability to generate hepatocyte-like cells from a commercially available cell source would find interesting applications in liver tissue engineering.

Sero-prevalence of Human Immunodeficiency Virus and hepatitis ...

African Journals Online (AJOL)

Sero-prevalence of Human Immunodeficiency Virus and hepatitis viruses and their correlation with CD4 T-cell lymphocyte counts in pregnant women in the Buea Health District of Cameroon. Rebecca Enow Tanjong, Pride Teyim, Henry Lucien Kamga, Edwin Suh Neba, Theresia Nkuo-Akenji ...

Prevalence of hepatitis C Antibody in Human Immunodeficiency ...

African Journals Online (AJOL)

Background: Hepatitis C virus (HCV) is a major public health problem for Human Immunodeficiency virus (HIV) infected population. Both infections share same routes of transmission, and quite often co-exist, with dual infections associated with reciprocal and mutually more rapid progression than either infection alone.

Biosynthesis, isolation and characterization of {sup 57}Fe-enriched Phaseolus vulgaris ferritin after heterologous expression in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Hoppler, Matthias [ETH Zurich, Laboratory of Human Nutrition, Zurich (Switzerland); Meile, Leo [ETH Zurich, Laboratory of Food Biotechnology, Zurich (Switzerland); Walczyk, Thomas [National University of Singapore, Department of Chemistry and Department of Biochemistry, Singapore (Singapore)

2008-01-15

Ferritin is the major iron storage protein in the biosphere. Iron stores of an organism are commonly assessed by measuring the concentration of the protein shell of the molecule in fluids and tissues. The amount of ferritin-bound iron, the more desirable information, still remains inaccessible owing to the lack of suitable techniques. Iron saturation of ferritin is highly variable, with a maximum capacity of 4,500 iron atoms per molecule. This study describes the direct isotopic labeling of a complex metalloprotein in vivo by biosynthesis, in order to measure ferritin-bound iron by isotope dilution mass spectrometry. [{sup 57}Fe]ferritin was produced by cloning and overexpressing the Phaseolus vulgaris ferritin gene pfe in Escherichia coli in the presence of {sup 57}FeCl{sub 2}. Recombinant ferritin was purified in a fully assembled form and contained approximately 1,000 iron atoms per molecule at an isotopic enrichment of more than 95% {sup 57}Fe. We did not find any evidence of species conversion of the isotopic label for at least 5 months of storage at -20 C. Transfer efficiency of enriched iron into [{sup 57}Fe]ferritin of 20% was sufficient to be economically feasible. Negligible amounts of non-ferritin-bound iron in the purified [{sup 57}Fe]ferritin solution allows for use of this spike for quantification of ferritin-bound iron by isotope dilution mass spectrometry. (orig.)

One window-period donation in two years of individual donor-nucleic acid test screening for hepatitis B, hepatitis C and human immunodeficiency virus

Directory of Open Access Journals (Sweden)

Jose Eduardo Levi

2013-06-01

Full Text Available Objective: To describe general data on nucleic acid/serology testing and report the first hepatitis B-nucleic acid testing yield case of an immunized donor in Brazil. Methods: A total of 24,441 donations collected in 2010 and 2011 were submitted to individual nucleic acid testing for hepatitis B, hepatitis C and human immunodeficiency virus using the TaqMan® MPX kit (Roche on the Cobas s201 platform, in addition to routine screening for serological markers. Nucleic acid testing-reactive donations were further evaluated by real-time polymerase chain reaction using Cobas AmpliPrep/Cobas TaqMan hepatitis B virus, hepatitis C virus and human immunodeficiency virus tests. Results: Thirty-two donations were reactive by nucleic acid testing, 31 were also serologically reactive and one first-time donor was identified as having hepatitis B in the window period. Follow-up samples showed increasing titers of anti-HBs rising from 19 UI/mL in the index donation to 109 IU/mL seven months later attributable to his vaccination history. Curiously, this donor was never reactive for HbsAg nor for anti-HBc. In the yield donation, he was concomitantly reactive for syphilis (enzyme immunoassay and fluorescent treponemal antibody-absorption; venereal disease research laboratory non-reactive. Overall, six donors (0.02% were characterized as occult hepatitis B. A total of 35% of the confirmed (recombinant immunoblot assay positive hepatitis C donations were nucleic acid testing non-reactive and no human immunodeficiency virus "elite controller" was identified. Conclusion: The yield rate (1:24,441; 95% confidence interval: 1:9,537 - 1:89,717 contrasts to the North American rate (1:410,540 donations and strongly advocates the adoption of nucleic acid testing for hepatitis B in Brazil despite the increasing rate of anti-HBs reactive subjects due to the successful immunization program.

Radioimmunoassay and some properties of human antibodies to hepatitis B core antigen

Energy Technology Data Exchange (ETDEWEB)

Neurath, A R; Szmuness, W; Stevens, C E; Strick, N; Harley, E J [New York Blood Center, N.Y. (USA)

1978-03-01

A solid-phase radioimmunoassay for antibodies to hepatitis B core antigen (anti-HBsub(c)) is described. Polystyrene beads coated with anti-HBsub(c), hepatitis B core antigen prepared from pooled sera of humans infected with hepatitis B virus (HBV) and /sup 125/I-labelled anti-HBsub(c) were used for the test. Distinct patterns of development and changes of anti-HBsub(c) and their immunological properties are all related to variations of other markers specific for HBV infections. Knowledge concerning the detailed features of the immune response to hepatitis B core antigen may provide deeper insight into the pathogenesis of HBV infections.

Human immunodeficiency virus (HIV) seropositivity and hepatitis B ...

African Journals Online (AJOL)

Method: A total of 130 donors comprising 120 commercial donors and 10 voluntary donors were tested for antibodies to human immunodeficiency virus and hepatitis B surface antigen in Benin city using Immunocomb HIV - 1 and 2 Biospot kit and Quimica Clinica Aplicada direct latex agglutination method respectively.

Counter-attack on viral hepatitis. [Hepatitis A; Hepatitis B

Energy Technology Data Exchange (ETDEWEB)

Prozesky, O W [Pretoria Univ. (South Africa). Dept. of Medical Virology; Jupp, P G; Joubert, J J; Taylor, M B; Grabow, W O.K.

1985-07-01

The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B.

Structure of the human hepatic triglyceride lipase gene

International Nuclear Information System (INIS)

Cai, Shengjian; Wong, D.M.; Chen, Sanhwan; Chan, L.

1989-01-01

The structure of the human hepatic triglyceride lipase gene was determined from multiple cosmid clones. All the exons, exon-intron junctions, and 845 bp of the 5' and 254 bp of the 3' flanking DNA were sequenced. Comparison of the exon sequences to three previously published cDNA sequences revealed differences in the sequence of the codons for residue 133, 193, 202, and 234 that may represent sequence polymorphisms. By primer extension, hepatic lipase mRNA initiates at an adenine 77 bases upstream of the translation initiation site. The hepatic lipase gene spans over 60 kb containing 9 exons and 8 introns, the latter being all located within the region encoding the mature protein. The exons are all of average size (118-234 bp). Exon 1 encodes the signal peptide, exon 4, a region that binds to the lipoprotein substrate, and exon 5, an evolutionarily highly conserved region of potential catalytic function, and exons 6 and 9 encode sequences rich in basic amino acids thought to be important in anchoring the enzyme to the endothelial surface by interacting with acidic domains of the surface glycosaminoglycans. The human lipoprotein lipase gene has been recently reported to have an identical exon-intron organization containing the analogous structural domains. The observations strongly support the common evolutionary origin of these two lipolytic enzymes

The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

Energy Technology Data Exchange (ETDEWEB)

Cornell, Thomas A. [Department; Division; Srivastava, Yogesh [Genome; Jauch, Ralf [Genome Institute of Singapore, Singapore; Genome; Fan, Rongli [Division; Orner, Brendan P. [Department; Division

2017-07-19

Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understand the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.

Prevalence of hepatitis C Antibody in Human Immunodeficiency ...

African Journals Online (AJOL)

2015-10-25

Oct 25, 2015 ... Abstract: Background: Hepatitis. C virus (HCV) is a major public health problem for Human Immu- nodeficiency virus (HIV) infected population. Both infections share same routes of transmission, and quite often co-exist, with dual infections associated with recipro- cal and mutually more rapid pro- gression ...

Rate of Iron Transfer Through the Horse Spleen Ferritin Shell Determined by the Rate of Formation of Prussian Blue and Fe-desferrioxamine Within the Ferritin Cavity

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Zhang, Bo; Watt, Richard K.; Galvez, Natividad; Dominquez-Vera, Jose M.; Watt, Gerald D.

2005-01-01

Iron (2+ and 3+) is believed to transfer through the three-fold channels in the ferritin shell during iron deposition and release in animal ferritins. However, the rate of iron transit in and out through these channels has not been reported. The recent synthesis of [Fe(CN)(sub 6)](3-), Prussian Blue (PB) and desferrioxamine (DES) all trapped within the horse spleen ferritin (HoSF) interior makes these measurements feasible. We report the rate of Fe(2+) penetrating into the ferritin interior by adding external Fe(2+) to [Fe(CN)(sub 6)](3-) encapsulated in the HoSF interior and measuring the rate of formation of the resulting encapsulated PB. The rate at which Fe(2+) reacts with [Fe(CN)(sub 6)](3-) in the HoSF interior is much slower than the formation of free PB in solution and is proceeded by a lag period. We assume this lag period and the difference in rate represent the transfer of Fe(2+) through the HoSF protein shell. The calculated diffusion coefficient, D approx. 5.8 x 10(exp -20) square meters per second corresponds to the measured lag time of 10-20 s before PB forms within the HoSF interior. The activation energy for Fe(2+) transfer from the outside solution through the protein shell was determined to be 52.9 kJ/mol by conducting the reactions at 10 to approximately 40 C. The reaction of Fe(3+) with encapsulated [Fe(CN)6](4-) also readily forms PB in the HoSF interior, but the rate is faster than the corresponding Fe(2+) reaction. The rate for Fe(3+) transfer through the ferritin shell was confirmed by measuring the rate of the formation of Fe-DES inside HoSF and an activation energy of 58.4 kJ/mol was determined. An attempt was made to determine the rate of iron (2+ and 3+) transit out from the ferritin interior by adding excess bipyridine or DES to PB trapped within the HoSF interior. However, the reactions are slow and occur at almost identical rates for free and HoSF-encapsulated PB, indicating that the transfer of iron from the interior through the

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

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Lídia Cedó

Full Text Available Human hepatic lipase (hHL is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT. In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL-mediated free fatty acid (FFA lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

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Cedó, Lídia; Santos, David; Roglans, Núria; Julve, Josep; Pallarès, Victor; Rivas-Urbina, Andrea; Llorente-Cortes, Vicenta; Laguna, Joan Carles; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

2017-01-01

Human hepatic lipase (hHL) is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL) is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT). In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL)-mediated free fatty acid (FFA) lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

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DeVita, M V; Frumkin, D; Mittal, S; Kamran, A; Fishbane, S; Michelis, M F

2003-11-01

Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of requirements.

Iron and ferritin dependent ROS distribution impact Arabidopsis root system architecture.

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Reyt, Guilhem; Boudouf, Soukaina; Boucherez, Jossia; Gaymard, Frédéric; Briat, Jean-Franois

2014-11-09

Iron (Fe) homeostasis is integrated with the production of Reactive Oxygen Species (ROS) whose distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana (Arabidopsis) root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin and RSA is in part mediated by the H 2 O 2 /O 2 .- balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Further, meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

Studies on the 2-site immunoradiometric assay of serum ferritin and its applications for diagnosis of iron deficiency

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Koseki, J.; Niitsu, Y. (Sapporo Medical Coll. (Japan). Cancer Research Inst.)

1980-10-01

The 2-site immunoradiometric assay using paper discs as a solid phase material was established for the measurement of serum ferritin. The standard curve was found the range from 0.5ng -- 500ng ferritin per ml and the sensitivity limit of the assay was 0.1ng ferritin per ml. The clinical value of serum ferritin assay was then investigated for diagnosis of iron deficiency. The mean serum ferritin concentrations of normal subjects were greater for males (119.8+-55.5ng/ml) than for females (56.5+-55.5ng/ml) although this sex difference was not distinct beyond the age of 45. All 15 patients with iron deficient anemia had serum ferritin concentrations below the normal range, whereas in other anemias including anemia associated with chronic inflammation, pernicious anemia, aplastic anemia, serum ferritin concentrations were normal or elevated. In 116 apparently normal subjects, 13.8% of total females had abnormally low serum ferritin concentrations with normal hemoglobin levels. The cytochrome c oxidase activity of peripheral leucocytes from those subjects were generally depleted. Most of them frequently suffered from easy fatigability, weakness, and dizziness and these complications were clearly relieved by the administration of iron. Measurement of serum ferritin was found to be quite useful for diagnosis and assessment of iron deficient states.

Lack of a relationship between serum ferritin levels and coronary atherosclerosis evaluated by coronary arteriography

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W.C. Manfroi

1999-03-01

Full Text Available Many clinical and epidemiological studies have demonstrated the relationship between serum ferritin and ischemic heart disease. In the present study we evaluated the relationship between coronary heart disease (CHD and serum ferritin levels in patients submitted to coronary arteriography. We evaluated 307 patients (210 (68.7% males; median age: 60 years who were submitted to coronary angiography, measurement of serum ferritin and identification of clinical events of ischemic heart disease. Serum ferritin is reported as quartiles. Ninety-six patients (31.27% had normal coronary angiography (group 1 and 211 (68.73% had coronary heart disease (group 2. Of the patients with CHD, 61 (28.9% had serum ferritin levels higher than 194 ng/ml (4th quartile, as opposed to only 14 (14.58% of those without CHD (P = 0.0067. In the 2nd quartile, 39 patients (18.48% had CHD, while 35 patients (36.46% had normal coronary arteries (P = 0.00064. Multivariate analysis of the data showed that the difference between groups was not statistically significant (P = 0.33. We conclude that there is no independent relationship between coronary heart disease and increased levels of serum ferritin.

Encapsulation of β-carotene within ferritin nanocages greatly increases its water-solubility and thermal stability.

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Chen, Lingli; Bai, Guangling; Yang, Rui; Zang, Jiachen; Zhou, Ting; Zhao, Guanghua

2014-04-15

Carotenoids may play a number of potential health benefits for human. However, their use in food industry is limited mostly because of their poor water-solubility and low thermal stability. Ferritins are widely distributed in nature with a shell-like structure which offers a great opportunity to improve the water-solubility and thermal stability of the carotenoids by encapsulation. In this work, recombinant human H-chain ferritin (rHuHF) was prepared and used to encapsulate β-carotene, a typical compound among carotenoids, by taking advantage of the reversible dissociation and reassembly characteristic of apoferritin in different pH environments. Results from high-performance liquid chromatography (HPLC), UV/Vis spectroscopy and transmission electron microscope (TEM) indicated that β-carotene molecules were successfully encapsulated within protein cages with a β-carotene/protein molar ratio of 12.4-1. Upon such encapsulation, these β-carotene-containing apoferritin nanocomposites were water-soluble. Interestingly, the thermal stability of the β-carotene encapsulated within apoferritin nanocages was markedly improved as compared to free β-carotene. These new properties might be favourable to the utilisation of β-carotene in food industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assay of serum ferritin by two different radioimmunometric methods and its clinical significance

International Nuclear Information System (INIS)

Kaltwasser, J.P.; Werner, E.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Frankfurt am Main

1977-01-01

Serum ferritin was measured by two different radioimmunometric methods a) the Addison assay, b) a commercial radioimmunoassay. Iron storage in the body was determined using 59 Fe. A dose correlation was found between serum ferritin and iron storage in the body. (AJ) [de

Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population.

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Gordeuk, Victor R; Reboussin, David M; McLaren, Christine E; Barton, James C; Acton, Ronald T; McLaren, Gordon D; Harris, Emily L; Reiss, Jacob A; Adams, Paul C; Speechley, Mark; Phatak, Pradyumna D; Sholinsky, Phyliss; Eckfeldt, John H; Chen, Wen-Pin; Passmore, Leah; Dawkins, Fitzroy W

2008-08-01

How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 microg/L (men), >200 microg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 microg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 microg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but 900 microg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 microg/L in male C282Y homozygotes is predictive of moderately increased iron stores. Copyright 2008 Wiley-Liss, Inc.

Human Immunodeficiency Virus and Hepatitis C Virus Co-infection ...

African Journals Online (AJOL)

Human Immunodeficiency Virus and Hepatitis C Virus Co-infection in Cameroon: Investigation of the Genetic Diversity and Virulent ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL · RESOURCES ... DNA sequencing, and bioinformatics tools for sequence management and analysis.

Ferritin Blood Test: MedlinePlus Lab Test Information

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... K. Brunner & Suddarth's Handbook of Laboratory and Diagnostic Tests. 2nd Ed, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott Williams & Wilkins; c2014. Ferritin, Serum; 296 p. Lab Tests ...

Novel Functional Changes during Podocyte Differentiation: Increase of Oxidative Resistance and H-Ferritin Expression

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Emese Bányai

2014-01-01

Full Text Available Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H2O2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well.

Clinical Significance of Serum Ferritin at Diagnosis in Patients With Acute Myeloid Leukemia: A YACHT Multicenter Retrospective Study.

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Tachibana, Takayoshi; Andou, Taiki; Tanaka, Masatsugu; Ito, Satomi; Miyazaki, Takuya; Ishii, Yoshimi; Ogusa, Eriko; Koharazawa, Hideyuki; Takahashi, Hiroyuki; Motohashi, Kenji; Aoki, Jun; Nakajima, Yuki; Matsumoto, Kenji; Hagihara, Maki; Hashimoto, Chizuko; Taguchi, Jun; Fujimaki, Katsumichi; Fujita, Hiroyuki; Fujisawa, Shin; Kanamori, Heiwa; Nakajima, Hideaki

2018-06-01

A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML). The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients. The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003). Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group. Copyright © 2018 Elsevier Inc. All rights reserved.

Studies on the 2-site immunoradiometric assay of serum ferritin and its applications for diagnosis of iron deficiency

International Nuclear Information System (INIS)

Koseki, Junichi; Niitsu, Yoshiro

1980-01-01

The 2-site immunoradiometric assay using paper discs as a solid phase material was established for the measurement of serum ferritin. The standard curve was found the range from 0.5ng -- 500ng ferritin per ml and the sensitivity limit of the assay was 0.1ng ferritin per ml. The clinical value of serum ferritin assay was then investigated for diagnosis of iron deficiency. The mean serum ferritin concentrations of normal subjects were greater for males (119.8+-55.5ng/ml) than for females (56.5+-55.5ng/ml) although this sex difference was not distinct beyond the age of 45. All 15 patients with iron deficient anemia had serum ferritin concentrations below the normal range, whereas in other anemias including anemia associated with chronic inflammation, pernicious anemia, aplastic anemia, serum ferritin concentrations were normal oe elevated. In 116 apparently normal subjects, 13.8% of total females had abnormally low serum ferritin concentrations with normal hemoglobin levels. The cytochrome c oxidase activity of peripheral leucocytes from those subjects were generally depleted. Most of them frequently suffered from easy fatiguability, weakness, and dizziness and these complications were clearly relieved by the administration of iron. Measurement of serum ferritin was found to be quite useful for diagnosis and assessment of iron deficient states. (author)

Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review.

Science.gov (United States)

Lin, Kuan-Yin; Chen, Guan-Jhou; Lee, Yu-Lin; Huang, Yi-Chia; Cheng, Aristine; Sun, Hsin-Yun; Chang, Sui-Yuan; Liu, Chun-Eng; Hung, Chien-Ching

2017-05-28

Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.

Differential gene expression analysis of in vitro duck hepatitis B virus infected primary duck hepatocyte cultures

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Issac Aneesh

2011-07-01

Full Text Available Abstract Background The human hepatitis B virus (HBV, a member of the hepadna viridae, causes acute or chronic hepatitis B, and hepatocellular carcinoma (HCC. The duck hepatitis B virus (DHBV infection, a dependable and reproducible model for hepadna viral studies, does not result in HCC unlike chronic HBV infection. Information on differential gene expression in DHBV infection might help to compare corresponding changes during HBV infection, and to delineate the reasons for this difference. Findings A subtractive hybridization cDNA library screening of in vitro DHBV infected, cultured primary duck hepatocytes (PDH identified cDNAs of 42 up-regulated and 36 down-regulated genes coding for proteins associated with signal transduction, cellular respiration, transcription, translation, ubiquitin/proteasome pathway, apoptosis, and membrane and cytoskeletal organization. Those coding for both novel as well as previously reported proteins in HBV/DHBV infection were present in the library. An inverse modulation of the cDNAs of ten proteins, reported to play role in human HCC, such as that of Y-box binding protein1, Platelet-activating factor acetylhydrolase isoform 1B, ribosomal protein L35a, Ferritin, α-enolase, Acid α-glucosidase and Caspase 3, copper-zinc superoxide dismutase (CuZnSOD, Filamin and Pyruvate dehydrogenase, was also observed in this in vitro study. Conclusions The present study identified cDNAs of a number of genes that are differentially modulated in in vitro DHBV infection of primary duck hepatocytes. Further correlation of this differential gene expression in in vivo infection models would be valuable to understand the little known aspects of the hepadnavirus biology.

Potentiometric assessment of iron release during ferritin reduction by exogenous agents.

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Vladimirova, Lilia S; Kochev, Valery K

2010-09-01

This work studied the possibilities for quantitative determination of iron mobilization in connection with ferritin reduction by ascorbic acid (vitamin C) and sodium dithionite in vitro. The iron storage protein was incubated with an excess of reductant in aerobic conditions in the absence of complexing agents in the medium. The release of Fe(2+) was let to go to completion, and the overall content of Fe(2+) in the solution was evaluated with the aid of potentiometric titration using Ce(4+) as an oxidizing titrant. Results suggest a moderate iron efflux under the influence of the chosen reducing agents. Although such a reduction of the protein mineral core by dihydroxyfumarate contributes greatly to the iron mobilization, ferritin behavior with vitamin C and dithionite seems to be different. Although redox properties of dihydroxyfumarate are determined by hydroxyl groups similar to those of ascorbic acid, the two compounds differ significantly in structure, and this could be the basis for an explanation of the specificities in their interaction with ferritin. As revealed by the study, potentiometric titration promises to be a reliable tool for evaluation of the amount of Fe(2+) present in the solution as a result of the reduction of the ferritin's mineral core. 2010 Elsevier Inc. All rights reserved.

Assessment of serum ferritin levels in thalassemia and non-thalassemia patients presented with anemia

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Mohammed Mahdi Abdulomohsin AL-Zubaidi

2015-01-01

Objectives: The aim of this study was to assess serum ferritin levels in B-thalassemia patients, and to compare it with non-thalassemic anemia and healthy control. Materials and methods : A prospective cross sectional study conducted at Thalassemia Center in Ibn Al- Baladi Hospital for Children and Women during the period from1st February to 30th May 2014 during their attendance to out-patient clinic. A total .number of 101 patients complaining of anemia (51 patients with thalassemia, 50 with non-thalassemia in addition to 50 healthy subjects considered as control. All patients were tested for Serum ferritin levels and all results were obtained through automated quantitative test for use Vidas machine Results : The mean serum ferritin levels in cases of thalassemia was 9542 ± 782 ng/ml while serum ferritin levels in control sample was 138 ± 323 ng/ml in male and 28 ± 108 ng/ml in female . in patients with non-thalassemia anemia, the levels of serum ferritin was 1 ± 80 ng/ml. Age of all patients in this study ranged from 3day-9year .the age of thalassemia patients ranged from 1-6 year and p-value was(0.23 while the age of patients with non-thalassemia anemia was 1-5 year and p-value was (0.11. Conclusion: This study confirm that serum ferritin is high in patients wih thalassemia than non thalassemia.

The Effect of Image Potential on the Current-Voltage Characteristics of a Ferritin-layer

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Eunjung Bang

2010-11-01

Full Text Available Considering for the concept of power storage systems, such as those used to supply power to microelectronic devices, ferritins have aroused a lot of interests for applications in bioelectrochemical devices. And electron transfer rates from the proteins to electrode surface are key determinants of overall performance and efficiency of the ferritin-based devices. Here we have investigated the electron transport mechanism of ferritin layer which was immobilized on an Au electrode. The current-voltage (I-V curves are obtained by a conductive atomic force microscope (c-AFM as a function of contact area between AFM tip and the ferritin layer. In the low voltage region, I-V curves are affected by both Fowler-Nordheim tunneling and image force. On the other hand, the experimental results are consistent with a Simmons model in a high voltage region, indicating that, as the voltage increases, the image potential has a dominant effect on the electron transport mechanism. These results are attributed to the film-like character of the ferritin layer, which generates an image potential to lower the barrier height in proportion to the voltage increment.

Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

Science.gov (United States)

Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

2012-01-01

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P 1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P 1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage

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Hopkinson, Branden M; Madsen, Claus Desler; Kalisz, Mark

2017-01-01

Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells...... of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction...

The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus.

Science.gov (United States)

Flisiak, Robert; Horban, Andrzej; Gallay, Philippe; Bobardt, Michael; Selvarajah, Suganya; Wiercinska-Drapalo, Alicja; Siwak, Ewa; Cielniak, Iwona; Higersberger, Jozef; Kierkus, Jarek; Aeschlimann, Christian; Grosgurin, Pierre; Nicolas-Métral, Valérie; Dumont, Jean-Maurice; Porchet, Hervé; Crabbé, Raf; Scalfaro, Pietro

2008-03-01

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.

Epidemiological studies on viral infections and co-infections : Human immunodeficiency virus, hepatitis C virus and human papillomavirus

NARCIS (Netherlands)

van Santen, D.K.

2018-01-01

The research described in this thesis aimed to increase our understanding of the incidence, disease progression and treatment of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and human papillomavirus (HPV) infections and co-infections in key populations. Chapter 1 contains an overview

Prevalence of hepatitis B, hepatitis C and human immunodeficiency ...

African Journals Online (AJOL)

Background. Hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV are common blood-borne infections unevenly distributed across regions in Nigeria. Few population-based prevalence studies have been done in Nigeria. Objective. To determine the prevalence of HBV, HCV and HIV and risk factors for infection with ...

The possible role of tumor antigen CA 15-3, CEA and ferritin in malignant and benign disease

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Nafija Serdarević

2012-09-01

Full Text Available Introduction: Serum CA15-3 has been one of the most reliable tumor markers used in monitoring of breast cancer patients. To increase its sensitivity, the combined measurement of other tumor markers (CEA and ferritin with CA15-3 was investigated. The aim of this study was determination of CA 15-3, CEA and ferritin in female patients with breast cancer, lung cancer and mastitisMethods: 300 patients with carcinoma, hospitalized at Department of Gynecologic Oncology and Department for Oncology at the University Clinics Center of Sarajevo and 200 healthy subjects were compared.Results: In patients with breast cancer the mean value of tumor markers were CEA 155.61 ng/mL, CA 15-3 106.38 U/mL and ferritin 197.03 ng/mL. In patients with lung cancer CEA was 58.97 ng/ml, CA 15-3 40.62 U/mL and ferritin 544.16 ng/mL. Patients with mastitis had CEA 5.17 ng/mL, CA 15-3 112.67 U/mL and ferritin 174.92 ng/mL. The control group had values of tumor markers CEA 1.62 ng/mL, CA 15-3 11.72 U/mL and ferritin 85.35 ng/mL. We found good correlation between CA 15-3 and CEA correlation coeffi cient was r = 0.750. There was a low correlation between CA 15-3 and ferritin with correlation coeffi cient r = 0.274.Conclusions: The CA 15-3 and CEA are useful markers in patients with confi rmed diagnosis of breast and lung cancers. The ferritin concentration has not increased in patients with breast cancer but it increased inlung patients. The future study has to make investigations of tumor markers and ferritin in different stage of breast cancer.

Long-term culture of human liver tissue with advanced hepatic functions.

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Ng, Soon Seng; Xiong, Anming; Nguyen, Khanh; Masek, Marilyn; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A; Voedisch, Amy; Shaw, Kate; Rashid, Sheikh Tamir; Frank, Curtis W; Cho, Nam Joon; Glenn, Jeffrey S

2017-06-02

A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.

Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples

International Nuclear Information System (INIS)

Hsia, Chu Chieh; Chizhikov, Vladimir E.; Yang, Amy X.; Selvapandiyan, Angamuthu; Hewlett, Indira; Duncan, Robert; Puri, Raj K.; Nakhasi, Hira L.; Kaplan, Gerardo G.

2007-01-01

Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type-1 (HIV-1) are transfusion-transmitted human pathogens that have a major impact on blood safety and public health worldwide. We developed a microarray multiplex assay for the simultaneous detection and discrimination of these three viruses. The microarray consists of 16 oligonucleotide probes, immobilized on a silylated glass slide. Amplicons from multiplex PCR were labeled with Cy-5 and hybridized to the microarray. The assay detected 1 International Unit (IU), 10 IU, 20 IU of HBV, HCV, and HIV-1, respectively, in a single multiplex reaction. The assay also detected and discriminated the presence of two or three of these viruses in a single sample. Our data represent a proof-of-concept for the possible use of highly sensitive multiplex microarray assay to screen and confirm the presence of these viruses in blood donors and patients

Construction of a cDNA library for sea cucumber Acaudina leucoprocta and differential expression of ferritin peptide

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Zhou, Jun; Hou, Fujing; Li, Ye; Su, Xiurong; Li, Taiwu; Jin, Chunhua

2016-07-01

Acaudina leucoprocta is an edible sea cucumber of economic interest that is widely distributed in China. Little information is available concerning the molecular genetics of this species although such knowledge would contribute to a better understanding of the optimal conditions for its aquaculture and its mechanisms of defense against disease. Therefore, we constructed a cDNA library and, based on bioinformatics analysis of the sequences, the functions of 75% of the cDNAs were identified, including those involved in cell structure, energy metabolism, mitochondrial function, and signal transduction pathways. Approximately 25% of genes in the library were unmatched. The gene for A. leucoprocta ferritin was also cloned. The predicted amino-acid sequence of ferritin displayed significant homology with other sea-cucumber counterparts but indicated that it was a new member of the ferritin family. Semiquantitative real-time RT-PCR indicated the highest levels of ferritin mRNA expression in the intestine. A polyclonal antibody of ferritin was also produced. These data provide a set of molecular tools essential for further studies of the functions of ferritin protein in A. leucoprocta.

Committee Opinion No. 655 Summary: Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus Infections in Obstetrician-Gynecologists.

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2016-02-01

To prevent transmission of bloodborne pathogens, it is important that health care providers adhere to standard precautions, follow fundamental infection-control principles, and use appropriate procedural techniques. All obstetrician-gynecologists who provide clinical care should receive the hepatitis B virus vaccine series. The Society for Healthcare Epidemiology of America has established guidelines for the management of health care providers who are infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV). The guidelines categorize representative obstetric and gynecologic procedures according to level of risk of bloodborne pathogen transmission and include recommendations for health care provider clinical activities, based on these categories and viral burden. It is important to note that when no restrictions are recommended, careful supervision should be carried out as highlighted. These recommendations provide a framework within which to consider such cases; however, each case should be independently considered in context by the expert review panel.

Relationship of serum ferritin level and tic severity in children with Tourette syndrome.

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Ghosh, Debabrata; Burkman, Elizabeth

2017-08-01

Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS. Children tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up. In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron. Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins

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Venn-Watson, Stephanie K.; Parry, Celeste; Baird, Mark; Stevenson, Sacha; Carlin, Kevin; Daniels, Risa; Smith, Cynthia R.; Jones, Richard; Wells, Randall S.; Ridgway, Sam; Jensen, Eric D.

2015-01-01

Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome. PMID:26200116

Evaluation of Usefulness of hs-CRP and Ferritin Assays in Patients with Nasal Polyps

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Robert Partyka

2014-01-01

Full Text Available Background. Chronic nature of the nasal polyps, tendency to recurrence, and lack of satisfying treatment need the diagnostic’s parameters which show early inflammatory state as ferritin and hs-CRP. The Aim of Study. Assessment of hs-CRP and ferritin blood levels in nasal polyps patients in evaluation of treatment efficacy. Methods. All 38 patients were divided into 2 groups. Group I included 19 patients with anti-inflammatory therapy 2 weeks after surgery. Group II included 19 patients without anti-inflammatory therapy 2 weeks after surgery. The levels of hs-CRP and ferritin have been assessed before and 2 and 6 weeks after surgical treatment. Results. Research showed statistically significant difference of ferritin’s concentration between examined groups 6 weeks after surgery (P<0.05 and statistically significant difference of hs-CRP concentration 2 and 6 weeks after surgery (P<0.05. Conclusion. (1 The analysis of serum ferritin and hs-CRP concentrations can be useful in early postoperative detection of inflammatory state in patients with nasal polyps and for the effectiveness of therapy. (2 Lack of correlation between mean ferritin and hs-CRP serum levels, at each diagnostic and monitoring stage, shows that they are independent and cannot be determined interchangeably.

Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

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Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

2014-03-01

Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Hepatitis c and human rights: comparison of legal experience of Ukraine and Georgia.

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Senyuta, Iryna Y

2018-01-01

A comparative legal research of human rights provision in Ukraine and Georgia, in the aspect of combating viral HCV, was conducted. Ukrainian advocacy experience and Georgian strategic litigation experience with regard to human rights and HCV was analyzed. Key international instruments, which lay the conceptual foundations as well as outline the measures, which are directed at human rights in patient care provision and fighting viral hepatitis, were elucidated. Attention was paid to the Global health sector strategy. Viral hepatitis, 2016 - 2021 [1], which, for the first time, defined a global strategy on fighting viral hepatitis, in particular HCV and envisaged the advocacy vectors. The frames of interaction of the human rights in patient care concept and public health, which consists in realization of certain human rights were elucidated and the necessity to embody the human rights in patient care concept into the state policy in the field of public health was determined. It was found out that a common international problem in combating HCV is a deficiency of financial resources, which are necessary for effective fighting the epidemics and guarantee equal access to treatment for every person. The international community outlined five most important spheres, which require investments and will catalyze the measures, which need to be taken in order to fight hepatitis. Analysis of the Ukrainian experience was focused on the issue of donated blood safety and successful advocacy campaigns, which were carried out in order to promote the adoption of programs on prophylactics, diagnostics and treatment of HCV both on national and regional levels. Examples of ensuring the rights of the marginalized groups during HCV treatment, in particular of the people who inject drugs, people living with HIV, participants of the antiterrorist operation were provided. Interesting and important is the experience of Georgia concerning human rights protection in the ECtHR, which has a legal

Nanoscale film formation of ferritin and its application to biomemory device

International Nuclear Information System (INIS)

Kim, Sang-Uk; Lee, Taek; Lee, Jin-Ho; Yagati, Ajay Kumar; Min, Junhong; Choi, Jeong-Woo

2009-01-01

A redox protein, ferritin is used as a functional constituent of the developed biomemory device. The concept of molecular device mainly depends on the solidification of biomolecules of interest and on the realization of properties of molecule immobilized on a selected substrate. Here, we immobilized the biomolecule, ferritin protein on gold substrate using an organic linker 11-mercaptoundecanoic acid (11-MUA). The immobilization of the protein on the gold substrate was confirmed by surface plasmon spectroscopy, Raman spectroscopy, and atomic force microscopy (AFM). The basic two memory functions, reading and writing of the developed biomemory device, were investigated by open-circuit potential amperometry (OCPA) using the redox property of the biomolecule of interest. The surface topography investigation by scanning tunneling microscopy (STM) shows that the robustness of the ferritin-based biomemory device was validated by the repeated electrochemical performance. These results show the developed biomemory device as a step towards the protein-based nanobiochip.

Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

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de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

2018-05-02

This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

Ferrimagnetic ferritin cage nanoparticles used as MRI contrast agent

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Cai, Y.; Cao, C.; Zhang, T.; Xu, H.; Pan, Y.

2017-12-01

The nano-sized ferrimagnetic ferritin cage nanoparticles are ideal materials for understanding of superparamagnetism, biomimetic synthesis of ultrafine magnetic particles and their application in biomedicine. Ferrimagnetic M-HFn nanoparticles with size of magnetite cores in a mean size ranges from 2.7 nm to 5.3 nm were synthesized through loading different amount of iron into recombinant human H chain ferritin (HFn) shells. Both the saturation magnetization (Ms) and blocking temperature (Tb) were increased with the size of ferrimagnetic cores. In essence, magnetic resonance imaging (MRI) analysis showed that the synthesized M-HFn nanoparticles (5.3 nm magnetite core) has extremely high transverse relaxivity (r2) values up to 320.9 mM-1S-1, which indicate that M-HFn nanoparticles are promising negative contrast agent in early detection of tumors. In addition, the longitudinal relaxivity (r1) (10.4 mM-1S-1) and r2/r1 ratio ( 2.2) of M-HFn nanoparticles ( 2.7 nm magnetite core in diameter) will make it a considerable potential as a positive contrast agent in MRI. This means the M-HFn nanoparticles can be used as dual functional MR contrast agent. Acute toxicity study of M-HFn in rats showed that a dosage of 20 mg Fe/kg makes no abnormalities by serum biochemical and hematological analysis as well as histopathological examination. Compared with a similar commercial contrast agent, combidex (with a clinical dosage of 2.7 mg Fe/kg), it indicates that M-HFn nanoparticle is of a relative safe ferrimagnetic nanoparticle when used in vivo.

Initial Serum Ferritin Predicts Number of Therapeutic Phlebotomies to Iron Depletion in Secondary Iron Overload

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Panch, Sandhya R.; Yau, Yu Ying; West, Kamille; Diggs, Karen; Sweigart, Tamsen; Leitman, Susan F.

2014-01-01

Background Therapeutic phlebotomy is increasingly used in patients with transfusional siderosis to mitigate organ injury associated with iron overload (IO). Laboratory response parameters and therapy duration are not well characterized in such patients. Methods We retrospectively evaluated 99 consecutive patients undergoing therapeutic phlebotomy for either transfusional IO (TIO, n=88; 76% had undergone hematopoietic transplantation) or non-transfusional indications (hyperferritinemia or erythrocytosis) (n=11). CBC, serum ferritin (SF), transferrin saturation, and transaminases were measured serially. Phlebotomy goal was an SF< 300 mcg/L. Results Mean SF prior to phlebotomy among TIO and nontransfusional subjects was 3,093 and 396 mcg/L, respectively. Transfusion burden in the TIO group was 94 ± 108 (mean ± SD) RBC units; about half completed therapy with 24 ± 23 phlebotomies (range 1–103). One-third was lost to follow-up. Overall, 15% had mild adverse effects, including headache, nausea, and dizziness, mainly during first phlebotomy. Prior transfusion burden correlated poorly with initial ferritin and total number of phlebotomies to target (NPT) in the TIO group. However, NPT was strongly correlated with initial SF (R2=0.8; p<0.0001) in both TIO and nontransfusional groups. ALT decreased significantly with serial phlebotomy in all groups (mean initial and final values, 61 and 39 U/L; p = 0.03). Conclusions Initial SF but not transfusion burden predicted number of phlebotomies to target in patients with TIO. Despite good treatment tolerance, significant losses to follow-up were noted. Providing patients with an estimated phlebotomy number and follow-up duration, and thus a finite endpoint, may improve compliance. Hepatic function improved with iron off-loading. PMID:25209879

Relationship between Plasma Ferritin Level and Siderocyte Number in Splenectomized β-Thalassemia/HbE Patients

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A. Tripatara

2012-01-01

Full Text Available Introduction. In iron overload status, excess iron deposits in reticuloendothelial cells and tissues and can be detected using Prussian blue staining. The aim of this paper was to investigate the relationship between siderocyte numbers and plasma ferritin levels (a practically standard marker of iron overload in the blood of the splenectomized and nonsplenectomized β-thalassemia/HbE patients, who are at risk of iron overload. Methods. EDTA blood samples from 64 patients with 35 splenectomized and 29 nonsplenectomized β-thalassemia/HbE patients, who received regular blood transfusions, and 20 normal individuals were investigated for siderocyte numbers, plasma ferritin levels, and complete blood counts. Results. The average percent siderocytes in splenectomized and nonsplenectomized β-thalassemia/HbE patients were 11.5% and 0.08%, respectively, and plasma ferritin levels of 2,332 μg/L and 1,279 μg/L, respectively. Percent siderocytes showed a good correlation with plasma ferritin levels only in splenectomized patients (r=0.69, P<0.001. A receiver operating curve analysis from splenectomized patients’ data indicated that siderocytes at 3% cut-off are the best predictor for plasma ferritin level ≥1,000 μg/L with 92.9% sensitivity and 42.9% specificity. Conclusion. Circulating siderocyte numbers can be used as a screening test for the assessment of the iron overload in splenectomized β-thalassemia/HbE patients in the place where serum ferritin is not available.

The Novel C24D Synthetic Polypeptide Inhibits Binding of Placenta Immunosuppressive Ferritin to Human T Cells and Elicits Anti–Breast Cancer Immunity In Vitro and In Vivo

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Inna Solodeev

2014-09-01

Full Text Available Immune tolerance mechanisms supporting normal human pregnancy are exploited by breast cancer and other malignancies. We cloned from human placenta and breast cancer cells the novel human immunomodulator named placenta immunosuppressive ferritin (PLIF. PLIF is composed of a ferritin heavy chain–like domain and a novel cytokine-like domain, named C48. Both intact PLIF and C48 inhibit T cell proliferation. Blocking PLIF by specific antibodies in a tolerant breast cancer model in nude mice resulted in tumor cell apoptosis and rejection. This prompted us to study active immune preventive strategies targeting PLIF activity. Currently, we report on the design and synthesis of the novel C24D polypeptide, which inhibits the binding of PLIF to T cells and therefore inhibits the immune suppressive effect of PLIF. The effect of C24D on the generation of anti–breast cancer cytotoxic T lymphocytes (CTLs was studied in vitro in cultures of MCF-7 (HLA-A2+ or T47D (HLA-A2− breast cancer cells incubated with peripheral blood mononuclear cells (PBMCs from healthy blood donors. We found that C24D treatment exclusively induced development of CTLs. On reactivation by their specific target cells, the CTLs secreted interferon-γ and induced target apoptosis. Anti–MCF-7 CTLs were cross-cytotoxic to MDA-MB-231 (HLA-A2+ triple-negative breast cancer but not to T47D. Moreover, C24D treatment in vivo inhibited the growth of MCF-7 tumors engrafted in immune-compromised nude mice transfused with naïve allogeneic human PBMCs. Our results demonstrate that C24D treatment breakdown breast cancer induced tolerance enabling the initiation of effective anti-tumor immune response.

Serum ferritin concentration in early pregnancy and risk of subsequent development of gestational diabetes: A prospective study

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Sedigheh Soheilykhah

2017-08-01

Full Text Available Background: Elevated serum ferritin concentration is associated with insulin resistance and diabetes. Recently it has also been described in gestational diabetes mellitus (GDM. Objective: A prospective study was done to determine whether there was a relationship between serum ferritin concentration in early pregnancy and the risk of GDM. Materials and Methods: A study was performed on 1,384 pregnant women with gestational age of 12-16 weeks. A blood sample was obtained for measurement of ferritin in the first trimester. Diagnosis of GDM was done by 75 gr oral glucose tolerance test between 24-28 wk. Results: Women who developed GDM had a higher concentration of serum ferritin than women who did not develop GDM (p=0.01. A ferritin concentration of 45 ng/ml was calculated to be the 75th percentile for healthy pregnant women. Considering this level 32% in the GDM group and 25.2%of normal subjects exhibited high ferritin levels (p=0.01. The risk of GDM with these high levels of ferritin was 1.4-fold higher than that for subjects with lower concentrations. The Odds Ratio was 1.4 (95% CI= 1-1.87 (p=0.01. After adjusted for age Odds Ratio was 1.38 (95% CI=1.02-1.86 (p=0.03 and after adjustment for pre-pregnancy Body Mass index, the adjusted odds ratio was 1.31 (CI= 0.96-1.79 (p=0.08. After multivariable adjustment (age and body mass index, the adjusted odds ratio was 1.3 (0.95-1.8 (p=0.09. Conclusion: High serum ferritin can be regarded as a significant risk factor for the development of gestational diabetes.

Production of antisera and development of radioimmunoassay for serum T3, T4, and ferritin

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Elhag, Omer Mohamed Abdalla [Department of Biochemistry, Faculty of Veterinary Science, University of Khartoum, Khartoum (Sudan)

1998-05-01

In this study twelve local rabbits and sixteen New-zealand rabbits were subjected to immunization against T3 and T4 immunogens. Two local sheep (ovis aris) were immunized against human liver ferritin. The T3 and T4 immunogens were prepared by conjugation of the haptens to carrier proteins (bovine serum albumin ``BSA`` and horse serum protein ``HSP``), using water soluble carboiimide as coupling agent. The local and New-zealand rabbits were immunized against these conjugates emulsified in freund`s complete adjuvant (FCA) in the first and second injections, and emulsified in freund`s incomplete adjuvant (FIA) in the following injections. The blood samples obtained from rabbits after each injection were tested for antibodies as well as for the effect of immunization on rabbits biochemical and haematological parameters. The blood samples obtained from sheep were tested for anti-ferritin antibodies using crude antiserum, then this antiserum was purified using ammonium sulphate. A part of it was adsorbed physically onto polystyrene beads while the other part was linked chemically to magnitisable particles inorder to develop to IRMAs. The purified antiferritin antibody was diluted 200,000 folds before being coated to polystyrene beads, and different dilutions were tried with coupling to magnetic solid phase. Optimization and validation procedures for the two IRMAs ferritin were performed. The results obtained showed poor response of rabbits to immunization against T3 and T4 immunogen conjugates, where the percent bound (B%) of tracer with the antibody ranged from (0.0-22%) for local rabbits using charcoal seperation technique, and (0.0-2.9%) using second antibody precipitation technique. The B% for the antiserum obtained from New-zealand rabbits ranged from (0.0-18.1) using second antibody precipitation technique. Serum T3, T4 and TSH of the immunized rabbits were measured and found to be not significantly different form the controls (p=0.2211, 0.098, 0.35 respectively

Production of antisera and development of radioimmunoassay for serum T3, T4, and ferritin

International Nuclear Information System (INIS)

Elhag, Omer Mohamed Abdalla

1998-05-01

In this study twelve local rabbits and sixteen New-zealand rabbits were subjected to immunization against T3 and T4 immunogens. Two local sheep (ovis aris) were immunized against human liver ferritin. The T3 and T4 immunogens were prepared by conjugation of the haptens to carrier proteins (bovine serum albumin ''BSA'' and horse serum protein ''HSP''), using water soluble carboiimide as coupling agent. The local and New-zealand rabbits were immunized against these conjugates emulsified in freund's complete adjuvant (FCA) in the first and second injections, and emulsified in freund's incomplete adjuvant (FIA) in the following injections. The blood samples obtained from rabbits after each injection were tested for antibodies as well as for the effect of immunization on rabbits biochemical and haematological parameters. The blood samples obtained from sheep were tested for anti-ferritin antibodies using crude antiserum, then this antiserum was purified using ammonium sulphate. A part of it was adsorbed physically onto polystyrene beads while the other part was linked chemically to magnitisable particles inorder to develop to IRMAs. The purified antiferritin antibody was diluted 200,000 folds before being coated to polystyrene beads, and different dilutions were tried with coupling to magnetic solid phase. Optimization and validation procedures for the two IRMAs ferritin were performed. The results obtained showed poor response of rabbits to immunization against T3 and T4 immunogen conjugates, where the percent bound (B%) of tracer with the antibody ranged from (0.0-22%) for local rabbits using charcoal seperation technique, and (0.0-2.9%) using second antibody precipitation technique. The B% for the antiserum obtained from New-zealand rabbits ranged from (0.0-18.1) using second antibody precipitation technique. Serum T3, T4 and TSH of the immunized rabbits were measured and found to be not significantly different form the controls (p=0.2211, 0.098, 0.35 respectively

Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

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Aziza, Samy Ali Hussein; Azab, Mohammed El-Said; El-Shall, Soheir Kamal

2014-08-01

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT

Evaluation and association of serum iron and ferritin levels in children with dental caries.

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Venkatesh Babu, N S; Bhanushali, Parin Vasant

2017-01-01

Iron deficiency anemia accounts for 90% of all types of anemia in the world. Although the prevalence has declined in recent years, it remains an important pediatric public health problem. Iron deficiency has also been associated with dental caries. It impairs salivary gland function causing reduced salivary secretion and buffering capacity leading to increased caries activity. The aim of the study is to explore an association between dental caries and serum levels of iron and ferritin in children aged 3-12 years. Subjectsand Methods: The study group included 120 children, hospitalized for uncomplicated medical problems. Blood reports were evaluated to determine serum iron and ferritin levels. Dental caries experience was assessed using deft index. The collected data were tabulated and analyzed using Student's t-test and Pearson's correlation coefficient. Out of 120 children, 38 children showed low serum iron levels of which 31 children had dental caries and nine out of 15 children in the high serum iron level group showed dental caries. High ferritin levels were seen in three children among which two children were caries-free and only one child had a low ferritin level who also had a positive deft score. Based on the results, it was concluded that there is an inverse association between serum iron levels and dental caries whereas there is no association between serum ferritin levels and dental caries.

Evaluation of the influence of UV/IR radiation on iron release from ferritin

International Nuclear Information System (INIS)

Gritzkov, M.; Kochev, V.; Vladimirova, L

2010-01-01

In the present work the influence of UV/IR radiation on the iron-releasing process from ferritin is investigated. The ferritins are a family of iron-storing proteins playing a key role in the biochemical reactions between iron and oxygen-processes of exclusive importance for the existence of all living organisms. The iron is stored within the ferritin core in the form of insoluble crystals containing Fe(III). Therefore for its release, the mineral matrix has to be decomposed, usually through a reduction of Fe(III) to Fe(II). Our study considers the action of UV/IR radiation on the structure of the protein molecule. Eventual changes in the ferritin conformation under the irradiation could result in the change of channel forming regions responsible for the iron efflux. This can be assess by the quantity of Fe (II) obtained in a subsequent mobilization procedure evoked by exogenous reducing agents. In our case the content of the reduced iron is determined electrochemically by the method of potentiometric titration. As already was shown, this method promises to become highly useful for quantitative evaluation of released Fe 2+ . (Author)

Co–inection of hepatitis B and C viruses among human ...

African Journals Online (AJOL)

Introduction: The co–infection of Human immunodeficiency virus (HIV), Hepatitis B and C viruses remains a public health problem particularly in resource limited setting like Nigeria. Studies on these co–infections have been done principally among adult and pregnant women with limited information on the pediatric ...

Hepatitis E Virus Genotype 3 in Humans and Swine, Bolivia

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Cavallo, Annalisa; Gonzales, José Luis; Bonelli, Sara Irene; Valda, Ybar; Pieri, Angela; Segundo, Higinio; Ibañez, Ramón; Mantella, Antonia; Bartalesi, Filippo; Tolari, Francesco; Bartoloni, Alessandro

2011-01-01

We determined the seroprevalence of hepatitis E virus (HEV) in persons in 2 rural communities in southeastern Bolivia and the presence of HEV in human and swine fecal samples. HEV seroprevalence was 6.3%, and HEV genotype 3 strains with high sequence homology were detected. PMID:21801630

Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

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Sheetal Patel

2011-01-01

Full Text Available Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

"SERUM FERRITIN IN TYPE 2 DIABETES MELLITUS AND ITS RELATIONSHIP WITH HbA1c"

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F. Sharifi Sh. Sazandeh

2004-06-01

Full Text Available Diabetes mellitus (DM type 2 is one of the most common endocrine disorders affecting more than 135 million people in the world. The etiology of the disease is not fully understood, but recently subclinical hemochromatosis has been considered as one of the probable causes of DM. This study was carried out to examine the relationship between serum ferritin as a marker of iron overload with DM and HbA1c. This study was conducted on 97 patients with type 2 DM who were referred to Zanjan Diabetes Clinic. Ninety-four normal age-matched individuals were included in the study as the control group. Ferritin, hemoglobin, HbA1c, and fasting blood sugar were measured in blood samples. Exclusion criteria included anemia, or any other disease or drug that could affect ferritin levels. Results were analyzed statistically by Chi-square test, t-test and Pearson regression coefficient test. One hundred ninety-one cases including 97 diabetics (37 males and 60 females and 94 normal individuals were studied. There were no significant differences between the two groups regarding age, hemoglobin and body mass index. Mean serum ferritin was significantly higher in diabetics than in the control group (101±73 mg/ml vs. 43.5+42 mg/ml, p<0.001. There was no correlation between serum ferritin and HbA1c in diabetic patients of either sex. Ferritin levels in patients with DM is high, but not related to levels of HbA1c and blood glucose control.

Ferritin cage for encapsulation and delivery of bioactive nutrients: From structure, property to applications.

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Zang, Jiachen; Chen, Hai; Zhao, Guanghua; Wang, Fudi; Ren, Fazheng

2017-11-22

Ferritin is a class of naturally occurring iron storage proteins, which is distributed widely in animal, plant, and bacteria. It usually consists of 24 subunits that form a hollow protein shell with high symmetry. One holoferritin molecule can store up to 4500 iron atom within its inner cavity, and it becomes apoferritin upon removal of iron from the cavity. Recently, scientists have subverted these nature functions and used reversibly self-assembled property of apoferritin cage controlled by pH for the encapsulation and delivery of bioactive nutrients or anticancer drug. In all these cases, the ferritin cages shield their cargo from the influence of external conditions and provide a controlled microenvironment. More importantly, upon encapsulation, ferritin shell greatly improved the water solubility, thermal stability, photostability, and cellular uptake activity of these small bioactive compounds. This review aims to highlight recent advances in applications of ferritin cage as a novel vehicle in the field of food science and nutrition. Future outlooks are highlighted with the aim to suggest a research line to follow for further studies.

Ferritin glycosylated by chitosan as a novel EGCG nano-carrier: Structure, stability, and absorption analysis.

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Yang, Rui; Liu, Yuqian; Gao, Yunjing; Wang, Yongjin; Blanchard, Chris; Zhou, Zhongkai

2017-12-01

Ferritin is a shell-like carrier protein with an 8nm diameter cavity which endows a natural space to encapsulate food and drug components. In this work, phytoferritin was unprecedentedly glycosylated by chitosan to fabricate ferritin-chitosan Maillard reaction products (FCMPs) (grafting degree of 26.17%, 24h, 55°C). Results indicated that the amide I and II bands of ferritin were altered due to the chitosan grafting, whereas the ferritin spherical structure were retained. Simulated digestion analysis showed that the FCMPs were more resistant to pepsin and trypsin digestion as compared with ferritin alone. Furthermore, FCMPs were employed as carrier to encapsulate epigallocatechin gallate (EGCG) molecules with an encapsulation ratio of 12.87% (w/w), and the resulting FCMPs-EGCG complexes showed a slow release of EGCG in simulated gastrointestinal tract. Interestingly, different types of food components displayed different effects in EGCG release behavior from the FCMPs, wherein proanthocyanidin, milk and soy protein inhibited the EGCG release. In addition, the absorption of EGCG encapsulated in FCMPs in Caco-2 monolayer model was significantly improved as compared with free EGCG. This work provides a novel nano-vehicle for fabricating core-shell systems in food and drug delivery domain. Copyright © 2017 Elsevier B.V. All rights reserved.

A genetic risk factor for low serum ferritin levels in Danish blood donors

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Sørensen, Erik; Grau, Katrine; Berg, Trine

2012-01-01

BACKGROUND: Iron deficiency is a frequent side effect of blood donation. In recent years, several studies have described genetic variants associated with iron concentrations. However, the impact of these variants on iron levels is unknown in blood donors. Knowledge of genetic variants....../or restless leg syndrome (RLS) were investigated in two groups of female blood donors. The first group had low iron stores (serum ferritin ≤ 12 µg/L, n = 657), and the second group had normal to high iron stores (serum ferritin > 30 µg/L, n = 645). Genotype distribution for each of the SNPs was compared......: A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors....

Lack of evidence for metabolism of p-phenylenediamine by human hepatic cytochrome P450 enzymes

International Nuclear Information System (INIS)

Stanley, Lesley A.; Skare, Julie A.; Doyle, Edward; Powrie, Robert; D'Angelo, Diane; Elcombe, Clifford R.

2005-01-01

p-Phenylenediamine (PPD) is a widely used ingredient in permanent hair dyes; however, little has been published on its metabolism, especially with respect to hepatic cytochrome P450 (CYP)-mediated oxidation. This is regarded as a key step in the activation of carcinogenic arylamines that ultimately leads to the development of bladder cancer. Most epidemiology studies show no significant association between personal use of hair dyes and bladder cancer, but one recent study reported an increased risk of bladder cancer in women who were frequent users of permanent hair dyes. The aim of the present study was to use intact human hepatocytes, human liver microsomes, and heterologously expressed human CYPs to determine whether PPD is metabolised by hepatic CYPs to form an N-hydroxylamine. p-Phenylenediamine was N-acetylated by human hepatocytes to form N-acetylated metabolites, but there was no evidence for the formation of mono-oxygenated metabolites or for enzyme-mediated covalent binding of 14 C-PPD to microsomal protein. In contrast, 2-aminofluorene underwent CYP-mediated metabolism to ≥4 different hydroxylated metabolites. The lack of evidence for hepatic CYP-mediated metabolism of PPD is inconsistent with the hypothesis that this compound plays a causal role in the development of bladder cancer via a mode of action involving hepatic metabolism to an N-hydroxyarylamine

Kinetic Studies of Iron Deposition Catalyzed by Recombinant Human Liver Heavy, and Light Ferritins and Azotobacter Vinelandii Bacterioferritin Using O2 and H2O2 as Oxidants

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Bunker, Jared; Lowry, Thomas; Davis, Garrett; Zhang, Bo; Brosnahan, David; Lindsay, Stuart; Costen, Robert; Choi, Sang; Arosio, Paolo; Watt, Gerald D.

2005-01-01

The discrepancy between predicted and measured H2O2 formation during iron deposition with recombinant heavy human liver ferritin (rHF) was attributed to reaction with the iron protein complex [Biochemistry 40 (2001) 10832-10838]. This proposal was examined by stopped-flow kinetic studies and analysis for H2O2 production using (1) rHF, and Azotobacter vinelandii bacterial ferritin (AvBF), each containing 24 identical subunits with ferroxidase centers; (2) site-altered rHF mutants with functional and dysfunctional ferroxidase centers; and (3) rccombinant human liver light ferritin (rLF), containing 110 ferroxidase center. For rHF, nearly identical pseudo-first-order rate constants of 0.18 per second at pH 7.5 were measured for Fe(2+) oxidation by both O2 and H2O2, but for rLF, the rate with O2 was 200-fold slower than that for H2O2 (k-0.22 per second). A Fe(2+)/O2 stoichiometry near 2.4 was measured for rHF and its site altered forms, suggesting formation of H2O2. Direct measurements revealed no H2O2 free in solution 0.5-10 min after all Fe(2+) was oxidized at pH 6.5 or 7.5. These results are consistent with initial H2O2 formation, which rapidly reacts in a secondary reaction with unidentified solution components. Using measured rate constants for rHF, simulations showed that steady-state H2O2 concentrations peaked at 14 pM at approx. 600 ms and decreased to zero at 10-30 s. rLF did not produce measurable H2O2 but apparently conducted the secondary reaction with H2O2. Fe(2+)/O2 values of 4.0 were measured for AvBF. Stopped-flow measurements with AvBF showed that both H2O2 and O2 react at the same rate (k=0.34 per second), that is faster than the reactions with rHF. Simulations suggest that AvBF reduces O2 directly to H2O without intermediate H2O2 formation.

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton

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Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-01-01

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID:26553998

Magic ferritin: A novel chemotherapeutic encapsulation bullet

International Nuclear Information System (INIS)

Simsek, Ece; Akif Kilic, Mehmet

2005-01-01

The dissociation of apoferritin into subunits at pH 2 followed by its reformation at pH 7.4 in the presence of doxorubicin-HCl gives rise to a solution containing five doxorubicin-HCl molecules trapped within the apoferritin. This is the first report showing that ferritin can encapsulate an anti-cancer drug into its cavity

Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice

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Korenaga, Masaaki; Nishina, Sohji; Korenaga, Keiko; Tomiyama, Yasuyuki; Yoshioka, Naoko; Hara, Yuichi; Sasaki, Yusuke; Shimonaka, Yasushi; Hino, Keisuke

2015-01-01

Background & Aims Branched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis. Methods Male HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months. Results For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels. Conclusions BCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients. PMID:25156780

Iron- and ferritin-dependent reactive oxygen species distribution: impact on Arabidopsis root system architecture.

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Reyt, Guilhem; Boudouf, Soukaina; Boucherez, Jossia; Gaymard, Frédéric; Briat, Jean-Francois

2015-03-01

Iron (Fe) homeostasis is integrated with the production of reactive oxygen species (ROS), and distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe, which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe-mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin, and root system architecture (RSA) is in part mediated by the H2O2/O2·- balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Hepatitis A Virus and Hepatitis E Virus: Emerging and Re-Emerging Enterically Transmitted Hepatitis Viruses.

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Lemon, Stanley M; Walker, Christopher M

2018-05-07

Over the past two decades, progress in understanding human infections with hepatitis A virus (HAV) and hepatitis E virus (HEV) has been eclipsed by the priority of combating persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. During that time, the global burden of liver disease caused by enteric hepatitis viruses has not abated. Because of vaccines, hepatitis A has become increasingly a disease of adults instead of early childhood in many regions of the world, resulting in an age-related shift toward more severe disease. HEV has remained endemic in many developing countries, and in well-developed, economically advanced countries it is now recognized as a cause of chronic, progressive liver disease in individuals with compromised immunity. The goal of this collection of articles is to review recent progress and to shine a bright light on gaps in our understanding of how these viruses replicate, cause disease, interact with the liver and host immune system, and are transmitted, along with prospects for improved control in human populations. Renewed efforts to study and compare HAV and HEV biology in humans and animal models have high potential to enhance our understanding of host-pathogen balance in the liver, and may contribute ultimately to the control of other infectious diseases of the liver. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Heme-coordinated histidine residues form non-specific functional "ferritin-heme" peroxidase system: Possible and partial mechanistic relevance to oxidative stress-mediated pathology in neurodegenerative diseases.

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Esmaeili, Sajjad; Kooshk, Mohammad Reza Ashrafi; Asghari, Seyyed Mohsen; Khodarahmi, Reza

2016-10-01

Ferritin is a giant protein composed of 24 subunits which is able to sequester up to 4500 atoms of iron. We proposed two kinds of heme binding sites in mammalian ferritins and provided direct evidence for peroxidase activity of heme-ferritin, since there is the possibility that "ferritin-heme" systems display unexpected catalytic behavior like heme-containing enzymes. In the current study, peroxidase activity of heme-bound ferritin was studied using TMB(1), l-DOPA, serotonin, and dopamine, in the presence of H2O2, as oxidant substrate. The catalytic oxidation of TMB was consistent with first-order kinetics with respect to ferritin concentration. Perturbation of the binding affinity and catalytic behavior of heme-bound His-modified ferritin were also documented. We also discuss the importance of the peroxidase-/nitrative-mediated oxidation of vital molecules as well as ferritin-induced catalase inhibition using in vitro experimental system. Uncontrollable "heme-ferritin"-based enzyme activity as well as up-regulation of heme and ferritin may inspire that some oxidative stress-mediated cytotoxic effects in AD-affected cells could be correlated to ferritin-heme interaction and/or ferritin-induced catalase inhibition and describe its contribution as an important causative pathogenesis mechanism in some neurodegenerative disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

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Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

2009-01-01

Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent

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Elizabeth A. Hughes

2015-01-01

Full Text Available Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4 years, 50% men and 277 contemporaries living in Gujarati villages (47.6 (11.8 years, 41% men. Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P=0.005, irrespective of site, gender, and central obesity (P≤0.02, and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P<0.001. Diabetes was less in those with low ferritin (<20 mg/mL, P<0.008, and risk estimate = 0.35 (95% CI 0.15–0.81, as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P=0.001 and age (P<0.001. Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors.

Clinical survey of blood dyscrasias among Hiroshima A-bomb survivors by periodical health examination, (6). Serum ferritin determination of anemic patients

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Abe, T.; Dohy, H.; Okita, H. (Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology)

1980-11-01

Serum ferritin was determined in A-bomb survivors, and its significance was evaluated. A low-ferritin group included many of the females under the age of 50, who mostly had iron deficient anemia. A high-ferritin group included many older-aged A-bomb survivors who had secondary anemia due to hemochromatosis, paroxismal nocturnal hemoglobinuria (PNH), and multiple myeloma. Secondary anemia due to hemochromatosis, PNH, leukemia, and sideroblastic anemia was detected in those who were old and had underlying moderate or severe anemia with a high ferritin level. As the results of this investigation, blood examination combined with serum ferritin determination is valuable for diagnosis of anemia and detection of underlying diseases.

Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection

International Nuclear Information System (INIS)

Maier, K.; Gabriel, P.; Koscielniak, E.; Stierhof, Y.D.; Wiedmann, K.H.; Flehmig, B.; Vallbracht, A.

1988-01-01

The production of interferon (IFN) during a chromium-51 release assay with hepatitis A virus (HAV)-infected fibroblasts and autologous peripheral blood lymphocytes from patients with acute HAV infection was studied to determine whether IFN plays a role in immunopathogenesis of hepatitis A infection in humans. Skin fibroblasts of eight patients after acute HAV infection and from two control persons without history of current of past HAV infection were infected with HAV. Peripheral blood lymphocytes were collected at different times after the onset of icterus and tested in a chromium-51 release assay against autologous HAV-infected skin fibroblasts for their cytolytic and IFN-producing activity. The IFN produced during the assay was characterized and found to have the properties of human gamma IFN. Cytotoxicity and gamma IFN release were virus specific. The cell types responsible for both functions were characterized and found to be in the HLA-dependent T8 + lymphocyte subset. Considering that gamma IFN has an antiviral effect on persistent HAV infection in vitro and that it probably accounts for stimulation of HLA class I antigen expression on hepatocytes, these experimental results presented here demonstrate that human gamma IFN produced by HAV-specific T cells may participate in pathogenesis of hepatitis A infection in humans

Association of Increased Serum Ferritin With Impaired Muscle Strength/Quality in Hemodialysis Patients.

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Nakagawa, Chie; Inaba, Masaaki; Ishimura, Eiji; Yamakawa, Tomoyuki; Shoji, Shigeichi; Okuno, Senji

2016-07-01

We reported previously that muscle quality and muscle strength provide clinically relevant predictors for better survival in hemodialysis patients. Iron overload might impair muscle function by its accumulation in muscle in such patients. Serum ferritin, a marker for body iron store, was examined for its association with handgrip strength (HGS) and muscle quality which was defined as the ratio of HGS to arm lean mass measured with dual-energy X-ray absorptiometry. In 300 Japanese hemodialysis patients, age, hemodialysis duration, body mass index, and serum albumin were 58.0 ±12.0 (mean ± standard deviation) years, 4.2 (1.8-10.4) (median [25th-75th percentile]) years, 20.4 ± 2.8 kg/m(2), 4.0 ± 0.3 g/dL, respectively. Hemoglobin and hematocrit were 8.9 ± 1.2 g/dL, and 28.8 ± 3.9%, respectively, whereas transferrin saturation and serum ferritin were 29.8 ± 11.0% and 100 (54-172) ng/mL, respectively. Serum ferritin significantly correlated in a positive manner with the total dose of iron orally administered during the previous 6 months (r = 0.185, P = .0013). HGS and muscle quality were 23.1 ± 10.4 kg and 11.6 ± 3.8 kg/kg, respectively. In multivariate analysis to elucidate the factors associated with HGS and muscle quality in 300 hemodialysis patients, which included transferrin saturation and log serum ferritin, in addition to age, gender, hemodialysis duration, the presence/absence of diabetes, body mass index as independent variables, log serum ferritin emerged as a significant and independent factor which associated in a negative fashion with HGS (β = -0.091, P = .0395) and tendency toward negative association with muscle quality (β = -0.100, P = .0754). In summary, the present study demonstrated the significant association of serum ferritin with HGS and muscle quality in hemodialysis patients and thus suggested that we should be careful of iron overload to avoid its possible harmful effect on muscle in such patients. Copyright © 2016 National Kidney

Hepatitis C virus infection in the human immunodeficiency virus infected patient

DEFF Research Database (Denmark)

Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

2014-01-01

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and...

Clinical Significances of Serum Vitamin B12, Folate and Ferritin Levels in Patients with Malignant Tumors

International Nuclear Information System (INIS)

Monn, Youn Sung; Soung, In Whan; Kim, Sam Yong; Ro, Heung Kyu; Lee, Bok Hee

1987-01-01

In order to evaluate the clinical significances of the serum vitamin B 12 , folate and ferritin levels in patients with malignant tumors, the levels were measured in 10 normal control subjects, 70 patients with malignant tumors, 7 patients with liver cirrhosis and 25 patients with other benign diseases. The results are as follows: 1) In normal control subjects, mean serum values for vitamin B 12 , folate and ferritin level were 588.80±131.58 pg/ml, 5.59±1.52 ng/ml and 89.22±42.78 ng/ml retrospectively. 2) There was no significant difference in serum levels between patients with benign diseases and normal control subjects. 3) The serum vitamin B 12 and ferritin levels in patients with liver cirrhosis were significantly higher than in normal control, and the serum folate levels in these patients were lower than in normal control subjects. 4) The serum vitamin B 12 and ferritin levels in patients with malignant tumors were significantly higher than in normal control subjects, and the serum folate levels in these patients were significantly lower than in normal control subjects. The above results suggest that the serum vitamin B 12 and ferritin may be useful as tumor markers in patients with malignant tumors.

Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?

Science.gov (United States)

Barut, Sener; Dincer, Fatma; Sahin, Idris; Ozyurt, Huseyin; Akkus, Mehmet; Erkorkmaz, Unal

2010-01-01

Serum ferritin is one of the markers indicating hemophagocytosis that may have a role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). This study was designed to determine any correlation between serum ferritin and routine diagnostic laboratory markers of CCHF, and to investigate the relationship between serum ferritin levels and disease severity. Sixty-six patients with CCHF admitted to the hospital during the spring and summer months of 2006 and 2007 were included in the study. Serum ferritin levels were measured in sera obtained during the initial days of hospitalization. Data from 53 patients showing decreasing platelet counts over the first three days were used for further analysis and these patients were divided into two groups according to disease severity: group A included severe cases with lowest platelet counts 20x10(9)/l. Forty patients (60.6%) were male (mean age 43+/-17 years). Three patients died, thus the fatality rate was 4.5%. Fifty-one patients (77.3%) had abnormal serum ferritin levels, with levels above 500 ng/ml in 62.1%. There was a significant negative correlation between ferritin levels and concordant platelet counts (p or =1862ng/ml had a sensitivity of 87.5% and a specificity of 83.8% in differentiating severe cases from mild ones. Increased serum ferritin levels may suggest a significant role of hemophagocytosis in the pathogenesis of CCHF and may be a useful marker for diagnosis, disease activity, and prognosis. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Patients blood serum ferritin concentrations changes associated with Caesium-137 incorporation

International Nuclear Information System (INIS)

Shishkyina, V.V.; Chebotar'ova, E.D.; Zamyatyin, S.S.; Vlasenko, O.O.

1993-01-01

The results of radioimmune study of ferritin and carcinoembryonic antigen in 60 persons: 35 those who took part in liquidation of the Chernobyl accident and incorporated 25.9-70.4 MBq of Cesium-137,25 residents of Rivno Region with 7.4-203.5 MBq of the radionuclide in the organism are reported. The increased concentration of ferritin and carcinoembryonic antigen in blood serum was noted to be determined more often in the residents of the areas polluted with Caesium-137 than in l iquidators . The tumor markers levels depended to some extent on bad habits (smoking, alcohol) and existing chronic diseases of the alimentary system

Age dependent in vitro metabolism of bifenthrin in rat and human hepatic microsomes.

Science.gov (United States)

Nallani, Gopinath C; Chandrasekaran, Appavu; Kassahun, Kelem; Shen, Li; ElNaggar, Shaaban F; Liu, Zhiwei

2018-01-01

Bifenthrin, a pyrethroid insecticide, undergoes oxidative metabolism leading to the formation of 4'-hydroxy-bifenthrin (4'-OH-BIF) and hydrolysis leading to the formation of TFP acid in rat and human hepatic microsomes. In this study, age-dependent metabolism of bifenthrin in rats and humans were determined via the rates of formation of 4'-OH-BIF and TFP acid following incubation of bifenthrin in juvenile and adult rat (PND 15 and PND 90) and human (18years) liver microsomes. Furthermore, in vitro hepatic intrinsic clearance (CL int ) of bifenthrin was determined by substrate consumption method in a separate experiment. The mean V max (±SD) for the formation of 4'-OH-BIF in juvenile rat hepatic microsomes was 25.0±1.5pmol/min/mg which was significantly lower (pbifenthrin occurs primarily via oxidative pathway with relatively lesser contribution (~30%) from hydrolytic pathway in both rat and human liver microsomes. The CL int values for bifenthrin, determined by monitoring the consumption of substrate, in juvenile and adult rat liver microsomes fortified with NADPH were 42.0±7.2 and 166.7±20.5μl/min/mg, respectively, and the corresponding values for human liver microsomes were 76.0±4.0 and 21.3±1.2μl/min/mg, respectively. The data suggest a major species difference in the age dependent metabolism of bifenthrin. In human liver microsomes, bifenthrin is metabolized at a much higher rate in juveniles than in adults, while the opposite appears to be true in rat liver microsomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

DEFF Research Database (Denmark)

Sundelin, E. I.O.; Gormsen, Lars C; Jensen, J. B.

2017-01-01

the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin...... was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates......Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding...

Iron environment in ferritin with large amounts of phosphate, from Azotobacter vinelandii and horse spleen, analyzed using Extended X-ray Absorption fine Structure (EXAFS)

International Nuclear Information System (INIS)

Rohrer, J.S.; Islam, Q.T.; Sayes, D.E.; Theil, E.C.; Watt, G.D.

1990-01-01

The iron core of proteins in the ferritin family displays structural variations that includes phosphate content was well as the number and the degree of ordering of the iron atoms. Earlier studies had shown that ferritin iron cores naturally high in phosphate, e.g., Azotobacter vinelandii (AV) ferritin had decreased long-range order. Here, the influence of phosphate on the local structure around iron in ferritin cores is reported, comparing the EXAFS of AV ferritin, reconstituted ferritin and native horse spleen ferritin. In contrast, when the phosphate content was high in AV ferritin and horse spleen ferritin reconstituted with phosphate, the average iron atom had five to six phosphorus neighbors at 3.17 angstrom. Moreover, the number of detectable iron neighbors was lower when phosphate was high or present during reconstitution and the interatomic distance was longer indicating that some phosphate bridges neighboring iron atoms. However, the decrease in the number of detectable iron-iron neighbors compared to HSF and the higher number of Fe-P interactions relative to Fe-Fe interactions suggest that some phosphate ligands were chain termini, or blocked crystal growth, and/or introduced defects which contributed both to the long-range disorder and to altered redox properties previously observed in AV ferritin

Iron stores in 70-year-old Danish men and women. Evaluation in 469 individuals by serum ferritin and hemoglobin

DEFF Research Database (Denmark)

Milman, N; Schultz-Larsen, K

1994-01-01

Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S-ferritin le......Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S......-ferritin levels. Men had a median S-ferritin of 114 micrograms/L, 5-95 percentile 28-373 micrograms/L; 2.4% had values depleted iron stores), 3.5% values from 15-30 micrograms/L (i.e., small iron stores), and 94.1% values > 30 micrograms/L (e.g., replete iron stores); 74.4% had values...

Correlation between malnutrition and prognosis of hepatitis A in Uygur children

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ZHANG Jian

2015-08-01

Full Text Available Objective To analyze the correlation between malnutrition and prognosis in Uyghur pediatric patients with hepatitis A in Hetian of Xinjiang Uyghur Autonomous Region, China. Methods The clinical data of 342 children with hepatitis A admitted to the Infectious Disease Hospital of Hetian from January 2014 to May 2015 were retrospectively analyzed and the patients were divided into malnutrition group with 136 patients and normal nutrition group with 206 patients according to the Z-scores. The data of complete blood count, liver function test, biochemical indices, blood lipids, blood coagulation, and hospitalization days and costs were compared between the two groups. Comparison of categorical data between the two groups was made by chi-square test and comparison of continuous data between the two groups was made by t test. Results Compared with the normal nutrition group, the malnutrition group had significantly lower values of breastfeeding rate, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, serum ferritin, glucose, serum albumin, and plasma thromboplastin antecedent but higher values of alanine transaminase, total bilirubin, total bile acid, cholesterol, and hospitalization days and costs (P＜0.05. Conclusion Compared with the normal nutrition pediatric patients with hepatitis A, the malnutrition pediatric patients with hepatitis A have more severe iron deficiency anemia, hepatic damage, and abnormal metabolism of carbohydrates and fatty acids, so their recovery time is longer and the hospitalization costs are higher. To effectively protect Uygur children, hepatitis A vaccination in due course and the children′s growth and development monitoring are recommended.

Effect of the structure of gallic acid and its derivatives on their interaction with plant ferritin.

Science.gov (United States)

Wang, Qunqun; Zhou, Kai; Ning, Yong; Zhao, Guanghua

2016-12-15

Gallic acid and its derivatives co-exist with protein components in foodstuffs, but there is few report on their interaction with proteins. On the other hand, plant ferritin represents not only a novel class of iron supplement, but also a new nanocarrier for encapsulation of bioactive nutrients. However, plant ferritin is easy to be degraded by pepsin in the stomach, thereby limiting its application. Herein, we investigated the interaction of gallic acid and its derivatives with recombinant soybean seed H-2 ferritin (rH-2). We found that these phenolic acids interacted with rH-2 in a structure-dependent manner; namely, gallic acid (GA), methyl gallate (MEGA) and propyl gallate (PG) having three HO groups can bind to rH-2, while their analogues with two HO groups cannot. Consequently, such binding largely inhibited ferritin degradation by pepsin. These findings advance our understanding of the relationship between the structure and function of phenolic acids. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunocytochemical analysis of the subcellular distribution of ferritin in Imperata cylindrica (L.) Raeuschel, an iron hyperaccumulator plant.

Science.gov (United States)

de la Fuente, Vicenta; Rodríguez, Nuria; Amils, Ricardo

2012-05-01

Ferritin is of interest at the structural and functional level not only as storage for iron, a critical element, but also as a means to prevent cell damage produced by oxidative stress. The main objective of this work was to confirm by immunocytochemistry the presence and the subcellular distribution of the ferritin detected by Mösbauer spectroscopy in Imperata cylindrica, a plant which accumulates large amounts of iron. The localization of ferritin was performed in epidermal, parenchymal and vascular tissues of shoots and leaves of I. cylindrica. The highest density of immunolabeling in shoots appeared in the intracellular space of cell tissues, near the cell walls and in the cytoplasm. In leaves, ferritin was detected in the proximity of the dense network of the middle lamella of cell walls, following a similar path to that observed in shoots. Immunolabeling was also localized in chloroplasts. The abundance of immunogold labelling in mitochondria for I. cylindrica was rather low, probably because the study dealt with tissues from old plants. These results further expand the localization of ferritin in cell components other than chloroplasts and mitochondria in plants. Copyright © 2011 Elsevier GmbH. All rights reserved.

FTH1P3, a Novel H-Ferritin Pseudogene Transcriptionally Active, Is Ubiquitously Expressed and Regulated during Cell Differentiation.

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Maddalena Di Sanzo

Full Text Available Ferritin, the major iron storage protein, performs its essential functions in the cytoplasm, nucleus and mitochondria. The variable assembly of 24 subunits of the Heavy (H and Light (L type composes the cytoplasmic molecule. In humans, two distinct genes code these subunits, both belonging to complex multigene families. Until now, one H gene has been identified with the coding sequence interrupted by three introns and more than 20 intronless copies widely dispersed on different chromosomes. Two of the intronless genes are actively transcribed in a tissue-specific manner. Herein, we report that FTH1P3, another intronless pseudogene, is transcribed. FTH1P3 transcript was detected in several cell lines and tissues, suggesting that its transcription is ubiquitary, as it happens for the parental ferritin H gene. Moreover, FTH1P3 expression is positively regulated during the cell differentiation process.

Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

DEFF Research Database (Denmark)

Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne

2016-01-01

AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment......, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION: DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV...

Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells

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Joseph Ignatius Irudayam

2015-12-01

Full Text Available Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5, hepatoblast (day 15 and hepatocyte-like cells (day 21 were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21 had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation.

Tissue-specific histochemical localization of iron and ferritin gene ...

Indian Academy of Sciences (India)

ficient and inappropriate diet is a severe nutritional problem. (Goto et al. 2001) that affects ... Ferritin is an iron storage protein which stores 4500 iron atoms in its central ... content in a high-economic-value indica rice variety (Oryza sativa L. cv.

Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

OpenAIRE

Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

1988-01-01

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems...

Two kinds of ferritin protect ixodid ticks from iron overload and consequent oxidative stress.

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Remil Linggatong Galay

Full Text Available Ticks are obligate hematophagous parasites that have successfully developed counteractive means against their hosts' immune and hemostatic mechanisms, but their ability to cope with potentially toxic molecules in the blood remains unclear. Iron is important in various physiological processes but can be toxic to living cells when in excess. We previously reported that the hard tick Haemaphysalis longicornis has an intracellular (HlFER1 and a secretory (HlFER2 ferritin, and both are crucial in successful blood feeding and reproduction. Ferritin gene silencing by RNA interference caused reduced feeding capacity, low body weight and high mortality after blood meal, decreased fecundity and morphological abnormalities in the midgut cells. Similar findings were also previously reported after silencing of ferritin genes in another hard tick, Ixodes ricinus. Here we demonstrated the role of ferritin in protecting the hard ticks from oxidative stress. Evaluation of oxidative stress in Hlfer-silenced ticks was performed after blood feeding or injection of ferric ammonium citrate (FAC through detection of the lipid peroxidation product, malondialdehyde (MDA and protein oxidation product, protein carbonyl. FAC injection in Hlfer-silenced ticks resulted in high mortality. Higher levels of MDA and protein carbonyl were detected in Hlfer-silenced ticks compared to Luciferase-injected (control ticks both after blood feeding and FAC injection. Ferric iron accumulation demonstrated by increased staining on native HlFER was observed from 72 h after iron injection in both the whole tick and the midgut. Furthermore, weak iron staining was observed after Hlfer knockdown. Taken together, these results show that tick ferritins are crucial antioxidant molecules that protect the hard tick from iron-mediated oxidative stress during blood feeding.

Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

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Ruchi Sharma

2010-01-01

Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

Coinfection of Hepatic Cell Lines with Human Immunodeficiency Virus and Hepatitis B Virus Leads to an Increase in Intracellular Hepatitis B Surface Antigen▿

Science.gov (United States)

Iser, David M.; Warner, Nadia; Revill, Peter A.; Solomon, Ajantha; Wightman, Fiona; Saleh, Suha; Crane, Megan; Cameron, Paul U.; Bowden, Scott; Nguyen, Tin; Pereira, Cândida F.; Desmond, Paul V.; Locarnini, Stephen A.; Lewin, Sharon R.

2010-01-01

Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Coinfection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals. PMID:20357083

Coinfection of hepatic cell lines with human immunodeficiency virus and hepatitis B virus leads to an increase in intracellular hepatitis B surface antigen.

Science.gov (United States)

Iser, David M; Warner, Nadia; Revill, Peter A; Solomon, Ajantha; Wightman, Fiona; Saleh, Suha; Crane, Megan; Cameron, Paul U; Bowden, Scott; Nguyen, Tin; Pereira, Cândida F; Desmond, Paul V; Locarnini, Stephen A; Lewin, Sharon R

2010-06-01

Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Coinfection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals.

Pegvisomant-Induced Cholestatic Hepatitis in an Acromegalic Patient with UGT1A1 ​⁎ 28 Mutation

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Maria Susana Mallea-Gil

2016-01-01

Full Text Available Pegvisomant (PEGv is a growth hormone receptor antagonist approved for the treatment of acromegaly; one of its documented adverse effects is reversible elevation of hepatic enzymes. We report a 39-year-old male acromegalic patient with a pituitary macroadenoma who underwent transsphenoidal surgery. The patient’s condition improved but GH and IGF-I levels did not normalize; as a consequence, we first administered dopamine agonists and then somatostatin receptor ligands (SRLs with poor response. PEGv 15 mg every other day was added to lanreotide 120 mg monthly. The patient developed a severe hepatitis five months after starting the combination therapy. Elevated ferritin, iron, and transferrin saturation suggested probable hepatitis due to haemochromatosis. We performed a liver biopsy which showed an acute cholestatic hepatitis consistent with toxic etiology. A heterozygous genotype UGT1A1​⁎28 polymorphism associated with Gilbert’s syndrome was also found in this Argentine patient. The predominant clinical presentation resembled an acute cholestatic hepatitis associated with severe hemosiderosis, a different and new pattern of PEGv hepatotoxicity.

Comparative Pathology of Hepatitis A Virus and Hepatitis E Virus Infection.

Science.gov (United States)

Cullen, John M; Lemon, Stanley M

2018-04-30

Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause acute, self-limiting hepatic infections that are usually spread by the fecal-oral route in humans. Naturally occurring and experimental infections are possible in a variety of nonhuman primates and, in the case of HEV, a number of other species. Many advances in understanding the pathogenesis of these viruses have come from studies in experimental animals. In general, animals infected with these viruses recapitulate the histologic lesions seen in infected humans, but typically with less severe clinical and histopathological manifestations. This review describes the histopathologic changes associated with HAV and HEV infection in humans and experimental animals. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Occurrence of water-borne enteric viruses in two settlements based in Eastern Chad: analysis of hepatitis E virus, hepatitis A virus and human adenovirus in water sources.

Science.gov (United States)

Guerrero-Latorre, Laura; Carratala, Anna; Rodriguez-Manzano, Jesus; Calgua, Byron; Hundesa, Ayalkibet; Girones, Rosina

2011-09-01

Hepatitis E virus (HEV) is a common cause of water-borne acute hepatitis in areas with poor sanitation. In 2004 an outbreak of HEV infection affected around 2,000 people in Eastern Chad (Dar Sila). This paper describes the decrease in the incidence of acute jaundice syndrome (AJS) from 2004 until 2009 when a mean incidence of 0.48 cases/1,000 people/year was recorded in the region. Outbreaks of AJS were identified in some of the camps in 2007 and 2008. Moreover, water samples from drinking water sources were screened for human adenoviruses considered as viral indicators and for hepatitis A virus and HEV. Screening of faecal samples from donkeys for HEV gave negative results. Some of the samples were also analysed for faecal coliforms showing values before disinfection treatment between 3 and >50 colony forming units per 100 mL. All water samples tested were negative for HEV and HAV; however, the presence of low levels of human adenoviruses in 4 out of 16 samples analysed indicates possible human faecal contamination of groundwater. Consequently, breakdowns in the treatment of drinking water and/or increased excretion of hepatitis viruses, which could be related to the arrival of a new population, could spread future outbreaks through drinking water.

Genetic factors influencing ferritin levels in 14,126 blood donors

DEFF Research Database (Denmark)

Sørensen, Erik; Rigas, Andreas S; Thørner, Lise W

2015-01-01

BACKGROUND: Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN...... AND METHODS: The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain...... with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION: Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron...

Blood mercury can be a factor of elevated serum ferritin: analysis of Korea National Health and Nutrition Examination Survey (KNHANES 2008-2012).

Science.gov (United States)

Joo, Nam-Seok; Choi, Young-Hwa; Yeum, Kyung-Jin; Park, Soo-Jung; Choi, Beomhee; Kim, Young-Sang

2015-03-01

Serum ferritin as well as blood mercury are reported to be associated with chronic inflammation. However, the relation between serum ferritin and blood mercury has not yet been established. We utilized the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012) 10,977 subjects (5433 males and 5544 females). To evaluate the association of serum ferritin and blood mercury cross-sectionally, complex sample analysis was conducted after adjustment for the relevant variables. Serum concentrations of ferritin and blood mercury were higher in males than in females (115.7 ± 1.7 vs. 40.9 ± 0.7 ng/mL and 5.0 ± 0.1 vs. 3.6 ± 0.1 μg/L, respectively). Serum ferritin and blood mercury concentrations had significant correlations in both genders after adjustment (r = 0.062, P mercury (P = 0.007) in males. The adjusted odds ratio of having the highest tertile of serum ferritin in the top tertile of blood mercury in males was 1.52 (95 % confidence interval (CI), 1.05-2.21). Thus, the current study indicates that blood mercury concentration can be a factor for the elevated serum ferritin concentration.

Human hepatic carbohydrate metabolism. Dynamic observation using 13C MRS without proton decoupling

International Nuclear Information System (INIS)

Ikehira, H.; Obata, T.; Koga, M.; Yoshida, K.

1997-01-01

Purpose: Dynamic natural-abundance 13 C MR spectroscopy (MRS) studies without proton decoupling were performed in the human liver using commercial 1.5 T MR equipment. Material and methods: A single tuned custom-made circular surface coil with an OD of 20 cm operating at 16.04 MHz was used for the 13 C study. Seventy-five grams of glucose dissolved in water was administered for the natural-abundance 13 C-MRS dynamic study which lasted for approximately 40 to 60 min. Data acquisition was broken into 20-min and 1.7-min blocks. Localized proton shimming with a whole-body coil was performed with sufficient volume to include the observing area of the surface coil; the line width of the water signal was less than 20 Hz. Results and Conclusion: The glucose and glycogen spectra were clearly visible at 80 to 120 ppm after oral administration of the glucose solution. These data demonstrate that dynamic hepatic carbohydrate metabolism can be observed with commercially available MR equipment. Given that the human hepatic glycogen pool reaches maximum level within less than 10 min, this technique should provide a direct diagnosis of hepatic carbohydrate metabolic disorders. (orig.)

Serum ferritin in normal subjects and assessment of iron status during pregnancy

International Nuclear Information System (INIS)

Eltayeb, Ahmed Eltayeb

1997-12-01

This study was conducted with two main objectives;the estimation of serum ferritin level in normal subjects in khartoum area and the assessment of iron status during pregnancy at second and third trimesters. To fulfill the first objective,two hundred and sixty symptoms-free subjects were included in the study,103 males with ages ranging from 15 to 36 years and 157 females with ages ranging from 15 to 45 years.Serum ferritin was determined by radioimmunoassay (RIA). It was found that the mean concentration of male serum ferritin was much higher than that of the females. For the assessment of iron status during pregnancy,eighty five normal pregnant women were included in the study at the start of the second trimester.Two blood samples were taken during the second trimester and two blood samples during the third trimester. The height of all subjects was measured.The weights of the subjects were measured with each sample. All subjects were under iron-supplementations throughout the gestation period.Sixty four normal non pregnant women were included in the study to serve as controls. No significant difference was observed in the mean haemoglobin concentrations but the PCV of the non-pregnant women was higher than that of the pregnant women at different stages of gestation. MCV, MCH and MCHC values of the non-pregnant women were lower than those of the pregnant women at different stages of gestation. Serum iron and transferrin saturation of the non-pregnant women were higher than those of the pregnant women,this difference was statistically significant at weeks (16 -18) and weeks (22-24). Serum ferritin of the non-pregnant women was higher than that of the pregnant women and decreased continously during the prgnancy, but this decrease was not statistically significant. Iron deficiency anaemia was observed in both pregnant and non-pregnant women. The best parameter which could be used as a marker for iron deficiency is serum ferritin. Iron supplementations corrected for

Serum ferritin in normal subjects and assessment of iron status during pregnancy

Energy Technology Data Exchange (ETDEWEB)

Eltayeb, Ahmed Eltayeb [Sudan Atomic Energy Commission, Khartoum (Sudan)

1997-12-01

This study was conducted with two main objectives;the estimation of serum ferritin level in normal subjects in khartoum area and the assessment of iron status during pregnancy at second and third trimesters. To fulfill the first objective,two hundred and sixty symptoms-free subjects were included in the study,103 males with ages ranging from 15 to 36 years and 157 females with ages ranging from 15 to 45 years.Serum ferritin was determined by radioimmunoassay (RIA). It was found that the mean concentration of male serum ferritin was much higher than that of the females. For the assessment of iron status during pregnancy,eighty five normal pregnant women were included in the study at the start of the second trimester.Two blood samples were taken during the second trimester and two blood samples during the third trimester. The height of all subjects was measured.The weights of the subjects were measured with each sample. All subjects were under iron-supplementations throughout the gestation period.Sixty four normal non pregnant women were included in the study to serve as controls. No significant difference was observed in the mean haemoglobin concentrations but the PCV of the non-pregnant women was higher than that of the pregnant women at different stages of gestation. MCV, MCH and MCHC values of the non-pregnant women were lower than those of the pregnant women at different stages of gestation. Serum iron and transferrin saturation of the non-pregnant women were higher than those of the pregnant women,this difference was statistically significant at weeks (16 -18) and weeks (22-24). Serum ferritin of the non-pregnant women was higher than that of the pregnant women and decreased continously during the prgnancy, but this decrease was not statistically significant. Iron deficiency anaemia was observed in both pregnant and non-pregnant women. The best parameter which could be used as a marker for iron deficiency is serum ferritin. Iron supplementations corrected for

Zinc, ferritin, magnesium and copper in a group of Egyptian children with attention deficit hyperactivity disorder

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Mahmoud Magdy M

2011-12-01

Full Text Available Abstract Background Attention deficit hyperactivity disorder is a behavioral syndrome of childhood characterized by inattention, hyperactivity and impulsivity. There were many etiological theories showed dysfunction of some brain areas that are implicated in inhibition of responses and functions of the brain. Minerals like zinc, ferritin, magnesium and copper may play a role in the pathogenesis and therefore the treatment of this disorder. Objective This study aimed to measure levels of zinc, ferritin, magnesium and copper in children with attention deficit hyperactivity disorder and comparing them to normal. Methods This study included 58 children aged 5-15 years with attention deficit hyperactivity disorder attending Minia University Hospital from June 2008 to January 2010. They were classified into three sub-groups: sub-group I included 32 children with in-attentive type, sub-group II included 10 children with hyperactive type and sub-group III included 16 children with combined type according to the DSM-IV criteria of American Psychiatric Association, 2000. The control group included 25 apparently normal healthy children. Results Zinc, ferritin and magnesium levels were significantly lower in children with attention deficit hyperactivity disorder than controls (p value 0.04, 0.03 and 0.02 respectively, while copper levels were not significantly different (p value 0.9. Children with inattentive type had significant lower levels of zinc and ferritin than controls (p value 0.001 and 0.01 respectively with no significant difference between them as regards magnesium and copper levels (p value 0.4 and 0.6 respectively. Children with hyperactive type had significant lower levels of zinc, ferritin and magnesium than controls (p value 0.01, 0.02 and 0.02 respectively with no significant difference between them as regards copper levels (p value 0.9. Children with combined type had significant lower levels of zinc and magnesium than controls (p value 0

Serum ferritin, serum nitric oxide, and cognitive function in pediatric thalassemia major

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Septiana Nur Qurbani

2017-06-01

Full Text Available Background Hemolysis and repeated blood transfusions in children with thalassemia major cause iron overload in various organs, including the brain, and may lead to neurodegeneration. Hemolysis also causes decreased levels of nitric oxide, which serves as a volume transmitter and slow dynamic modulation, leading to cognitive impairment. Objective To assess for correlations between serum ferritin as well as nitric oxide levels and cognitive function in children with thalassemia major.  Methods This analytical study with cross-sectional design on 40 hemosiderotic thalassemia major patients aged 6−14 years, was done at the Thalassemia Clinic in Dr. Hasan Sadikin Hospital, Bandung, West Java, from May to June 2015. Serum ferritin measurements were performed by an electrochemiluminescence immunoassay; serum nitric oxide was assayed by a colorimetric procedure based on Griess reaction; and cognitive function was assessed by the Wechsler Intelligence Scale for Children test. Statistical analysis was done using Spearman’s Rank correlation, with a significance value of 0.05. Results Abnormal values in verbal, performance, and full scale IQ were found in 35%, 57.5% and 57.5%, respectively. Serum nitric oxide level was significantly correlated with performance IQ (P=0.022, but not with verbal IQ (P=0.359 or full scale IQ (P=0.164. There were also no significant correlations between serum ferritin level and full scale, verbal, or performance IQ (P=0.377, 0.460, and 0.822, respectively. Conclusion Lower serum nitric oxide level is significantly correlated to lower cognitive function, specifically in the performance IQ category. However, serum ferritin level has no clear correlation with cognitive function.

The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

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Sivgin, Serdar; Karamustafaoglu, Mehmet Fatih; Yildizhan, Esra; Zararsiz, Gokmen; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2016-08-01

Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin < 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin ≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P ≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P < .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

Room-temperature susceptometry predicts biopsy-determined hepatic iron in patients with elevated serum ferritin.

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Maliken, Bryan D; Avrin, William F; Nelson, James E; Mooney, Jody; Kumar, Sankaran; Kowdley, Kris V

2012-01-01

There is an ongoing clinical need for novel methods to measure hepatic iron content (HIC) noninvasively. Both magnetic resonance imaging (MRI) and superconducting quantum interference device (SQUID) methods have previously shown promise for estimation of HIC, but these methods can be expensive and are not widely available. Room-temperature susceptometry (RTS) represents an inexpensive alternative and was previously found to be strongly correlated with HIC estimated by SQUID measurements among patients with transfusional iron overload related to thalassemia. The goal of the current study was to examine the relationship between RTS and biochemical HIC measured in liver biopsy specimens in a more varied patient cohort. Susceptometry was performed in a diverse group of patients with hyperferritinemia due to hereditary hemochromatosis (HHC) (n = 2), secondary iron overload (n = 3), nonalcoholic fatty liver disease (NAFLD) (n = 2), and chronic viral hepatitis (n = 3) within one month of liver biopsy in the absence of iron depletion therapy. The correlation coefficient between HIC estimated by susceptometry and by biochemical iron measurement in liver tissue was 0.71 (p = 0.022). Variance between liver iron measurement and susceptometry measurement was primarily related to reliance on the patient's body-mass index (BMI) to estimate the magnetic susceptibility of tissue overlying the liver. We believe RTS holds promise for noninvasive measurement of HIC. Improved measurement techniques, including more accurate overlayer correction, may further improve the accuracy of liver susceptometry in patients with liver disease.

Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

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Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

2011-05-01

Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Correlation between the dielectric properties and biological activities of human ex vivo hepatic tissue

International Nuclear Information System (INIS)

Wang, Hang; You, Fusheng; Fu, Feng; Dong, Xiuzhen; Shi, Xuetao; He, Yong; Yang, Min; Yan, Qingguo

2015-01-01

Dielectric properties are vital biophysical features of biological tissues, and biological activity is an index to ascertain the active state of tissues. This study investigated the potential correlation between the dielectric properties and biological activities of human hepatic tissue with prolonged ex vivo time through correlation and regression analyses. The dielectric properties of 26 cases of normal human hepatic tissue at 10 Hz to 100 MHz were measured from 15 min after isolation to 24 h at 37 °C with 90% humidity. Cell morphologies, including nucleus area (NA) and alteration rate of intercellular area (ICAR), were analyzed as indicators of biological activities. Conductivity, complex resistivity, and NA exhibited opposing changes 1 h after isolation. Relative permittivity and ex vivo time were not closely correlated (p > 0.05). The dielectric properties measured at low frequencies (i.e. <1 MHz) were more sensitive than those measured at high frequencies in reflecting the biological activity of ex vivo tissue. Highly significant correlations were found between conductivity, resistivity and the ex vivo time (p < 0.05) as well as conductivity and the cell morphology (p < 0.05). The findings indicated that establishing the correlation between the dielectric properties and biological activities of human hepatic tissue is of great significance for promoting the role of dielectric properties in biological science, particularly in human biology. (paper)

Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

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Jessica M. V. Pino

2017-05-01

Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

Using Bovine Viral Diarrhea Virus (BVDV) As Surrogate for Human Hepatitis C Virus

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This test is designed to validate virucidal effectiveness claims for a product to be registered as a virucide. It determines the potential of the test agent to disinfect hard surfaces contaminated with human Hepatitis C virus (HCV).

Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

Science.gov (United States)

Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

1988-11-01

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.

Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

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Andreas Bitter

2015-01-01

Full Text Available Background/Aims: Sterol regulatory element-binding protein (SREBP 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

Peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Marchesini, Emanuela; Iorio, Alfonso

2009-01-01

OBJECTIVES: The aim of this study was to assess the effects of peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus (HIV). METHODS: Trials were identified through manual and electronic searches. Randomized trials comparing peginterferon plus ribavirin...... with other antiviral treatments for patients with chronic hepatitis C and HIV were included. The primary outcome measure was virological response at the end of treatment and after > or =6 months (sustained). Intention-to-treat meta-analyses including data on all patients who were randomized were carried out....... RESULTS: Seven randomized trials were eligible for inclusion. The patients included had chronic hepatitis C and stable HIV and were not previously treated with interferon or ribavirin (treatment naive). The mean dosages were 180 or 1.5 microg/kg once weekly for peginterferon and 800 mg daily for ribavirin...

Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients.

Science.gov (United States)

Thomas, C; Kobold, U; Balan, S; Roeddiger, R; Thomas, L

2011-04-01

Biochemical markers of iron deficiency do not distinguish iron-deficient anemia (IDA) from the anemia of chronic disease (ACD) and the combined state of ACD/IDA. Serum hepcidin-25 might be a marker resolving this problem. We investigated the extent to which serum hepcidin-25 enables the differentiation of the states above in comparison with the ferritin index plot, the so-called Thomas plot [soluble transferrin receptor (sTfR)/log ferritin and the reticulocyte hemoglobin content (CHr)]. Serum hepcidin-25 was determined in 155 anemic patients who were classified as having latent iron deficiency (latent ID), IDA, ACD, or ACD/IDA using the ferritin index plot (Thomas plot). Hepcidin-25 was determined using an isotope-dilution micro-HPLC-tandem mass spectrometry method. The ability to discriminate among these states based on serum hepcidin-25 alone or in combination with the CHr was evaluated in a receiver operating characteristic curve analysis and a comparison with the recently established ferritin index plot. Serum hepcidin-25 correlated with ferritin and the ferritin index. Use of a hepcidin-25 cutoff level of ≤4 nmol/l allowed the differentiation of IDA from ACD and ACD/IDA. Furthermore, the discrimination of ACD/IDA from ACD required combination with CHr in a new plot (hepcidin-25 and the CHr). The hepcidin-25 plot and the ferritin index plot showed a good correspondence in the differentiation of iron states in patients with anemia. Patients with IDA can be differentiated from ACD and ACD/IDA but not ACD from ACD/IDA based on hepcidin-25 alone. The combination of hepcidin-25 with CHr in the hepcidin-25 plot was useful for the differentiation of the states above. © 2010 Blackwell Publishing Ltd.

Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey.

Science.gov (United States)

Han, Ling-ling; Wang, Yu-xia; Li, Jia; Zhang, Xiao-lei; Bian, Che; Wang, He; Du, Shufa; Suo, Lin-na

2014-11-01

This study examines gender differences in associations of serum ferritin and diabetes, metabolic syndrome (MetS), and obesity in Chinese. Based on a nationwide, population-based China Health and Nutrition survey this study included 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, ferritin, and transferrin data were collected. Ferritin concentrations were higher in men than women (201.55 ± 3.6 versus 80.46 ± 1.64 ng/mL, p obesity, and overweight were 8.05, 8.97, 4.67, 25.88% among men and 14.23, 6.58, 5.81, 26.82% among women, respectively. Elevated ferritin concentrations were associated with higher body mass index, waist circumference, lipids, insulin, glucose (all p obesity (p = 0.010), overweight (p gender difference in associations between ferritin and MetS, obesity, and diabetes in Chinese adults. Further evaluations of the variation in gender on these associations are warranted to understand the mechanisms behind gender differences. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

Science.gov (United States)

Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

2015-09-01

Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably

Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

Science.gov (United States)

1979-03-01

tech- jects prior to their participation included standard radio- ques , using- radioisotopes ("SFe and S"Tcm-- diphospho- graphic surveys for evidence of... es were apparent by the third dive day for iron and the iv than ABN. It is of interest that no VGE were heard ajt seventh dive day for ferrtin. No...source of the increased amounts of ferritin levels in acute bepatocellular damage from serum ferritin and iron found during these dives ap.- paracetamol

The Correlation between Troponin and Ferritin Serum Levels in the Patients with Major Beta-Thalassemia

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Iraj Shahramian

2013-06-01

Full Text Available Background: Thalassemia is a hereditary hemoglobinopathy whose most common complication is cardiac involvement which ends up in these patients’ death. Since troponin is a sensitive and specific marker for the detection of microinfarct, we studied the relationship between troponin and ferritin serum levels for early diagnosis of cardiac involvement in these patients. Materials and Methods: This case-control study was performed on 80 patients, including 40 patients with major thalassemia and normal echocardiography and 40 healthy volunteers ranging from 6 months to 16 years old. All the children were examined and the eligible children who were not infected with known heart disease, iron deficiency anemia, kidney disease, diabetes, fever, and systemic diseases were enrolled into the study after obtaining written informed consents from their parents. At 8:00 A.M. before breakfast, 5cc blood was drawn from these children. After collecting the samples, ferritin and troponin serum levels were evaluated using ELISA and electro- kymonolonsense methods, respectively. The gathered data were analyzed through the SPSS statistical software (v. 20 and T-test. Besides, P value<0.05 was considered as statistically significant. Results: The study results revealed a significant difference between the two groups regarding the mean of the serum levels of troponin (P=0.045 and ferritin (P=0.001. In this study, no significant correlation was observed between serum troponin and ferritin levels and age and BMI in the two groups. Also, no significant relationship was found between serum troponin level and sex (P=0.264. Conclusions: In microinfarct, troponin increases independent of ferritin; therefore, it can be used for early detection of cardiac involvement in thalassemia patients to determine the sub-clinical effects.

PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans

DEFF Research Database (Denmark)

Bezy, Olivier; Tran, Thien T; Pihlajamäki, Jussi

2011-01-01

C57BL/6J and 129S6/Sv (B6 and 129) mice differ dramatically in their susceptibility to developing diabetes in response to diet- or genetically induced insulin resistance. A major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encoding...... tolerance, and reduced hepatosteatosis with aging. Conversely, mice with liver-specific overexpression of PKCδ developed hepatic insulin resistance characterized by decreased insulin signaling, enhanced lipogenic gene expression, and hepatosteatosis. Therefore, changes in the expression and regulation...... of PKCδ between strains of mice and in obese humans play an important role in the genetic risk of hepatic insulin resistance, glucose intolerance, and hepatosteatosis; and thus PKCδ may be a potential target in the treatment of metabolic syndrome....

Body iron and individual prophylaxis in pregnancy-should the iron dose be adjusted according to serum  ferritin?

DEFF Research Database (Denmark)

Milman, N; Byg, KE; Bergholt, T

2006-01-01

ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin ...This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy...... and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum...

Occurrence and Recurrence of Hepatocellular Carcinoma Were Not Rare Events during Phlebotomy in Older Hepatitis C Virus-Infected Patients

Science.gov (United States)

Kanda, Tatsuo; Nakamoto, Shingo; Yasui, Shin; Nakamura, Masato; Miyamura, Tatsuo; Wu, Shuang; Jiang, Xia; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

2014-01-01

The use of phlebotomy is relatively common for ‘difficult-to-treat by antiviral therapies’ hepatitis C virus (HCV)-infected patients and for certain patients having chronic liver diseases with an iron overload of the liver. In the present study, we retrospectively analyzed patients treated with phlebotomy and their adverse events. We observed the occurrence and recurrence of hepatocellular carcinoma, and the appearance of ascites in some patients infected with HCV as well as the reduction of serum ferritin and alanine aminotransferase levels. Severe adverse events necessitating a cessation of phlebotomy occurred independently of α-fetoprotein (>10 ng/ml) in patients infected with HCV according to multivariate logistic regression analysis. These findings may serve as a basis for phlebotomy especially in older patients with chronic hepatitis C. PMID:24926259

Transfusion-associated hepatitis before the screening of blood for hepatitis risk factors

DEFF Research Database (Denmark)

Engle, Ronald E; Bukh, Jens; Alter, Harvey J

2014-01-01

%) with HBV alone, and one (3%) with both viruses. Overall, 100% of patients with hepatitis and 39% of those without hepatitis were infected with HBV and/or HCV; one patient was also infected with hepatitis E virus. The donor carrier rate for HBV and/or HCV was estimated to be more than 6%; contemporaneously......%) developed biochemical evidence of hepatitis; of these, 20 (67%) were infected with hepatitis C virus (HCV) alone, four (13%) with hepatitis B virus (HBV) alone, and six (20%) with both viruses. Among the 36 patients who did not develop hepatitis, four (11%) were newly infected with HCV alone, nine (25...... prepared pooled normal human plasma was also contaminated with multiple hepatitis viruses. CONCLUSION: TAH virus infections were a larger problem than perceived 50 years ago and HCV was the predominant agent transmitted. All hepatitis cases could be attributed to HCV and/or HBV and hence...

Hepatic Iron Quantification on 3 Tesla (3 T Magnetic Resonance (MR: Technical Challenges and Solutions

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Muhammad Anwar

2013-01-01

Full Text Available MR has become a reliable and noninvasive method of hepatic iron quantification. Currently, most of the hepatic iron quantification is performed on 1.5 T MR, and the biopsy measurements have been paired with R2 and R2* values for 1.5 T MR. As the use of 3 T MR scanners is steadily increasing in clinical practice, it has become important to evaluate the practicality of calculating iron burden at 3 T MR. Hepatic iron quantification on 3 T MR requires a better understanding of the process and more stringent technical considerations. The purpose of this work is to focus on the technical challenges in establishing a relationship between T2* values at 1.5 T MR and 3 T MR for hepatic iron concentration (HIC and to develop an appropriately optimized MR protocol for the evaluation of T2* values in the liver at 3 T magnetic field strength. We studied 22 sickle cell patients using multiecho fast gradient-echo sequence (MFGRE 3 T MR and compared the results with serum ferritin and liver biopsy results. Our study showed that the quantification of hepatic iron on 3 T MRI in sickle cell disease patients correlates well with clinical blood test results and biopsy results. 3 T MR liver iron quantification based on MFGRE can be used for hepatic iron quantification in transfused patients.

Binding analysis of ferritin with heme using α-casein and biotinylated-hemin: detection of heme-binding capacity of Dpr derived from heme synthesis-deficient Streptococcus mutans.

Science.gov (United States)

Mieno, Ayako; Yamamoto, Yuji; Yoshikawa, Yasunaga; Watanabe, Kiyotaka; Mukai, Takao; Orino, Koichi

2013-01-01

Bacterial and mammalian ferritins are known to bind heme. The use of α-casein and biotinylated hemin could be applicable to detection of protein-bound heme and of proteins with heme-binding capacity, respectively. Although commercial horse spleen ferritin and purified horse spleen ferritin (L:H subunit ratio=4) bound to an α-casein-coated plate, and this binding could be inhibited by hemin, recombinant iron-binding protein (rDpr), derived from heme-deficient Streptococcus mutans and expressed in Escherichia coli, did not bind to an α-casein-coated plate. Both horse spleen ferritins bound to α-casein-immobilized beads. Commercial horse spleen ferritin and rDpr showed direct binding to hemin-agarose beads. After preincubation of commercial horse spleen ferritin or rDpr with biotinylated hemin, they showed indirect binding to avidin-immobilized beads through biotinylated hemin. These results demonstrate that α-casein is useful for detection of heme-binding ferritin and that both hemin-agarose and the combination of biotinylated hemin and avidin-beads are useful for detection of the heme-binding capacity of ferritin. In addition, this study also revealed that Dpr, a decameric iron-binding protein, from heme-deficient cells binds heme.

The participation of human hepatic P450 isoforms, flavin-containing monooxygenases and aldehyde oxidase in the biotransformation of the insecticide fenthion

International Nuclear Information System (INIS)

Leoni, Claudia; Buratti, Franca M.; Testai, Emanuela

2008-01-01

Although fenthion (FEN) is widely used as a broad spectrum insecticide on various crops in many countries, very scant data are available on its biotransformation in humans. In this study the in vitro human hepatic FEN biotransformation was characterized, identifying the relative contributions of cytochrome P450 (CYPs) and/or flavin-containing monooxygenase (FMOs) by using single c-DNA expressed human enzymes, human liver microsomes and cytosol and CYP/FMO-specific inhibitors. Two major metabolites, FEN-sulfoxide and FEN-oxon (FOX), are formed by some CYPs although at very different levels, depending on the relative CYP hepatic content. Formation of further oxidation products and the reduction of FEN-sulfoxide back to FEN by the cytosolic aldehyde oxidase enzyme were ruled out. Comparing intrinsic clearance values, FOX formation seemed to be favored and at low FEN concentrations CYP2B6 and 1A2 are mainly involved in its formation. At higher levels, a more widespread CYP involvement was evident, as in the case of FEN-sulfoxide, although a higher efficiency of CYP2C family was suggested. Hepatic FMOs were able to catalyze only sulfoxide formation, but at low FEN concentrations hepatic FEN sulfoxidation is predominantly P450-driven. Indeed, the contribution of the hepatic isoforms FMO 3 and FMO 5 was generally negligible, although at high FEN concentrations FMO's showed activities comparable to the active CYPs, accounting for up to 30% of total sulfoxidation. Recombinant FMO 1 showed the highest efficiency with respect to CYPs and the other FMOs, but it is not expressed in the adult human liver. This suggests that FMO 1 -catalysed sulfoxidation may represent the major extra-hepatic pathway of FEN biotransformation

Porcine circovirus type 2 ORF4 protein binds heavy chain ferritin

Indian Academy of Sciences (India)

Porcine circovirus type 2 ORF4 protein binds heavy chain ferritin. Qizhuang Lv Kangkang Guo Tao Wang ... Keywords. Cellular protein; FHC; ORF4 protein; porcine circovirus type 2 (PCV2); yeast two-hybrid ... Journal of Biosciences | News ...

Reactivity of ferrihydrite and ferritin in relation to surface structure, size, and nanoparticle formation studied for phosphate and arsenate

NARCIS (Netherlands)

Hiemstra, T.; Zhao, Wei

2016-01-01

Ferritin (Ftn) is a natural protein that can store metal (hydr)oxide nanoparticles of tunable size in its cavity and bind oxyanions. This quality can be used in water purification by applying nanotechnology. As our study suggests, the adsorption behavior of engineered ferritin strongly resembles

Effects of cigarette smoking and exposure to cadmium and lead on phenotypic variability of hepatic CYP2A6 and renal function biomarkers in men

International Nuclear Information System (INIS)

Satarug, Soisungwan; Ujjin, Pailin; Vanavanitkun, Yuvaree; Nishijo, Muneko; Baker, Jason R.; Moore, Michael R.

2004-01-01

Effects of cigarette smoking and exposure to dietary cadmium (Cd) and lead (Pb) on urinary biomarkers of renal function and phenotypic variability of cytochrome P450 2A6 (CYP2A6) were investigated in a group of 96 healthy Thai men with mean age of 36.7 year (19-57 years). In non-smokers, Cd burden increased with age (r = 0.47, P < 0.001). In current smokers, Cd burden increased with both age (r = 0.45, P = 0.01) and number of cigarettes smoked per day (r = 0.32, P = 0.05). Cd-linked renal tubular dysfunction was seen in both smokers and non-smokers, but Pb-linked glomerular dysfunction was seen in smokers only, possibly due to more recent exposure to high levels of Cd and Pb, as reflected by 30-50% higher serum Cd and Pb levels in smokers than non-smokers (P < 0.05). Exposure to dietary Cd and Pb appeared to be associated with mild tubular dysfunction whereas dietary exposure plus cigarette smoking was associated with tubular plus glomerular dysfunction. Hepatic CYP2A6 activity in non-smokers showed a positive association with Cd burden (adjusted β = 0.38, P = 0.006), but it showed an inverse correlation with Pb (adjusted β = -0.29, P = 0.003), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. In contrast, CYP2A6 activity in current smokers did not correlate with Cd or Pb, but it showed a positive correlation with serum ferritin levels (r = 0.45, P = 0.01). These finding suggest that Pb concentrations in the liver probably were too low to inhibit hepatic synthesis of heme and CYP2A6 and that the concurrent induction of hepatic CYP2A6 and ferritin was probably due to cigarette smoke constituents other than Cd and Pb

Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors.

Science.gov (United States)

Yang, Guanghua; Si-Tayeb, Karim; Corbineau, Sébastien; Vernet, Rémi; Gayon, Régis; Dianat, Noushin; Martinet, Clémence; Clay, Denis; Goulinet-Mainot, Sylvie; Tachdjian, Gérard; Tachdjian, Gérard; Burks, Deborah; Vallier, Ludovic; Bouillé, Pascale; Dubart-Kupperschmitt, Anne; Weber, Anne

2013-07-19

Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

Science.gov (United States)

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Use of radioimmunodetection of carcinoembryonic antigen (CEA) and ferritin in diagnosis of lung cancer

International Nuclear Information System (INIS)

Zamyatin, S.S.; Zakharychev, V.D.

1989-01-01

To study the diagnostic value of radioimmunoassay (RIA) of carcinoembryonic antigen (CEA) and ferritin the level of this markers under lung cancer depending on the tumor localization and the process stage is determined. It is shown that determination of CEA and ferritin level in a number of patients with the peripheral lung cancer allows on the confirm the diagnosis. In case of the central cancer an increase of CEA level testifies to the tumor germination into the adjacent organs and lung tissue and allows one to determine the stage and operability of the disease. 10 refs.; 3 tabs

Serum ferritin level is higher in male adolescents with obesity: results from the Korean National Health and Nutrition Examination Survey 2010

Directory of Open Access Journals (Sweden)

Yeon Jin Jeon

2013-09-01

Full Text Available PurposePrevious reports show an association between high serum ferritin levels and metabolic syndrome (MS in adults. In adolescents, little information is available with obesity and serum ferritin levels.MethodsThis is a cross-sectional study. Data were obtained from the 5th Korean National Health and Nutrition Examination Survey (K-NHANES conducted during 2010 by the Korean Ministry of Health and Welfare. A total of 849 subjects aged 10-18 years participated in the 2010 survey. A body mass index (BMI ≥95th percentile for age and sex or a BMI ≥25 was used to diagnose as obesity.ResultsThe weighted prevalence of obesity was 13.4% (62/462 in male and 8.5% (33/387 in female. We observed significantly higher serum ferritin in male than in female (mean±standard error [SE], 50.5±2.3 µU/L vs. 30.6±1.3 µU/L; P<0.0001. In male, serum ferritin is positively correlated with age (P<0.0001. White blood cell (WBC count, serum fasting blood sugar, triglyceride (TG, total cholesterol, low-density lipoprotein, insulin, homeostasis model assessment-insulin resistance (HOMA-IR, systolic and diastolic blood pressure, and ferritin levels were higher and high-density lipoprotein (HDL were lower in the obesity than in the normal group. In female adolescents, WBC count, TG, insulin, and HOMA-IR were higher and HDL were lower in the obesity than in the normal group. In male, serum ferritin levels showed positive association with obesity (β=21.196, P=0.016.ConclusionSerum ferritin levels appear to be associated with obesity in Korean male adolescents.

Expression of hsp70 and ferritin in embryos of the copepod Acartia tonsa (Dana) during transition between subitaneous and quiescent state

DEFF Research Database (Denmark)

Nilsson, Birgitte; Jepsen, Per Meyer; Rewitz, Kim Furbo

2014-01-01

Subitaneous eggs of the neritic calanoid copepod Acartia tonsa (Dana) are capable of entering a resting state called quiescence to overcome adverse environmental conditions. Although physiological changes associated with this transition have been described, the molecular mechanisms are thus far...... for ferritin during the recovery phase toward hatching. This suggests that ferritin is a protein needed when embryos of A. tonsa enter quiescence. Both hsp70 and ferritin are required during recovery from quiescent to subitaneous state when embryogenesis continues toward egg hatching....

Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

Directory of Open Access Journals (Sweden)

Robim M. Rodrigues

2016-06-01

Full Text Available This data set is composed of transcriptomics analyses of (i liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF and (ii hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC. Data from primary human hepatocytes was also added to the data set “Open TG-GATEs: a large-scale toxicogenomics database” (Igarashi et al., 2015 [1]. Changes in gene expression due to acetaminophen intoxication as well as comparative information between human in vivo and in vitro samples are provided. The microarray data have been deposited in NCBI׳s Gene Expression Omnibus and are accessible through GEO Series accession number GEO: GSE74000. The provided data is used to evaluate the predictive capacity of each hepatic in vitro system and can be directly compared with large-scale publically available toxicogenomics databases. Further interpretation and discussion of these data feature in the corresponding research article “Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems” (Rodrigues et al., 2016 [2].

Fe{sub 3}O{sub 4} magnetic core coated by silver and functionalized with N-acetyl cysteine as novel nanoparticles in ferritin adsorption

Energy Technology Data Exchange (ETDEWEB)

Akduman, Beguem [Faculty of Science and Arts, Adnan Menderes University, Department of Chemistry (Turkey); Uygun, Murat [Kocarl Latin-Small-Letter-Dotless-I Vocational and Training School, Adnan Menderes University (Turkey); Uygun, Deniz Aktas, E-mail: daktas@adu.edu.tr [Faculty of Science and Arts, Adnan Menderes University, Department of Chemistry (Turkey); Antalik, Marian [Institute of Experimental Physics, Slovak Academy of Science, Department of Biophysics (Slovakia)

2013-04-15

A novel metal-chelate affinity matrix utilizing N-acetyl cysteine as a metal chelating agent was synthesized. For this, magnetic Fe{sub 3}O{sub 4} core was coated with silver by chemical reduction. Then, these magnetic silver nanoparticles were covered with N-acetyl cysteine, and Fe{sup 3+} was chelated to this modified magnetic silver nanoparticle. These magnetic nanoparticles were characterized by SEM, AFM, EDX, and ESR analysis. Synthesized nanoparticles were spherical and average size is found to be 69 nm. Fe{sup 3+} chelated magnetic silver nanoparticles were used for the adsorption of ferritin from its aqueous solution. Optimum conditions for the ferritin adsorption experiments were performed at pH 6.0 phosphate buffer and 25 Degree-Sign C of medium temperature and the maximum ferritin adsorption capacity is found to be 89.57 mg/g nanoparticle. Ferritin adsorption onto magnetic silver nanoparticles was increased with increasing ferritin concentration while adsorption capacity was decreased with increasing ionic strength. Affinity of the magnetic silver nanoparticles to the ferritin molecule was shown with SPR analysis. It was also observed that the adsorption capacity of the magnetic silver nanoparticles was not significantly changed after the five adsorption/desorption cycles.

Serum vitamin B12, folic acid and ferritin levels in patients with migraine

Directory of Open Access Journals (Sweden)

Abdullah Acar

2011-06-01

Full Text Available OBJECTIVE: It has been reported that disability due to migraine may be reduced with homocysteine-lowering treatment including folic acid and vitamin B12. In addition, recently the periaqueductal gray matter iron deposits have been found to be increased in migraine patients. There are few studies regarding vitamin B12, folic acid, ferritin and transferrin levels in patients with migraine. The aims of this study was to measure vitamin B12, folic acid, ferritin and transferrin levels in patients with migraine and compare them with the control group. METHODS: Fifty-one consecutive newly diagnosed migraine patients who did not receive any vitamin supplement medication were enrolled. The study group consisted of 51 patients, suffering from migraine with aura (n= 23 and migraine without aura (n= 28. The control group consisted of 28 healthy participants without history of headache, anemia and vitamin supplement. Serum vitamin B12, folic acid, ferritin and transferin levels were measured using a chemiluminescence method. RESULTS: Migraine patients had significantly lower concentrations of vitamin B12 and folic acid compared with the healthy controls (for vitamin B12; 215.6±133.7 pg/ml vs. 289.9±12 pg/ml, respectively, p=0.005; for folic acid; 6.74 ± 4.31 pg/ml vs. 8.47 ± 1.85 pg/ml, respectively, p=0.048. The vitamin B12 levels were found to be significantly lower during attacks in migraine patients than in interictal periods (177.3 ± 139.2 pg/ml vs 252.5 ± 119.5 pg/ml, p=0.043. There were no differences in folic acid, ferritin, and transferritin levels between during attacks and in interictal period of patients with migraine (p>0.05. The ferritin levels were found to be significantly lower during attacks in migraine patients than in interictal periods (43.4 ± 41.1 mg/ml, vs 75.4 ± 51.7, mg/ml, p=0.018. CONCLUSION: Migraine patients had lower serum vitamin B12 and folic acid levels than healthy subjects. These findings supported that vitamin B12

Correlation between PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients.

Science.gov (United States)

Dragović, Gordana; Sumarac-Dumanovic, Mirjana; Khawla, Al Musalhi; Soldatović, Ivan; Andjić, Mladen; Jevtović, Djordje; Nair, Devaki

2018-06-22

Data about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients' age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = -0.282; p = 0.025). PAI-1 (Rho = 0.334; p = 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α, IL-1 β, IFN �

Hemoglobin, ferritin, vitamin B12 and helicobacter pylori infection: a study in patients underwent upper GI endoscopy at civil hospital karachi

International Nuclear Information System (INIS)

Zuberi, B.F.; Asar, S.; Qadeer, R.; Baloch, I.; Saeed, M.

2007-01-01

To compare hemoglobin, ferritin, and vitamin B12 levels in patients undergoing upper GI endoscopy according to their Helicobacter pylori status. All patients undergoing upper GI Endoscopy were selected, while patients of active peptic ulcers, malignancy, varices, malabsorption and recent blood donation were excluded. Blood samples for CBC, serum ferritin and vitamin B12 were collected and H.pylori status was ascertained by urease test on gastric biopsy. Differences in mean values of age, ferritin, hemoglobin, MCV and vitamin B12 were done by students t-test. Significant confounding factors were identified on multivariate analysis and were further analyzed by univariate analysis. Two hundred and eighty-five subjects were studied, including 171 males and 114 females. H-pylori was positive in 214 (75.1%) patients. Significantly low levels of hemoglobin (p =0.0), ferritin (p = 0.0) and vitamin B12 (p = 0.0) were found in patients with H-pylori infection. Gender, menopause, contraception and history of peptic ulcer disease were identified as significant confounders. Significantly low levels of hemoglobin, ferritin and vitamin B12 were found in patients with H-pylori infection. (author)

Characterization of ferritin 2 for the control of tick infestations

Czech Academy of Sciences Publication Activity Database

Hajdušek, Ondřej; Almazán, C.; Loosová, Gabriela; Villar, M.; Canales, M.; Grubhoffer, L.; Kopáček, Petr; de la Fuente, J.

2010-01-01

Roč. 28, č. 17 (2010), s. 2993-2998 ISSN 0264-410X R&D Projects: GA AV ČR IAA600960910; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : tick ferritin 2 * tick-protective vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.572, year: 2010

Crystallographic study of the inorganic part of the ferritin molecule

International Nuclear Information System (INIS)

Lawrence, J.J.

1969-01-01

Diffraction data given by ferritin core, essentially made up of an iron hydroxide, let us propose, for hypothesis, a hexagonal unit cell (a = 11.79 Angstrom c = 9.90 Angstrom). This product cannot be identified with any known iron hydroxide but its diffraction diagram shows some similarities with that δ FeOOH. (author) [fr

Revelation of endogenously bound Fe{sup 2+} ions in the crystal structure of ferritin from Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Thiruselvam, Viswanathan [Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025 (India); Sivaraman, Padavattan [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Kumarevel, Thirumananseri, E-mail: kumarevel.thirumananseri@riken.jp [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Structural Biology Laboratory, RIKEN Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Ponnuswamy, Mondikalipudur Nanjappagounder, E-mail: mnpsy2004@yahoo.com [Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025 (India)

2014-10-24

Highlights: • Crystal structure of ferritin was determined. • Endogenously expressed iron’s were identified. • Binuclear iron sites were observed at A and B active sites. - Abstract: Ferritin is an iron regulatory protein. It is responsible for storage and detoxification of excess iron thereby it regulates iron level in the body. Here we report the crystal structure of ferritin with two endogenously expressed Fe atoms binding in both the sites. The protein was purified and characterized by MALDI-TOF and N-terminal amino acid sequencing. The crystal belongs to I4 space group and it diffracted up to 2.5 Å. The structural analysis suggested that it crystallizes as hexamer and confirmed that it happened to be the first report of endogenously expressed Fe ions incorporated in both the A and B sites, situated in between the helices.

Hepatic drug clearance following traumatic injury.

Science.gov (United States)

Slaughter, R L; Hassett, J M

1985-11-01

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

Science.gov (United States)

Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

2017-07-01

In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes

Energy Technology Data Exchange (ETDEWEB)

Ohhira, Shuji; Watanabe, Masatomo; Matsui, Hisao [Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, 321-0293, Tochigi (Japan)

2003-03-01

Tributyltin and triphenyltin are metabolized by cytochrome P-450 system enzymes, and their metabolic fate may contribute to the toxicity of the chemicals. In the current study, the in vitro metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes was investigated to elucidate the metabolic competence for these compounds in humans. The metabolic reaction using microsome-NADPH system that is usually conducted was not applicable to in vitro metabolism of organotins, especially triphenyltin. We therefore examined the effects of dithiothreitol (DTT), one of the antioxidants for sulfhydryl groups, to determine the in vitro metabolism of tributyltin and triphenyltin. As a result, the treatment with 0.1 mM DTT in vitro increased the activity of the microsomal monooxygenase system for metabolism of tributyltin as well as triphenyltin; the total yield of tributyltin and triphenyltin metabolites as tin increased, respectively, by approximately 1.8 and 8.9 times for rat, 2.1 and 1.2 times for hamster, and 1.6 and 1.5 times for human. It is suggested that the organotins directly inactivate cytochrome P-450 because of the interaction with critical sulfhydryl groups of the hemoprotein. We confirmed the utility of this in vitro metabolic system using DTT in the hepatic microsomes of phenobarbital (PB)-pretreated and untreated hamsters. Thus, the in vitro metabolic system described here was applied to a comparative study of the metabolism of organotins in rats, hamsters and humans. Tributyltin was metabolized more readily than triphenyltin in all the species. In humans, the in vitro metabolic pattern resembled that of hamsters, which were susceptible to in vivo triphenyltin toxicity because of incompetent metabolism. It is possible that the hamster is a qualitatively and quantitatively suitable animal model for exploring the influence of tributyltin and triphenyltin in humans. (orig.)

Prevalence of human immunodeficiency virus, syphilis, hepatitis B and C in blood donations in Namibia.

Science.gov (United States)

Mavenyengwa, Rooyen T; Mukesi, Munyaradzi; Chipare, Israel; Shoombe, Esra

2014-05-05

Transfusion Transmissible Infections (TTIs) such as Human Immunodeficiency Virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV) are infections which are common in some communities in Southern Africa. It is important to screen blood donations for these infections. This is a retrospective study which involved reviewing of previous blood donation records for the year 2012 in Namibia. The records were analyzed to determine the prevalence of HIV, syphilis, Hepatitis B and C among blood donations with regard to gender, age and geographical region of the donors. The findings indicated a significantly low prevalence of HIV, syphilis, HBsAg and anti-Hepatitis C among the blood donations. A low infection rate of 1.3% by any of the four tested TTIs was found among the blood donations given by the donor population in Namibia in 2012. The blood donations given by the donor population in Namibia has a low infection rate with the HIV, syphilis, HBsAg and anti-HCV. A strict screening regime must continue to be used as the infections are still present albeit in small numbers.

Counter-attack on virol hepatitis

International Nuclear Information System (INIS)

Prozesky, O.W.; Jupp, P.G.; Joubert, J.J.; Taylor, M.B.; Grabow, W.O.K.

1985-01-01

The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B

Opposite associations of trunk and leg fat depots with plasma ferritin levels in middle-aged and older Chinese men and women.

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Hongyu Wu

Full Text Available BACKGROUND: Few data have been published on the associations of ferritin with trunk and leg fat depots. We aimed to investigate these associations in a Chinese population. METHODOLOGY: Trunk fat mass and leg fat mass were determined in a cross-sectional sample of 1,150 Chinese (479 men and 671 women aged 50-70 years by dual-energy X-ray absorptiometry scan. Fasting plasma ferritin was measured. PRINCIPAL FINDINGS: Plasma ferritin was positively correlated with waist circumference, waist-to-hip ratio, total body fat and trunk fat mass, but inversely correlated with leg fat mass in men (r = 0.16, 0.26, 0.19, 0.22 and -0.12, respectively, all P<0.05 and women (r = 0.16, 0.16, 0.08, 0.17 and -0.12, respectively, all P<0.05. Multivariate regression analysis showed that ferritin levels increased with larger trunk fat mass (β = 0.33 ± 0.08 for men and β = 0.21 ± 0.05 for women, both P<0.001 while decreased with larger leg fat mass (β = -0.12 ± 0.09, P = 0.15 for men; and β = -0.14 ± 0.05, P = 0.005 for women. Moreover, plasma ferritin levels decreased with increasing tertile of leg fat mass among each tertile of trunk fat mass. CONCLUSION: This is the first study to report the opposite associations of trunk and leg fat depots with plasma ferritin levels.

A preliminary discussion of angiographic anatomy and variations of rabbit hepatic vessels and catheterization methods of hepatic artery

International Nuclear Information System (INIS)

Wang Diaodong; Yang Renjie; Zhang Hongzhi; Sun Hongliang

2006-01-01

Objective: To study the normal angiographic anatomy and variations of rabbit hepatic vessels, and explore the optimal method for hepatic artery catheterization. Methods: 30 rabbits were divided into two groups randomly. Modified surgical method and interventional method were used to catheterize hepatic artery respectively, and followed by angiography to demonstrate the normal anatomy and variations of rabbit celiac artery, hepatic artery and portal vein. Results: The route and distribution of rabbit celiac artery and hepatic artery were very different from human's. The commonly seen variation showed the differences in branching bifurcation of hepatic-gastric artery, with the incidence of 13.3%. The rates of successfully hepatic artery catheterization with surgical and interventional methods were 86.6%(13/15) and 80%(12/15) respectively (P>0.05). The surgical method will not be successful, whenever there's variation. Conclusion: The normal anatomy and variation of rabbit celiac artery and hepatic artery are quite different from human's. Both surgical and interventional catheterizations could be rather successful but possessing advantages and disadvantages of each its own. (authors)

[History of viral hepatitis].

Science.gov (United States)

Fonseca, José Carlos Ferraz da

2010-01-01

The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

A smart platform for hyperthermia application in cancer treatment: cobalt-doped ferrite nanoparticles mineralized in human ferritin cages.

Science.gov (United States)

Fantechi, Elvira; Innocenti, Claudia; Zanardelli, Matteo; Fittipaldi, Maria; Falvo, Elisabetta; Carbo, Miriam; Shullani, Valbona; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Ferretti, Anna Maria; Ponti, Alessandro; Sangregorio, Claudio; Ceci, Pierpaolo

2014-05-27

Magnetic nanoparticles, MNPs, mineralized within a human ferritin protein cage, HFt, can represent an appealing platform to realize smart therapeutic agents for cancer treatment by drug delivery and magnetic fluid hyperthermia, MFH. However, the constraint imposed by the inner diameter of the protein shell (ca. 8 nm) prevents its use as heat mediator in MFH when the MNPs comprise pure iron oxide. In this contribution, we demonstrate how this limitation can be overcome through the controlled doping of the core with small amount of Co(II). Highly monodisperse doped iron oxide NPs with average size of 7 nm are mineralized inside a genetically modified variant of HFt, carrying several copies of α-melanocyte-stimulating hormone peptide, which has already been demonstrated to have excellent targeting properties toward melanoma cells. HFt is also conjugated to poly(ethylene glycol) molecules to increase its in vivo stability. The investigation of hyperthermic properties of HFt-NPs shows that a Co doping of 5% is enough to strongly enhance the magnetic anisotropy and thus the hyperthermic efficiency with respect to the undoped sample. In vitro tests performed on B16 melanoma cell line demonstrate a strong reduction of the cell viability after treatment with Co doped HFt-NPs and exposure to the alternating magnetic field. Clear indications of an advanced stage of apoptotic process is also observed from immunocytochemistry analysis. The obtained data suggest this system represents a promising candidate for the development of a protein-based theranostic nanoplatform.

The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

DEFF Research Database (Denmark)

Perry, Rachel J; Samuel, Varman T.; Petersen, Kitt Mia Falck

2014-01-01

Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding...... of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol...... activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes....

Iron and zinc complexation in wild-type and ferritin-expressing wheat grain: implications for mineral transport into developing grain

DEFF Research Database (Denmark)

Neal, Andrew L; Geraki, Kalotina; Borg, Søren

2013-01-01

of modified complexation of both metals in transgenic grain overexpressing wheat ferritin. For zinc, there is a consistent doubling of the number of complexing phosphorus atoms. Although there is some EXAFS evidence for iron phytate in ferritin-expressing grain, there is also evidence of a structure lacking......We have used synchrotron-based X-ray fluorescence and absorption techniques to establish both metal distribution and complexation in mature wheat grains. In planta, extended X-ray absorption fine structure (EXAFS) spectroscopy reveals iron phytate and zinc phytate structures in aleurone cells...... of ferritin-expressing grains is quite different from that in wild-type grain. This may explain why the raised levels of minerals transported to the developing grain accumulate within the crease region of the transgenic grain....

Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus

OpenAIRE

El-Bacha , Tatiana; Midlej , Victor; Silva , Ana Paula Pereira Da; Costa , Leandro Silva Da; Benchimol , Marlene; Galina , Antonio; Poian , Andrea T. Da

2007-01-01

Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus correspondence: Corresponding author. Fax: +55 21 22708647. (El-Bacha, Tatiana) (El-Bacha, Tatiana) Laboratorio de Bioquimica de Virus, Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro - RJ-Brasil--> , Av. Bauhinia n? 400 ? CCS Bloco H 2? andar--> , sala 22. Ilha do Governador--> ...

The possible role of tumor antigen CA 15-3, CEA and ferritin in malignant and benign disease

OpenAIRE

Nafija Serdarević; Samira Mehanović

2012-01-01

Introduction: Serum CA15-3 has been one of the most reliable tumor markers used in monitoring of breast cancer patients. To increase its sensitivity, the combined measurement of other tumor markers (CEA and ferritin) with CA15-3 was investigated. The aim of this study was determination of CA 15-3, CEA and ferritin in female patients with breast cancer, lung cancer and mastitisMethods: 300 patients with carcinoma, hospitalized at Department of Gynecologic Oncology and Department for Oncology a...

Molecular MR imaging of cancer gene therapy. Ferritin transgene reporter takes the stage

International Nuclear Information System (INIS)

Hasegawa, Sumitaka; Furukawa, Takako; Saga, Tsuneo

2010-01-01

Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic efficacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene. (author)

Unanticipated increases in hepatic steatosis among human immunodeficiency virus patients receiving mineralocorticoid receptor antagonist eplerenone for non-alcoholic fatty liver disease.

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Chaudhury, Chloe S; Purdy, Julia B; Liu, Chia-Ying; Morse, Caryn G; Stanley, Takara L; Kleiner, David; Hadigan, Colleen

2018-05-01

Non-alcoholic fatty liver disease is common in human immunodeficiency virus, but there are no approved therapies. The aim of this open-label proof-of-concept study was to determine the effect of the mineralocorticoid receptor antagonist eplerenone on hepatic fat in human immunodeficiency virus-infected patients with hepatic fat ≥5% by magnetic resonance spectroscopy. Five subjects received eplerenone (25 mg daily × 1 week followed by 50 mg daily × 23 weeks). Laboratory tests were done at each visit, and the primary endpoint, change in hepatic fat content, was determined by MRI spectroscopy at baseline and week 24. The study was stopped early after observing unexpected significant increases in hepatic fat at week 24 (mean increase 13.0 ± 7.3%, P = .02). The increases in steatosis were accompanied by a tendency for transaminase values to decrease (alanine aminotransferase mean change -14 ± 16 IU/L, P = .14). There were no consistent changes in other metabolic parameters or blood pressure. Repeat assessment of hepatic steatosis 1-2 months after stopping study medication revealed improvements in steatosis towards baseline values. The unexpected observation of increased hepatic steatosis with the administration of eplerenone led to early termination of the investigation. While limited because of the small number of participants and the open-label design, this study provides data to suggest that mineralocorticoid receptor antagonism with eplerenone may not be an effective approach to treat hepatic steatosis in human immunodeficiency virus or the general population. Additional research is needed to determine the pathophysiological mechanism behind these unanticipated observations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reference values for serum ferritin and percentage of transferrin saturation in Korean children and adolescents.

Science.gov (United States)

Oh, Hea Lin; Lee, Jun Ah; Kim, Dong Ho; Lim, Jung Sub

2018-03-01

Ferritin reference values vary by age, gender, and ethnicity. We aimed to determine reference values of serum ferritin (SF) and the percentage of transferrin saturation (TSAT) for Korean children and adolescents. We analyzed data from 2,487 participants (1,311 males and 1,176 females) aged 10-20 years from the Korea National Health and Nutrition Examination Survey (2010-2012). We calculated age- and gender-stratified means and percentile values for SF and TSAT. We first plotted mean SF and TSAT by gender and according to age. In males, mean SF tended to be relatively constant among participants aged 10 to 14 years, with an upward trend thereafter. Mean SF trended downward among female participants until the age of 15 years and remained constant thereafter. Thus, significant gender differences in ferritin exist from the age of 14 years. High levels of SF were associated with obesity, and lower SF levels were associated with anemia and menarche status. We established reference values of SF and TSAT according to age and gender. The reference values for SF calculated in this study can be used to test the association between SF values and other defined diseases in Korean children and adolescents.

Age-Dependent Human Hepatic Carboxylesterase 1 (Ces1) and Carboxylesterase 2 (Ces2) Postnatal Ontogeny

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Human hepatic carboxylesterase 1 and 2 (CES1 and CES2) are important for ester- and amide- bond containing pharmaceutical and environmental chemical disposition. Despite concern regarding juvenile sensitivity to such compounds, CES1 and CES2 ontogeny has not been well characteriz...

Seroprevalence of hepatitis and human immuno-deficiency virus in multitransfused patients from a pediatric hematology clinic

Directory of Open Access Journals (Sweden)

Suar Çakı Kılıç

2008-12-01

Full Text Available OBJECTIVE: Transfusion transmitted hepatitis has been a severe problem in Turkey in pediatric cancer patients and in chronic congenital anemia. The aim of the present study was to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency virus infections in these patients in a University Hospital. METHODS: Multi-transfused 66 children (59 acute leukemia, 6 thalassemia major, 1 severe hereditary spherocytosis diagnosed and followed-up between May, 2000 and December, 2006 were evaluated. Screening of all the patients for HbsAg, anti-HBs, anti-HBc, anti-HCV and anti-HIV was performed at presentation and during the last follow-up. Serologic studies of leukemic patients were also repeated at the end of the chemotherapy. Hepatitis B vaccination was administered to unvaccinated patients with anemia. All blood products were provided by Blood Bank of the Center. RESULTS: No patient was found HBsAg, anti-HCV or anti-HIV positive at diagnosis and at the end of the therapy. There was history of hepatitis B vaccination in only 42% of the patients at diagnosis due to administration of this vaccine to newborns since 1998. At the beginning of the study, 45 % (n=27 of the leukemic patients were immune for hepatitis B, but after completion of the intensive chemotherapy seropositivity persisted in only 28.8 % (n=17. CONCLUSION: Transmission of these viruses is no longer a real problem even in multitransfused immunosuppressed children in Pediatric Hematology Units as a result of the improvements in screening of voluntary blood donors, administration of disposable material in clinics and vaccination by hepatitis B.

Optical diagnostic of hepatitis B (HBV) and C (HCV) from human blood serum using Raman spectroscopy

International Nuclear Information System (INIS)

Anwar, Shahzad; Firdous, Shamaraz

2015-01-01

Hepatitis is the second most common disease worldwide with half of the cases arising in the developing world. The mortality associated with hepatitis B and C can be reduced if the disease is detected at the early stages of development. The aim of this study was to investigate the potential of Raman spectroscopy as a diagnostic tool to detect biochemical changes accompanying hepatitis progression. Raman spectra were acquired from 20 individuals with six hepatitis B infected patients, six hepatitis C infected patients and eight healthy patients in order to gain an insight into the determination of biochemical changes for early diagnostic. The human blood serum was examined at a 532 nm excitation laser source. Raman characteristic peaks were observed in normal sera at 1006, 1157 and 1513 cm −1 , while in the case of hepatitis B and C these peaks were found to be blue shifted with decreased intensity. New Raman peaks appeared in HBV and HCV infected sera at 1194, 1302, 844, 905, 1065 and 1303 cm −1 respectively. A Mat lab subroutine and frequency domain filter program is developed and applied to signal processing of Raman scattering data. The algorithms have been successfully applied to remove the signal noise found in experimental scattering signals. The results show that Raman spectroscopy displays a high sensitivity to biochemical changes in blood sera during disease progression resulting in exceptional prediction accuracy when discriminating between normal and malignant. Raman spectroscopy shows enormous clinical potential as a rapid non-invasive diagnostic tool for hepatitis and other infectious diseases. (letter)

Optical diagnostic of hepatitis B (HBV) and C (HCV) from human blood serum using Raman spectroscopy

Science.gov (United States)

Anwar, Shahzad; Firdous, Shamaraz

2015-06-01

Hepatitis is the second most common disease worldwide with half of the cases arising in the developing world. The mortality associated with hepatitis B and C can be reduced if the disease is detected at the early stages of development. The aim of this study was to investigate the potential of Raman spectroscopy as a diagnostic tool to detect biochemical changes accompanying hepatitis progression. Raman spectra were acquired from 20 individuals with six hepatitis B infected patients, six hepatitis C infected patients and eight healthy patients in order to gain an insight into the determination of biochemical changes for early diagnostic. The human blood serum was examined at a 532 nm excitation laser source. Raman characteristic peaks were observed in normal sera at 1006, 1157 and 1513 cm-1, while in the case of hepatitis B and C these peaks were found to be blue shifted with decreased intensity. New Raman peaks appeared in HBV and HCV infected sera at 1194, 1302, 844, 905, 1065 and 1303 cm-1 respectively. A Mat lab subroutine and frequency domain filter program is developed and applied to signal processing of Raman scattering data. The algorithms have been successfully applied to remove the signal noise found in experimental scattering signals. The results show that Raman spectroscopy displays a high sensitivity to biochemical changes in blood sera during disease progression resulting in exceptional prediction accuracy when discriminating between normal and malignant. Raman spectroscopy shows enormous clinical potential as a rapid non-invasive diagnostic tool for hepatitis and other infectious diseases.

Ferritin from the Pacific abalone Haliotis discus hannai: Analysis of cDNA sequence, expression, and activity.

Science.gov (United States)

Qiu, Reng; Kan, Yunchao; Li, Dandan

2016-02-01

Ferritin plays an important role in iron homeostasis due to its ability to bind and sequester large amounts of iron. In this study, the gene encoding a ferritin (HdhFer2) was cloned from Pacific abalone (Haliotis discus hannai). The full-length cDNA of HdhFer2 contains a 5'-UTR of 121 bp, an ORF of 516 bp, and a 3'-UTR of 252 bp with a polyadenylation signal sequence of AATAAA and a poly(A) tail. It also contains a 31 bp iron-responsive element (IRE) in the 5'-UTR position, which is conserved in many ferritins. HdhFer2 consists of 171 amino acid residues with a predicted molecular weight (MW) ∼19.8 kDa and a theoretical isoelectric point (PI) of 4.84. The deduced amino acid sequence of HdhFer2 contains two ferritin iron-binding region signatures (IBRSs). HdhFer2 mRNA was detected in a wide range of tissues and was dominantly expressed in the gill. Infection with the bacterial pathogen Vibrio anguillarum significantly upregulated HdhFer2 expression in a time-dependent manner. Recombinant HdhFer2 (rHdhFer2) purified from Escherichia coli was able to bind ferrous iron in a concentration-dependent manner. In summary, these results suggest that HdhFer2 is a crucial protein in the iron-withholding defense system, and plays an important role in the innate immune response of abalone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatitis B and C virus co-infections in human immunodeficiency virus positive North Indian patients

Science.gov (United States)

Gupta, Swati; Singh, Sarman

2006-01-01

AIM: To determine the prevalence of hepatitis B and C virus infections in human immunodeficiency virus (HIV) -positive patients at a tertiary care hospital in New Delhi, India. METHODS: Serum samples from 451 HIV positive patients were analyzed for HBsAg and HCV antibodies during three years (Jan 2003-Dec 2005). The control group comprised of apparently healthy bone-marrow and renal donors. RESULTS: The study population comprised essentially of heterosexually transmitted HIV infection. The prevalence rate of HBsAg in this population was 5.3% as compared to 1.4% in apparently healthy donors (P < 0.001). Though prevalence of HCV co-infection (2.43%) was lower than HBV in this group of HIV positive patients, the prevalence was significantly higher (P < 0.05) than controls (0.7%). Triple infection of HIV, HBV and HCV was not detected in any patient. CONCLUSION: Our study shows a significantly high prevalence of hepatitis virus infections in HIV infected patients. Hepatitis viruses in HIV may lead to faster progression to liver cirrhosis and a higher risk of antiretroviral therapy induced hepatotoxicity. Therefore, it would be advisable to detect hepatitis virus co-infections in these patients at the earliest. PMID:17106941

Assessment of iron status of Sudanese pregnant women by serum ferritin

International Nuclear Information System (INIS)

Eltayeb, E.A.; Khangi, F.A.; Satti, G.M.; Abu Salab, A.

2004-03-01

Eighty five normal pregnant women were included in the study at the start of the second trimester. Two blood samples were taken during the second trimester and two blood samples during the third trimester. The height of all subjects was measured. The weights of the subjects were under iron-supplementation throughout the gestation period. Sixty four normal non-parentage women were included in the study to serve as controls. Iron status was assessed for the groups with following parameters, haemoglobin (Hb), packed corpuscular volume (PCV), red blood cells count, peripheral blood film, mean corpuscular volume (MCV), mean cell haemoglobin (MCH), Mean haemoglobin concentration (MCH C), serum iron (Si), total iron binding capacity (T IBC), serum transferrin saturation (Ts) and serum ferritin (Sf). No significant difference was observed in the mean haemoglobin concentrations but the PCV of the non-pregnant women was higher than that of the pregnant women at different stages of gestation (p<0.05). MCV, MCH and MCH C values of the non-pregnant women were lower than those of the of the pregnant at different stages of gestation (p<0.05). Serum iron and transferrin saturation of the non-pregnant women were higher than those of the pregnant women, this difference was statistically significant at weeks (16-18) and (22-24) (p<0.05). Serum ferritin of the non-pregnant women was higher than that of the pregnant women and decreased continuously during the pregnancy, but this decrease was not statistically significant. Iron deficiency anaemia was observed in both pregnant and non-pregnant women. The best parameter that could be used as a marker for iron deficiency is serum ferritin. Iron supplementation s corrected for haemoglobin but not for iron status, but more studies were needed to cover this issue using different parameters.(Author)

Molecular cloning and copy number variation of a ferritin subunit (Fth1 and its association with growth in freshwater pearl mussel Hyriopsis cumingii.

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Zhiyi Bai

Full Text Available Iron is one of the most important minor elements in the shells of bivalves. This study was designed to investigate the involvement of ferritin, the principal protein for iron storage, in shell growth. A novel ferritin subunit (Fth1 cDNA from the freshwater pearl mussel (Hyriopsis cumingii was isolated and characterized. The complete cDNA contained 822 bp, with an open reading frame (ORF of 525 bp, a 153 bp 5' untranslated region (UTR and a 144 bp 3' UTR. The complete genomic DNA was 4125 bp, containing four exons and three introns. The ORF encoded a protein of 174 amino acids without a signal sequence. The deduced ferritin contained a highly conserved motif for the ferroxidase center comprising seven residues of a typical vertebrate heavy-chain ferritin. It contained one conserved iron associated residue (Try27 and iron-binding region signature 1 residues. The mRNA contained a 27 bp iron-responsive element with a typical stem-loop structure in the 5'-UTR position. Copy number variants (CNVs of Fth1 in two populations (PY and JH were detected using quantitative real-time PCR. Associations between CNVs and growth were also analyzed. The results showed that the copy number of the ferritin gene of in the diploid genome ranged from two to 12 in PY, and from two to six in JH. The copy number variation in PY was higher than that in JH. In terms of shell length, mussels with four copies of the ferritin gene grew faster than those with three copies (P<0.05, suggesting that CNVs in the ferritin gene are associated with growth in shell length and might be a useful molecular marker in selective breeding of H. cumingii.

A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens.

Science.gov (United States)

Lapierre, Pascal; Djilali-Saiah, Idriss; Vitozzi, Susana; Alvarez, Fernando

2004-04-01

Autoimmune hepatitis (AIH) is characterized by an immune-mediated injury of the hepatic parenchyma of unknown pathogenesis. Type 2 AIH is identified by the presence of anti-liver-kidney microsomes type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) autoantibodies. The current study shows that a murine model of AIH can be generated by DNA immunization against type 2 AIH self-antigens (P450 2D6 and formiminotransferase-cyclodeaminase). A pCMV plasmid containing the N-terminal region of mouse CTLA-4 and the antigenic region of human CYP2D6 (672-1,377 bp) and human formiminotransferase cyclodeaminase (FTCD; 1,232-1,668 bp) was used for DNA immunization of C57BL/6 female mice. Immunized mice showed elevated levels of alanine aminotransferase (ALT), with peaks at 4 and 7 months postinjection. Periportal, portal, and intralobular liver inflammatory infiltrates were observed at histology. Mainly CD4+ lymphocytes, but also CD8+ and B lymphocytes, were found in the liver. Cytotoxic-specific T cells were found in both the liver and spleen of these animals. Mice developed anti-LKM1 and anti-LC1 antibodies of immunoglobulin G2 (IgG2) subclass, against specific mouse autoantigens. The ALT levels correlated with both the presence of anti-LKM1/anti-LC1 antibodies and the presence of liver necroinflammation. In conclusion, in mice, DNA immunization against human autoantigens breaks tolerance and induces an autoimmune liver disease. Molecular mimicry between foreign and self-antigens explains the liver injury. This model of AIH resembles human type 2 AIH and will be helpful for the study of its pathogenesis.

In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee

NARCIS (Netherlands)

R. Heijtink; W. Paulij; P.A.C. van Bergen (Patrick); M.H. van Roosmalen (Mark); D. Rohm; B. Eichentopf (Bertram); E. Muchmore; A.D.M.E. Osterhaus (Albert); R.A. de Man (Robert)

1999-01-01

textabstractA 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks

H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

KAUST Repository

Zolea, Fabiana

2015-10-09

The redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.

H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

KAUST Repository

Zolea, Fabiana; Biamonte, Flavia; Candeloro, Patrizio; Di Sanzo, Maddalena; Cozzi, Anna; Di Vito, Anna; Quaresima, Barbara; Lobello, Nadia; Trecroci, Francesca; Di Fabrizio, Enzo M.; Levi, Sonia; Cuda, Giovanni; Costanzo, Francesco

2015-01-01

The redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.

Relationship between high serum ferritin level and glaucoma in a South Korean population: the Kangbuk Samsung health study.

Science.gov (United States)

Gye, Hyo Jung; Kim, Joon Mo; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Sung, Ki Chul; Lee, Mi Yeon; Park, Ki Ho

2016-12-01

To investigate the association between serum ferritin levels and glaucoma in a South Korean population. This retrospective cross-sectional study included 164 029 subjects who underwent screening at Kangbuk Samsung Hospital Health Screening Center between August 2012 and July 2013. All subjects underwent a physical examination, answered sociodemographic and behavioural questions, and provided samples for laboratory analyses. A digital fundus photograph of both eyes was taken, and all photographs were reviewed by ophthalmologists. The ophthalmologists determined if an eye had glaucoma based on criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and the appearance of the retinal nerve fibre layer and optic disc. The mean serum ferritin level was 56.98 ng/mL in women and 223.82 ng/mL in men. After adjusting for age, serum iron, total iron-binding capacity (TIBC), transferrin saturation, white blood cell (WBC) count, high-sensitivity C-reactive protein (HsCRP) and total vitamin D level, males in the highest quartile for serum ferritin level had a higher OR for glaucoma than males in the lowest quartile (OR=1.176, 95% CI 1.030 to 1.342, p=0.016); we did not observe this relationship among women. Other markers of iron metabolism, such as iron level, transferrin saturation and TIBC, and inflammation measures, including WBC, HsCRP and total vitamin D, were not associated with glaucoma. High serum ferritin level was associated with a high risk of glaucoma in men, but not in women. Because serum ferritin is related to oxidative stress and inflammation, it might play a role in glaucoma development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer

International Nuclear Information System (INIS)

Sasaki, Y.; Imaoka, S.; Hasegawa, Y.

1985-01-01

Changes in the distribution of the hepatic blood flow induced by intra-arterial infusion of angiotensin II (AT-II) were studied in human hepatic cancers using extremely short-lived radioisotope (RI) (krypton 81 m [/sup 81m/Kr]; half-life, 13 seconds). After the start of continuous infusion of AT-II, the radioactivity of the tumor showed about a two-fold increase, whereas that of the nontumor region decreased to about one half as much as the level before the infusion. Consequently, the mean ratio of the arterial blood flow in the tumor region to that in the nontumor region (T/N ratio) increased to 3.30 (P less than 0.001). The T/N ratio showed a peak before the peripheral blood pressure reached the maximum, and thereafter tended to decrease. Intra-arterial infusion of AT-II raised the T/N ratio more obviously than did intravenous infusion of the drug, with less rise in the peripheral blood pressure. It is believed that intra-arterial infusion chemotherapy with local use of AT-II enables better accessibility of chemotherapeutic drugs to tumors

Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection

Directory of Open Access Journals (Sweden)

Keeffe Emmet B

2005-09-01

Full Text Available Abstract Hepatitis B virus (HBV and hepatitis C virus (HCV coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed.

Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity

NARCIS (Netherlands)

Sliepen, Kwinten; Ozorowski, Gabriel; Burger, Judith A.; van Montfort, Thijs; Stunnenberg, Melissa; Labranche, Celia; Montefiori, David C.; Moore, John P.; Ward, Andrew B.; Sanders, Rogier W.

2015-01-01

Background: Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation. Findings: We describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein trimers (BG505 SOSIP.664). Trimer-bearing

Detection of Osteopontin in the pericyst of human hepatic Echinococcus granulosus.

Science.gov (United States)

Peng, Xinyu; Li, Jianhui; Wu, Xiangwei; Zhang, Shijie; Niu, Jianhua; Chen, Xiaoping; Yao, Jin; Sun, Hong

2006-12-01

It aims at investigating the expression and distribution of the Osteopontin (OPN) in the pericyst of human hepatic Echinococcus granulosus and their related significances. Sixty pericysts excised by "sub-adventitial cystectomy" were studied. OPN was detected in 80% (48/60) of cysts by Western blotting and distributed in the side of "exocyst" layer directing to the parasite, also macrophages were identified in the vicinity of OPN by immunohistochemistry staining. The coexpression of OPN and CD68 was observed by immunofluorescence double labeling and analyzed by Image-Pro Plus 5.1; with special stain techniques, variable degrees of calcium deposits were observed in 80% (48/60) cysts, and the calcium deposits concurrencely found with the OPN expression. The selective distribution of OPN, calcium in the "exocyst" provides a new pathological evidence for the "sub-adventitial cystectomy" we developed. The pericyst of hepatic E. granulosus consists of two detachable layers with different formative mechanisms: the "exocyst" layer directing towards the cyst of parasite was the result of granulomatous reaction; also the results suggest OPN is one regulator in the granulomatous reaction and calcification of "exocyst".

Elevated serum ferritin concentration is associated with incident type 2 diabetes mellitus in a Chinese population: A prospective cohort study.

Science.gov (United States)

Chen, Ling; Li, Yufeng; Zhang, Fang; Zhang, Simin; Zhou, Xianghai; Ji, Linong

2018-03-08

We aimed to evaluate the association between serum ferritin levels and incident type 2 diabetes mellitus risk in a Chinese population. This cohort study assessed 2225 Chinese individuals aged 25-75 years. Diabetes mellitus was diagnosed using the 1999 World Health Organization definition with a median follow-up period of 20 months. Cox proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (CI) for incident diabetes when serum ferritin concentrations increased by one standard deviation. During the follow-up period, 112 cases (62 men and 50 women) of type 2 diabetes mellitus were identified. Baseline serum ferritin levels were higher in the diabetes than the non-diabetes group. After adjusting for age, body mass index, waist circumference, mean arterial pressure, fasting plasma glucose, fasting insulin, hemoglobin A1c, total cholesterol, high-density lipoprotein cholesterol, alanine transaminase and triglyceride levels, family history of diabetes mellitus, pork meat consumption, neutrophil/lymphocyte ratio, education, and annual household income, the hazard ratios for incident diabetes corresponding to one standard deviation increase in serum ferritin levels were 1.17 (95% CI 1.03, 1.34), 1.20 (95% CI 1.003, 1.43), and 1.03 (95% CI 0.82, 1.31) for the total population, men, and women, respectively. High serum ferritin levels were associated with a higher risk of incident type 2 diabetes mellitus independent of traditional risk factors in the total population and men. Copyright © 2018 Elsevier B.V. All rights reserved.

Giving It Our Best Shot? Human Papillomavirus and Hepatitis B Virus Immunization Among Refugees, Massachusetts, 2011-2013.

Science.gov (United States)

Berman, Rachel Stein; Smock, Laura; Bair-Merritt, Megan H; Cochran, Jennifer; Geltman, Paul L

2017-06-22

The receipt rate of hepatitis B virus vaccine among adolescents in the United States is high, while the receipt rate of human papillomavirus vaccine is low. Rates have not been closely studied among refugees, whose home countries have high rates of disease caused by these viruses. We examined human papillomavirus and hepatitis B virus immunization rates among 2,269 refugees aged 9 to 26 years who resettled in Massachusetts from 2011 through 2013. This was a secondary analysis of data from their medical screenings. We used binary logistic regression to assess characteristics associated with immunization and bivariate analyses to compare refugee immunization rates with those of the general US population. Forty-five percent of US adolescents aged 13 to 17 years received 1 dose of human papillomavirus vaccine, compared with 68% of similarly aged refugees. Males (adjusted odds ratio [aOR], 0.62; 95% confidence interval [CI], 0.52-0.74), refugees older than 13 years (aOR, 0.74; 95% CI, 0.60-0.93), and refugees not from Sub-Saharan Africa (aOR, 0.74; 95% CI, 0.59-0.92) were less likely to receive human papillomavirus vaccine, while arrivals in 2012 through 2013 were more likely (aOR, 1.6; 95% CI, 1.3-1.9) than those arriving in 2011. Refugees older than 13 years were less likely to receive 2 doses of hepatitis B virus vaccine (aOR, 0.49; 95% CI, 0.37-0.63) than older refugees. Specialized post-arrival health assessment may improve refugees' immunization rates.

The association of markers of oxidative-inflammatory status with malnutrition in hemodialysis patients with serum ferritin lower than 500 ng/mL

Directory of Open Access Journals (Sweden)

Simone Gonçalves de Almeida

2013-03-01

Full Text Available INTRODUCTION: Enhanced inflammatory-oxidative status is well established in chronic kidney disease. OBJECTIVE: The objective of this study was to evaluate the oxidative- inflammatory status and iron indices in patients undergoing maintenance hemodialysis (HD with serum ferritin lower than 500ng/mL, and to correlate them with nutritional status. METHOD: In a cross-sectional survey 35 HD patients (23 with normal nutritional status, 12 with Protein-Energy-Wasting syndrome, PEW, and healthy volunteers (n = 35 were studied. Serum concentration of iron, ferritin, transferrin saturation, malondialdehyde (MDA, protein carbonyl (PC, high-sensitive serum C -reactive protein (hs-CRP and blood counts were determined. The nutritional status was determined by anthropometric and biochemical criteria. RESULTS: HD patients showed low values of hemoglobin and higher values of ferritin, MDA and PC when compared with healthy volunteers. HD subjects with PEW had higher values of PC and hs-PCR as compared to HD patients with normal nutritional status. A multiple logistic regression analysis showed that the independent variables PC (Wald Statistic 4.25, p = 0.039 and hs-CRP (Wald Statistic 4.83, p = 0.028 where related with the patients' nutritional condition. CONCLUSION: In HD patients with serum ferritin below 500 ng/mL was observed one association of the markers of oxidative stress and inflammation with poor nutritional status independently of serum ferritin, gender and age.

Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

DEFF Research Database (Denmark)

Pedersen, Court; Breindahl, Morten; Aggarwal, Naresh

2012-01-01

This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A......, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone....

Clinical significance of determination of changes of serum ferritin, MMP-2 and MMP-9 levels and after transfusion of red blood cells in patients with chronic nephritis

International Nuclear Information System (INIS)

Yuan Haitao; Li Xinhua; He Haoming

2010-01-01

Objective: To explore the changes of serum Ferritin, MMP-2 and MMP-9 contents after transfusion of red blood cells in patients with chronic nephritis. Methods: Serum Ferritin (with RIA) and serum MMP-2, MMP-9 (with ELISA) levels were measured in 32 patients with chronic nephritis both before and after a course of transfusion of red blood cells and 35 controls. Results: Before transfusion, the serum Ferritin, MMP-9 levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Determination of serum Ferritin, MMP-2 and MMP-9 levels is clinically useful for management of patients with chronic nephritis. (authors)

Mitochondrial Ferritin Deletion Exacerbates β-Amyloid-Induced Neurotoxicity in Mice

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Peina Wang

2017-01-01

Full Text Available Mitochondrial ferritin (FtMt is a mitochondrial iron storage protein which protects mitochondria from iron-induced oxidative damage. Our previous studies indicate that FtMt attenuates β-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt on β-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type and Ftmt knockout mice were infused intracerebroventricularly (ICV with Aβ25–35 to establish an Alzheimer’s disease model. Knockout of Ftmt significantly exacerbated Aβ25–35-induced learning and memory impairment. The Bcl-2/Bax ratio in mouse hippocampi was decreased and the levels of cleaved caspase-3 and PARP were increased. The number of neuronal cells undergoing apoptosis in the hippocampus was also increased in Ftmt knockout mice. In addition, the levels of L-ferritin and FPN1 in the hippocampus were raised, and the expression of TfR1 was decreased. Increased MDA levels were also detected in Ftmt knockout mice treated with Aβ25–35. In conclusion, this study demonstrated that the neurological impairment induced by Aβ25–35 was exacerbated in Ftmt knockout mice and that this may relate to increased levels of oxidative stress.

Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.

Science.gov (United States)

Depalma, Ralph G; Hayes, Virginia W; Chow, Bruce K; Shamayeva, Galina; May, Patricia E; Zacharski, Leo R

2010-06-01

This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death. Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with

Human immunodeficiency virus (HIV) seropositivity and hepatitis B surface antigenemia (HBSAG) among blood donors in Benin city, Edo state, Nigeria.

Science.gov (United States)

Umolu, Patience Idia; Okoror, Lawrence Ehis; Orhue, Philip

2005-03-01

Human Immunodeficiency Virus and Hepatitis B virus are blood borne pathogens that can be transmitted through blood transfusion and could pose a huge problem in areas where mechanisms of ensuring blood safety are suspect. This study became necessary in a population where most of the blood for transfusion is from commercial blood donors. A total of 130 donors comprising 120 commercial donors and 10 voluntary donors were tested for antibodies to human immunodeficiency virus and hepatitis B surface antigen in Benin city using Immunocomb HIV - 1 and 2 Biospot kit and Quimica Clinica Aplicada direct latex agglutination method respectively. Thirteen (10%) samples were HIV seropositive and 7(5.8%) were HBsAg positive. The age bracket 18 - 25years had the highest numbers of donors and also had the highest number of HBsAg positive cases (7.8%) while the age group 29 - 38years had highest number of HIV seropositive cases. High prevalence of HIV antibodies and Hepatitis B surface antigen was found among commercial blood donors. Appropriate and compulsory screening of blood donors using sensitive methods, must be ensured to prevent post transfusion hepatitis and HIV.

Human leukocyte antigen-e alleles are associated with hepatitis c virus, torque teno virus, and toxoplasma co-infections but are not associated with hepatitis b virus, hepatitis d virus, and GB virus c co-infections in human immunodeficiency virus patients

Directory of Open Access Journals (Sweden)

Afiono Agung Prasetyo

2016-01-01

Full Text Available Context: Data regarding the distribution of Human Leukocyte Antigen (HLA-E alleles and their association with blood-borne pathogen infections/co-infections are limited for many populations, including Indonesia. Aims: The aim of this study was to analyze the association between HLA-E allelic variants and infection with blood-borne pathogens such as hepatitis B virus (HBV, hepatitis C virus (HCV, hepatitis D virus (HDV, torque teno virus (TTV, GB virus C (GBV-C, and Toxoplasma gondii (T. gondii in Indonesian Javanese human immunodeficiency virus (HIV patients. Settings and Design: A total of 320 anti-HIV-positive blood samples were analyzed for HBV, HCV, HDV, TTV, GBV-C, and T. gondii infection status and its association with HLA-E allelic variants. Materials and Methods: Nucleic acid was extracted from plasma samples and used for the molecular detection of HBV DNA, HCV RNA, HDV RNA, TTV DNA, and GBV-C RNA, whereas hepatitis B surface antigen, anti-HCV, immunoglobulin M and G (IgM and IgG anti-T. gondii were detected through serological testing. The blood samples were genotyped for HLA-E loci using a sequence-specific primer-polymerase chain reaction. Statistical Analysis Used: Either the Chi-square or Fisher′s exact test was performed to analyze the frequency of HLA-E alleles and blood-borne pathogen infections in the population. Odds ratios (ORs were calculated to measure the association between the antibodies found and the participants′ possible risk behaviors. A logistic regression analysis was used to assess the associations. Results: HLA-EFNx010101/0101 was associated with HCV/TTV co-infection (adjusted OR [aOR]: 3.5; 95% confidence interval [CI]: 1.156-10.734; P = 0.027 and IgM/IgG anti-Toxo positivity (aOR: 27.0; 95% CI: 3.626-200.472; P = 0.001. HLA-EFNx010103/0103 was associated with TTV co-infection (aOR: 2.7; 95% CI: 1.509-4.796; P = 0.001. Conclusions: HLA-E alleles in Indonesian Javanese HIV patients were found to be associated

Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

Science.gov (United States)

Fan, Kelong; Jiang, Bing; Guan, Zhe; He, Jiuyang; Yang, Dongling; Xie, Ni; Nie, Guohui; Xie, Can; Yan, Xiyun

2018-04-10

Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

Current Knowledge on Hepatitis E.

Science.gov (United States)

Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa

2015-06-28

Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin(®).

Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

National Research Council Canada - National Science Library

Gilman, Sara C; Hunter, Jr., W. L; Mooney, L. W

1979-01-01

.... during these simulated dives progressive and correlated increases in serum ferritin and iron occurred. No significant changes were observed in bilirubin, hemoglobin, neurloplasmia, transferrin, cooper, or total iron binding capacity...

Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

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Lun Yang

Full Text Available Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1

International Nuclear Information System (INIS)

Wang, Ai-Guo; Seo, Sang-Beom; Moon, Hyung-Bae; Shin, Hye-Jun; Kim, Dong Hoon; Kim, Jin-Man; Lee, Tae-Hoon; Kwon, Ho Jeong; Yu, Dae-Yeul; Lee, Dong-Seok

2005-01-01

It is generally thought that histone deacetylases (HDACs) play important roles in the transcriptional regulation of genes. However, little information is available concerning the specific functions of individual HDACs in disease states. In this study, two transgenic mice lines were established which harbored the human HDAC1 gene. Overexpressed HDAC1 was detected in the nuclei of transgenic liver cells, and HDAC1 enzymatic activity was significantly higher in the transgenic mice than in control littermates. The HDAC1 transgenic mice exhibited a high incidence of hepatic steatosis and nuclear pleomorphism. Molecular studies showed that HDAC1 may contribute to nuclear pleomorphism through the p53/p21 signaling pathway

Phosphate and arsenate removal efficiency by thermostable ferritin enzyme from Pyrococcus furiosus using radioisotopes

KAUST Repository

Sevcenco, Ana-Maria; Paravidino, Monica; Vrouwenvelder, Johannes S.; Wolterbeek, Hubert Th.; van Loosdrecht, Mark C.M.; Hagen, Wilfred R.

2015-01-01

Oxo-anion binding properties of the thermostable enzyme ferritin from Pyrococcus furiosus were characterized with radiography. Radioisotopes 32P and 76As present as oxoanions were used to measure the extent and the rate of their absorption

Sensitive genotyping of foodborne-associated human noroviruses and hepatitis A virus using an array-based platform

Science.gov (United States)

The viral pathogens, human norovirus (NoV) and hepatitis A virus (HAV), are significant contributors of foodborne associated outbreaks. To develop a typing tool for foodborne viruses, a focused, low-density DNA microarray was developed in conjunction with a rapid and high-throughput fluorescent meth...

Assembly of Modified Ferritin Proteins on Carbon Nanotubes and its Electrocatalytic Activity for Oxygen Reduction

Science.gov (United States)

Kim, Jae-Woo; Lillehei, Peter T.; Park, Cheol

2012-01-01

Highly effective dispersions of carbon nanotubes (CNTs) can be made using a commercially available buffer solution. Buffer solutions of 3-(N-morpholino)-propanesulfonic acid (MOPS), which consists of a cyclic ring with nitrogen and oxygen heteroatoms, a charged group, and an alkyl chain greatly enhance the dispersibility and stability of CNTs in aqueous solutions. Additionally, the ability of biomolecules, especially cationized Pt-cored ferritins, to adhere onto the well-dispersed CNTs in the aqueous buffer solution is also improved. This was accomplished without the use of surfactant molecules, which are detrimental to the electrical, mechanical, and other physical properties of the resulting products. The assembled Pt-cored ferritin proteins on the CNTs were used as an electrocatalyst for oxygen reduction

Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

Science.gov (United States)

Ito, Yuki; Nakamura, Toshiki; Yanagiba, Yukie; Ramdhan, Doni Hikmat; Yamagishi, Nozomi; Naito, Hisao; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

2012-01-01

Dibutylphthalate (DBP), di(2-ethylhexyl)phthalate (DEHP), and di(2-ethylhexyl)adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα) and humanized PPARα (hPPARα) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR. PMID:22792086

Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

Directory of Open Access Journals (Sweden)

Yuki Ito

2012-01-01

Full Text Available Dibutylphthalate (DBP, di(2-ethylhexylphthalate (DEHP, and di(2-ethylhexyladipate (DEHA are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα and humanized PPARα (hPPARα mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control, 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg, DEHP (977, 1953 mg/kg, and DEHA (926, 1853 mg/kg, respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR.

HIV and other predictors of serum folate, serum ferritin, and hemoglobin in pregnancy

DEFF Research Database (Denmark)

Friis, Henrik; Gomo, E; Kæstel, Pernille

2001-01-01

BACKGROUND: Folate and iron status and hemoglobin concentrations are important to maternal and infant health. OBJECTIVE: Our goal was to identify predictors of serum folate, serum ferritin, and hemoglobin. DESIGN: This was a cross-sectional study of 1669 pregnant women (22-35 wk of gestation) in ...

Evaluation of the Ramco kit for serum ferritin assay

Energy Technology Data Exchange (ETDEWEB)

Dempster, W S; Knight, G J [Red Cross War Memorial Children' s Hospital, Cape Town (South Africa). Department of Paediatrics and Child Health; Jacobs, P [Cape Town Univ. (South Africa). Dept. of Haematology

1979-12-22

The determination of serum ferritin levels may be of diagnostic importance in medicine. To establish whether values obtained using a commercially available kit (Ramco) were adequate for this purpose, a comparison was undertaken using a two-site immunoradiometric assay that had been developed and standardized in our laboratories. Over the range 6..mu..g/l to greater than 2 000 ..mu..g/l there was a correlation coefficient between the two methods of 0,8284 (P smaller than 0,001). It is concluded that the Ramco kit is suitable for use in clinical practice.

Drug-binding ability of human serum albumin at children with chronic virus hepatitis radiochemical definition method

International Nuclear Information System (INIS)

Kim, A.A.; Dadakhanov, J.A.; Djuraeva, G.T.; Shukurov, B.V.; Mavlyanov, I.R.

2006-01-01

Full text: The chronic virus hepatitis produces numerous abnormalities of liver function. The viruses of B, C, D, F and G hepatitis possess the ability to cause chronically proceeding diseases. Earlier we have found that binding ability of serum albumin at patients with acute forms of virus hepatitis is authentically reduced in comparison with the given parameters of control group. At an acute virus hepatitis B with middle severity the reducing of binding ability of serum albumin was observed at 70 % of patients. At an acute virus hepatitis A the reduce of binding ability of serum albumin is less expressed than at acute virus hepatitis B. At of chronic virus intoxication in human organism there is a formation and accumulation of toxic compounds in the excessive concentrations, which are not inherent to a normal metabolism. One of universal mechanisms of reaction of an organism on the increasing concentration of metabolism products is formation of complexes of various compounds with blood plasma proteins. The formation in an organism of endo- and exotoxins excessive concentrations results in blocking the binding centers of albumin molecule that causes the change of its complexing ability. The purpose of the present research: investigation of binding ability of serum albumin with use of radiochemical method at children with a chronic virus hepatitis B and C. Materials and methods. Under clinical observation there were 52 children in the age from 3 till 14 years. From them at 32 the chronic virus hepatitis B was confirmed, at 20 chronic virus - hepatitis C. Etiological diagnostics was carried out by definition of specific markers of a hepatitis B and C method IFA and PCR. Binding ability of serum albumin was defined by radiochemical method with use of the tritium labeled no-spa (drotaverine hydrochloride). The control group consists from 10 conditionally health children of similar age. Results and their discussion. The results of investigation have shown, that at a

Actinide uptake by transferrin and ferritin metalloproteins

International Nuclear Information System (INIS)

Den Auwer, C.; Llorens, I.; Moisy, Ph.; Vidaud, C.; Goudard, F.; Barbot, C.; Solari, P.L.; Funke, H.

2005-01-01

In order to better understand the mechanisms of actinide uptake by specific biomolecules, it is essential to explore the intramolecular interactions between the cation and the protein binding site. Although this has long been done for widely investigated transition metals, very few studies have been devoted to complexation mechanisms of actinides by active chelation sites of metalloproteins. In this field, X-ray absorption spectroscopy has been extensively used as a structural and electronic metal cation probe. The two examples that are presented here are related to two metalloproteins in charge of iron transport and storage in eukaryote cells: transferrin and ferritin. U(VI)O 2 2+ , Np(IV) and Pu(IV) have been selected because of their possible role as contaminant from the geosphere. (orig.)

A study of some aspects of auto immunity in children with thalassemia major

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El Adham, E.K

2008-01-01

This study is subjected to estimate the study of the most common autoimmune complications in thalassemia and the prevalence of different auto antibodies so as to evaluate its correlation with personal data including age, sex, growth parameters, Hepatitis C virus infection ferritin level and type of iron chelation therapy methodology : Different Abs including anti cardiolipin, antitistone, ANA, Anti erythropoietin by ELISA technique Hepatitis C virus by ELISA. Ferritin by IRMA (Immune radiometric assay), Protein C, S. Antithrombin III by ELISA result of the study were analyzed by appropriate statistical methods .The results showed that age of Hepatitis C virus negative cases was significantly lower than Hepatitis C virus Positive cases, ferritin levels were significantly higher in patients on defripone than those as desferrioxamine, anti erythropoietin was detected in 93.3% of cases regarding the antithrombotic factors deficiency. Protein C was deficient in 26.67% of cases. Protein S was deficient in 13.33% only and no cases showed anti thrombin III deficiency. No special relation was found between these abnormalities and type of chelation , Conclusions: Auto immunity may be a cofactor in the development of life threatening complication

The development of IRMA method of hepatocarcinoma ferritin and its preliminary clinical application

International Nuclear Information System (INIS)

Ying Jilin; Deng Jinglan; Lin Guocheng; Fu Chenghua; Liu Yanfang; Xu Liqing

1993-01-01

The double antibody sandwich IRMA method using human hepatocarcinoma ferritin (HF) and anti-HF monoclonal antibody has been established. The intra-assay or inter-assay CV value (%) is 4.1 ∼ 7.3 or 5.1 ∼ 10.9 respectively. The effective assay range of HF is 5 ∼ 640 μg/L. The mean value of recovery rate is 102.5%. The serum HF specimen were measured in 75 cases of normal persons and 230 cases of carcinoma patients. The results showed that the normal value of male or female was 14.3 +- 10.9 μg/L or 11.6 +- 7.0 μg/L, and there was no statistical difference. The serum HF levels in patients of hepatocarcinoma and pulmonary carcinoma were strikingly higher than normal (P<0.001), and also HF levels in patients of breast and pancreas cancer were apparently higher than normal (P<0.05). It has suggested that HF IRMA method has diagnostic significance in above related tumors

The development of IRMA method of hepatocarcinoma ferritin and its preliminary clinical application

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Jilin, Ying; Jinglan, Deng; Guocheng, Lin; Chenghua, Fu; Yanfang, Liu; Liqing, Xu [Fourth Military Medical Coll., Xi' an (China). First Affiliated Hospital

1993-08-01

The double antibody sandwich IRMA method using human hepatocarcinoma ferritin (HF) and anti-HF monoclonal antibody has been established. The intra-assay or inter-assay CV value (%) is 4.1 [approx] 7.3 or 5.1 [approx] 10.9 respectively. The effective assay range of HF is 5 [approx] 640 [mu]g/L. The mean value of recovery rate is 102.5%. The serum HF specimen were measured in 75 cases of normal persons and 230 cases of carcinoma patients. The results showed that the normal value of male or female was 14.3 +- 10.9 [mu]g/L or 11.6 +- 7.0 [mu]g/L, and there was no statistical difference. The serum HF levels in patients of hepatocarcinoma and pulmonary carcinoma were strikingly higher than normal (P<0.001), and also HF levels in patients of breast and pancreas cancer were apparently higher than normal (P<0.05). It has suggested that HF IRMA method has diagnostic significance in above related tumors.

[Epidemiologic aspects of human immunodeficiency virus and hepatitis virus infections].

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Diarra, M; Konate, A; Minta, D; Sounko, A; Dembele, M; Toure, C S; Kalle, A; Traore, H H; Maiga, M Y

2006-01-01

In order to determinate the prevalence of hepatitis B virus and hepatitis C virus among patients infected by the HIV, We realized a transverse survey case--control in hepato-gastro-enterological ward and serology unity of National Institute of Research in Public health (INRSP). Our sample was constituted with 100 patients HIV positive compared to 100 controls HIV negative. The viral markers research has been made by methods immuno-enzymatiqueses of ELISA 3rd generation. Tests permitted to get the following results: Hepatitis B surface antigen (HBs Ag) was positive among 21% with patients HIV positive versus 23% among control (p = 0,732); Antibody to hepatitis C virus (anti-HCV ab) was present among 23% with patients HIV positive versus 0% among control (p <0,05). Female was predominant among co-infections patient, but without statistic link (p = 0,9 and p = 0,45); The co-infection HBV- HCV was significatively linked to age beyond 40 years (p = 0,0005). Co-infections with HIV infection and hepatitis virus are not rare and deserve to be investigated.

Internalisation of hepatitis C virus core protein by human conjunctival fibroblasts.

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Rajalakshmy, A R; Malathi, J; Madhavan, H N; Bhaskar, S; Iyer, G K

2016-01-01

Recent studies indicate that hepatitis C virus (HCV) proteins can mediate innate immune response and inflammation in conjunctival fibroblasts which contributes to the pathology of dry eye condition associated with chronic HCV infection. The present study investigates the phagocytic potential of human conjunctival fibroblasts (HCFj) for HCV core protein. HCFj cells were incubated with HCV core antigen for different periods of time, and fluorescent micrographs were taken to observe protein internalisation. HCFj cells were capable of internalising HCV core antigen within 1 h; this gives an insight into another molecular mechanism which may contribute towards HCV-associated conjunctival inflammation.

Links between human LINE-1 retrotransposons and hepatitis virus-related hepatocellular carcinoma

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Honda, Tomoyuki

2016-05-01

Hepatocellular carcinoma (HCC) accounts for approximately 80% of liver cancers, the third most frequent cause of cancer mortality. The most prevalent risk factors for HCC are infections by hepatitis B or hepatitis C virus. Findings suggest that hepatitis virus-related HCC might be a cancer in which LINE-1 retrotransposons, often termed L1, activity plays a potential role. Firstly, hepatitis viruses can suppress host defense factors that also control L1 mobilization. Secondly, many recent studies also have indicated that hypomethylation of L1 affects the prognosis of HCC patients. Thirdly, endogenous L1 retrotransposition was demonstrated to activate oncogenic pathways in HCC. Fourthly, several L1 chimeric transcripts with host or viral genes are found in hepatitis virus-related HCC. Such lines of evidence suggest a linkage between L1 retrotransposons and hepatitis virus-related HCC. Here, I briefly summarize current understandings of the association between hepatitis virus-related HCC and L1. Then, I discuss potential mechanisms of how hepatitis viruses drive the development of HCC via L1 retrotransposons. An increased understanding of the contribution of L1 to hepatitis virus-related HCC may provide unique insights related to the development of novel therapeutics for this disease.

Predicting C282Y Homozygote Genotype for Hemochromatosis Using Serum Ferritin and Transferrin Saturation Values from 44,809 Participants of the HEIRS Study

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Andrew Lim

2014-01-01

Full Text Available INTRODUCTION: The simultaneous interpretation of serum ferritin level and transferrin saturation has been used as a clinical guide to diagnose genetic hemochromatosis. The Hemochromatosis and Iron Overload Screening (HEIRS Study screened 101,168 North American participants for serum ferritin level and transferrin saturation, and C282Y genotyping for the HFE gene.

Elevated serum ferritin and mercury concentrations are associated with hypertension; analysis of the fourth and fifth Korea national health and nutrition examination survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010).

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Choi, Beomhee; Yeum, Kyung-Jin; Park, Soo-Jung; Kim, Kyu-Nam; Joo, Nam-Seok

2015-01-01

The impact of simultaneously elevated serum ferritin and mercury concentrations on hypertension in the general population is not known. To determine the association of serum ferritin and mercury concentrations with hypertension, 6213 subjects (3060 men and 3153 women) over 20 years of age from 2008 to 2010 Korea National Health and Nutrition Examination Survey were divided into tertiles according to serum ferritin and mercury concentrations in each gender. Serum ferritin (258.2 vs. 94.8 pmol/L) and mercury concentrations (28.4 vs. 19.9 nmol/L) were higher in men than in women. Serum ferritin (men; P = 0.029, women; P mercury (men; P mercury concentrations in both men (r = 0.193, P mercury tertiles increased after proper adjustments. Furthermore, significantly higher odds ratios of hypertension were found in the second (OR = 1.86, 95% CI; 1.05-3.30), and third (OR = 1.84, 95% CI; 1.01-3.36) tertiles of serum ferritin with the top tertile of serum mercury in men. The current study indicate that serum ferritin and mercury concentrations are associated with the prevalence of hypertension and that simultaneously elevated serum ferritin and mercury concentrations are related to the risk for hypertension in men. © 2013 The Authors. The Environmental Toxicology published by Wiley Periodicals, Inc.

Discovery of a novel hepatovirus (Phopivirus of seals) related to human Hepatitis A Virus

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Anthony. S.J.,; St. Leger, J.A; Liang, E.; Hicks, A.L.; Sanchez-Leon, M.D; Ip, Hon S.; Jain, K.; Lefkowitch, J. H.; Navarrete-Macias, I.; Knowles, N.; Goldstein, T.; Pugliares, K.; Rowles, T.; Lipkin, W.I.

2015-01-01

Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV.

Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus.

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Shyamala, Venkatakrishna

2014-01-01

In the last few decades through an awareness of transfusion transmitted infections (TTI), a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV). However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP) and occult HBV infections (OBI). Effective mode of nucleic acid technology (NAT) testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID) format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus

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Venkatakrishna Shyamala

2014-01-01

Full Text Available In the last few decades through an awareness of transfusion transmitted infections (TTI, a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV, Hepatitis C virus (HCV, and Hepatitis B virus (HBV. However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP and occult HBV infections (OBI. Effective mode of nucleic acid technology (NAT testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

Relationship between serum ferritin levels and sarcopenia in Korean females aged 60 years and older using the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3), 2008-2009.

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Kim, Tae Ho; Hwang, Hee-Jin; Kim, Sang-Hwan

2014-01-01

It has been suggested that elevated serum ferritin is associated with several metabolic disorders. However, there is no reported study assessing any association between serum ferritin and sarcopenia despite the close relationship between sarcopenia and metabolic disorders. We investigated whether serum ferritin was associated with sarcopenia in older Koreans. We conducted a cross-sectional study based on data acquired in the second and third years (2008-9) of the fourth Korean National Health and Nutrition Examination Survey. In total, 952 men (mean age 69.0 years) and 1,380 women (mean age 69.3 years) aged 60 years and older completed a body composition study using dual energy X-ray absorptiometry. Serum ferritin levels were measured. Sarcopenia was defined as an appendicular skeletal mass as a percentage of body weight that was less than two standard deviations below the gender-specific mean for young adults. Serum ferritin levels were lower in women than in men. Women with sarcopenia showed a higher level of serum ferritin than women without sarcopenia (men: without sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL). The prevalence of sarcopenia increased as the tertile of serum ferritin increased. However, statistical significance was only seen in elderly women (1(st) tertile 6.3%, 2(nd) tertile 8.0%, 3(rd) tertile 12.0%; p = 0.008). Without adjustment, compared with those in the lowest tertile of serum ferritin level, participants in the highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26-3.23) for sarcopenia in women. After adjusting for known risk factors, the OR for sarcopenia was 1.74 (95% CI = 1.02-2.97) in women. There was no statistically significant association between sarcopenia and serum ferritin tertiles in men. Elevated serum ferritin levels were associated with an increased prevalence of sarcopenia in women but not in men from a representative sample

Time- and cell-type specific changes in iron, ferritin, and transferrin in the gerbil hippocampal CA1 region after transient forebrain ischemia

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Dae Young Yoo

2016-01-01

Full Text Available In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H, and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1-2 days and then increased once again within the CA1 region at 4-7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4-7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.

A consensus for occupational health management of healthcare workers infected with human immunodeficiency virus, hepatitis B virus, and / or hepatitis C virus.

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Ishimaru, Tomohiro; Wada, Koji; Smith, Derek R

2017-05-25

Occupational health management plays an important role in the prevention of provider-to-patient transmission in healthcare workers infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV). Therefore, the Japan Society for Occupational Health's Research Group on Occupational Health for Health Care Workers has proposed a consensus for the management of healthcare workers infected with HIV, HBV, and/or HCV based on recent evidence for each concerned group. The consensus recommends that: (1) employers in medical institutions should establish a policy of respecting the human rights of healthcare workers, management strategies for occupational blood exposure, and occupational health consultation; (2) occupational health staff should appropriately assess the risk of provider-to-patient transmission of HIV, HBV, and/or HCV infection and rearrange their tasks if necessary. When conducting risk assessment, occupational health staff should obtain informed consent and then cooperate with the physician in charge as well as infection control experts in the workplace; (3) healthcare workers infected with HIV, HBV, and/or HCV should disclose their employment to their treating physician and consult with their doctor regarding the need for special considerations at work; and (4) supervisors and colleagues in medical institutions should correctly understand the risks of HIV, HBV, and HCV infection and should not engage in any behavior that leads to discrimination against colleagues infected with HIV, HBV, and/or HCV.

Coordinated defects in hepatic long chain fatty acid metabolism and triglyceride accumulation contribute to insulin resistance in non-human primates.

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Subhash Kamath

Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by accumulation of triglycerides (TG in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant.To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR and lean insulin sensitive (IS baboons in relation with hepatic and peripheral insulin sensitivity.Twenty baboons with varying grades of adiposity were studied. Hepatic (liver and peripheral (mainly muscle insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance.Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA was greater than saturated (LC-SFA fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons.Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.

Seroprevalence of Hepatitis B surface antigen, antibodies to the Hepatitis C virus, and human immunodeficiency virus in a hospital-based population in Jaipur, Rajasthan

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Sood Smita

2010-01-01

Full Text Available Background: Hepatitis B, hepatitis C, and HIV infections are a serious global and public health problem. To assess the magnitude and dynamics of disease transmission and for its prevention and control, the study of its seroprevalence is important. A private hospital catering to the needs of a large population represents an important center for serological surveys. Available data, at Rajasthan state level, on the seroprevalence of these bloodborne pathogens is also very limited. Objective: A study was undertaken to estimate the seroprevalence of hepatitis B surface antigen (HBsAg and antibodies to hepatitis C (anti-HCV Ab and human immunodeficiency virus (anti-HIV Ab in both the sexes and different age groups in a hospital-based population in Jaipur, Rajasthan. Materials and Methods: Serum samples collected over a period of 14 months from patients attending OPDs and admitted to various IPDs of Fortis Escorts Hospital, Jaipur, were subjected within the hospital-based lab for the detection of HBsAg and anti-HCV Ab and anti-HIV Ab using rapid card tests. This was followed by further confirmation of all reactive samples by a microparticle enzyme immunoassay (Abbott AxSYM at Super Religare Laboratories (formerly SRL Ranbaxy Reference Lab, Mumbai. Results: The seroprevalence of HBsAg was found to be 0.87%, of anti-HCV Ab as 0.28%, and of anti-HIV Ab as 0.35%. Conclusion: The study throws light on the magnitude of viral transmission in the community in the state of Rajasthan and provides a reference for future studies.

Hepatitis B virus, hepatitis C virus and human immunodeficiency virus infection in undocumented migrants and refugees in southern Italy, January 2012 to June 2013.

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Coppola, Nicola; Alessio, Loredana; Gualdieri, Luciano; Pisaturo, Mariantonietta; Sagnelli, Caterina; Caprio, Nunzio; Maffei, Rita; Starace, Mario; Angelillo, Italo Francesco; Pasquale, Giuseppe; Sagnelli, Evangelista

2015-01-01

Screening of undocumented migrants or refugees for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections has been offered free of charge and free from bureaucratic procedures since 2012 at four primary-level clinical centres in Naples and Caserta, Italy. Of 926 undocumented migrants and refugees visiting one of the primary-level clinical centres from January 2012 to June 2013, 882 (95%) were screened for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (anti-HBc) and antibodies against HCV and HIV. Of the 882 individuals enrolled, 78 (9%) were HBsAg positive, 35 (4%) anti-HCV positive and 11 (1%) anti-HIV positive (single infections); seven (1%) had more than one infection (three were HBsAg positive). Of the 801 HBsAg-negative patients, 373 (47%) were anti-HBc positive. The HBsAg-positivity rate was high (14%; 62/444) in individuals from sub-Saharan Africa and intermediate in those from eastern Europe (6%; 12/198), northern Africa (2%; 2/80) and Bangladesh, India, Pakistan and Sri Lanka (the 'India-Pakistan area') (3%; 4/126). Anti-HCV was detected in 9/126 (7%) individuals originating from the India-Pakistan area, in 12/198 (6%) from eastern Europe, in 17/444 (4%) from sub-Saharan and in 2/80 (2%) from northern Africa. The HBV, HCV and HIV infections in the undocumented migrants and refugees screened serve as a reminder to the Italian healthcare authorities to carry out extensive screening and educational programmes for these populations.

Prevalence of and risk factors for hepatic steatosis and nonalcoholic Fatty liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

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Williamson, Rachel M; Price, Jackie F; Glancy, Stephen; Perry, Elisa; Nee, Lisa D; Hayes, Peter C; Frier, Brian M; Van Look, Liesbeth A F; Johnston, Geoffrey I; Reynolds, Rebecca M; Strachan, Mark W J

2011-05-01

Type 2 diabetes is an established risk factor for development of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and clinical correlates of these conditions in a large cohort of people with type 2 diabetes. A total of 939 participants, aged 61-76 years, from the Edinburgh Type 2 Diabetes Study (ET2DS)-a large, randomly selected population of people with type 2 diabetes-underwent liver ultrasonography. Ultrasound gradings of steatosis were compared with magnetic resonance spectroscopy in a subgroup. NAFLD was defined as hepatic steatosis in the absence of a secondary cause (screened by questionnaire assessing alcohol and hepatotoxic medication use, plasma hepatitis serology, autoantibodies and ferritin, and record linkage to determine prior diagnoses of liver disease). Binary logistic regression was used to analyze independent associations of characteristics with NAFLD. Hepatic steatosis was present in 56.9% of participants. After excluding those with a secondary cause for steatosis, the prevalence of NAFLD in the study population was 42.6%. Independent predictors of NAFLD were BMI, lesser duration of diabetes, HbA(1c), triglycerides, and metformin use. These remained unchanged after exclusion of participants with evidence of hepatic fibrosis from the group with no hepatic steatosis. Prevalences of hepatic steatosis and NAFLD were high in this unselected population of older people with type 2 diabetes, but lower than in studies in which ultrasound gradings were not compared with a gold standard. Associations with features of the metabolic syndrome could be used to target screening for this condition.

Isolation and partial characterization of two porcine spleen ferritin fractions with different electrophoretic mobility

NARCIS (Netherlands)

C.M. Van Gelder (Carin); M.I.E. Huijskes-Heins (M. I E); D. Klepper (D.); W.L. van Noort (W.); M.I. Cleton-Soeteman (Maud); H.G. van Eijk (Henk)

1996-01-01

textabstractFerritin isolated from porcine spleen could routinely be separated in two fractions on nondenaturating gradient gels. Both fractions could be isolated with a purity of 96% when applied to two serially linked columns, each 200 cm in length, packed respectively with Sepharose 4B and

An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

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Martha J Harding

2010-04-01

Full Text Available Widely accessible small animal models suitable for the study of hepatitis C virus (HCV in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice.We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH within a vascularized rat collagen type I/human fibronectin (rCI/hFN gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC in severe combined immunodeficient X beige (SCID/bg mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7 mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM components and/or hepatocyte growth factor (HGF-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM analyses of gel tissue.The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

Studies on the propagation in cell culture and the infectivity for baboons of human hepatitis A virus

International Nuclear Information System (INIS)

Taylor, M.B.

1985-05-01

Current aspects of hepatitis A and hepatitis A virus (HAV) research and the techniques used for the propagation and monitoring of HAV and HAV antigen (HA Ag) production in vitro and HAV infection in vivo, and its sequelae are reviewed. Radioimmunoassay, immunofluorescence and electron microscopic techniques for the demonstration of HA Ag were adapted for this investigation. The cell-adapted strain of HAV(MBB) was successfully propagated in the human hepatoma cell line PLC/PRF/5 at 32 degrees Celsius. A crystalline structure was demonstrated in the cytoplasm of HAV-infected cells by thin-section electron microscopy. The origin and significance of this structure is uncertain. A possible temperature variant of HAV (strain MBB) or an HAV-related baboon virus was detected in PLC/PRF/5 cells maintained at 37 degrees Celsius after infection with a faecal extract prepared from baboons which had been infected with the cell-cultured HAV. Baboons, both free-ranging and in captivity, were found to have antibodies to HAV, which suggests susceptibility to human HAV or another cross-reacting virus. The experimental infection of the Cape baboon orally, intravenously or by both routes with HAV were investigated. The results of the study suggest reasons for the presence of anti-HAV antibodies in certain baboon populations and show that the baboon is not an ideal model for hepatitis A investigations

Studies on the propagation in cell culture and the infectivity for baboons of human hepatitis A virus

Energy Technology Data Exchange (ETDEWEB)

Taylor, M B

1985-01-01

Current aspects of hepatitis A and hepatitis A virus (HAV) research and the techniques used for the propagation and monitoring of HAV and HAV antigen (HA Ag) production in vitro and HAV infection in vivo, and its sequelae are reviewed. Radioimmunoassay, immunofluorescence and electron microscopic techniques for the demonstration of HA Ag were adapted for this investigation. The cell-adapted strain of HAV(MBB) was successfully propagated in the human hepatoma cell line PLC/PRF/5 at 32 degrees Celsius. A crystalline structure was demonstrated in the cytoplasm of HAV-infected cells by thin-section electron microscopy. The origin and significance of this structure is uncertain. A possible temperature variant of HAV (strain MBB) or an HAV-related baboon virus was detected in PLC/PRF/5 cells maintained at 37 degrees Celsius after infection with a faecal extract prepared from baboons which had been infected with the cell-cultured HAV. Baboons, both free-ranging and in captivity, were found to have antibodies to HAV, which suggests susceptibility to human HAV or another cross-reacting virus. The experimental infection of the Cape baboon orally, intravenously or by both routes with HAV were investigated. The results of the study suggest reasons for the presence of anti-HAV antibodies in certain baboon populations and show that the baboon is not an ideal model for hepatitis A investigations.

Diagnostic relevance of radioiron-absorption-measurements and immunoradiometric serum-ferritin-assay in the evaluation of iron stores

International Nuclear Information System (INIS)

Heinrich, H.C.

1978-01-01

Negative iron balance and enhanced iron demand respectively causes deficient iron stores (prelatent iron deficiency) with increased iron absorption, later on decrease of serum iron and increase of transferrin (latent Fe deficiency) and at least iron deficient anemia (manifest iron deficiency). In prelatend iron deficiency diagnostic 59 Fe 2+ absorption is increased and the RES cells do not show storage iron cytochemically. In latent iron deficiency in addition serum iron, transferrin iron saturation and serum ferritin is decreased and hypochromic mikrocytic anemia completes the signs of manifest iron deficiency. Besides rare cases of primary hemochromatosis and marked hyperdasia of ineffective erythropoiesis in homocygotic beta-thalassemia, hereditary non-spherocytic hemolytic anemia caused by pyruvate kinase deficiency and some sideroblastic anemias increased 59 Fe 2+ absorption is a reliable measure of exhausted iron stores. In these exceptional cases differential diagnosis between sideroachrestic and siderosensitive iron deficiency anemia can be made by measurement of serum iron and serum ferritin respectively. The etiology of iron deficiency is to be cleared by measurement of 59 Fe absorption from 59 Fe 2+ and 59 Fe-marked meat with consecutive estimation of whole body 59 Fe elimination. Shortly after completion or during oral iron therapy serum ferritin concentration is not suitable to evaluate the content of iron stores. (orig.) [de

Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions.

Science.gov (United States)

Kotler, Donald P

2009-03-01

Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

Clinical assessment of hepatic functional reserve using 99mTc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases. Validation of the use of SPECT and a new indicator

International Nuclear Information System (INIS)

Onodera, Yuya; Tamaki, Nagara; Miyasaka, Kazuo; Takahashi, Kazuei; Sugai, Yukio; Togashi, Tadashi

2003-01-01

It is generally known that scintigraphy of 99m Tc diethylenetriamine pentaacetic acid-galactosyl human serum albumin ( 99m Tc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of 99m Tc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases. A liver phantom (a 50% concentration of 99m Tc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of 99m Tc-GSA was divided by a syringe SPECT of 99m Tc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method. 99m Tc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects. The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r=0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mild

Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam.

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Van Nguyen, Dung; Van Nguyen, Cuong; Bonsall, David; Ngo, Tue Tri; Carrique-Mas, Juan; Pham, Anh Hong; Bryant, Juliet E; Thwaites, Guy; Baker, Stephen; Woolhouse, Mark; Simmonds, Peter

2018-02-28

Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus , while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.

Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system.

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Choi, Young-Jun; Kim, Hyemin; Kim, Ji-Woo; Yoon, Seokjoo; Park, Han-Jin

2018-05-01

The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism. Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (p formation, were increased in HLCs cultured in the 3D system. In particular, 3D spheroidal culture increased expression of CES1 and BCHE, which encode hepatic esterases (p 3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.

Nonhuman Primate Models of Hepatitis A Virus and Hepatitis E Virus Infections.

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Lanford, Robert E; Walker, Christopher M; Lemon, Stanley M

2018-04-23

Although phylogenetically unrelated, human hepatitis viruses share an exclusive or near exclusive tropism for replication in differentiated hepatocytes. This narrow tissue tropism may contribute to the restriction of the host ranges of these viruses to relatively few host species, mostly nonhuman primates. Nonhuman primate models thus figure prominently in our current understanding of the replication and pathogenesis of these viruses, including the enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV), and have also played major roles in vaccine development. This review draws comparisons of HAV and HEV infection from studies conducted in nonhuman primates, and describes how such studies have contributed to our current understanding of the biology of these viruses. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Relationship between serum ferritin levels and sarcopenia in Korean females aged 60 years and older using the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009.

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Tae Ho Kim

Full Text Available CONTEXT: It has been suggested that elevated serum ferritin is associated with several metabolic disorders. However, there is no reported study assessing any association between serum ferritin and sarcopenia despite the close relationship between sarcopenia and metabolic disorders. OBJECTIVE: We investigated whether serum ferritin was associated with sarcopenia in older Koreans. DESIGN AND SETTING: We conducted a cross-sectional study based on data acquired in the second and third years (2008-9 of the fourth Korean National Health and Nutrition Examination Survey. PARTICIPANTS: In total, 952 men (mean age 69.0 years and 1,380 women (mean age 69.3 years aged 60 years and older completed a body composition study using dual energy X-ray absorptiometry. MEASUREMENTS: Serum ferritin levels were measured. Sarcopenia was defined as an appendicular skeletal mass as a percentage of body weight that was less than two standard deviations below the gender-specific mean for young adults. RESULTS: Serum ferritin levels were lower in women than in men. Women with sarcopenia showed a higher level of serum ferritin than women without sarcopenia (men: without sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL. The prevalence of sarcopenia increased as the tertile of serum ferritin increased. However, statistical significance was only seen in elderly women (1(st tertile 6.3%, 2(nd tertile 8.0%, 3(rd tertile 12.0%; p = 0.008. Without adjustment, compared with those in the lowest tertile of serum ferritin level, participants in the highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26-3.23 for sarcopenia in women. After adjusting for known risk factors, the OR for sarcopenia was 1.74 (95% CI = 1.02-2.97 in women. There was no statistically significant association between sarcopenia and serum ferritin tertiles in men. CONCLUSIONS: Elevated serum ferritin levels were

Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles.

Science.gov (United States)

Lee, Jong-Hwan; Seo, Hyuk Seong; Kwon, Jung-Hyuk; Kim, Hee-Tae; Kwon, Koo Chul; Sim, Sang Jun; Cha, Young Joo; Lee, Jeewon

2015-07-15

Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90%. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100% sensitivity and 100% specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

An evaluation of the Ramco kit for serum ferritin assay

International Nuclear Information System (INIS)

Dempster, W.S.; Knight, G.J.; Jacobs, P.

1979-01-01

The determination of serum ferritin levels may be of diagnostic importance in medicine. To establish whether values obtained using a commercially available kit (Ramco) were adequate for this purpose, a comparison was undertaken using a two-site immunoradiometric assay that had been developed and standardized in our laboratories. Over the range 6μg/l to greater than 2 000 μg/l there was a correlation coefficient between the two methods of 0,8284 (P smaller than 0,001). It is concluded that the Ramco kit is suitable for use in clinical practice

[Current status of vitamin A deficiency in preschool children in Dongguan, China and the effect of vitamin A on serum ferritin and red blood cell parameters].

Science.gov (United States)

Zhang, Zhen-Hong; Ni, Ming; Hu, Yuan

2018-03-01

To investigate the current status of vitamin A deficiency in preschool children in Dongguan, China, as well as the effect of vitamin A on serum ferritin, red blood cell, and reticulocyte parameters. Cluster sampling was performed from April 2015 to December 2016 to select 2 085 preschool children (3-6 years old) without any disease in Dongguan. Routine blood test, reticulocyte count, serum ferritin measurement, hemoglobin electrophoresis, and vitamin A measurement were performed for all children. The associations of age and sex with vitamin A and serum ferritin concentrations were analyzed. The effect of vitamin A concentration on serum ferritin, red blood cell, and reticulocyte parameters and the effect of reduced iron storage caused by vitamin A deficiency on red blood cell parameters were evaluated. Of the 2 085 children, 140 (6.71%) had reduced iron storage, and 678 (32.52%) had vitamin A deficiency. Among the 678 children with vitamin A deficiency, 647 (95.4%) had subclinical deficiency and 31 (4.6%) had clinical deficiency. There was no significant difference in vitamin A concentration between boys and girls, however girls had a significantly higher serum ferritin concentration than boys (P<0.05). The clinical vitamin A deficiency group had a significantly higher serum ferritin concentration than the subclinical vitamin A deficiency group and the normal group (P<0.05). In cases of vitamin A deficiency, the reduced iron storage group had significant reductions in mean corpuscular volume and mean corpuscular hemoglobin than the normal iron storage group (P<0.05). Compared with the normal vitamin A group, the vitamin A deficiency group had significantly lower hemoglobin concentration, mean corpuscular hemoglobin, red blood cell count, hematocrit, absolute reticulocyte count, reticulocyte percentage, and reticulocyte hemoglobin content, as well as a significantly higher mean corpuscular volume (P<0.05). Vitamin A deficiency is prevalent in preschool children

Recent advances in Hepatitis E virus.

Science.gov (United States)

Meng, X J

2010-03-01

Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the family Hepeviridae. At least four major genotypes of HEV have been recognized: genotypes 1 and 2 are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans and several other animals in both developing and industrialized countries. Besides humans, strains of HEV have been genetically identified from swine, chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and ORF3 proteins are translated from a single bicistronic mRNA and overlap each other but neither overlaps ORF1. The recent determination of the 3D crystal structure of the HEV capsid protein should facilitate the development of vaccines and antivirals. The identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by swine HEV raise public health concerns for zoonosis. Accumulating evidence indicated that hepatitis E is a zoonotic disease and pigs and more likely other animal species are reservoirs for HEV. This article provides an overview of the recent advances in hepatitis E and its causative agent, including nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal models.

Serum iron, ferritin, transferrin and haptoglobin concentration variations during repeated show jumping competition in horse

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Anna Assenza

2016-01-01

Full Text Available Modifications of the iron profile in athlete horses during two international three star (*** show jumping competitions performed in two consecutive weekends were evaluated. Serum iron, ferritin, transferrin, and haptoglobin were assessed in 12 well-trained Italian Saddle horses. Blood samplings were performed before the first day of competition (R1, within 10 min from the end of each competition (J1, J2 and on the day after competition (R2. The same plan was followed during the second weekend (J3, J4 and R3. One-way repeated measures analysis of variance (ANOVA was applied on obtained data, and a significant effect of exercise (P < 0.05 on all studied indices was found. These results suggest that serum iron, transferrin, ferritin and haptoglobin are responsive to intense exercise and could be considered important indicators that may give important information about the horse’s performance.

Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate

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Keitaro Yokoyama

2017-05-01

Discussion: It is suggested that not only iron load but also the erythropoiesis-stimulating agent dose reduction may be involved in ferritin elevation during ferric citrate hydrate treatment, resulting in a decrease of erythropoietin resistance index.

An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential.

Directory of Open Access Journals (Sweden)

Ayaka Yanagida

Full Text Available Hepatoblasts, hepatic stem/progenitor cells in liver development, have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In regenerative medicine and drug screening for the treatment of severe liver diseases, human induced pluripotent stem (iPS cell-derived mature functional hepatocytes are considered to be a potentially good cell source. However, induction of proliferation of these cells is difficult ex vivo. To circumvent this problem, we generated hepatic progenitor-like cells from human iPS cells using serial cytokine treatments in vitro. Highly proliferative hepatic progenitor-like cells were purified by fluorescence-activated cell sorting using antibodies against CD13 and CD133 that are known cell surface markers of hepatic stem/progenitor cells in fetal and adult mouse livers. When the purified CD13(highCD133(+ cells were cultured at a low density with feeder cells in the presence of suitable growth factors and signaling inhibitors (ALK inhibitor A-83-01 and ROCK inhibitor Y-27632, individual cells gave rise to relatively large colonies. These colonies consisted of two types of cells expressing hepatocytic marker genes (hepatocyte nuclear factor 4α and α-fetoprotein and a cholangiocytic marker gene (cytokeratin 7, and continued to proliferate over long periods of time. In a spheroid formation assay, these cells were found to express genes required for mature liver function, such as cytochrome P450 enzymes, and secrete albumin. When these cells were cultured in a suitable extracellular matrix gel, they eventually formed a cholangiocytic cyst-like structure with epithelial polarity, suggesting that human iPS cell-derived hepatic progenitor-like cells have a bipotent differentiation ability. Collectively these data indicate that this novel procedure using an in vitro expansion system is useful for not only liver regeneration but also for the determination of molecular mechanisms that

Molecular characterization of the iron binding protein ferritin in Eisenia andrei earthworms

Czech Academy of Sciences Publication Activity Database

Procházková, Petra; Dvořák, Jiří; Šilerová, Marcela; Roubalová, Radka; Škanta, František; Halada, Petr; Bilej, Martin

2011-01-01

Roč. 485, č. 2 (2011), s. 73-80 ISSN 0378-1119 R&D Projects: GA ČR GA206/07/0378; GA ČR GD310/08/H077; GA AV ČR IAA600200704; GA MŠk 2B06155; GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50200510 Keywords : Earthworms * Invertebrates * Ferritin Subject RIV: EC - Immunology Impact factor: 2.341, year: 2011

Dual Infection with Hepatitis B and Epstein-Barr Virus Presenting with Severe Jaundice, Coagulopathy, and Hepatitis B Virus Chronicity Outcome

OpenAIRE

Rao, Sirish C.; Ashraf, Imran; Mir, Fazia; Samiullah, Sami; Ibdah, Jamal A.; Tahan, Veysel

2017-01-01

Patient: Female, 34 Final Diagnosis: HBV and EBV dual infection Symptoms: Jaundice ? fatigue ? anorexia ? subjective weight loss Medication: ? Clinical Procedure: ? Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Hepatitis B virus (HBV) has been reported as a coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Case Report: A 34-year-old female presented to ...

Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.

Science.gov (United States)

Kim, Chai-Wan; Addy, Carol; Kusunoki, Jun; Anderson, Norma N; Deja, Stanislaw; Fu, Xiaorong; Burgess, Shawn C; Li, Cai; Ruddy, Marcie; Chakravarthy, Manu; Previs, Steve; Milstein, Stuart; Fitzgerald, Kevin; Kelley, David E; Horton, Jay D

2017-08-01

Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074 increased plasma triglycerides by 200%. To further investigate, mice that lack ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation of SREBP-1c and increased VLDL secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin D and ferritin correlation with chronic neck pain using standard statistics and a novel artificial neural network prediction model.

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Eloqayli, Haytham; Al-Yousef, Ali; Jaradat, Raid

2018-02-15

Despite the high prevalence of chronic neck pain, there is limited consensus about the primary etiology, risk factors, diagnostic criteria and therapeutic outcome. Here, we aimed to determine if Ferritin and Vitamin D are modifiable risk factors with chronic neck pain using slandered statistics and artificial intelligence neural network (ANN). Fifty-four patients with chronic neck pain treated between February 2016 and August 2016 in King Abdullah University Hospital and 54 patients age matched controls undergoing outpatient or minor procedures were enrolled. Patients and control demographic parameters, height, weight and single measurement of serum vitamin D, Vitamin B12, ferritin, calcium, phosphorus, zinc were obtained. An ANN prediction model was developed. The statistical analysis reveals that patients with chronic neck pain have significantly lower serum Vitamin D and Ferritin (p-value artificial neural network can be of future benefit in classification and prediction models for chronic neck pain. We hope this initial work will encourage a future larger cohort study addressing vitamin D and iron correction as modifiable factors and the application of artificial intelligence models in clinical practice.

Relationship between Serum Ferritin Levels and Sarcopenia in Korean Females Aged 60 Years and Older Using the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3), 2008–2009

Science.gov (United States)

Kim, Tae Ho; Hwang, Hee-Jin; Kim, Sang-Hwan

2014-01-01

Context It has been suggested that elevated serum ferritin is associated with several metabolic disorders. However, there is no reported study assessing any association between serum ferritin and sarcopenia despite the close relationship between sarcopenia and metabolic disorders. Objective We investigated whether serum ferritin was associated with sarcopenia in older Koreans. Design and Setting We conducted a cross-sectional study based on data acquired in the second and third years (2008–9) of the fourth Korean National Health and Nutrition Examination Survey. Participants In total, 952 men (mean age 69.0 years) and 1,380 women (mean age 69.3 years) aged 60 years and older completed a body composition study using dual energy X-ray absorptiometry. Measurements Serum ferritin levels were measured. Sarcopenia was defined as an appendicular skeletal mass as a percentage of body weight that was less than two standard deviations below the gender-specific mean for young adults. Results Serum ferritin levels were lower in women than in men. Women with sarcopenia showed a higher level of serum ferritin than women without sarcopenia (men: without sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL). The prevalence of sarcopenia increased as the tertile of serum ferritin increased. However, statistical significance was only seen in elderly women (1st tertile 6.3%, 2nd tertile 8.0%, 3rd tertile 12.0%; p = 0.008). Without adjustment, compared with those in the lowest tertile of serum ferritin level, participants in the highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26–3.23) for sarcopenia in women. After adjusting for known risk factors, the OR for sarcopenia was 1.74 (95% CI = 1.02–2.97) in women. There was no statistically significant association between sarcopenia and serum ferritin tertiles in men. Conclusions Elevated serum ferritin levels were associated

Serum-ferritin and iron absorption for the study of body iron stored in the Thai population

International Nuclear Information System (INIS)

Plehachinda, R.

1984-05-01

Measurements of serum ferritin by an ''in-house'' immunoradiometric assay (IRMA) method were used in conjunction with estimations of gastro-intestinal iron absorption from a standard test dose of ferrous ascorbate, measurements of blood haemoglobin and measurements of other haematological parameters to study body iron status in various population groups and to assess changes in body iron status after food-iron fortification. The IRMA method particularly covered the lower range of serum ferritin levels from 0.5 to 10 μg/litre, corresponding to iron deficiency. Quality control indicated satisfactory assay performance. In preliminary studies, serum ferritin level was found to be well correlated with gastro-intestinal iron absorption as an indicator of body iron status. Normal adult male subjects in Bangkok showed levels of 21-314 μg/litre and normal adult female levels of 13-173 μg/litre, in general agreement with values reported by other authors. Measurements were then extended to subjects in an area of north-eastern Thailand where iron-deficiency was common, to assess the effectiveness of food-iron fortification programmes. Measurements were also made on male blood donors in Bangkok, pregnant female subjects in Bangkok and north-eastern Thailand, school children in an area of southern Thailand where hookworm infestation was common and schoolchildren and adult female subjects in an area of northern Thailand where goitre was endemic. The results of all these studies are presented

The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins.

Science.gov (United States)

Szurowska, Edyta; Sikorska, Katarzyna; Izycka-Swieszewska, E; Nowicki, Tomasz; Romanowski, Tomasz; Bielawski, Krzysztof P; Studniarek, Michał

2010-01-27

There are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing. MRI shows changes of liver intensity in patients with hepatic iron overload. Changes in MR signal are an indirect consequence of change of relaxation times T2 and T2*, that can be directly measured. The purpose of the study was to evaluate usefulness of MR imaging in the detection of hepatic iron overload in patients with cirrhosis of different origins. MR imaging at 1.5T was prospectively performed in 44 patients with liver cirrhosis who had undergone liver biopsy with histopathological assessment of hepatic iron deposits. In all patients the following sequences were used: SE, Express, GRE in T2 and T1-weighted images. Signal intensity (SI) was measured on images obtained with each T2 weighted sequence by means of regions of interest, placed in the liver and paraspinal muscles. The correlation between iron overload, histopathological score, serum ferritin and SI ratio was analyzed. In 20 patients with iron overload confirmed by the biopsy, the liver parenchyma demonstrated lower signal intensity than that of paraspinal muscles. This effect was visible only in 8 patients with hepatic iron overload in Express T2-weighted images. Higher signal intensity of liver than that of skeletal muscles on GRE - T2 weighted images was noted in 24 patients with cirrhosis and without elevated hepatic iron concentration. We observed a correlation between low and high iron concentration and liver to muscle SI ratio. MR imaging is a useful and fast noninvasive diagnostic tool for the detection of liver iron overload in patients with cirrhosis of different origins.Liver to muscle SI ratio in GRE-T2-weighted sequence facilitates to differentiate patients with low and high degree of hepatic iron overload, which correlates

Hepatitis B virus evasion from cGAS sensing in human hepatocytes.

Science.gov (United States)

Verrier, Eloi R; Yim, Seung-Ae; Heydmann, Laura; El Saghire, Houssein; Bach, Charlotte; Turon-Lagot, Vincent; Mailly, Laurent; Durand, Sarah C; Lucifora, Julie; Durantel, David; Pessaux, Patrick; Manel, Nicolas; Hirsch, Ivan; Zeisel, Mirjam B; Pochet, Nathalie; Schuster, Catherine; Baumert, Thomas F

2018-04-20

Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic GMP-AMP synthase (cGAS) was identified as a DNA sensor. In this study, we aimed to investigate the functional role of cGAS in sensing of HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss- and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes and HBV-infected human liver chimeric mice. Here we show that cGAS is expressed in the human liver, primary human hepatocytes and human liver chimeric mice. While naked relaxed-circular HBV DNA is sensed in a cGAS-dependent manner in hepatoma cell lines and primary human hepatocytes, host cell recognition of viral nucleic acids is abolished during HBV infection, suggesting escape from sensing, likely during packaging of the genome into the viral capsid. While the hepatocyte cGAS pathway is functionally active, as shown by reduction of viral cccDNA levels in gain-of-function studies, HBV infection suppressed cGAS expression and function in cell culture models and humanized mice. HBV exploits multiple strategies to evade sensing and antiviral activity of cGAS and its effector pathways. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

International Nuclear Information System (INIS)

Thalheimer, Andreas; Waaga-Gasser, Ana M; Otto, Christoph; Bueter, Marco; Illert, Bertram; Gattenlohner, Stefan; Gasser, Martin; Meyer, Detlef; Fein, Martin; Germer, Christoph T

2009-01-01

The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. We injected immunoincompetent nude mice intraportally with different numbers (1 × 10 5 , 1 × 10 6 and 5 × 10 6 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Only the injection of 1 × 10 6 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 10 6 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD

Enhanced iron and zinc accumulation in genetically engineered pineapple plants using soybean ferritin gene.

Science.gov (United States)

Mhatre, Minal; Srinivas, Lingam; Ganapathi, Thumballi R

2011-12-01

Pineapple (Ananas comosus L. Merr., cv. "Queen") leaf bases were transformed with Agrobacterium tumefaciens strain EHA 105 harboring the pSF and pEFESF plasmids with soybean ferritin cDNA. Four to eight percent of the co-cultivated leaf bases produced multiple shoots 6 weeks after transfer to Murashige and Skoog's medium supplemented with α-naphthalene acetic acid 1.8 mg/l, indole-3-butyric acid 2.0 mg/l, kinetin 2.0 mg/l, cefotaxime 400 mg/l, and kanamycin 50 mg/l. Putatively transformed shoots (1-2 cm) were selected and multiplied on medium of the same composition and elongated shoots (5 cm) were rooted on liquid rooting medium supplemented with cefotaxime 400 mg/l and kanamycin 100 mg/l. The rooted plants were analyzed through PCR, genomic Southern analysis, and reverse transcription PCR. The results clearly confirmed the integration and expression of soybean ferritin gene in the transformed plants. Atomic absorption spectroscopic analysis carried out with six independently transformed lines of pSF and pEFE-SF revealed a maximum of 5.03-fold increase in iron and 2.44-fold increase in zinc accumulation in the leaves of pSF-transformed plants. In pEFE-SF-transformed plants, a 3.65-fold increase in iron and 2.05-fold increase in zinc levels was observed. Few of the transgenic plants were hardened in the greenhouse and are being grown to maturity to determine the enhanced iron and zinc accumulation in the fruits. To the best of our knowledge this is the first report on the transformation of pineapple with soybean ferritin for enhanced accumulation of iron and zinc content in the transgenic plants.

Epidemiology of hepatitis B and hepatitis C in Lebanon.

Science.gov (United States)

Abou Rached, Antoine; Abou Kheir, Selim; Saba, Jowana; Ammar, Walid

2016-03-01

Hepatitis B and C are two potentially life threatening liver infections. Lebanon is ranked as a zone of moderate endemicity. This study aimed to determine the prevalence of hepatitis B and C in Lebanon and their distribution according to age, region and sex. This national prospective cross-sectional study was conducted from January 2011 till December 2012 in the six Lebanese Governorates in collaboration with municipalities, the Ministry of Public Health, Health Centres and dispensaries. An upcoming screening for hepatitis B and C was announced? in different districts of each Governorate. All individuals presenting to local laboratory, not known to have chronic hepatitis, were asked for a blood sample and answered a questionnaire addressing sex, age, place of birth and residence. Screening tests were "Abbots" for hepatitis B and "Human Hexagon" for hepatitis C. PCR testing was used to confirm the positivity of the previous tests. Of 31147 individuals screened, 542 had a rapid test positive for HBV (prevalence 1.74%, 95% CI 1.6-1.89) with a male to female ratio of 1.08. This prevalence was higher in the South and Nabatieh (1.9%) compared to Beirut (0.73%). Of 31,147 individuals screened, 64 had a rapid test positive for HCV (prevalence 0.21%, 95% CI 0.16-0.27) with a male to female ratio of 0.85. This prevalence was higher in Nabatieh (0.61%) compared to Mount Lebanon (0.08%). The prevalence of HBV and HCV in Lebanon is 1.74% and 0.21%, respectively with a higher prevalence in South and Nabatieh districts. These data rank Lebanon amongst countries with low endemicity for both viruses. Decrease in the prevalence of HBV is due to awareness campaign as well as success of the MOPH National Hepatitis Program in vaccinating all new born since 1998 and in screening and vaccinating high risk groups. Copyright © 2016 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Making the invisible visible: searching for human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2 in Brazilian patients with viral hepatitis B and C

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Adele Caterino-de-Araujo

Full Text Available With this study, the authors hope to alert clinicians regarding the presence of human T-cell lymphotropic virus type 1 and 2 (HTLV-1/-2 infections in patients with viral hepatitis B and C in Brazil. HTLV-1/-2 were detected in 1.3% of hepatitis B virus (HBV- and 5.3% of hepatitis C virus (HCV-infected blood samples sent for laboratory viral load measurements. A partial association of human immunodeficiency virus (HIV-1 and HTLV-1/-2 infection was detected in patients with HCV (HIV+, 27.3%, whereas this association was almost 100% in HBV-infected patients (HIV+, all except one. The high prevalence of HTLV-1/-2 infection among patients with hepatitis C was of concern, as HTLV-1/-2 could change the natural course of subsequent liver disease. The authors suggest including HTLV-1/-2 serology in the battery of tests used when following patients with viral hepatitis in Brazil, regardless of the HIV status.

Making the invisible visible: searching for human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in Brazilian patients with viral hepatitis B and C.

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Caterino-de-Araujo, Adele; Alves, Fabiana Aparecida; Campos, Karoline Rodrigues; Lemos, Marcílio Figueiredo; Moreira, Regina Célia

2018-02-01

With this study, the authors hope to alert clinicians regarding the presence of human T-cell lymphotropic virus type 1 and 2 (HTLV-1/-2) infections in patients with viral hepatitis B and C in Brazil. HTLV-1/-2 were detected in 1.3% of hepatitis B virus (HBV)- and 5.3% of hepatitis C virus (HCV)-infected blood samples sent for laboratory viral load measurements. A partial association of human immunodeficiency virus (HIV)-1 and HTLV-1/-2 infection was detected in patients with HCV (HIV+, 27.3%), whereas this association was almost 100% in HBV-infected patients (HIV+, all except one). The high prevalence of HTLV-1/-2 infection among patients with hepatitis C was of concern, as HTLV-1/-2 could change the natural course of subsequent liver disease. The authors suggest including HTLV-1/-2 serology in the battery of tests used when following patients with viral hepatitis in Brazil, regardless of the HIV status.

Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus

NARCIS (Netherlands)

de Vries-Sluijs, Theodora E. M. S.; Reijnders, Jurriën G. P.; Hansen, Bettina E.; Zaaijer, Hans L.; Prins, Jan M.; Pas, Suzan D.; Schutten, Martin; Hoepelman, Andy I. M.; Richter, Clemens; Mulder, Jan W.; de Man, Rob A.; Janssen, Harry L. A.; van der Ende, Marchina E.

2010-01-01

BACKGROUND & AIMS: We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy. METHODS: We performed a multicenter, prospective

Identification of rodent homologs of hepatitis C virus and pegiviruses

DEFF Research Database (Denmark)

Kapoor, Amit; Simmonds, Peter; Scheel, Troels K H

2013-01-01

UNLABELLED: Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity...... into the origins of human infections and enhances our ability to study their pathogenesis and explore preventive and therapeutic interventions. Horses are the only reported host of nonprimate homologs of hepatitis C virus (HCV). Here, we report the discovery of HCV-like viruses in wild rodents. The majority of HCV...... of small-animal models for HCV, the most common infectious cause of liver failure and hepatocellular carcinoma after hepatitis B virus, and help to explore the health relevance of the highly prevalent human pegiviruses....

Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma

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Yuan CS

2016-06-01

Full Text Available Chuanshu Yuan, Kai Yang, Hong Tang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1, squamous cell carcinoma antigen (SCCAg, ferritin, carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, and α-fetoprotein (AFP for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC. Methods: One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. Results: The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (P<0.05. The levels of CA19-9 and AFP showed no significant difference between patients with OSCC/OPSCC, benign tumor, and healthy group (P>0.05. The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II was significantly higher than that of benign tumor and healthy control group (P<0.05. However, the levels of serum SCCAg, ferritin, CEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05. The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (P<0.05. The diagnostic cutoff levels of Cyfra21

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

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Jalalzadeh, M; Shekari, E; Mirzamohammadi, F; Ghadiani, M H

2012-05-01

Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

Hepatitis E as a Zoonosis.

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Widén, Frederik

2016-01-01

Hepatitis E (HE) virus infection is not limited to spread from human to human but also occurs between animals and more importantly as zoonotic spread from animals to humans. Genotyping of strains from hepatitis E virus-infected patients has revealed that these infections are not all caused by genotypes 1 or 2 but often by genotypes 3 or 4. Therefore, it is important to understand the striking difference between the spread of genotypes 1 and 2 in countries with poor sanitary standards and the spread of genotypes 3 and 4 in countries with good sanitary standards. The number of animal species known to be infected with HEV is expanding rapidly. The finding of HEV in new host species always raises the question regarding the zoonotic potential of these newfound strains. However, as new strains are found, the complexity increases.Certain genotypes are known to have the ability of zoonotic spread from certain animal species and these animals may even constitute an infection reservoir. Some animal species may contribute to zoonotic infections albeit on a smaller scale, while others are believed to be of minor or no importance at all. This chapter reviews possible sources of zoonotic hepatitis E virus infection.

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

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Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

2016-11-01

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

The induction of autoimmune hepatitis in the human leucocyte antigen‐DR4 non‐obese diabetic mice autoimmune hepatitis mouse model

Science.gov (United States)

Yuksel, M.; Xiao, X.; Tai, N.; Vijay, G. M.; Gülden, E.; Beland, K.; Lapierre, P.; Alvarez, F.; Hu, Z.; Colle, I.; Ma, Y.

2016-01-01

Summary Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti‐smooth muscle actin and/or anti‐nuclear, anti‐liver kidney microsomal type 1 (anti‐LKM1) and anti‐liver cytosol type 1 (anti‐LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)‐DR3, ‐DR7 and ‐DR13. HLA‐DR4 has the second strongest association with adult AIH, after HLA‐DR3. We investigated the role of HLA‐DR4 in the development of AIH by immunization of HLA‐DR4 (DR4) transgenic non‐obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti‐LKM1/anti‐LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)‐1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild‐type (WT) NOD mice. Our results demonstrate that HLA‐DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD‐1 expression may result in spontaneous activation of key immune cell subsets, such as antigen‐presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID:27414259

Seroprevalence of Human Immunodeficiency Virus, Hepatitis B ...

African Journals Online (AJOL)

surface antigen (HBsAg), syphilis and HCV from the antenatal records. The data were extracted by two trained assistants. Hepatitis B surface antigen and antibodies to HCV were determined using Clinotech diagnostic enzyme linked immunosorbent assay (ELISA) test kits (Clinotech Laboratories,. USA; batch/lot no. for ...

Nanovaccine for immunotherapy and reduced hepatitis-B virus in humanized model.

Science.gov (United States)

Dewangan, Hitesh Kumar; Pandey, Tarun; Singh, Sanjay

2017-11-27

Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune responses. The lack of an appropriate small animal model for chronic hepatitis, a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B viral (HBV) infection. In this study, for enhancing the antibody production efficiency the prepared polymeric HBsAg-loaded nanoparticles (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that were engrafted with peripheral blood mononuclear cells (PBMCs), which was already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice. In the present study, after the vaccination detected the high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-Y (IFN-Y) secreting T cells in serum, determined by specific ELISA technique. During the entire observation period, unvaccinated animals showed lower concentration of specific IgG secreting B cells and IFN-Y secreting T cells found in comparison to vaccinated mice group. Chronic HBV carrier PBMCs transplanted into the chimera failed to produce antigen and increased the antibodies production due to vaccination. Furthermore, another advantage was that the viral gene expression and viral DNA replication was no longer observed in vaccinated group. This prepared nanovaccine formulations is better for the cure of Hepatitis B viral infection carrier. Therefore, specific memory responses were elicited by vaccination with Hepatitis B virus surface (HBsAg) antigen of chimeric mice transplanted with PBMCs derived from HBV donors.

Carcinogen-Induced Hepatic Tumors in KLF6+/- Mice Recapitulate Aggressive Human Hepatocellular Carcinoma Associated with p53 Pathway Deregulation

NARCIS (Netherlands)

Tarocchi, Mirko; Hannivoort, Rebekka; Hoshida, Yujin; Lee, Ursula E.; Vetter, Diana; Narla, Goutham; Villanueva, Augusto; Oren, Moshe; Llovet, Josep M.; Friedman, Scott L.

Inactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental

Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

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Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

2016-06-01

Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Biliary Secretion of Quasi-Enveloped Human Hepatitis A Virus

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Asuka Hirai-Yuki

2016-12-01

Full Text Available Hepatitis A virus (HAV is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replication in vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut. To assess whether eHAV and nonenveloped virus egress from cells via vectorially distinct pathways, we studied infected polarized cultures of Caco-2 and HepG2-N6 cells. Most (>99% progeny virions were released apically from Caco-2 cells, whereas basolateral (64% versus apical (36% release was more balanced with HepG2-N6 cells. Both apically and basolaterally released virions were predominantly enveloped, with no suggestion of differential vectorial release of eHAV versus naked virions. Basolateral to apical transcytosis of either particle type was minimal (<0.02%/h in HepG2-N6 cells, arguing against this as a mechanism for differences in membrane envelopment of serum versus fecal virus. High concentrations of human bile acids converted eHAV to nonenveloped virions, whereas virus present in bile from HAV-infected Ifnar1−/−Ifngr1−/− and Mavs−/− mice banded over a range of densities extending from that of eHAV to that of nonenveloped virions. We conclude that nonenveloped virions shed in feces are derived from eHAV released across the canalicular membrane and stripped of membranes by the detergent action of bile acids within the proximal biliary canaliculus.

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

Science.gov (United States)

Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

Feature Hepatitis: Hepatitis Can Strike Anyone

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... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

Molecular status of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus among transgender commercial sex workers in Surakarta, Indonesia

Science.gov (United States)

Prasetyo, Afiono Agung; Sari, Yulia; Dharmawan, Ruben; Marwoto

2017-02-01

Sexual contact and other risk behavior among transgender working as commercial sex workers are important factors for sexual and blood-borne virus (BBV) infections. However, there no data concerning the molecular status of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) circulated among transgender working as commercial sex workers. Blood samples obtained from transgender working as commercial sex workers in Surakarta were examined for HIV antibodies, HBsAg and HCV antibodies, respectively, by immunological assays. All blood samples were also subjected for viral nucleic acid extraction and molecular detection of HIV, HBV and HCV by nested RT-PCR. The PCR products were purified from agarose gels, and the nucleotide sequences were retrieved and molecular analyzed. HIV, HBV and HCV was detected in 26.9% (7/26), 19.2% (5/26) and 46.2% (12/26), respectively. HIV CRF01_AE and B were found to be circulating in the community. HBV genotype B3 predominated, followed by C1. HCV genotype 1a predominated among HCV-infected transgender working as commercial sex workers, followed by 1c, 3a, and 4a. HIV, HBV, and HCV were found circulating in the transgender working as commercial sex workers in Surakarta, Indonesia.

Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen

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Arnaud Carpentier

2016-05-01

Full Text Available The establishment of protocols to differentiate human pluripotent stem cells (hPSCs including embryonic (ESC and induced pluripotent (iPSC stem cells into functional hepatocyte-like cells (HLCs creates new opportunities to study liver metabolism, genetic diseases and infection of hepatotropic viruses (hepatitis B and C viruses in the context of specific genetic background. While supporting efficient differentiation to HLCs, the published protocols are limited in terms of differentiation into fully mature hepatocytes and in a smaller-well format. This limitation handicaps the application of these cells to high-throughput assays. Here we describe a protocol allowing efficient and consistent hepatic differentiation of hPSCs in 384-well plates into functional hepatocyte-like cells, which remain differentiated for more than 3 weeks. This protocol affords the unique opportunity to miniaturize the hPSC-based differentiation technology and facilitates screening for molecules in modulating liver differentiation, metabolism, genetic network, and response to infection or other external stimuli.

Antioxidant capacity of parsley cells (Petroselinum crispum L.) in relation to iron-induced ferritin levels and static magnetic field.

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Rajabbeigi, Elham; Ghanati, Faezeh; Abdolmaleki, Parviz; Payez, Atefeh

2013-12-01

This study was aimed to evaluate antioxidant response of parsley cells to 21 ppm iron and static magnetic field (SMF; 30 mT). The activity of catalase (CAT) and ascorbate peroxidase (APX) and the contents of malonyldialdehyde, iron and ferritin were measured at 6 and 12 h after treatments. Exposure to SMF increased the activity of CAT in treated cells, while combination of iron and SMF treatments as well as iron supply alone decreased CAT activity, compared to that of control cells. Combination of SMF with iron treatment reduced iron content of the cells and ameliorated mal effect of iron on CAT activity. All treatments reduced APX activity; however, the content of total ascorbate increased in response to iron and SMF+iron. The results showed that among the components of antioxidant system of parsley cells, enhanced activity of CAT in SMF-treated cells and increase of ascorbate in SMF+Fe-treated ones were responsible for the maintenance of membranes integrity. Ferritin contents of SMF- and SMF+Fe-treated cells also decreased significantly 12 h after treatments, compared to those of the control cells. These results cast doubt on the proposed functions of ferritin as a putative reactive oxygen species detoxifying molecule.

Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry.

Science.gov (United States)

Kachko, Alla; Costafreda, Maria Isabel; Zubkova, Iryna; Jacques, Jerome; Takeda, Kazuyo; Wells, Frances; Kaplan, Gerardo; Major, Marian E

2018-03-15

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry, but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. Human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid receptor, did not enhance infection and a soluble form failed to neutralize HCV, although replacement of the mouse IgV domain with the human HAVCR1 IgV domain restored the enhancement of HCV infection. Mutations in the cytoplasmic tail revealed that direct HAVCR1 signaling is not required to enhance HCV infection. Our data show that the phospholipid-binding function and other determinant(s) in the IgV domain of human HAVCR1 enhance HCV infection. Although the exact mechanism is not known, it is possible that HAVCR1 facilitates entry by stabilizing or enhancing attachment, leading to direct interactions with specific receptors, such as CD81. IMPORTANCE Hepatitis C virus (HCV) enters cells through a multifaceted process. We identified the human hepatitis A virus cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry. Our findings that the

Prevalence of Hepatitis A Virus Antibody in Portuguese Travelers: A New Paradigm.

Science.gov (United States)

Rocha, Sónia; Tejo, Sandra; Ferreira, Eugénia; Trindade, Luís; Rabadão, Eduardo; Marques, Nuno; Saraiva da Cunha, José

2017-08-31

In Portugal, the prevalence of hepatitis A virus infection has decreased in the past decades, especially in young adults. The aim of this study was to detect the prevalence of antibody to hepatitis A virus in a population observed in our Travel Clinic. Antibodies against hepatitis A, hepatitis B, hepatitis C and human immunodeficiency virus were tested using standard enzyme immunoassay in patients older than 18. The exclusion criteria were: prior vaccination for hepatitis A virus, previous diagnosis of infection with hepatitis B virus, hepatitis C virus and/or human immunodeficiency virus, foreign travelers and long-term expatriates. We applied an epidemiological survey and data was statistically analyzed with SPSS® 18.0. In the 665 travelers studied, natural immunity to hepatitis A virus was present in 57.6% (n = 383). They were stratified into 8 age groups and for each one hepatitis A immunity was clarified: 5.0% (n = 1) in 18 - 25 years, 32.3% (n = 21) in 26 - 30 years, 40.9% (n = 47) in 31 - 35 years, 45.8% (n = 54) in 36 - 40 years, 68.7% (n = 79) in 41 - 45 years, 70.1% (n = 68) in 46 - 50 years, 80.8% (n = 63) in 51 - 55 years and 87.7% (n = 50) over 56 years old. In those who accepted further screening, positivity for hepatitis B core antibody was found in 0.6% (n = 3) travelers, hepatitis C virus infection in 1.1% (n = 6) and human immunodeficiency virus infection in 0.5% (n = 3) whose previous status was unknown. The most frequent travel destination was sub-Saharan Africa (72.6%; n = 483). We found 49.1% (n = 260) travelers under 50 years old susceptible to hepatitis A virus infection and for those between 40 and 50 years, 30.7% (n = 65) still need vaccine protection. Across age groups there is a trend towards lower prevalence of hepatitis A virus antibody, in particular among youngsters, when compared with older Portuguese studies.

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity.

Science.gov (United States)

Andrews, Mónica; Soto, Néstor; Arredondo-Olguín, Miguel

2015-01-01

The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

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Michiko Itoh

Full Text Available Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

Characterization of the arsenite oxidizer Aliihoeflea sp. strain 2WW and its potential application in the removal of arsenic from groundwater in combination with Pf-ferritin.

Science.gov (United States)

Corsini, Anna; Colombo, Milena; Muyzer, Gerard; Cavalca, Lucia

2015-09-01

A heterotrophic arsenite-oxidizing bacterium, strain 2WW, was isolated from a biofilter treating arsenic-rich groundwater. Comparative analysis of 16S rRNA gene sequences showed that it was closely related (98.7 %) to the alphaproteobacterium Aliihoeflea aesturari strain N8(T). However, it was physiologically different by its ability to grow at relatively low substrate concentrations, low temperatures and by its ability to oxidize arsenite. Here we describe the physiological features of strain 2WW and compare these to its most closely related relative, A. aestuari strain N8(T). In addition, we tested its efficiency to remove arsenic from groundwater in combination with Pf-ferritin. Strain 2WW oxidized arsenite to arsenate between pH 5.0 and 8.0, and from 4 to 30 °C. When the strain was used in combination with a Pf-ferritin-based material for arsenic removal from natural groundwater, the removal efficiency was significantly higher (73 %) than for Pf-ferritin alone (64 %). These results showed that arsenite oxidation by strain 2WW combined with Pf-ferritin-based material has a potential in arsenic removal from contaminated groundwater.

Prevalence of high-risk human papilloma virus among women with hepatitis C virus before liver transplantation.

Science.gov (United States)

Tarallo, P A; Smolowitz, J; Carriero, D; Tarallo, J; Siegel, A; Jia, H; Emond, J C

2013-08-01

We sought to assess the prevalence and risk factors for high-risk human papillomavirus (HPV) infection among female liver transplant (LT) candidates. Traditional health screening before LT listing has included Pap smear and is typically carried out by the patient's local provider. The prevalence of high-risk HPV in this population has not been studied. With Institutional Review Board approval, 62 LT candidates received a liquid-based Pap smear with high-risk HPV testing as part of their pre-transplant evaluation by a single provider. Clinical variables included age, ethnicity, insurance status, prior Pap smear, and HPV results, HPV risk factors including age of first intercourse, number of lifetime partners, last sexual activity, smoking, birth control pill use, history of sexually transmitted infections, human immunodeficiency virus status, immunosuppressive medication, medical diagnoses, prescribed medications, and history of hepatitis A, B, C, or D. The 62 women had a median age of 56 years, and 39% had high-risk behavior known to be associated with HPV. Ten of 62 patients (16.1%) had high-risk HPV at baseline screening, 5 of whom had atypical cytology. All of the patients who were positive for high-risk HPV had an etiology of hepatitis C virus (HCV) as the underlying cause of liver disease, with the majority (90%) having no history of high-risk behavior for HPV. In contrast, all patients with high-risk behavior who were HCV negative were HPV negative. Fisher's exact test demonstrated a statistically significant relationship between HPV and HCV; odds ratio = 24.4, 95% confidence interval, 1.4, 438.7, P-value = 0.0013. None of the other potential risk factors were associated with HPV in this cohort. In this study, we provide evidence of a strong association between HCV and HPV in LT candidates, which has not been previously reported. HPV positivity was observed in non-sexually active women, suggesting a reactivation of dormant HPV. An association between

On the analysis of magnetization and Moessbauer data for ferritin

International Nuclear Information System (INIS)

Madsen, D E; Moerup, S; Hansen, M F; Bendix, J

2008-01-01

Experimental data for antiferromagnetic nanoparticles are often analyzed as if the particles were ferromagnetic. However, due to the volume dependence of the magnetization resulting from uncompensated spins, such analysis will yield erroneous results. This is demonstrated as we analyze ac and dc magnetization data as well as Moessbauer spectra obtained for ferritin. The values of the median energy barrier obtained from the different data are in very close agreement when a distribution of volumes and a volume dependence of the magnetization are taken into account. However, when the volume dependence of the magnetization is neglected, erroneous values of the anisotropy energy barrier and the attempt time τ 0 are obtained

Role of Breastfeeding and Complementary Food on Hemoglobin and Ferritin Levels in a Cambodian Cross-Sectional Sample of Children Aged 3 to 24 Months.

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Anika Reinbott

Full Text Available Iron deficiency derives from a low intake of dietary iron, poor absorption of iron, and high requirements due to growth as well as blood loss. An estimated number of about 50% of all anemia may be attributed to iron deficiency among young children in Cambodia.A cross-sectional survey was conducted in rural Cambodia in September 2012. Villages in pre-selected communes were randomly chosen using stunting as a primary indicator of nutritional status. In total, 928 randomly selected households with children aged 3-23 months were included. Hemoglobin, ferritin, soluble transferrin receptor (sTfR, and retinol binding protein (RBP were assessed from capillary blood samples. In addition, length/height and weight of mothers and children were taken and data on dietary diversity was collected. A child feeding index (CFI was created. Associations between biomarkers of iron and vitamin A status and nutritional status or food intake were explored.Anemia prevalence was highest among 6- to 12-months-olds (71%. Ferritin and sTfR inversely correlated and were significantly associated with hemoglobin concentrations. The consumption of animal source foods (ASF significantly impacts on the interaction between ferritin, sTfR and hemoglobin. Concentrations of RBP were significantly higher in children who had received a vitamin A supplement. The CFI was associated with sTfR and hemoglobin. Lower length and weight were associated with lower ferritin levels and showed an indirect effect on hemoglobin through ferritin.Nutrition programs targeting children under 2 years of age need to focus on the preparation of complementary foods with high nutrient density to sustainably prevent micronutrient deficiency and generally improve nutritional status. Future assessments of the micronutrient status should include identification of hemoglobinopathies and parasitic infections to better understand all causes of anemia in Cambodian infants and young children.German Clinical Trials

The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1-infected individuals: a randomized clinical trial.

Science.gov (United States)

Kotler, Donald P; He, Qing; Engelson, Ellen S; Albu, Jeanine B; Glesby, Marshall J

2016-01-01

Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. HIV+ subjects with abdominal obesity and IR (QUICKI≤0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy, visceral fat by MRI and IR by frequently sampled intravenous glucose tolerance tests at baseline and week 12. 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r=0.41; P=0.02) and QUICKI (r=0.39; P<0.05) were seen at baseline. IR rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percentage change decreased significantly (P<0.05) but did not change in Rosi (P=0.71). There were no correlations between changes in hepatic fat and VAT (P=0.4) or QUICKI (P=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum insulin-like growth factor-1 (IGF-1; P=0.09). Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of GH or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286).

Short repeats in the heme oxygenase 1 gene promoter is associated with increased levels of inflammation, ferritin and higher risk of type-2 diabetes mellitus.

Science.gov (United States)

Andrews, Mónica; Leiva, Elba; Arredondo-Olguín, Miguel

2016-09-01

We evaluated the relationship between the HO1 genotype, ferritin levels and the risk of type-2 diabetes and inflammation. Eight hundred thirty-five individuals were evaluated and classified according to their nutritional status and the presence of type-2 diabetes: 153 overweight (OW); 62 obese (OB); 55 type-2 diabetes mellitus (DM); 202 OWDM; 239 OBDM and 124 controls (C). We studied biochemical (glycemia, insulin, lipid profile, liver enzyme, creatinine, hsCRP), hematological (hemoglobin, free erythrocyte protoporphyrin, transferrin receptor and serum Fe and ferritin) and oxidative stress (SOD, GHS and TBARS) parameters. We determined heme oxygenase activity and the (GT)n polymorphism in its gene promoter. Individuals with diabetes, independent of nutritional status, showed high levels of ferritin and HO activity compared to control subjects. Allelic frequency was not different between the groups (Chi(2), NS) however, genotypes were different (Chi(2), P1). The SS (short-short) genotype was higher in all DM individuals compared to controls and MM was higher in controls. SM (short-medium) genotype was an independent risk factor for DM in logistic regression analysis. We observed high risk for type-2 diabetes mellitus in the presence of SM genotype and high levels of ferritin (OR adjusted: 2.7; 1.9-3.6; p1; compared to control group). It was also significantly related to inflammation. The SM genotype in HO1 gene promoter and ferritin levels were associated with higher risk for type-2 diabetes and for having a higher marker of inflammation, which is the main risk factor for the development of chronic diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

Efficiencies of Dye-Sensitized Solar Cells using Ferritin-Encapsulated Quantum Dots with Various Staining Methods

Science.gov (United States)

Perez, Luis

Dye-sensitized solar cells (DSSC) have the potential to replace traditional and cost-inefficient crystalline silicon or ruthenium solar cells. This can only be accomplished by optimizing DSSC's energy efficiency. One of the major components in a dye-sensitized solar cell is the porous layer of titanium dioxide. This layer is coated with a molecular dye that absorbs sunlight. The research conducted for this paper focuses on the different methods used to dye the porous TiO2 layer with ferritin-encapsulated quantum dots. Multiple anodes were dyed using a method known as SILAR which involves deposition through alternate immersion in two different solutions. The efficiencies of DSSCs with ferritin-encapsulated lead sulfide dye deposited using SILAR were subsequently compared against the efficiencies produced by cells using the traditional immersion method. It was concluded that both methods resulted in similar efficiencies (? .074%) however, the SILAR method dyed the TiO2 coating significantly faster than the immersion method. On a related note, our experiments concluded that conducting 2 SILAR cycles yields the highest possible efficiency for this particular binding method. National Science Foundation.

The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin.

Science.gov (United States)

Küberl, Andreas; Polen, Tino; Bott, Michael

2016-04-26

The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation.

Detection and Phylogenetic Analysis of Human Pegivirus (GBV-C) Among Blood Donors and Patients Infected With Hepatitis B Virus (HBV) in Qatar

OpenAIRE

AbuOdeh, Raed O.; Al-Absi, Enas; Ali, Nadima H.; Khalili, Makiyeh; Al-Mawlawi, Naema; Hadwan, Tameem A.; Al Thani, Asmaa A.; Nasrallah, Gheyath K.

2015-01-01

Human Pegivirus (HPgV), formerly GB virus-C/ Hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, is widely spread and has been reported to be associated with non-A–E hepatitis. To our knowledge, no previous study was conducted about HPgV in Qatar. Thus, the objectives of this study were as follows: (i) to determine the rates of HPgV infection in Qatar among healthy blood donors and HBV-infected patients, and (ii) to determine the most predominant HPgV gen...

Molecular status of Human Immunodeficiency Virus, Hepatitis B virus, and Hepatitis C virus among injecting drug male commercial sex workers in Surakarta, Indonesia

Science.gov (United States)

Agung Prasetyo, Afiono; Marwoto; Arifin Adnan, Zainal; Hartono

2018-05-01

Male commercial sex workers are one of the high-risk community for blood-borne viruses. However, there are no data concerning the molecular status of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) circulated among male commercial sex workers with injecting drug habits in Surakarta, Indonesia. Blood samples obtained from injecting drug male commercial sex workers in Surakarta were examined for HIV antibodies, HBsAg, and HCV antibodies, respectively, by immunological assays. Blood samples were also subjected to viral nucleic acid extraction and molecular detection of HIV, HBV, and HCV by nested (RT) PCRs. The PCR products were purified from agarose gels, and the nucleotide sequences were retrieved and molecular analyzed. HIV, HBV, and HCV were detected in 29.4% (10/34), 17.6% (6/34), and 52.9% (18/34), respectively. HIV CRF01_AE and B were found to be circulating in the community. HBV genotype B3 was predominated, followed by C1. HCV genotype 1a was predominated, followed by 1c, 3a, 1b, and 4a. HIV, HBV, and HCV were found circulating in the male commercial sex workers with injecting drug habits in Surakarta, Indonesia.

The influence of the human genome on chronic viral hepatitis outcome A influência do genoma humano no curso das hepatites virais crônicas

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Dahir Ramos de Andrade Júnior

2004-06-01

Full Text Available The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b protective alleles influencing hepatitis B virus (HBV and hepatitis C virus (HCV evolution; c prejudicial alleles influencing HBV and HCV; d candidate genes associated with HBV and HCV evolution; d other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others. Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.Os mecanismos que determinam o clearance ou a persistência da infecção viral nas hepatites virais crônicas não estão ainda bem identificados. O progresso no conhecimento sobre as ferramentas genéticas moleculares tem permitido detectar variações na resposta imune, que freqüentemente são associadas com polimorfismos do genoma humano. As diferenças na susceptibilidade do hospedeiro para as doenças infecciosas e a intensidade das doenças não podem ser atribuídas apenas à virulência do agente microbiano. Neste

A human cytochrome P-450 is recognized by anti-liver/kidney microsome antibodies in autoimmune chronic hepatitis.

Science.gov (United States)

Kiffel, L; Loeper, J; Homberg, J C; Leroux, J P

1989-02-28

1- Anti-liver/kidney microsome autoantibodies type 1 (anti-LKM1), observed in some children with chronic active hepatitis, were used to isolate their antigen in human liver microsomes. A protein, called P-LKM1 was thus purified. This protein was recognized by a rabbit antiserum directed against the related human cytochromes P-450 bufI and P-450 bufII. 2- A human liver microsomal protein immunoprecipitated with anti-LKM1 sera was also recognized by anti cytochromes P-450 bufI/II antibodies. 3- Anti-LKM1 antibodies potently inhibited microsomal bufuralol 1'-hydroxylation. These results displayed the possible identity between cytochrome P-450 bufI/II and LKM1 antigen.

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

NARCIS (Netherlands)

Schmeink, C.E.; Bekkers, R.L.M.; Josefsson, A.; Richardus, J.H.; Berndtsson Blom, K.; David, M.P.; Dobbelaere, K.; Descamps, D.

2011-01-01

BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV

Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood

NARCIS (Netherlands)

Müller, Viktor; Marée, Athanasius F.M.; Boer, R.J. de

2000-01-01

Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections have been estimated from plasma virus levels following perturbation of the chronically infected (quasi-) steady state. We extend previous models by also considering the large pool of virus

Association between Helicobacter pylori seropositivity and Hepatic Encephalopathy

International Nuclear Information System (INIS)

Behroozian, R.; Faramarzpur, M.; Rahimi, E.

2010-01-01

Objective: The knowledge on Helicobacter pylori (H. pylori) contribution in the pathology of the liver and biliary tract diseases in human is very limited. The aim of this study was to assess the probable association between H. pylori seropositivity and hepatic encephalopathy. Methodology: This is a case control study conducted through three groups, cirrhotics with hepatic encephalopathy (HE), cirrhotics without HE and healthy controls. All subjects were examined serologically for determination of IgG class antibodies to H. pylori based on ELISA technique. Results: H. pylori seropositivity was present in 88% cirrhotic patients with hepatic encephalopathy, 86% cirrhotics without hepatic encephalopathy and 66% healthy controls. Conclusion: According to our results, H. pylori seropositivity rate in cirrhotic patients with or without hepatic encephalopathy was higher than healthy controls. But H. pylori seropositivity rate was not significantly different among cirrhotics with hepatic encephalopathy and those without it.

Ferritin and body mass index predict cardiac dysfunction in female adolescents with anorexia of the restrictive type.

Science.gov (United States)

Docx, Martine K F; Weyler, Joost; Simons, Annik; Ramet, José; Mertens, Luc

2015-08-01

Decreased left ventricular mass index in anorexia nervosa is amply reported. The aim of this study is to identify non-burdensome predictors of reduced left yentricular mass/height (cLVM) in a cohort of adolescent restrictive anorexic girls. This is a retrospective study of all anorexic girls of the restrictive type referred to our tertiary eating disorder unit between September 2002 and December 2012, for somatic assessment of weig ht loss. All subjects fulfilled DMS-IV criteria, without a family history of cardiac or cardiovascular diseases. In all, 283 restrictive anorexic girls (age: 14.63 +/- 1.65 y; body mass index: 15.72 +/- 1.81 kg/m2) were included. Ferritin and body mass index were independent, statistically significant predictors of the corrected left ventricular mass (P anorexia nervosa of the restrictive type. Two factors predicted decreased cLVM in our population: ferritin and BMI.

Hepatic steatosis : metabolic consequences

NARCIS (Netherlands)

Boer, Adriana Maria den

2006-01-01

In this thesis we focused on the causes and consequences of hepatic steatosis. Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance and type 2 diabetes mellitus. The mechanism

Ancient hepatitis B viruses from the Bronze Age to the Medieval period

DEFF Research Database (Denmark)

Mühlemann, Barbara; Jones, Terry C.; Damgaard, Peter de Barros

2018-01-01

Hepatitis B virus (HBV) is a major cause of human hepatitis. There is considerable uncertainty about the timescale of its evolution and its association with humans. Here we present 12 full or partial ancient HBV genomes that are between approximately 0.8 and 4.5 thousand years old. The ancient se...

Hepatitis C

Science.gov (United States)

... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

The Genetic and Molecular Studies of Hepatitis C Virus: A Review ...

African Journals Online (AJOL)

The role of Hepatitis viruses, particularly Hepatitis c virus (HCV) as human pathogen and their transmission have been of interest over the years. The virus is a small (55-65nm in size), included in Group IV, enveloped, positive sense, single stranded RNA virus, the family Flaviviridae, genus Hepacivirus, and Hepatitis c virus ...

To choose the cut-off point of ferritin for differentiation between benign from malignant pleural-peritoneal effusion

International Nuclear Information System (INIS)

Yang Liu; Yang Wenjing; Liu Junfeng; Yu Jiuru

2005-01-01

To explore the level of ferritin for differentiating the benign from malignant pleural and peritoneal effusion, 218 pleural-peritoneal effusion samples from patients with different kinds of diseases were determined for ferritin (P Ft ) by RIA, in the meanwhile serum ferritin (S Ft ) was also determined. According to clinical diagnosis, these samples were divided into two groups: benign and malignant. P Ft and S Ft were compared between these two groups, and the ratio of P Ft to S Ft was counted. The ROC curve was used to choose the best cut-off point P Ft for differentiating benign from malignant pleural and peritoneal effusion. The results showed that in the benign effusion group the P Ft was 142.4±38.6 μg/L, S Ft was 89.7±43.5 μg/L, and P Ft / S Ft was 1.46±0.55, whereas in the group of malignant effusion the corresponding figures were 576.5±239.l μg/L, 189.±81.7 μg/L, and 3.67±1.48, respectively. The cut-off point for differentiating benign from malignant pleural and peritoneal effusion was 400 μg/L. Our differentiation standards are: P Ft ≥400 μg/L,P Ft /S Ft ≥3 for the malignant pleural and peritoneal ef- fusion, and P Ft Ft /S Ft <3 for the benign effusion. The sensitivity is 84.5%, the specificity is 87.5%, and the accuracy is 92.8%. (authors)

Prophylactic Hepatitis E Vaccine.

Science.gov (United States)

Zhang, Jun; Zhao, Qinjian; Xia, Ningshao

2016-01-01

Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.

Molecular cloning, expression and isolation of ferritins from two tick species - Ornithodoros moubata and Ixodes ricinus

Czech Academy of Sciences Publication Activity Database

Kopáček, Petr; Ždychová, J.; Yoshiga, T.; Weise, C.; Rudenko, Natalia; Law, J. H.

2003-01-01

Roč. 33, č. 1 (2003), s. 103-113 ISSN 0965-1748 R&D Projects: GA ČR GA206/00/0266 Institutional research plan: CEZ:AV0Z6022909; CEZ:MSM 123100003 Keywords : ferritin * iron metabolism * tick Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.358, year: 2003

New models of hepatitis E virus replication in human and porcine hepatocyte cell lines

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Hepatitis E virus (HEV) causes acute, enterically-transmitted hepatitis. It is associated with large epidemics in tropical and subtropical regions where it is endemic or with sporadic cases in non-endemic regions. Unlike other hepatitis viruses, HEV has several animal reservoirs. Phylogenetic studie...

Molecular Biology and Infection of Hepatitis E Virus

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Yuchen Nan

2016-09-01

Full Text Available Hepatitis E virus (HEV is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotype 3 and 4 are zoonotic, whereas those from genotype 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.

Iron overload and genotype 3 are associated with liver steatosis in chronic hepatitis C Sobrecarga de hierro y genotipo 3 se asocian a la presencia de esteatosis en la hepatitis C

Directory of Open Access Journals (Sweden)

L. I. Fernández Salazar

2004-12-01

Full Text Available Objective: to determine epidemiological, biochemical, virological, and histological factors associated with liver steatosis in chronic hepatitis C. Subjects: the medical histories of 53 patients biopsied for chronic hepatitis C diagnosis between June 2000 and December 2002 were retrospectively studied. Epidemiological, biochemical, and virological data were collected. Patients with hepatitis B virus or human immunodeficiency virus coinfection were excluded. Liver biopsy specimens were reviewed and scored by one pathologist. Weight and height were measured at liver biopsy time. The statistic association between qualitative and quantitative variables and the presence of liver steatosis was studied. Results: steatosis was identified in 52% of biopsies. There was no statistic association with age, sex, method of transmission, duration of infection, alcohol consumption, other diseases, body mass index, glucose, triglycerides, cholesterol, AST, ALT, GGT, alkaline phosphatase, bilirubin, or viral load. Liver steatosis was associated with serum iron, transferrin saturation, and ferritin. Genotype 3 was also associated with steatosis. Piecemeal necrosis, hepatocellular injury, Kupffer cell hyperplasia, liver iron, and portal fibrosis were also associated with steatosis. A multivariate analysis showed that genotype 3, Kupffer cell hyperplasia, and liver iron were associated with the presence of steatosis. Conclusions: liver steatosis in chronic hepatitis C associates with genotype 3, Kupffer cell hyperplasia, and iron overload. Hepatic steatosis also associates with greater inflammation and fibrosis, and must be considered to contribute to disease progression.Objetivo: determinar los factores epidemiológicos, analíticos, virológicos e histológicos a los que se asocia la esteatosis en la hepatitis C. Pacientes: se revisaron de forma retrospectiva 53 historias clínicas de pacientes biopsiados consecutivamente desde junio de 2000 a dicembre de 2002. Se

Hepatitis C virus infection and risk of coronary artery disease

DEFF Research Database (Denmark)

Roed, Torsten; Lebech, Anne-Mette; Kjaer, Andreas

2012-01-01

Several chronic infections have been associated with cardiovascular diseases, including Chlamydia pneumoniae, human immunodeficiency virus and viral hepatitis. This review evaluates the literature on the association between chronic hepatitis C virus (HCV) infection and the risk of coronary artery...

Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma.

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Yuan, Chuanshu; Yang, Kai; Tang, Hong; Chen, Dan

2016-01-01

At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1), squamous cell carcinoma antigen (SCCAg), ferritin, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and α-fetoprotein (AFP) for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC). One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (Ptumor, and healthy group (P>0.05). The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II) was significantly higher than that of benign tumor and healthy control group (PCEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05). The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV) were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (PCEA were 2.17, 0.72, 109.95, and 1.99 ng/mL, respectively. The sensitivities were 60.36%, 73.37%, 81.66%, and 66.27%, respectively. The specificities were 81.03%, 68.10%, 40.52%, and 61.21%, respectively. Cyfra21-1, SCCAg, ferritin, and CEA had diagnostic values for patients with OSCC/OPSCC. Meanwhile, Cyfra21-1 had better early diagnostic value for patients with OSCC/OPSCC.

The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1 infected individuals; a randomized clinical trial

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Kotler, Donald P; He, Qing; Engelson, Ellen S; Albu, Jeanine B; Glesby, Marshall J

2016-01-01

Background Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. Methods HIV+ subjects with abdominal obesity and IR (QUICKI ≤ 0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination, or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy (MRS), visceral fat by MRI, and IR by frequently sampled IV glucose tolerance tests at baseline and week 12. Results 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r = 0.41, p=0.02) and QUICKI (r = 0.39, p<0.05) were seen at baseline. Insulin resistance rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percent change decreased significantly (p<0.05) but did not change in Rosi (p=0.71). There were no correlations between changes in hepatic fat and VAT (p=0.4) or QUICKI (p=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum IGF-1 (p=0.09). Conclusions Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of growth hormone or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286). PMID:25536669

Hepatitis A through E (Viral Hepatitis)

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... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

Energy Technology Data Exchange (ETDEWEB)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: j.oben@ucl.ac.uk [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)

2012-01-06

Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

International Nuclear Information System (INIS)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI; Roskams, Tania; Oben, Jude A.

2012-01-01

Highlights: ► Cigarette smoke may induce liver fibrosis via nicotine receptors. ► Nicotine induces proliferation of hepatic stellate cells (HSCs). ► Nicotine activates hepatic fibrogenic pathways. ► Nicotine receptor antagonists attenuate HSC proliferation. ► Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine – which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed – RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-α2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-β1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type (α1, β1, delta and epsilon) and neuronal type (α3, α6, α7, β2 and β4) nAChR subunits at the mRNA level. Among these subunits, α3, α7, β1 and ε were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-α2 and TGF-β1 mRNA expression were significantly upregulated by nicotine and inhibited by mecamylamine. α1 and α3-nAChR mRNA expression was significantly upregulated in NASH fibrosis compared to normal livers. Conclusion: Nicotine at levels in smokers’ blood is pro-fibrogenic, through

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.

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Ma, Xuanyi; Qu, Xin; Zhu, Wei; Li, Yi-Shuan; Yuan, Suli; Zhang, Hong; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Zanella, Fabian; Feng, Gen-Sheng; Sheikh, Farah; Chien, Shu; Chen, Shaochen

2016-02-23

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

The Faraday effect of natural and artificial ferritins.

Science.gov (United States)

Koralewski, M; Kłos, J W; Baranowski, M; Mitróová, Z; Kopčanský, P; Melníková, L; Okuda, M; Schwarzacher, W

2012-09-07

Measurements of the Faraday rotation at room temperature over the light wavelength range of 300-680 nm for horse spleen ferritin (HSF), magnetoferritin with different loading factors (LFs) and nanoscale magnetite and Fe(2)O(3) suspensions are reported. The Faraday rotation and the magnetization of the materials studied present similar magnetic field dependences and are characteristic of a superparamagnetic system. The dependence of the Faraday rotation on the magnetic field is described, excluding HSF and Fe(2)O(3), by a Langevin function with a log-normal distribution of the particle size allowing the core diameters of the substances studied to be calculated. It was found that the specific Verdet constant depends linearly on the LF. Differences in the Faraday rotation spectra and their magnetic field dependences allow discrimination between magnetoferritin with maghemite and magnetite cores which can be very useful in biomedicine.

The Faraday effect of natural and artificial ferritins

International Nuclear Information System (INIS)

Koralewski, M; Kłos, J W; Baranowski, M; Mitróová, Z; Kopčanský, P; Melníková, L; Okuda, M; Schwarzacher, W

2012-01-01

Measurements of the Faraday rotation at room temperature over the light wavelength range of 300–680 nm for horse spleen ferritin (HSF), magnetoferritin with different loading factors (LFs) and nanoscale magnetite and Fe 2 O 3 suspensions are reported. The Faraday rotation and the magnetization of the materials studied present similar magnetic field dependences and are characteristic of a superparamagnetic system. The dependence of the Faraday rotation on the magnetic field is described, excluding HSF and Fe 2 O 3 , by a Langevin function with a log-normal distribution of the particle size allowing the core diameters of the substances studied to be calculated. It was found that the specific Verdet constant depends linearly on the LF. Differences in the Faraday rotation spectra and their magnetic field dependences allow discrimination between magnetoferritin with maghemite and magnetite cores which can be very useful in biomedicine. (paper)

Synthetic Polymer with a Structure-Driven Hepatic Deposition and Curative Pharmacological Activity in Hepatic Cells