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Sample records for carbohydrate-deficient transferrin levels

  1. Carbohydrate deficient transferrin (CDT) in alcoholic cirrhosis: a kinetic study

    Henriksen, Jens Henrik; Grønbaek, M; Møller, Søren

    1997-01-01

    BACKGROUND/AIMS: Carbohydrate deficient transferrin has been introduced as a marker of excessive alcohol intake. The present study was undertaken in order to measure the circulating level of carbohydrate deficient transferrin in patients with alcoholic cirrhosis and to assess arteriovenous kinetics...... of carbohydrate deficient transferrin in liver and kidney. METHODS/RESULTS: The median value of serum carbohydrate deficient transferrin was 16.0 U/l in patients with alcoholic cirrhosis (n = 41), and this value was not significantly different from that of a normal control group (median 17.4 U/l, n = 55, ns......). Carbohydrate deficient transferrin was significantly higher in patients with cirrhosis and high current alcohol intake than in abstaining patients (20 vs. 14 U/l, p 50 g/day) had a significantly higher carbohydrate deficient transferrin...

  2. Pregnancy and variations of carbohydrate-deficient transferrin levels measured by the candidate reference HPLC method.

    Bianchi, Vincenza; Ivaldi, Alessandra; Raspagni, Alessia; Arfini, Carlo; Vidali, Matteo

    2011-01-01

    Contrasting data are available on the diagnostic accuracy of carbohydrate-deficient transferrin (CDT) during pregnancy. These differences may depend in part on how CDT was evaluated and expressed. Here, we report on variations of CDT levels in pregnant women using the high performance liquid chromatography (HPLC) candidate reference method. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, mean corpuscular volume, serum transferrin, urine and serum ethyl glucuronide and CDT were measured in 64 women, self-reporting as non-alcohol abusers (age: median 34, IQR: 28-38), at different stages of normal pregnancy (gestational weeks: median 28, IQR: 8-33). CDT was expressed as percentage of disialotransferrin to total transferrin (%CDT). Transferrin was associated with both %CDT (r = 0.66; P pregnancy trimester (first trimester: mean 1.01% (SD 0.19); second trimester: 1.30% (SD 0.14); third trimester: 1.53% (SD 0.22); ANOVA P pregnancy trimesters (P pregnancy and CDT could be more complex. The diagnostic accuracy of CDT for detecting alcohol abuse in a legal context may be limited in pregnant women and the effect of gestational age should be considered.

  3. Advanced gestational age increases serum carbohydrate-deficient transferrin levels in abstinent pregnant women.

    Bakhireva, Ludmila N; Cano, Sandra; Rayburn, William F; Savich, Renate D; Leeman, Lawrence; Anton, Raymond F; Savage, Daniel D

    2012-01-01

    Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients. Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method. At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as 'positive' for this biomarker at recruitment and at term, respectively (P = 0.011 ). These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further.

  4. The characteristics of transferrin variants by carbohydrate-deficient transferrin tests using capillary zone electrophoresis.

    Yoo, Gilsung; Kim, Juwon; Yoon, Kap Joon; Lee, Jong-Han

    2018-04-17

    Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice. © 2018 Wiley Periodicals, Inc.

  5. Carbohydrate-deficient transferrin--a valid marker of alcoholism in population studies? Results from the Copenhagen City Heart Study

    Grønbaek, M; Becker, U; Henriksen, Jens Henrik Sahl

    1995-01-01

    Carbohydrate-deficient transferrin (CDT) was analyzed by a modified radioimmunoassay test in a random population sample of 400 individuals, and results were compared with reported alcohol intake derived from a structured questionnaire. Among the 180 men, the test was found to be acceptable...... with respect to detecting harmful alcohol intake (> 35 beverages/week) and alcohol intake above the recommended level (21 beverages/week), although the positive predictive values were low. Among the 220 women, the test was invalid with low predictive values. CDT was compared with other known markers of high...... alcohol intake, and it was observed that CDT had higher sensitivity and specificity than AST and short Michigan Alcoholism Screening Test (sMAST) in men, whereas the positive and negative predictive values were low in all tests. A combination of CDT and AST proved to be a better marker of both harmful...

  6. The Alcohol Use Disorders Identification Test and carbohydrate-deficient transferrin in alcohol-related sickness absence.

    Hermansson, Ulric; Helander, Anders; Brandt, Lena; Huss, Anders; Rönnberg, Sten

    2002-01-01

    Previous studies have shown that elevated, risky levels of alcohol consumption may lead to higher rates of sickness absence. However, no studies have examined the Alcohol Use Disorders Identification Test (AUDIT) or serum carbohydrate-deficient transferrin (CDT) in relation to sickness absence in the workplace. The purpose of this study was to examine the relationship between sick-days, 12 months before screening, and the AUDIT and CDT (CDTect kit). Serum gamma-glutamyltransferase also was used for comparison. The study was carried out over 36 months in a large workplace and formed part of an ongoing controlled study. In conjunction with a routine health examination, employees were offered the opportunity to undergo an alcohol screening. Absence data were obtained from the company payroll system, and sickness absence was analyzed by using a three-ordinal level cumulative logistic model on the number of sick-days. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Of the 989 subjects who participated in the study, 193 (19.5%) screened positive in relation to either the AUDIT (>or=8 points) or CDT (women), or both. Employees who screened positive with the AUDIT had a significantly higher proportion of sick-days (p = 0.047) compared with those who screened negative (OR = 1.4, CI 1.0-1.9). Neither long, continuous periods of sickness absence nor absence on Mondays or Fridays gave a clear indication of individuals who screened positive on the AUDIT or CDT test. Our data indicate that individuals with moderately elevated or risky levels of alcohol consumption show an increase in sick-days. Accordingly, workplaces have a good reason for using a more systematic approach to alcohol screening in routine workplace health examinations.

  7. Use of finger-prick dried blood spots (fpDBS) and capillary electrophoresis for carbohydrate deficient transferrin (CDT) screening in forensic toxicology.

    Bertaso, Anna; Sorio, Daniela; Vandoros, Anthula; De Palo, Elio F; Bortolotti, Federica; Tagliaro, Franco

    2016-10-01

    Continued progress in chronic alcohol abuse investigation requires the development of less invasive procedures for screening purposes. The application of finger-prick and related dried blood spots (fpDBS) for carbohydrate deficient transferrin (CDT) detection appears suitable for this aim. Therefore, the goal of this project was to develop a screening method for CDT using fpDBS with CZE analysis. Blood samples prepared by finger-prick were placed on DBS cards and left to air dry; each dried fpDBS disc was shredded into small pieces and suspended in acid solution (60 μL of HCl 120 mmol/L). After centrifugation (10 min at 1500 × g), the collected sample was adjusted to pH 3.5. After an overnight incubation, the pH was neutralised and an iron rich solution was added. After 1 h, CZE analysis was carried out. A group of 47 individuals was studied. Parallel serum samples were collected from each investigated subject and the %CDT for each sample was measured using HPLC and CZE techniques. The fpDBS transferrin sialo isoform electropherograms were similar to those obtained with serum. Moreover, fpDBS CZE CDT percentage levels demonstrated significant statistical correlation with those obtained from serum for both HPLC and CZE %CDT (p < 0.01; r 2 = 0.8913 and 0.8976, respectively), with %CDT from 0.8 to 13.7% for fpDBS and from 0.7 to 12.7% for serum. The newly developed fpDBS procedure for CDT analysis provides a simple and inexpensive tool for use in population screening. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Serum transferrin levels in children with protein-energy malnutrition

    Selime Aydoğdu

    2013-03-01

    Full Text Available Objective: Although the diagnosis of patients with severemalnutrition is easy, it is very difficult to recognize patientswith mild and moderate malnutrition. A variety of methodsattempts to develop for early diagnosis of these cases.In this study, we evaluated the serum transferrin and albuminlevels in children with mild, moderate and severeprotein-energy malnutrition (PEM.Materials and methods: Children admitted to our policlinic,aged between 3 and 25 months, 45 subjects withPEM and 39 healthy subjects (control group were evaluated.According to the Gomez, Waterlow and Kanawatisubjects with PEM were divided in 3 subgroups mild,moderate and severe PEM. Anthropometric measurementsand biochemical results of 4 groups were compared.Results: For albumin levels in mild to moderate PEMgroups, 37.7% sensitivity, and 28.5% specificity, positivepredictive value 54%; negative predictive value 16.6%was found. For severe PEM sensitivity, specificity, positivepredictive value and negative predictive value were71%, 62.5%, 45%, and 83.3% respectively.With respect to the levels of transferrin, a significant differencewas found between mild PEM-control and moderatePEM-control groups (p0.05.Conclusion: Our study results showed that albumin isa weak indicator in mild-moderate PEM. In these cases,serum transferrin level reduces before decreasing of albuminlevel, thus it may be an early sensitive finding thatcan be used as a sensitive parameter in the diagnosis ofearly stages of malnutrition.Key words: Protein energy malnutrition, children, albumin,transferrin

  9. An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

    Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

    2015-01-01

    A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

  10. Association between serum transferrin receptor levels and malaria ...

    Background: The relationship between body iron levels and malaria presents a complex interaction that provide variable and contradicting results. We designed a study to investigate associations between concentrations of biomarkers of body iron and malaria recurrence among children. Methods: We conducted a ...

  11. Effect of type of alcoholic beverages on carbohydrate-deficient transferrin, sialic acid, and liver enzymes

    Sillanaukee, P.; Gaag, M.S. van der; Sierksma, A.; Hendriks, H.F.J.; Strid, N.; Pönniö, M.; Nikkari, S.T.

    2003-01-01

    Background: There are only limited data obtained under well controlled conditions on the effects of moderate drinking on markers of alcohol use disorders. The aim of this study was to investigate the effects of moderate intake of different alcoholic beverages on these markers, including

  12. Total mortality by transferrin saturation levels: two general population studies and a metaanalysis

    Ellervik, Christina; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2011-01-01

    There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown.......There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown....

  13. Changes in iron levels, total iron binding capacity, transferrin saturation in race horses, before and after of physical exercise

    Gláucia Abramovitc

    2014-09-01

    Full Text Available ABSTRACT. Abramovitc G., Parra A.C. & Fernandes W.R. [Changes in iron levels, total iron binding capacity, transferrin saturation in race horses, before and after of physical exercise]. Variação de níveis séricos de ferro, da capacidade total de ligação do ferro e da saturação da transferrina em equinos de corrida, antes e após exercício físico. Revista Brasileira de Medicina Veterinária, 36(3:289-293, 2014. Departamento de Clínica Médica, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Rua Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitária, Butantã, São Paulo, SP 05508-270, Brasil. Email: wilsonrf@usp.br The preparation of the horse for physical activities in competition is directly related to important factors such as nutrition, muscle adaptation and blood profile, related to the concentration of serum iron, total capacity total iron binding capacity (TIBC and saturation of transferrin. This study aimed to evaluate the influence of exercise in iron levels, the total iron and transferrin saturation in race horses. One hundred and eleven samples of blood serum were collected from Thoroughbred horses, from the Jockey Club of São Paulo, aged between 3 and 4 years old, male and female, clinically healthy, practitioners turf competition, in sand or grass. The samples were obtained before exercise (control time and 30 minutes after exercise (post exercise. These animals were submitted to gallop training, of high intensity and short duration for this research. As a result, it was observed that the serum concentration of iron (Fe showed a statistically significant lowering post-exercise, due to organic re-balance of iron, while TIBC (total iron binding capacity showed a clear and significant increase in their serum levels due to increased needs of iron during and after exercise. The percentage of transferrin saturation in serum was shown to be lower post-exercise, probably due to the recruitment of

  14. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels

    Cotten, M.; Laengle-Rouault, F.; Kirlappos, H.; Wagner, E.; Mechtler, K.; Zenke, M.; Beug, H.; Birnstiel, M.L.

    1990-01-01

    The authors have subverted a receptor-mediated endocytosis event to transport genes into human leukemic cells. By coupling the natural iron-delivery protein transferrin to the DNA-binding polycations polylysine or protamine, they have created protein conjugates that bind nucleic acids and carry them into the cell during the normal transferrin cycle. They demonstrate here that this procedure is useful for a human leukemic cell line. They enhanced the rate of gene delivery by (i) increasing the transferrin receptor density through treatment of the cells with the cell permeable iron chelator desferrioxamine, (ii) interfering with the synthesis of heme with succinyl acetone treatment, or (iii) stimulating the degradation of heme with cobalt chloride treatment. Consistent with gene delivery as an endocytosis event, they show that the subsequent expression in K-562 cells of a gene included in the transported DNA depends upon the cellular presence of the lysosomotropic agent chloroquine. By contrast, monensin blocks transferrinfection, as does incubation of the cells at 18 degree C

  15. Iron status of Filipino infants and preschoolers using plasma ferritin and transferrin receptor levels.

    Kuizon, M D; Madriaga, J R; Desnacido, J A; Cheong, R L; Perlas, L A

    1996-06-01

    Iron status of 1,861 Filipino infants and preschoolers was evaluated by measurements of plasma ferritin (PF), transferrin receptor (TR) and hemoglobin (Hb). One group of subjects (Group I) consisted of all anemic subjects together with a systematic subsample from the Fourth National Nutrition Survey-Biochemical Phase. Results showed that depleted iron stores based on PF ( 8.5 mg/l) was present in higher proportion (80.0% and 73.7% for infants and preschoolers) which was comparable to the proportion of anemia (80.3%). In a subgroup of subjects from the Country Program for Children IV (Group 2) elevated TR was present in 61.4% of infants and 46.5% of preschoolers. A lower proportion of depleted iron stores of 22.7% in infants and 15.2% in preschoolers was observed. Correlation test showed that there was a closer relationship between Hb and TR (r = -0.42) than Hb and PF (r = 0.20) even if PF was expected to give a higher proportion of values below normal. The occurrence of anemia in the presence of elevated TR without any decrease in PF values suggest that the diagnostic ability of PF could be limited in the presence of infection. Therefore, future studies should include biochemical tests such as C-reactive proteins (CRP) to determine the extent of association between anemia and infection.

  16. Comparison of transferrin isoform analysis by capillary electrophoresis and HPLC for screening congenital disorders of glycosylation.

    Dave, Mihika B; Dherai, Alpa J; Udani, Vrajesh P; Hegde, Anaita U; Desai, Neelu A; Ashavaid, Tester F

    2018-01-01

    Transferrin, a major glycoprotein has different isoforms depending on the number of sialic acid residues present on its oligosaccharide chain. Genetic variants of transferrin as well as the primary (CDG) & secondary glycosylation defects lead to an altered transferrin pattern. Isoform analysis methods are based on charge/mass variations. We aimed to compare the performance of commercially available capillary electrophoresis CDT kit for diagnosing congenital disorders of glycosylation with our in-house optimized HPLC method for transferrin isoform analysis. The isoform pattern of 30 healthy controls & 50 CDG-suspected patients was determined by CE using a Carbohydrate-Deficient Transferrin kit. The results were compared with in-house HPLC-based assay for transferrin isoforms. Transferrin isoform pattern for healthy individuals showed a predominant tetrasialo transferrin fraction followed by pentasialo, trisialo, and disialotransferrin. Two of 50 CDG-suspected patients showed the presence of asialylated isoforms. The results were comparable with isoform pattern obtained by HPLC. The commercial controls showed a <20% CV for each isoform. Bland Altman plot showed the difference plot to be within +1.96 with no systemic bias in the test results by HPLC & CE. The CE method is rapid, reproducible and comparable with HPLC and can be used for screening Glycosylation defects. © 2017 Wiley Periodicals, Inc.

  17. Serum transferrin receptor in polycythemia.

    Manteiga, R; Remacha, A F; Sardà, M P; Ubeda, J

    1998-10-01

    We measured serum transferrin receptor (sTfR) levels in 22 patients with polycythemia vera and in 26 cases of secondary polycythemia. In our study, raised sTfR levels in both polycythemia groups were related to iron deficiency.

  18. Transferrin Level Before Treatment and Genetic Polymorphism in HFE Gene as Predictive Markers for Response to Adalimumab in Crohn's Disease Patients.

    Repnik, Katja; Koder, Silvo; Skok, Pavel; Ferkolj, Ivan; Potočnik, Uroš

    2016-08-01

    Tumor necrosis factor α inhibitors (anti-TNF) have improved treatment of several complex diseases, including Crohn's disease (CD). However, the effect varies and approximately one-third of the patients do not respond. Since blood parameters as well as genetic factors have shown a great potential to predict response during treatment, the aim of the study was to evaluate response to anti-TNF treatment with adalimumab (ADA) between genes HFE and TF and haematological parameters in Slovenian refractory CD patients. Single nucleotide polymorphisms (SNPs) rs1799852 in gene TF and rs2071303 in gene HFE were genotyped in 68 refractory CD patients for which response has been measured using inflammatory bowel disease questionnaire (IBDQ) index. Haematological parameters and IBDQ index were determined before therapy and after 4, 12, 20 and 30 weeks. We found novel strong association between SNP rs2071303 in gene HFE and response to ADA treatment, particularly patients with G allele comparing to A allele had better response after 20 weeks (p = 0.008). Further, we found strong association between transferrin level at baseline and treatment response after 12, 20 and 30 weeks, where average transferrin level before therapy was lower in responders (2.38 g/L) compared to non-responders (2.89 g/L, p = 0.005). Association was found between transferrin level in week 30 and SNP rs1799852 (p = 0.023), and between MCHC level before treatment and SNP rs2071303 (p = 0.007). Our results suggest that SNP in gene HFE as well as haematological markers serve as promising prognostic markers of response to anti-TNF treatment in CD patients.

  19. Iron, transferrin and myelinogenesis

    Sergeant, C. E-mail: sergeant@cenbg.in2p3.fr; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F

    2003-09-01

    Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5{sup '} and 3{sup '} untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

  20. Iron, transferrin and myelinogenesis

    Sergeant, C.; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F.

    2003-01-01

    Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport

  1. Benefit of carbohydrate deficient transferrin in detecting chronic alcohol abuse in the elderly: study protocol for a multicentre, non-randomized, open-label study

    Cécile Schnell

    2016-01-01

    Ethics: The Committee for the Protection of Persons located in Strasbourg, France, delivered a favourable opinion on the study project. Informed consent: The physician or the health network′s care coordinator informs the patient about the study protocol and obtains the patient′s assent. The investigator completes a non-opposition file and a copy is given to the patient and to his/her relative or helper.

  2. Ceruloplasmin/Transferrin Ratio Changes in Alzheimer's Disease

    Rosanna Squitti

    2011-01-01

    Full Text Available The link between iron and Alzheimer's disease (AD has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf. Cp/Tf and transferrin saturation increased in AD patients. Cp/Tf ratios also correlated positively with peroxide levels and negatively with serum iron concentrations. Elevated values of ceruloplasmin, peroxides, and Cp/Tf inversely correlated with MMSE scores. Isolated medial temporal lobe atrophy positively correlated with Cp/Tf and negatively with serum iron. All these findings indicate that the local iron accumulation found in brain areas critical for AD should be viewed in the frame of iron systemic alterations.

  3. Acquisition of iron from transferrin regulates reticulocyte heme synthesis

    Ponka, P.; Schulman, H.M.

    1985-01-01

    Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up 59 Fe from [ 59 Fe]SIH and incorporate it into heme to a much greater extent than from saturating concentrations of [ 59 Fe]transferrin. Also, Fe-SIH stimulates [2- 14 C]glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate 59 Fe incorporation into heme from either [ 59 Fe]transferrin or [ 59 Fe]SIH but does reverse the inhibition of 59 Fe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes

  4. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

    Bapat, Prachi R; Satav, Ashish R; Husain, Aliabbas A; Shekhawat, Seema D; Kawle, Anuja P; Chu, Justin J; Purohit, Hemant J; Daginawala, Hatim F; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

  5. Aluminum stimulates uptake of non-transferrin bound iron and transferrin bound iron in human glial cells

    Kim, Yongbae; Olivi, Luisa; Cheong, Jae Hoon; Maertens, Alex; Bressler, Joseph P.

    2007-01-01

    Aluminum and other trivalent metals were shown to stimulate uptake of transferrin bound iron and nontransferrin bound iron in erytholeukemia and hepatoma cells. Because of the association between aluminum and Alzheimer's Disease, and findings of higher levels of iron in Alzheimer's disease brains, the effects of aluminum on iron homeostasis were examined in a human glial cell line. Aluminum stimulated dose- and time-dependent uptake of nontransferrin bound iron and iron bound to transferrin. A transporter was likely involved in the uptake of nontransferrin iron because uptake reached saturation, was temperature-dependent, and attenuated by inhibitors of protein synthesis. Interestingly, the effects of aluminum were not blocked by inhibitors of RNA synthesis. Aluminum also decreased the amount of iron bound to ferritin though it did not affect levels of divalent metal transporter 1. These results suggest that aluminum disrupts iron homeostasis in Brain by several mechanisms including the transferrin receptor, a nontransferrin iron transporter, and ferritin

  6. The effect of glycosylation on the transferrin structure: A molecular dynamic simulation analysis.

    Ghanbari, Z; Housaindokht, M R; Bozorgmehr, M R; Izadyar, M

    2016-09-07

    Transferrins have been defined by the highly cooperative binding of iron and a carbonate anion to form a Fe-CO3-Tf ternary complex. As such, the layout of the binding site residues affects transferrin function significantly; In contrast to N-lobe, C-lobe binding site of the transferrin structure has been less characterized and little research which surveyed the interaction of carbonate with transferrin in the C-lobe binding site has been found. In the present work, molecular dynamic simulation was employed to gain access into the molecular level understanding of carbonate binding site and their interactions in each lobe. Residues responsible for carbonate binding of transferrin structure were pointed out. In addition, native human transferrin is a glycoprotein that two N-linked complex glycan chains located in the C-lobe. Usually, in the molecular dynamic simulation for simplifying, glycan is removed from the protein structure. Here, we explore the effect of glycosylation on the transferrin structure. Glycosylation appears to have an effect on the layout of the binding site residue and transferrin structure. On the other hand, sometimes the entire transferrin formed by separated lobes that it allows the results to be interpreted in a straightforward manner rather than more parameters required for full length protein. But, it should be noted that there are differences between the separated lobe and full length transferrin, hence, a comparative analysis by the molecular dynamic simulation was performed to investigate such structural variations. Results revealed that separation in C-lobe caused a significant structural variation in comparison to N-lobe. Consequently, the separated lobes and the full length one are different, showing the importance of the interlobe communication and the impact of the lobes on each other in the transferrin structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

    Małgorzata Duda

    2009-01-01

    Full Text Available Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Recent studies have reported that transferrin plays a crucial role in the local regulation of ovarian function, apart from its iron-binding characteristic. Therefore, the present study was undertaken to explore the possible role of transferrin in porcine granulosa cells function by examining its influence on aromatase activity, the most important indicator of follicular cell differentiation. In the first series of studies, pig granulosa cells isolated from small, immature follicles were cultured in the presence of transferrin alone (10 microg/ml or 100 microg/ml or with the addition of FSH (100ng/ml. The second series of studies was undertaken to determine transferrin-stimulated granulosa cells ability to aromatize exogenous testosterone (1x10(-7M. One hour after the establishment of cultures an aromatase inhibitor CGS16949A was added to test its influence on estradiol production. After 48 hours, cultures were terminated and cells were processed for immunocytochemical staining of aromatase. Media were frozen for further estradiol level analysis. Positive immunostaining for aromatase was found in all granulosa cell cultures. The intensity of immunostaining was always stronger in cultures supplemented with FSH whereas the addition of transferrin had no effect. Granulosa cells in vitro synthesized the highest amount of estradiol after the addition of FSH and exogenous testosterone as measured radioimmunologically. Concomitant treatment with FSH and transferrin caused an inhibition of FSH-stimulated aromatase activity. The production of estradiol also declined in the presence of FSH, testosterone and transferrin. This study demonstrates that transferrin had a dose-dependent inhibitory effect on FSH-stimulated aromatase activity, which was confirmed by radioimmunoassay. Our results indicate

  8. The structural basis of transferrin sequestration by transferrin-binding protein B

    Calmettes, Charles; Alcantara, Joenel; Yu, Rong-Hua; Schryvers, Anthony B.; Moraes, Trevor F. (Toronto); (Calgary)

    2012-03-28

    Neisseria meningitidis, the causative agent of bacterial meningitis, acquires the essential element iron from the host glycoprotein transferrin during infection through a surface transferrin receptor system composed of proteins TbpA and TbpB. Here we present the crystal structures of TbpB from N. meningitidis in its apo form and in complex with human transferrin. The structure reveals how TbpB sequesters and initiates iron release from human transferrin.

  9. Transferrin metabolism in alcoholic liver disease

    Potter, B.J.; Chapman, R.W.; Nunes, R.M.; Sorrentino, D.; Sherlock, S.

    1985-01-01

    The metabolism of transferrin was studied using purified 125 I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated

  10. Kinetics of Transferrin and Transferrin-Receptor during Iron Transport through Blood Brain Barrier

    Khan, Aminul; Liu, Jin; Dutta, Prashanta

    2017-11-01

    Transferrin and its receptors play an important role during the uptake and transcytosis of iron by blood brain barrier (BBB) endothelial cells to maintain iron homeostasis in BBB endothelium and brain. In the blood side of BBB, ferric iron binds with the apo-transferrin to form holo-transferrin which enters the endothelial cell via transferrin receptor mediated endocytosis. Depending on the initial concentration of iron inside the cell endocytosed holo-transferrin can either be acidified in the endosome or exocytosed through the basolateral membrane. Acidification of holo-transferrin in the endosome releases ferrous irons which may either be stored and used by the cell or transported into brain side. Exocytosis of the holo-transferrin through basolateral membrane leads to transport of iron bound to transferrin into brain side. In this work, kinetics of internalization, recycling and exocytosis of transferrin and its receptors are modeled by laws of mass action during iron transport in BBB endothelial cell. Kinetic parameters for the model are determined by least square analysis. Our results suggest that the cell's initial iron content determines the extent of the two possible iron transport pathways, which will be presented in this talk Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

  11. Adaptation of transferrin protein and glycan synthesis

    G. de Jong (Gerard); W.L. van Noort (W.); R.A. Feelders (Richard); C.M.H. de Jeu-Jaspars (Nel); H.G. van Eijk (Henk)

    1992-01-01

    textabstractWe report the patterns of variability in transferrin structure in pregnancy, iron deficiency anemia, women using oral contraceptives, nonanaemic rheumatoid arthritis, iron deficient rheumatoid arthritis and anemia of the chronic diseases. Changes in microheterogeneity were assessed by

  12. Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery

    Singh, Rahul Pratap [Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Sharma, Gunjan [Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005 (India); Sonali [Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Singh, Sanjay [Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005 (India); Patne, Shashikant C.U. [Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Pandey, Bajarangprasad L. [Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Koch, Biplob, E-mail: kochbiplob@gmail.com [Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005 (India); Muthu, Madaswamy S., E-mail: muthubits@rediffmail.com [Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005 (India); Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India)

    2016-10-01

    The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). D-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC{sub 50} values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24 h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P < 0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™. - Highlights: • It shows the development of transferrin conjugated MWCNT formulation of DTX for the effective treatment of lung cancer. • Evaluated the cellular uptake, cytotoxicity, cellular apoptosis, cell cycle, and ROS level of the DTX/C6 loaded MWCNT. • The IC{sub 50} values demonstrated that the transferrin conjugated MWCNT could be 136-fold more effective than Docel™. • Safety of the DTX formulations were studied by the measurements of ALP, LDH and total protein count levels in BAL fluid. • Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™ in lung cancer delivery.

  13. Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery

    Singh, Rahul Pratap; Sharma, Gunjan; Sonali; Singh, Sanjay; Patne, Shashikant C.U.; Pandey, Bajarangprasad L.; Koch, Biplob; Muthu, Madaswamy S.

    2016-01-01

    The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). D-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC_5_0 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24 h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P < 0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™. - Highlights: • It shows the development of transferrin conjugated MWCNT formulation of DTX for the effective treatment of lung cancer. • Evaluated the cellular uptake, cytotoxicity, cellular apoptosis, cell cycle, and ROS level of the DTX/C6 loaded MWCNT. • The IC_5_0 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more effective than Docel™. • Safety of the DTX formulations were studied by the measurements of ALP, LDH and total protein count levels in BAL fluid. • Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™ in lung cancer delivery.

  14. Hemin inhibits internalization of transferrin by reticulocytes and promotes phosphorylation of the membrane transferrin receptor

    Cox, T.M.; O'Donnell, M.W.; Aisen, P.; London, I.M.

    1985-01-01

    Addition of hemin to reticulocytes inhibits incorporation of iron from transferrin. Heme also regulates protein synthesis in immature erythroid cells through its effects on phosphorylation of the initiation factor eIF-2. The authors have examined its effects on endocytosis of iron-transferrin and phosphorylation of the transferrin receptor. Hemin reduced iron transport but increased cell-associated transferrin. During uptake of 125 I-labeled transferrin in the steady state, the use of a washing technique to dissociate bound transferrin on the cell membrane showed that radioligand accumulated on the surface of hemin-treated cells. Receptor phosphorylation was investigated by immunoprecipitation of reticulocyte extracts after metabolic labeling with [ 32 P]P/sub i/. In the absence of ligand, phosphorylated receptor was chiefly localized on cell stroma. Exposure to transferrin increased cytosolic phosphorylated receptor from 15-30% to approximately 50% of the total, an effect overcome by hemin treatment. The findings suggest a possible relationship of phosphorylation to endocytosis of the transferrin receptor in reticulocytes

  15. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    Bukovsky Antonin

    2008-07-01

    Full Text Available Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells, placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3 and abnormal (n = 9 pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.

  16. Specificity of chicken and mammalian transferrins in myogenesis

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

  17. Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias

    Muta, K.; Nishimura, J.; Ideguchi, H.; Umemura, T.; Ibayashi, H.

    1987-01-01

    To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125 I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects. Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125 I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast

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

    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.

  19. Radiogallium localization in tumors: blood binding and transport and the role of transferrin

    Vallabhajosula, S.R.; Harwig, J.F.; Siemsen, J.K.; Wolf, W.

    1980-01-01

    As a crucial step toward the understanding of the tumor localization of gallium, we have re-investigated its binding and transport in blood. The studies were performed in vivo by injection of gallium-67 citrate in rabbits, and in vitro by incubation of gallium-67 citrate with individual plasma proteins. By ultrafiltration and gel filtration chromatography, rabbit plasma samples showed essentially complete protein binding, whereas dialysis indicated considerable nonprotein-bound gallium, the amount depending on the dialysis medium. According to electrophoresis, total binding was inversely proportional to electrophoresis time. Affinity chromatography showed all gallium to be bound to transferrin, whereas electrophoresis caused continuous dissociation of gallium from transferrin, with the resulting unbound radioactivity appearing in various other protein bands. Similarly, the binding of gallium to transferrin in the in vitro incubation studies was inversely proportional to electrophoresis time, whereas ultrafiltration and gel filtration chromatography showed all gallium to be transferrin-bound. No binding of gallium to other proteins, such as albumin, was observed. This study demonstrates that gallium at the tracer level in blood is exclusively bound to and transported by transferrin, and indicates that electrophoresis and dialysis of easily dissociable metal complexes are subject to significant artifacts. Accurate determination of protein binding of radiopharmaceuticals requires a combination of analytical techniques and cautious interpretation of the results

  20. Competitive advantage of diferric transferrin in delivering iron to reticulocytes.

    Huebers, H A; Csiba, E; Huebers, E; Finch, C A

    1983-01-01

    Radioiron- and radioiodine-labeled forms of human diferric and monoferric transferrin and apotransferrin, isolated by preparative isoelectric focusing, were used to define transferrin-iron uptake by human reticulocytes. In mixtures of human diferric and monoferric transferrin, the diferric molecule had a constant 7-fold advantage in delivering iron to reticulocytes, as compared with the 2-fold advantage when single solutions of mono- and diferric transferrins were compared. This was shown to be due to competitive interaction in iron delivery, probably at a common membrane-receptor binding site for transferrin. Apotransferrin did not interfere with the iron-donating process and its limited cellular uptake was inhibited in noncompetitive fashion by diferric transferrin. PMID:6572005

  1. The influence of maternal smoking on transferrin sialylation and fetal biometric parameters.

    Wrześniak, Marta; Królik, Małgorzata; Kepinska, Marta; Milnerowicz, Halina

    2016-10-01

    Transferrin is a glycosylated protein responsible for transporting iron, an essential metal responsible for proper fetal development. Tobacco is a heavily used xenobiotic having a negative impact on the human body and pregnancy outcomes. Aims of this study was to examine the influence of tobacco smoking on transferrin sialic acid residues and their connection with fetal biometric parameters in women with iron-deficiency. The study involved 173 samples from pregnant women, smokers and non-smokers, iron deficient and not. Transferrin sialylation was determined by capillary electrophoresis. The cadmium (Cd) level was measured by atomic absorption and the sialic acid concentration by the resorcinol method. Women with iron deficiencies who smoked gave birth earlier than non-smoking, non-iron-deficient women. The Cd level, but not the cotinine level, was positively correlated with transferrin sialylation in the blood of iron-deficient women who smoked; 3-, 4-, 5- and 6-sialoTf correlated negatively with fetal biometric parameters in the same group. It has been shown the relationship between Cd from tobacco smoking and fetal biometric parameters observed only in the iron deficient group suggests an additive effect of these two factors, and indicate that mothers with anemia may be more susceptible to Cd toxicity and disturbed fetal development. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Elevated transferrin saturation and risk of diabetes

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Andersen, Henrik Ullits

    2011-01-01

    OBJECTIVE We tested the hypothesis that elevated transferrin saturation is associated with an increased risk of any form of diabetes, as well as type 1 or type 2 diabetes separately. RESEARCH DESIGN AND METHODS We used two general population studies, The Copenhagen City Heart Study (CCHS, N = 9......,121) and The Copenhagen General Population Study (CGPS, N = 24,195), as well as a 1:1 age- and sex-matched population-based case-control study with 6,129 patients with diabetes from the Steno Diabetes Centre and 6,129 control subjects, totaling 8,535 patients with diabetes and 37,039 control subjects. RESULTS...

  3. Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid

    Moos, Torben; Morgan, Evan H.

    1998-01-01

    Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake......Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake...

  4. Transferrin Family Genes in the Brown Planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) in Response to Three Insecticides.

    Wu, Shun-Fan; Li, Jian; Zhang, Yong; Gao, Cong-Fen

    2018-02-09

    Transferrins are involved in iron metabolism, immunity, xenobiotics tolerance, and development in eukaryotic organisms including insects. However, little is known about the relationship between transferrins and insecticide toxicology and resistance. Three transferrin family genes, NlTsf1, NlTsf2, and NlTsf3, of the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae)a major insect pest of rice field in Asia, had been identified and characterized in this study. Quantitative polymerase chain reaction results demonstrated that NlTsf1 was significantly higher than the other two genes in different tissues. All of them were expressed at higher levels in abdomen and head than in antenna, leg, stylet, and thorax. Compared with the control, the expression of three N. lugens transferrin family genes decreased dramatically 24 h after treatment with buprofezin, pymetrozine and imidacloprid. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. Actinide uptake by transferrin and ferritin metalloproteins

    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.)

  6. Biodistribution of Ru-97-labeled DTPA, DMSA and transferrin

    Som, P.; Oster, Z.H.; Fairchild, R.G.; Atkins, H.L.; Brill, A.B.; Gil, M.C.; Srivastava, S.C.; Meinken, G.E.; Goldman, A.G.; Richards, P.

    1980-01-01

    Ruthenium-97 is being produced at the Brookhaven Linac Isotope Producer (BLIP). The favorable physical properties of Ru-97 and chemical reactivity of ruthenium offer a potential for using this isotope to label compounds useful for delayed scanning. Diethylenetriamine pentaacetic acid (DTPA), 2,3-Dimercaptosuccinic acid (DMSA), and Transferrin (TF) were labeled with Ru-97-chloride. Ru-97-DTPA and In-111-DTPA, injected intravenously, showed similar organ distribution, kinetics, and more than 80% excretion by 0.5 h. Ru-97-DTPA and In-111-DTPA injected into the cisterna magna of dogs showed similar kinetics in brain, blood, and urinary bladder. The energy deposited by 1 mCi In-111-DTPA is twice that from 1 mCi Ru-97-DTPA. High quality camera images of the CSF space in the dog were obtained with both isotopes. Ru-97-DMSA was prepared with and without the addition of SnCl 2 .2H 2 O. Tin-free DMSA was rapidly excreted via the kidneys, whereas for maximum cortical deposition, the tin-containing preparation was superior. This compound is suitable for delayed imaging of both normal and impaired kidneys. Tissue distribution studies were performed in abscess-bearing rats with Ru-97-transferrin. Although blood levels were higher than with Ga-67-citrate, the abscess had twice as much Ru-97-TF as Ga-67-citrate and the Ru-97 muscle activity was one-third that of Ga-67. Imaging of abscess-bearing rabbits with Ru-97-TF visualized the abscesses as early as 1/2 hr after injection. Since the initial images visualize the abscess so clearly and since the TF portion of the compound binds to the abscess, Tc-99m-TF is being studied for the same purpose. Ru-97-labeled compounds are a promising replacement for In-111 and possibly also for Ga-67 compounds with the advantages of lower radiation dose and high quality image

  7. Annotating MYC status with 89Zr-transferrin imaging.

    Holland, Jason P; Evans, Michael J; Rice, Samuel L; Wongvipat, John; Sawyers, Charles L; Lewis, Jason S

    2012-10-01

    A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of (89)Zr-desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of (89)Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

  8. The physiological significance of transferrin microheterogeneity : an interpretation of the role of N-linked glycans in transferrin and iron metabolism /

    G. de Jong (Gerardus)

    1993-01-01

    textabstractThe starting point for this thesis was the observation that when attempts are made to separate monoferric transferrins from diferric transferrin by isoelectric focusing, in addition to what was thought to represent the pure monoferric transferrins, a great number of additional bands

  9. Clone and expression of human transferrin receptor gene: a marker gene for magnetic resonance imaging

    Li Li; Liu Lizhi; Lv Yanchun; Liu Xuewen; Cui Chunyan; Wu Peihong; Liu Qicai; Ou Shanxing

    2007-01-01

    Objective: To clone human transferrin receptor (hTfR) gene and construct expression vector producing recombination protein. Methods: Human transferrin receptor gene cDNA was amplified by RT-PCR from human embryonic liver and lung tissue. Recombinant pcDNA3-hTfR and pEGFP-Cl-hTfR plasmids were constructed and confirmed by DNA sequencing. These plasmids were stably transfected into the HEK293 cells. The protein expression in vitro was confirmed by Western Blot. The efficiency of expression and the location of hTfR were also investigated by fluorescence microscopy and confocal fluorescence microscopy. Results: The full length cDNA of hTfR gene (2332 bp) was cloned and sequenced. The hTfR (190 000) was overexpressed in transfected HEK293 cells by Western blot analysis. Fluorescence micrographs displayed that the hTfR was expressed at high level and located predominantly in the cell surface. Conclusions: Human transferrin receptor (hTfR) gene has been successfully cloned and obtained high-level expression in HEK293 cells, and the recombination protein of hTfR distributed predominantly in the cell membrane. (authors)

  10. Soluble transferrin receptor: a differentiating marker between iron deficiency anaemia and anaemia of chronic disorders

    Saboor, M.; Moinuddin, A.; Naureen, A.

    2012-01-01

    Background: Iron deficiency anaemia and anaemia of chronic disorders are the two major causes of microcytic and hypochromic anaemia. Many times the diagnosis of these conditions becomes difficult through conventional laboratory tests. Determination of soluble transferrin receptors is a helpful laboratory test for the differential diagnosis of these conditions. The study was conducted to evaluate the role of soluble transferrin receptors in the differential diagnosis between iron deficiency anaemia and anaemia of chronic disorders. Methods: A total of 80 blood samples were evaluated, i.e., 20 samples from normal adult male, 20 samples from normal adult female, 20 samples from iron deficiency anaemia group and 20 samples from patients with anaemia of chronic disorders. Soluble transferrin receptors were determined by ELISA technique using Quantikine IVD kit (R and D Systems). Results: There was significant difference in the levels of sTfR in iron deficiency anaemia and anaemia of chronic disorders. Statistically non-significant difference was observed between the levels of sTfR in patients with anaemia of chronic disorders as compared to normal control group. Conclusion: The sTfR determination can be used as a reliable differentiating marker in the diagnosis of iron deficiency anaemia and anaemia of chronic disorders. (author)

  11. Synthesis and characterization of human transferrin-stabilized gold nanoclusters

    Le Guevel, Xavier; Schneider, Marc; Daum, Nicole

    2011-01-01

    Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals ( em = 695 nm). Structural investigation and photophysical measurements show a high population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight Plus tests show no cytotoxicity of these labelled proteins in cells (1 μg ml -1 -1 mg ml -1 ). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting.

  12. Seminal transferrin in the seminal quality evaluation of hemodialytic patients

    Gilmar Pereira Silva

    2018-03-01

    Full Text Available Objective: to verify the association between seminal quality and seminal transferrin (ST level and fertility index in patients undergoing chronic hemodialysis (CH. Material and methods: This is a cross-sectional study in a group of 60 men (case undergoing CH for more than 6 months, and a group of 30 healthy men (control, aged 18-60 years, without clinical or laboratory signs of infection/inflammation. Spermiogram was performed, fertility index (FI was calculated and ST and sex hormones (SH levels were measured, including follicle-stimulating hormone, luteinizing hormone, total testosterone, and prolactin. Results: All individuals were eugonadal. No differences for age (49.47 ± 5.56, 47.90 ± 6.2, p = 0.22 were observed between cases and controls, whereas there were significant differences between the individuals in the case and control groups with respect to the mean FI (p = 0.000, seminal parameters (SP (p = 0.000, and ST levels (40.12 ± 08.25 vs 73.32 ± 06.8, p = 0.000. ST levels were correlated with FI (r = 0.787, p = 0.00 and SP (motility: r = 0.857, p = 0.000; vitality: r = 0.551, p = 0.000; density: r = 0.850, p = 0.000; normal morphology: r = 0.386, p = 0.000. Linear regression model showed relationship of ST levels with total sperm motility (R2 = 0.701; p = 0.000 and and FI (R2 = 0.569; p = 0.000. Conclusions: Our results suggest that seminal quality is associated with ST levels and FI and that it can be used the initial investigation of subfertility/infertility of patients undergoing chronic hemodialysis..

  13. Phorbol diesters and transferrin modulate lymphoblastoid cell transferrin receptor expression by two different mechanisms

    Alcantara, O.; Phillips, J.L.; Boldt, D.H.

    1986-01-01

    Expression of transferrin receptors (TfR) by activated lymphocytes is necessary for lymphocyte DNA synthesis and proliferation. Regulation of TfR expression, therefore, is a mechanism by which the lymphocyte's proliferative potential may be directed and controlled. The authors studied mechanisms by which lymphoblastoid cells modulate TfR expression during treatment with phorbol diesters or iron transferrin (FeTf), agents which cause downregulation of cell surface TfR. Phorbol diester-induced TfR downregulation occurred rapidly, being detectable at 2 min and reaching maximal decreases of 50% by 15 min. It was inhibited by cold but not by agents that destabilize cytoskeletal elements. Furthermore, this downregulation was reversed rapidly by washing or by treatment with the membrane interactive agent, chlorpromazine. In contrast, FeTf-induced TfR downregulation occurred slowly. Decreased expression of TfR was detectable only after 15 min and maximal downregulation was achieved after 60 min. Although FeTf-induced downregulation also was inhibited by cold, it was inhibited in addition by a group of microtubule destabilizing agents (colchicine, vinblastine, podophyllotoxin) or cytochalasin B, a microfilament inhibitor. Furthermore, FeTf-induced downregulation was not reversed readily by washing or by treatment with chlorpromazine. Phorbol diesters cause TfR downregulation by a cytoskeleton-independent mechanism. These data indicate that TfR expression is regulated by two independent mechanisms in lymphoblastoid cells, and they provide the possibility that downregulation of TfR by different mechanisms may result in different effects in these cells

  14. Cloning and characterization of transferrin cDNA and rapid detection of transferrin gene polymorphism in rainbow trout (Oncorhynchus mykiss).

    Tange, N; Jong-Young, L; Mikawa, N; Hirono, I; Aoki, T

    1997-12-01

    A cDNA clone of rainbow trout (Oncorhynchus mykiss) transferrin was obtained from a liver cDNA library. The 2537-bp cDNA sequence contained an open reading frame encoding 691 amino acids and the 5' and 3' noncoding regions. The amino acid sequences at the iron-binding sites and the two N-linked glycosylation sites, and the cysteine residues were consistent with known, conserved vertebrate transferrin cDNA sequences. Single N-linked glycosylation sites existed on the N- and C-lobe. The deduced amino acid sequence of the rainbow trout transferrin cDNA had 92.9% identities with transferrin of coho salmon (Oncorhynchus kisutch); 85%, Atlantic salmon (Salmo salar); 67.3%, medaka (Oryzias latipes); 61.3% Atlantic cod (Gadus morhua); and 59.7%, Japanese flounder (Paralichthys olivaceus). The long and accurate polymerase chain reaction (LA-PCR) was used to amplify approximately 6.5 kb of the transferrin gene from rainbow trout genomic DNA. Restriction fragment length polymorphisms (RFLPs) of the LA-PCR products revealed three digestion patterns in 22 samples.

  15. Monocyte transferrin-iron uptake in hereditary hemochromatosis

    Sizemore, D.J.; Bassett, M.L.

    1984-01-01

    Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells

  16. Isoforms of transferrin in psoriasis patients abusing alcohol

    P. Hoefkens (Peter); E.M. Higgins; R.J. Ward (Roberta); H.G. van Eijk (Henk)

    1997-01-01

    textabstractThe different isoforms of transferrin have been quantified by isoelectric focusing in the sera of psoriasis patients with and without a history of abusing alcohol. In both male and female psoriasis subjects abusing alcohol, there were significant increases in the

  17. Nonrandom distribution of iron in circulating human transferrin.

    Zak, O; Aisen, P

    1986-07-01

    By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C-terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.

  18. Transferrin variation and genetic structure of reindeer populations in Scandinavia

    Knut H. Røed

    1987-06-01

    Full Text Available Polyacrylamide gel electrophoresis was used to analyse transferrin variation in herds of semi-domestic reindeer from Scandinavia. The results are compared with previously reported values for other populations of both semi-domestic and wild reindeer using the same techniques as in the present study. In all populations the number of alleles was high, ranging from seven to eleven, and the heterozygosity was correspondingly high, with a mean of 0.749. This high genetic variation in all populations suggests that inbreeding is not widespread among Scandinavian reindeer. The pattern of allele frequency distribution indicates a high degree of genetic heterogeneity in the transferrin locus, both between the different semi-domestic herds and between the different wild populations. The mean value of genetic distance was 0.069 between semi-domestic herds and 0.091 between wild populations. Between semi-domestic and wild populations the genetic distance was particularly high, with a mean of 0.188. This high value was mainly due to a different pattern in the distribution of the two most common transferrin alleles: Tfu was most common among semi-domestic herds, while TfEI was most common among wild populations. These differences in transferrin allele distribution are discussed in relation to possible different origins of semi-domestic and wild reindeer in Scandinavia, or alternatively, to different selection forces acting on transferrin genotypes in semi-domestic and wild populations.Transferrin-variasjon og genetisk struktur hos rein i Skandinavia.Abstact in Norwegian / Sammendrag: Transferrin-variasjon i tamreinflokker ble analysert ved hjelp av polyacrylamid gel elektroforese. Resultatene er sammenlignet med verdier som tidligere er beskrevet for både tamrein og villrein hvor det ble benyttet samme metode som i denne undersøkelsen. I alle populasjonene ble det registrert et høyt antall alleler (7-11 og heterozygositeten var tilsvarende høy med en

  19. Association between serum transferrin receptor levels and malaria ...

    user

    ... and malaria is common in sub-Saharan Africa, and is a complex phenomenon. ... iron status and malaria incidence among children in a high malaria ... seasonally as cash crops. ... Children were followed for presence of malaria parasites by.

  20. Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

    Laskey, J.D.; Ponka, P.; Schulman, H.M.

    1986-01-01

    In many types of cells the synthesis of σ-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from 125 I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or 59 Fe-Tf (20 μM). Furthermore, in induced Friend cells 100 μM Fe-SIH stimulated 2- 14 C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells

  1. Transferrin Sialylation in Smoking and Non-Smoking Pregnant Women with Intrauterine Growth Restriction.

    Wrześniak, Marta; Kepinska, Marta; Bizoń, Anna; Milnerowicz-Nabzdyk, Ewa; Milnerowicz, Halina

    2015-01-01

    Transferrin (Tf) is a glycosylated protein responsible for transporting iron. Various sialylation levels of Tf are observed during physiological and pathological processes. We studied if the changes in iron stores as well as tobacco smoke may have an impact on foetal development and in consequence lead to intrauterine growth restriction (IUGR). In the third trimester of pregnancy, lower levels of 4-sialoTf isoform and higher levels of 5-sialoTf were observed in the serum of non-smoking women with IUGR in comparison to the control group. On the day of labour, level of 2-sialoTf was significantly lower and level of 3-sialo was Tf higher in the serum of non-smoking women. Level of 4-sialo was found lower in the serum of smoking women with IUGR than in the control group. The observed changes may suggest a connection between iron stores, transport of iron to the foetus and foetal development.

  2. Effect of transferrin saturation on internal iron exchange

    Bergamaschi, G.; Eng, M.J.; Huebers, H.A.; Finch, C.A.

    1986-01-01

    Radioiron was introduced into the intestinal lumen to evaluate absorption, injected as nonviable red cells to evaluate reticuloendothelial (RE) processing of iron, and injected as hemoglobin to evaluate hepatocyte iron processing. Redistribution of iron through the plasma was evaluated in control animals and animals whose transferrin was saturated by iron infusion. Radioiron introduced into the lumen of the gut as ferrous sulfate and as transferrin-bound iron was absorbed about half as well in iron-infused animals, and absorbed iron was localized in the liver. The similar absorption of transferrin-bound iron suggested that absorption of ferrous iron occurred via the mucosal cell and did not enter by diffusion. The decrease in absorption was associated with an increase in mucosal iron and ferritin content produced by the iron infusion. An inverse relationship (r = -0.895) was shown between mucosal ferritin iron and absorption. When iron was injected as nonviable red cells, it was deposited predominantly in reticuloendothelial cells of the spleen. Return of this radioiron to the plasma was only 6% of that in control animals. While there was some movement of iron from spleen to liver, this could be accounted for by intravascular hemolysis. Injected hemoglobin tagged with radioiron was for the most part taken up and held by the liver. Some 13% initially localized in the marrow in iron-infused animals was shown to be storage iron unavailable for hemoglobin synthesis. These studies demonstrate the hepatic trapping of absorbed iron and the inability of either RE cell or hepatocyte to release iron in the transferrin-saturated animal

  3. Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

    Arroyo-Pardo Eduardo

    2011-10-01

    Full Text Available Abstract Background Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs known to be related to iron metabolism were studied in menstruating women. Methods A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141 was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. Results Four variants, two in the transferrin gene (rs3811647, rs1799852 and two in the HFE gene (C282Y, H63D, explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. Conclusions In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

  4. Transferrin receptors on human reticulocytes: variation in site number in hematologic disorders

    Shumak, K.H.; Rachkewich, R.A.

    1984-01-01

    Assays of binding of 125iodine-labeled ( 125 I) human transferrin were used to study transferrin receptor sites on reticulocytes from 15 normal subjects and from 66 patients with various hematologic disorders. In normal subjects, few or no transferrin receptors were detected whereas the average number of receptors per reticulocyte varied greatly from patient to patient, ranging from 0 to 67,700 in samples, from 35 patients, on which Scatchard analysis of binding of [ 125 I]-transferrin was done. Marked heterogeneity in the number of reticulocyte transferrin receptors in different hematologic disorders was also found in assays with [ 125 I]-OKT9 (monoclonal antibody to the human transferrin receptor). The number of receptors was not correlated with either the reticulocyte count or the hemoglobin

  5. Productivity Analysis of the Botosani Karakul Sheep Depending on the Genetic Types of Serum Transferrin

    Gheorghe Hrincă

    2011-05-01

    Full Text Available The paper analyzes the sheep productivity of the Botosani Karakul breed in relation to their belonging in different transferrin genotypes. Thirteen electrophoretic phenotypes of transferrin have been identified in this breed. Experimental results show that it is possible to establish correlations between genetic types of serum transferrin and quantitative characteristics of production (meat, wool, milk in this breed depending on age and sex of animals. In lambs, the values of the productive parameters are more grouped in most transferrin genotypes, while in adult animals, more important differentiations of productivity occur among different transferrin genotypes. In adult animals, the productive differentiation among the genotypes Tf is more obvious in rams than in ewes. Irrespective of age and sex, the differences of productivity among transferrin genotypes, in their reciprocity, seldom present significant statistical assurance, a relatively frequent part of them is situated near the first critical threshold of significance, and most of them are unsignificant. Thus, a certain production metabolism is characteristic to each genotype transferrin. But the transferrin genotypes which enhance the sheep productivity, those that differ significantly from the rest of transferrin genotypes, deserve to be taken into account, in the selection works of this breed for its productive improvement.

  6. Iron exchange between transferrin molecules mediated by phosphate compounds and other cell metabolites.

    Morgan, E H

    1977-08-25

    The ability of a large number of cellular metabolites to release iron from transferrin was investigated by measuring the rate at which they could mediate iron exchange between two types of transferrin. Rabbit transferrin labelled with 59Fe was incubated with human apotransferrin in the presence of the metabolites. After varying periods of incubation the human transferrin was separated from the rabbit transferrin by immunoprecipitation. GTP, 2,3-diphosphoglycerate, ATP, ADP and citrate produced the most rapid exchange of iron between the two types of transferrin, but many other compounds showed some degree of activity. Iron exchange mediated by the organic phosphates had the characteristics of a single first-order reaction and was sensitive to changes of incubation temperature and pH. The activation energy for the exchange reaction was approx. 13 kcal/mol. The rate of iron exchange from the oxalate - iron - transferrin complex was much lower than from bicarbonate - iron - transferrin. It is concluded that several organic phosphates have the capacity of releasing iron from transferrin. These compounds may represent the means by which the iron is released during the process of cellular uptake.

  7. Transferrin variation and evolution of Canadian barren-ground caribou

    Knut H. Røed

    1990-09-01

    Full Text Available Blood samples were obtained from 95 barren-ground caribou (Rangifer tarandus groenlandicus of the Beverly herd in Northwest Territories, Canada. Polyacrylamid gel electrophoresis was used to score for genetic variation in the locus coding for transferrin. The pattern of allele frequency distribution are compared with previously reported values of Eurasian tundra reindeer (R.t. tarandus, Alaska caribou (R.t. granti, Peary caribou (R.t. pearyi, and Svalbard reindeer (R.t. platyrhynchus. In the Beverly herd a total of 21 different transferrin alleles were detected. The amount of genetic variation was higher in the Canadian barren-ground caribou than what has been detected in other subspecies of reindeer/caribou. Highly gene-tical differences in the allele frequencies were detected between the Canadian barren-ground caribou and the other subspecies. The genetic identity analyses indicates approximately the same amount of genetic differentiation when the Canadian barren-ground caribou are compared with Alaska caribou as with the Peary caribou. The allele frequency pattern could be explained by a possible origin of the Canadian barren-ground caribou from an ancestral population which was genetical influenced by animals surviving the We-ichselian glaciation in refugia both in high Arctic, in Beringia, and south of the ice sheet.

  8. Clinical usefulness of 111In transferrin scintigraphy in colorectal cancer

    Hirano, Morihisa; Naruki, Yukihiko; Urita, Yosihisa; Nakatani, Naoto; Otsuka, Sachio; Noguchi, Masahiro; Takano, Masaaki; Maruyama, Yuuzou.

    1993-01-01

    As assessment was made regarding the clinical value of 111 In transferrin in scintigraphy on 28 lesions in 26 cases of colorectal cancer. The positive rate of colorectal cancer was high: 21 lesions out of the 28 (75%) were found to be positive. As for the location of cancer, there was a tendency for the positive rate to be high in the ascending and transverse colon. There was no obvious trend regarding Borrmann's classification, histological type, or macroscopic depth of invasion. There was a trend for cases in which the maximum diameter of the tumor was large and depth of invasion was in progress to be positive. Ten cases in which a specimen was resected were all shown to be positive by scintigraphy. Radioactivity in the tumorous regions was 4.41±2.96 times that of the non-tumorous regions. Moreover, tumorous tissue was strongly stained by the immuno-histological staining with anti-Tf-receptor antibody. From the above findings, it was considered that 111 In transferrin is clinically useful in scintigraphy, since it is evident that it accumulates in the tissue of colorectal cancer. (author)

  9. BLOOD PROTEIN TRANSFERRIN POLYMOROPHISM IN BLACK BENGAL GOAT

    Rajesh Paul

    2017-12-01

    Full Text Available The present investigation was carried out with an aim to explore the polymorphism of a blood protein tranferrin using starch gel electrophoresis technique in a total of unrelated 199 Black Bengal goats available in four different districts of West Bengal, India. Banding patterns of transferrin in starch gel revealed six phenovariants TfAA, TfAB, TfBC, TfBB, TfAC and TfCC comprising of three allelomorphs, TfA, TfB and TfC. The genotype frequencies were found to be observed 0.211, 0.347, 0.136, 0.106, 0.136 and 0.065 for six genotypes and the allelic frequencies were 0.452, 0.347 and 0.201 for three alleles, respectively. Result of Chi-square test revealed that the population under study was in Hardy Weinberg Equilibrium. There were polymorphism in Transferrin protein and the presence of differences among the frequencies of the three alleles by categories could be a source of genetic variation in Black Bengal goat.

  10. Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.

    Park, R J; Moon, J D

    2015-05-01

    The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50 years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  11. Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

    Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

    2016-02-01

    Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

  12. Complex formation of transferrin with tetravalent plutonium and cerium

    Subramanian, M.S.; Oomen, I.K.

    1981-01-01

    Gel filtration experiments with 239 Pu labelled In Vitro bovine serum showed that the metal ion is bound to the transferrin of the serum proteins as in the case of iron labelled serum. This was confirmed by polyacrylamide gel electrophoresis. The ovotransferrin prepared from chicken egg white which was devoid of hemopexin contaminant was found to complex both tetravalent plutonium and cerium giving visible absorption peak at 365 and 435 nm respectively. The binding capacity of ovotransferrin with tetravalent plutonium and cerium, determined by spectrophotometric titration indicates that two metal ions are bound to each protein molecule as in the case of iron. The average molecular weight computed from this binding capacity measurements was found to be 71,000-75,000. The number of protons liberated for each metal ion bound was found to be three as in the case of iron. (author)

  13. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart

    Wenjing Xu

    2015-10-01

    Full Text Available Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1 might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure.

  14. TTP specifically regulates the internalization of the transferrin receptor

    Tosoni, Daniela; Puri, Claudia; Confalonieri, Stefano

    2005-01-01

    Different plasma membrane receptors are internalized through saturable/noncompetitive pathways, suggesting cargo-specific regulation. Here, we report that TTP (SH3BP4), a SH3-containing protein, specifically regulates the internalization of the transferrin receptor (TfR). TTP interacts...... with endocytic proteins, including clathrin, dynamin, and the TfR, and localizes selectively to TfR-containing coated-pits (CCP) and -vesicles (CCV). Overexpression of TTP specifically inhibits TfR internalization, and causes the formation of morphologically aberrant CCP, which are probably fission impaired....... This effect is mediated by the SH3 of TTP, which can bind to dynamin, and it is rescued by overexpression of dynamin. Functional ablation of TTP causes a reduction in TfR internalization, and reduced cargo loading and size of TfR-CCV. Tyrosine phosphorylation of either TTP or dynamin prevents...

  15. Transferrin-facilitated lipofection gene delivery strategy: characterization of the transfection complexes and intracellular trafficking.

    Joshee, Nirmal; Bastola, Dhundy R; Cheng, Pi-Wan

    2002-11-01

    We previously showed that mixing transferrin with a cationic liposome prior to the addition of DNA, greatly enhanced the lipofection efficiency. Here, we report characterization of the transfection complexes in formulations prepared with transferrin, lipofectin, and DNA (pCMVlacZ) in various formulations. DNA in all the formulations that contain lipofectin was resistant to DNase I treatment. Transfection experiments performed in Panc 1 cells showed that the standard formulation, which was prepared by adding DNA to a mixture of transferrin and lipofectin, yielded highest transfection efficiency. There was no apparent difference in zeta potential among these formulations, but the most efficient formulation contained complexes with a mean diameter of three to four times that of liposome and the complexes in other gene delivery formulations. Transmission electron microscopic examination of the standard transfection complexes formulated using gold-labeled transferrin showed extended circular DNA decorated with transferrin as compared to extensively condensed DNA found in lipofectin-DNA complexes and heterogeneous structures in other formulations. By confocal microscopy, DNA and transferrin were found to colocalize at the perinuclear space and in the nucleus, suggesting cotransportation intracellularly, including nuclear transport. We propose that transferrin enhances the transfection efficiency of the standard lipofection formulation by preventing DNA condensation, and facilitating endocytosis and nuclear targeting.

  16. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    Zhou, Lin; Liu, Jihua; Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong; Yu, Boyang; Shen, Jian

    2013-01-01

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A–transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A–transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin

  17. Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis

    Laskey, J.; Webb, I.; Schulman, H.M.; Ponka, P.

    1988-01-01

    Transferrin is essential for cell proliferation and it was suggested that it may trigger a proliferative response following its interaction with receptors, serving as a growth factor. However, since the only clearly defined function of transferrin is iron transport, it may merely serve as an iron donor. To further clarify this issue, the authors took advantage of an iron chelate, ferric salicylaldehyde isonicotinoyl hydrazone (Fe-SIH), which they developed and previously demonstrated to efficiently supply iron to cells without using physiological transferrin receptor pathway. As expected, they observed that blocking monoclonal antibodies against transferrin receptors inhibited proliferation of both Raji and murine erythroleukemia cells. This inhibited cell growth was rescued upon the addition of Fe-SIH which was also shown to deliver iron to Raji cells in the presence of blocking anti-transferrin receptor antibodies. Moreover, blocking anti-transferrin receptor antibodies inhibited [ 3 H]thymidine incorporation into DNA and this inhibition could be overcome by added Fe-SIH. In addition, Fe-SIH slightly stimulated, while SIH (an iron chelator) significantly inhibited, DNA synthesis in phytohemagglutinin-stimulated peripheral blood lymphocytes. Taken together, these results indicate that the only function of transferrin supporting cell proliferation is to supply cells with iron

  18. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    Zhou, Lin [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Liu, Jihua [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong, E-mail: zhoujiahong@njnu.edu.cn [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Yu, Boyang, E-mail: boyangyu59@163.com [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Shen, Jian [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China)

    2013-09-15

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A-transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A-transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin.

  19. [Iron status with particular consideration of soluble transferrin receptors in children and youth with gastritis, with or without Helicobacter pylori infection].

    Mierzwa, Grazyna; Augustyńska, Beata; Czerwionka-Szaflarska, Mieczysława; Tyrakowski, Tomasz

    2006-09-01

    Role of Helicobacter pylori infection in chronic gastritis and gastric and/or duodenal ulcers is well known. Simultaneously there are some articles in literature considering H. pylori as a cause of extra-gastrointestinal illnesses such as atopic dermatitis, chronic urticaria or acne rosacea, hypotrophy, Schoenlein-Henoch disease, atherosclerosis or hypochromic anaemia. The aim of the study. was to asses iron status in aspect of plasmatic transferrin receptors concentration among children and youth with chronic gastritis with or without Helicobacter pylori infection. Forty one patients were included as a study group. Range of age was 9-18 years. All patients were diagnosed due to chronic abdominal pains. There were 13 males and 28 females. Blood was collected from every patient for blood cell count, iron, transferrin and transferrin receptors concentration (sTfR) assessment before endoscopy of upper gastrointestinal tract. Concentration of sTfR was higher than age norm among 29 (71%) of patients. Among patients with higher level of sTfR 20 (69%) had normal haemoglobin concentration and in this group 10 patients had H. pylori infection. During analysis of 12 patients with nornal level of sTfR normal haemoglobin concentration was found and among five of them H. pylori infection was stated. Among 21 patients without H. pylori infection 14 had normal level of sTfR and 7 had higher level of sTfR which means that 33% had hidden iron deficiency (involuntary of normal Hb concentrations). Among 15 of 20 patients with H. pylori infection level of sTfR was higher which means that 75% patients with infection had hidden iron deficiency (involuntary of normal Hb concentrations). Level of plasmatic transferrin receptors can be good and sensitive indicator of iron deficiency and can be helpful in differential diagnosis of hypochromic anaemia and anaemia caused by chronic illness including chronic gastritis with Helicobacter pylori infection.

  20. Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet.

    Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Mazur, Joanna; Gajewska, Joanna; Rowicka, Grażyna; Strucińska, Małgorzata; Chełchowska, Magdalena

    2017-12-01

    The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5-9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B 12 and a significantly higher intake of vitamin C (p vegetarians. Hematologic parameters and serum iron concentrations were within the reference range in both groups of children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p vegetarians than in omnivores. In children on a vegetarian diet, median hepcidin levels were lower (p vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.

  1. TRANSFERRIN POLYMORPHISM IN FOUR LOCAL BREEDS OF GOAT IN CENTRAL JAVA, INDONESIA

    E. Kurnianto

    2012-12-01

    Full Text Available The objectives of this study were to determine the gene frequency and individual heterozygosity of transferrin in four local breeds of goat in Central Java-Indonesia. The number of blood samples were taken from 96 heads of goat, in which each of breeds were 24 samples, those were Kejobong (Purbalingga regency, Ettawa Grade (Purworejo regency, Kacang (Grobogan regency and Jawarandu (Pemalang regency. Polyacrilamide Gel Electrophoresis was performed to detect the bands of blood plasm protein. Gen frequency was calculated using general formula of population genetics. Estimated heterozygosity and individual heterosizygosity were calculated to analysis the equilibrium condition of transferrin. Result showed there was two allele of transferrin, namely TfA and TfB. Gene frequency of TfA was higher than that of TfB. Transferrin gene and genotypes were in disequilibrium of Hardy-Weinberg Law.

  2. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.

    Stack, A G

    2014-08-01

    The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear.

  3. Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain.

    Somani, Sukrut; Blatchford, David R; Millington, Owain; Stevenson, M Lynn; Dufès, Christine

    2014-08-28

    The possibility of using genes as medicines to treat brain diseases is currently limited by the lack of safe and efficacious delivery systems able to cross the blood-brain barrier, thus resulting in a failure to reach the brain after intravenous administration. On the basis that iron can effectively reach the brain by using transferrin receptors for crossing the blood-brain barrier, we propose to investigate if a transferrin-bearing generation 3-polypropylenimine dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In vitro, the conjugation of transferrin to the polypropylenimine dendrimer increased the DNA uptake by bEnd.3 murine brain endothelioma cells overexpressing transferrin receptors, by about 1.4-fold and 2.3-fold compared to that observed with the non-targeted dendriplex and naked DNA. This DNA uptake appeared to be optimal following 2h incubation with the treatment. In vivo, the intravenous injection of transferrin-bearing dendriplex more than doubled the gene expression in the brain compared to the unmodified dendriplex, while decreasing the non-specific gene expression in the lung. Gene expression was at least 3-fold higher in the brain than in any tested peripheral organs and was at its highest 24h following the injection of the treatments. These results suggest that transferrin-bearing polypropylenimine dendrimer is a highly promising gene delivery system to the brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Targeted Delivery of Amoxicillin to C. trachomatis by the Transferrin Iron Acquisition Pathway.

    Jun Hai

    Full Text Available Weak intracellular penetration of antibiotics makes some infections difficult to treat. The Trojan horse strategy for targeted drug delivery is among the interesting routes being explored to overcome this therapeutic difficulty. Chlamydia trachomatis, as an obligate intracellular human pathogen, is responsible for both trachoma and sexually transmitted diseases. Chlamydia develops in a vacuole and is therefore protected by four membranes (plasma membrane, bacterial inclusion membrane, and bacterial membranes. In this work, the iron-transport protein, human serum-transferrin, was used as a Trojan horse for antibiotic delivery into the bacterial vacuole. Amoxicillin was grafted onto transferrin. The transferrin-amoxicillin construct was characterized by mass spectrometry and absorption spectroscopy. Its affinity for transferrin receptor 1, determined by fluorescence emission titration [KaffTf-amox = (1.3 ± 1.0 x 108], is very close to that of transferrin [4.3 x 108]. Transmission electron and confocal microscopies showed a co-localization of transferrin with the bacteria in the vacuole and were also used to evaluate the antibiotic capability of the construct. It is significantly more effective than amoxicillin alone. These promising results demonstrate targeted delivery of amoxicillin to suppress Chlamydia and are of interest for Chlamydiaceae and maybe other intracellular bacteria therapies.

  5. Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization.

    Li, Jinxia; Xing, Xueqing; Sun, Baoyun; Zhao, Yuliang; Wu, Zhonghua

    2017-10-18

    Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe 3+ or transferrin (Tf). Gd@C 82 (OH) 22 or C 60 (OH) 22 effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl 3 , GdCl 3 , C 60 (OH) 22 or Gd@C 82 (OH) 22 were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl 3 , GdCl 3 or C 60 (OH) 22 , but associated into tetramers in the presence of Gd@C 82 (OH) 22 . The larger change of SAXS shapes between Tf+C 60 (OH) 22 and Tf+FeCl 3 implies that C 60 (OH) 22 is bound to Tf, blocking the iron-binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C 82 (OH) 22 is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C 82 (OH) 22 and C 60 (OH) 22 on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Downregulation of transferrin receptor surface expression by intracellular antibody

    Peng Jilin; Wu Sha; Zhao Xiaoping; Wang Min; Li Wenhan; Shen Xin; Liu Jing; Lei Ping; Zhu Huifen; Shen Guanxin

    2007-01-01

    To deplete cellular iron uptake, and consequently inhibit the proliferation of tumor cells, we attempt to block surface expression of transferrin receptor (TfR) by intracellular antibody technology. We constructed two expression plasmids (scFv-HAK and scFv-HA) coding for intracellular single-chain antibody against TfR with or without endoplasmic reticulum (ER) retention signal, respectively. Then they were transfected tumor cells MCF-7 by liposome. Applying RT-PCR, Western blotting, immunofluorescence microscopy and immunoelectron microscope experiments, we insure that scFv-HAK intrabody was successfully expressed and retained in ER contrasted to the secreted expression of scFv-HA. Flow cytometric analysis confirmed that the TfR surface expression was markedly decreased approximately 83.4 ± 2.5% in scFv-HAK transfected cells, while there was not significantly decrease in scFv-HA transfected cells. Further cell growth and apoptosis characteristics were evaluated by cell cycle analysis, nuclei staining and MTT assay. Results indicated that expression of scFv-HAK can dramatically induce cell cycle G1 phase arrest and apoptosis of tumor cells, and consequently significantly suppress proliferation of tumor cells compared with other control groups. For First time this study demonstrates the potential usage of anti-TfR scFv-intrabody as a growth inhibitor of TfR overexpressing tumors

  7. Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection

    Murali K. Matta

    2018-02-01

    Full Text Available A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI, transferrin bound iron (TBI, drug bound iron (DI and total iron (TI in the same rat serum sample after intravenous (IV administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®. Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2 of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg.

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

    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.

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

    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.

  10. Soluble transferrin receptor as a marker of erythropoiesis in patients undergoing high-flux hemodialysis

    Pei Yin

    2017-11-01

    Full Text Available Anemia is a common complication in chronic kidney disease (CKD patients receiving hemodialysis. The effect of high-flux dialysis (HFD on anemia remains unclear. This prospective study aimed to evaluate the effect of HFD on anemia, and the potential of soluble transferrin receptor (sTfR as a marker of iron status and erythropoiesis in CKD patients on hemodialysis. Forty patients, who switched from conventional low-flux dialysis to HFD for 12 months, were enrolled in this study. The levels of sTfR, hemoglobin (Hb, iron, and nutritional markers, as well as the dose of recombinant human erythropoietin (rhEPO and use of chalybeate were determined at 0, 2, 6, and 12 months after starting HFD. HFD significantly increased the hemoglobin level and reduced sTfR level in CKD patients (p < 0.05. In addition, significant decreasing linear trends were observed for rhEPO dosage and chalybeate use (p < 0.05. The level of sTfR was positively correlated with the percentage of reticulocytes (RET%, rhEPO dose, and chalybeate use, while it was negatively correlated with Hb levels and total iron-binding capacity results (all p < 0.05. A univariate generalized estimating equation (GEE model showed that the Hb level, RET%, rhEPO dose, and chalybeate use were the variables associated with sTfR levels. A multivariate GEE model showed that the time points when hemodialysis was performed were the variables associated significantly with sTfR levels. Overall, our findings suggest that HFD can effectively improve renal anemia in hemodialysis patients, and sTfR could be used as a marker of erythropoiesis in HFD patients.

  11. Electrosynthesized MIPs for transferrin: Plastibodies or nano-filters?

    Zhang, Xiaorong; Yarman, Aysu; Erdossy, Júlia; Katz, Sagie; Zebger, Ingo; Jetzschmann, Katharina J; Altintas, Zeynep; Wollenberger, Ulla; Gyurcsányi, Róbert E; Scheller, Frieder W

    2018-05-15

    Molecularly imprinted polymer (MIP) nanofilms for transferrin (Trf) have been synthesized on gold surfaces by electro-polymerizing the functional monomer scopoletin in the presence of the protein target or around pre-adsorbed Trf. As determined by atomic force microscopy (AFM) the film thickness was comparable with the molecular dimension of the target. The target (re)binding properties of the electro-synthesized MIP films was evaluated by cyclic voltammetry (CV) and square wave voltammetry (SWV) through the target-binding induced permeability changes of the MIP nanofilms to the ferricyanide redox marker, as well as by surface plasmon resonance (SPR) and surface enhanced infrared absorption spectroscopy (SEIRAS) of the immobilized protein molecules. For Trf a linear concentration dependence in the lower micromolar range and an imprinting factor of ~5 was obtained by SWV and SPR. Furthermore, non-target proteins including the iron-free apo-Trf were discriminated by pronounced size and shape specificity. Whilst it is generally assumed that the rebinding of the target or of cross-reacting proteins exclusively takes place at the polymer here we considered also the interaction of the protein molecules with the underlying gold transducers. We demonstrate by SWV that adsorption of proteins suppresses the signal of the redox marker even at the bare gold surface and by SEIRAS that the treatment of the MIP with proteinase K or NaOH only partially removes the target protein. Therefore, we conclude that when interpreting binding of proteins to directly MIP-covered gold electrodes the interactions between the protein and the gold surface should also be considered. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

    Büyükkaragöz, Bahar; Akgun, Necat A; Bulus, Ayse D; Durmus Aydogdu, Sultan; Bal, Cengiz

    2017-04-01

    To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p 0.05) and significantly higher than controls (p iron treatment, sTfR decreased in both MA and A groups (p iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

  13. The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.

    Christal A Worthen

    2014-03-01

    Full Text Available Fine tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron-sensor, transferrin receptor 2 (TfR2, is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH. With the loss of functional TfR2, the liver produces about two-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin in the bloodstream, and hepatocytes treated with transferrin respond with a two-fold increase in hepcidin expression through stimulation of the BMP-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein (HFE, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

  14. Transferrin-derived synthetic peptide induces highly conserved pro-inflammatory responses of macrophages.

    Haddad, George; Belosevic, Miodrag

    2009-02-01

    We examined the induction of macrophage pro-inflammatory responses by transferrin-derived synthetic peptide originally identified following digestion of transferrin from different species (murine, bovine, human N-lobe and goldfish) using elastase. The mass spectrometry analysis of elastase-digested murine transferrin identified a 31 amino acid peptide located in the N2 sub-domain of the transferrin N-lobe, that we named TMAP. TMAP was synthetically produced and shown to induce a number of pro-inflammatory genes by quantitative PCR. TMAP induced chemotaxis, a potent nitric oxide response, and TNF-alpha secretion in different macrophage populations; P338D1 macrophage-like cells, mouse peritoneal macrophages, mouse bone marrow-derived macrophages (BMDM) and goldfish macrophages. The treatment of BMDM cultures with TMAP stimulated the production of nine cytokines and chemokines (IL-6, MCP-5, MIP-1 alpha, MIP-1 gamma, MIP-2, GCSF, KC, VEGF, and RANTES) that was measured using cytokine antibody array and confirmed by Western blot. Our results indicate that transferrin-derived peptide, TMAP, is an immunomodulating molecule capable of inducing pro-inflammatory responses in lower and higher vertebrates.

  15. Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type--implication of EPO, transferrin and transcobalamin losses.

    Toubiana, Julie; Schlageter, Marie-Hélène; Aoun, Bilal; Dunand, Olivier; Vitkevic, Renata; Bensman, Albert; Ulinski, Tim

    2009-04-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation and is responsible for a variety of urinary protein losses. We report the case of a 4-month-old girl with a particularly severe form (proteinuria approximately 150 g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly blood transfusions despite daily EPO (600 UI/kg) and iron supplementation. Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within the first 24 h after IV injection. However, plasma levels remained increased after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible for disturbed erythropoiesis.

  16. Tertiary structural changes and iron release from human serum transferrin.

    Mecklenburg, S L; Donohoe, R J; Olah, G A

    1997-08-01

    Iron release from human serum transferrin was investigated by comparison of the extent of bound iron, measured by charge transfer absorption band intensity (465 nm), with changes observed by small-angle solution X-ray scattering (SAXS) for a series of equilibrated samples between pH 5.69 and 7.77. The phosphate buffers used in this study promote iron release at relatively high pH values, with an empirical pK of 6.9 for the convolved release from the two sites. The spectral data reveal that the N-lobe release is nearly complete by pH 7.0, while the C-lobe remains primarily metal-laden. Conversely, the radius of gyration, Rg, determined from the SAXS data remains constant between pH 7.77 and 7.05, and the evolution of Rg between its value observed for the diferric protein at pH 7.77 (31.2+/-0.2 A) and that of the apo protein at pH 5.69 (33.9+/-0.4 A) exhibits an empirical pK of 6.6. While Rg is effectively constant in the pH range associated with iron release from the N-lobe, the radius of gyration of cross-section, Rc, increases from 16.9+/-0.2 A to 17.6+/-0.2 A. Model simulations suggest that two different rotations of the NII domain relative to the NI domain about a hinge deep in the iron-binding cleft of the N-lobe, one parallel with and one perpendicular to the plane of the iron-binding site, can be significantly advanced relative to their holo protein positions while yielding constant Rg and increased Rc values consistent with the scattering data. Rotation of the CII domain parallel with the C-lobe iron-binding site plane can partially account for the increased Rg values measured at low pH; however, no reasonable combined repositioning of the NII and CII domains yields the experimentally observed increase in Rg.

  17. Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system

    Clark, R.A.; Pearson, D.W.

    1989-01-01

    Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by (1) a failure to mobilize iron from iron-loaded transferrin, (2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and (3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species

  18. Assessment of a Radioimmunological Method to Measure Transferrin in Seminal Plasm

    Mallea Sanchez, L.; Estevez Gandara, A.; Navaroli Fernandez, F.; Machado Curbelo, A.J.

    1986-01-01

    A specific antiserum against human transferrin was obtained. It was titrated and used to develop a radioimmunological method to measure transferrin in seminal plasm, since the concentration of that protein could be a useful marker of testicular function in the clinical management of male infertility. The method showed good precision, accurateness and sensitivity, when it was assessed by standard statistical methods and accordingly it seems to be adequate for the intended purposes. The assessment of its value in the diagnosis and therapy of male infertility, will be the subject of future work. (author). 14 refs

  19. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron

    van der Ende, A.; du Maine, A.; Simmons, C. F.; Schwartz, A. L.; Strous, G. J.

    1987-01-01

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at

  20. The role of serum transferrin receptor in the diagnosis of iron deficiency.

    Remacha, A F; Sarda, M P; Parellada, M; Ubeda, J; Manteiga, R

    1998-11-01

    Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.

  1. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    Králová, Alena; Světlíková, M.; Madar, J.; Ulčová-Gallová, Z.; Bukovský, A.; Pěknicová, Jana

    2008-01-01

    Roč. 6, č. 27 (2008), s. 1-16 ISSN 1477-7827 R&D Projects: GA MŠk OE 211 Institutional research plan: CEZ:AV0Z50520701 Keywords : transferrin * monoclonal antibody * human placentae Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.634, year: 2008

  2. Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H

    2017-01-01

    Astrocytic brain tumors are the most frequent primary brain tumors. Treatment with radio- and chemotherapy has increased survival making prognostic biomarkers increasingly important. The aim of the present study was to investigate the expression and prognostic value of transferrin receptor-1 (TfR...

  3. Comparison of colorimetry and electrothermal atomic absorption spectroscopy for the quantification of non-transferrin bound iron in human sera.

    Jittangprasert, Piyada; Wilairat, Prapin; Pootrakul, Pensri

    2004-12-01

    This paper describes a comparison of two analytical techniques, one employing bathophenanthrolinedisulfonate (BPT), a most commonly-used reagent for Fe (II) determination, as chromogen and an electrothermal atomic absorption spectroscopy (ETAAS) for the quantification of non-transferrin bound iron (NTBI) in sera from thalassemic patients. Nitrilotriacetic acid (NTA) was employed as the ligand for binding iron from low molecular weight iron complexes present in the serum but without removing iron from the transferrin protein. After ultrafiltration the Fe (III)-NTA complex was then quantified by both methods. Kinetic study of the rate of the Fe (II)-BPT complex formation for various excess amounts of NTA ligand was also carried out. The kinetic data show that a minimum time duration (> 60 minutes) is necessary for complete complex formation when large excess of NTA is used. Calibration curves given by colorimetric and ETAAS methods were linear over the range of 0.15-20 microM iron (III). The colorimetric and ETAAS methods exhibited detection limit (3sigma) of 0.13 and 0.14 microM, respectively. The NTBI concentrations from 55 thalassemic serum samples measured employing BPT as chromogen were statistically compared with the results determined by ETAAS. No significant disagreement at 95% confidence level was observed. It is, therefore, possible to select any one of these two techniques for determination of NTBI in serum samples of thalassemic patients. However, the colorimetric procedure requires a longer analysis time because of a slow rate of exchange of NTA ligand with BPT, leading to the slow rate of formation of the colored complex.

  4. Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec

    Yu-Sheng Chen

    2018-01-01

    Full Text Available Proinsulin-transferrin fusion protein (ProINS-Tf has been designed and successfully expressed from the mammalian HEK293 cells (HEK-ProINS-Tf. It was found that HEK-ProINS-Tf could be converted into an activated form in the liver. Furthermore, HEK-ProINS-Tf was demonstrated as an extra-long acting insulin analogue with liver-specific insulin action in streptozotocin (STZ-induced type 1 diabetic mice. However, due to the low production yield from transfected HEK293 cells, there are other interesting features, including the oral bioavailability, which have not been fully explored and characterized. To improve the protein production yield, an alternative protein expression system, ExpressTec using transgenic rice (Oryza sativa L., was used. The intact and active rice-derived ProINS-Tf (ExpressTec-ProINS-Tf was successfully expressed from the transgenic rice expression system. Our results suggested that, although the insulin-like bioactivity of ExpressTec-ProINS-Tf was slightly lower in vitro, its potency of in vivo blood glucose control was considerably stronger than that of HEK-ProINS-Tf. The oral delivery studies in type 1 diabetic mice demonstrated a prolonged control of blood glucose to near-normal levels after oral administration of ExpressTec-ProINS-Tf. Results in this report suggest that ExpressTec-ProINS-Tf is a promising insulin analog with advantages including low cost, prolonged and liver targeting effects, and most importantly, oral bioactivity.

  5. The impact of maternal obesity on iron status, placental transferrin receptor expression and hepcidin expression in human pregnancy.

    Garcia-Valdes, L; Campoy, C; Hayes, H; Florido, J; Rusanova, I; Miranda, M T; McArdle, H J

    2015-04-01

    Obesity is associated with decreased iron status, possibly due to a rise in hepcidin, an inflammatory protein known to reduce iron absorption. In animals, we have shown that maternal iron deficiency is minimised in the foetus by increased expression of placental transferrin receptor (pTFR1), resulting in increased iron transfer at the expense of maternal iron stores. This study examines the effect of obesity during pregnancy on maternal and neonatal iron status in human cohorts and whether the placenta can compensate for decreased maternal iron stores by increasing pTFR1 expression. A total of 240 women were included in this study. One hundred and fifty-eight placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery. Maternal iron status was measured by determining serum transferrin receptor (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in maternal and cord blood was measured by ELISA and pTFR1 in placentas by western blotting and real-time RT-PCR. Low iron stores were more common in obese women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in obese than normal women (26.03±12.95 vs 18.00±10.77, PMaternal hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025), but not with neonatal values. mRNA and protein levels of pTFR1 were both inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2 P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039 with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI). The data support the hypothesis that obese pregnant women have a greater risk of iron deficiency and that hepcidin may be a regulatory factor. Further, we show that the placenta responds to decreased maternal iron status by increasing pTFR1 expression.

  6. Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.

    Schaffert, David H; Okholm, Anders H; Sørensen, Rasmus S; Nielsen, Jesper S; Tørring, Thomas; Rosen, Christian B; Kodal, Anne Louise B; Mortensen, Michael R; Gothelf, Kurt V; Kjems, Jørgen

    2016-05-01

    DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Serum iron, ferritin, transferrin and haptoglobin concentration variations during repeated show jumping competition in horse

    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.

  8. (111)Indium-transferrin for localization and quantification of gastrointestinal protein loss

    Simonsen, Jane Angel; Braad, Poul-Erik; Veje, Annegrete

    2009-01-01

    Objective. To evaluate the indium-111 ((111)In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. Methods. Fourteen patients and 15 healthy subjects underwent an (111)In-transferrin study consisting of abdominal scintigraphy, whole-body counting...... measurement and determination of plasma activity of (111)In during the course of 5 days. Two of the patients went through a subsequent chromium-51-trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. Results. The patients had a mean+/-SEM whole-body...... loss of (111)In of 10.9+/-2.9% for 96 h, while the healthy controls lost 1.8+/-1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0+/-1.0 h in patients and 12.1+/-1.5 h in controls (p=0.0007). Scintigraphically, patients had...

  9. Effect of wortmannin and phorbol ester on Paramecium fluid-phase uptake in the presence of transferrin

    J Wiejak

    2009-12-01

    Full Text Available The kinetics of the uptake of the fluid phase marker Lucifer Yellow (LY, and its alteration by wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI-3K, and the PKC modulators: GF 109203 X, an inhibitor, and phorbol ester, an activator was studied in eukaryotic model Paramecium aurelia. Spectrophotometric quantification of LY accumulation was performed in the presence or absence of transferrin, a marker of receptor-mediated endocytosis. Internalization of LY showed a curvilinear kinetics: the high initial rate of LYuptake (575 ng LY/ mg protein /hr decreased almost 5-fold within 15 min, reaching plateau at 126 ng/ mg protein /hr. Transferrin induced a small increase (7.5% in the fluid phase uptake rate (after 5 min followed by a small decrease at longer incubation times. Lucifer Yellow and transferrin (visualized by streptavidin– FITC were localized in Paramecium by 3-D reconstruction by confocal microscopy. LY showed a scattered, diffuse fluorescence typical of fluid phase uptake whereas transferrin accumulated in membrane-surrounded endosomes. Wortmannin did not affect LY accumulation but decreased it when transferrin was present in the incubation medium. This suggests an effect on the transferrin uptake pathway, presumably on the stage of internalization in “mixing” endosomes to which transferrin and LY were targeted. Phorbol ester diminished LY accumulation by 22% and this effect persisted up to 25 min of incubation. PKC inhibitor did not affect LY uptake. However, in the presence of transferrin, the LY uptake increased within the first 15 minutes followed by a rapid 20% decrease in comparison to the control. Such an effect of PKC modulators suggests that PMA action on fluid phase uptake is not directly mediated by PKC.

  10. Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis.

    Bruns, Tony; Nuraldeen, Renwar; Mai, Martina; Stengel, Sven; Zimmermann, Henning W; Yagmur, Eray; Trautwein, Christian; Stallmach, Andreas; Strnad, Pavel

    2017-02-01

    Iron represents an essential, but potentially harmful micronutrient, whose regulation has been associated with poor outcome in liver disease. Its homeostasis is tightly linked to oxidative stress, bacterial infections and systemic inflammation. To study the prognostic short-term significance of iron parameters in a cohort study of patients with decompensation of cirrhosis at risk of acute-on-chronic liver failure (ACLF). Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were determined in sera from 292 German patients hospitalized for decompensation of cirrhosis with ascites, of which 78 (27%) had ACLF. Short-term mortality was prospectively assessed 30 and 90 days after inclusion. Transferrin concentrations were significantly lower, whereas ferritin and TSAT were higher in patients with ACLF compared to patients without ACLF (P≤.006). Transferrin, TSAT and ferritin differentially correlated with the severity of organ failure, active alcoholism and surrogates of systemic inflammation and macrophage activation. As compared with survivors, 30-day non-survivors displayed lower serum transferrin (P=.0003) and higher TSAT (P=.003), whereas 90-day non-survivors presented with higher ferritin (P=.03) and lower transferrin (P=.02). Lower transferrin (continuous or dichotomized at 87 mg/dL) and consecutively higher TSAT (continuous or dichotomized >41%) indicated increased mortality within 30 days and remained significant after adjustment for organ failure and inflammation in multivariate regression models and across subgroups of patients. Among the investigated indicators of iron metabolism, serum transferrin concentration was the best indicator of organ failure and an independent predictor of short-term mortality at 30 days. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition.

    Sheokand, Navdeep; Kumar, Santosh; Malhotra, Himanshu; Tillu, Vikas; Raje, Chaaya Iyengar; Raje, Manoj

    2013-06-01

    The long held view is that mammalian cells obtain transferrin (Tf) bound iron utilizing specialized membrane anchored receptors. Here we report that, during increased iron demand, cells secrete the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which enhances cellular uptake of Tf and iron. These observations could be mimicked by utilizing purified GAPDH injected into mice as well as when supplemented in culture medium of model cell lines and primary cell types that play a key role in iron metabolism. Transferrin and iron delivery was evaluated by biochemical, biophysical and imaging based assays. This mode of iron uptake is a saturable, energy dependent pathway, utilizing raft as well as non-raft domains of the cell membrane and also involves the membrane protein CD87 (uPAR). Tf internalized by this mode is also catabolized. Our research demonstrates that, even in cell types that express the known surface receptor based mechanism for transferrin uptake, more transferrin is delivered by this route which represents a hidden dimension of iron homeostasis. Iron is an essential trace metal for practically all living organisms however its acquisition presents major challenges. The current paradigm is that living organisms have developed well orchestrated and evolved mechanisms involving iron carrier molecules and their specific receptors to regulate its absorption, transport, storage and mobilization. Our research uncovers a hidden and primitive pathway of bulk iron trafficking involving a secreted receptor that is a multifunctional glycolytic enzyme that has implications in pathological conditions such as infectious diseases and cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer

    Gao S

    2015-12-01

    Full Text Available Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,* 1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf-modified polyamidoamine dendrimer (PAMAM was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL-encoding plasmid open reading frame (pORF-hTRAIL, Trail, was condensed by Tf-modified PAMAM to form nanoparticles (NPs. PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days, temozolomide (24.5 days, PAMAM-PEG-Tf/pEGFP (19 days, or saline (17 days. The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the

  13. Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms.

    Kwon, Seok-Joon; Zhang, Fuming; Dordick, Jonathan S; Sonstein, William J; Linhardt, Robert J

    2015-10-01

    A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo-transferrin (aTF) biomarker, without interference from serum sialo-transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two-step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma.

    Malarvizhi, Giridharan Loghanathan; Retnakumari, Archana Payickattu; Nair, Shantikumar; Koyakutty, Manzoor

    2014-11-01

    Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing >75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in ~92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

    Mintun, M.A.; Dennis, D.R.; Welch, M.J.; Mathias, C.J.; Schuster, D.P.

    1987-01-01

    We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-( 68 Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of [ 68 Ga]citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escape rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury

  16. A new liquid chromatography-mass spectrometry-based method to quantitate exogenous recombinant transferrin in cerebrospinal fluid: a potential approach for pharmacokinetic studies of transferrin-based therapeutics in the central nervous systems.

    Wang, Shunhai; Bobst, Cedric E; Kaltashov, Igor A

    2015-01-01

    Transferrin (Tf) is an 80 kDa iron-binding protein that is viewed as a promising drug carrier to target the central nervous system as a result of its ability to penetrate the blood-brain barrier. Among the many challenges during the development of Tf-based therapeutics, the sensitive and accurate quantitation of the administered Tf in cerebrospinal fluid (CSF) remains particularly difficult because of the presence of abundant endogenous Tf. Herein, we describe the development of a new liquid chromatography-mass spectrometry-based method for the sensitive and accurate quantitation of exogenous recombinant human Tf in rat CSF. By taking advantage of a His-tag present in recombinant Tf and applying Ni affinity purification, the exogenous human serum Tf can be greatly enriched from rat CSF, despite the presence of the abundant endogenous protein. Additionally, we applied a newly developed (18)O-labeling technique that can generate internal standards at the protein level, which greatly improved the accuracy and robustness of quantitation. The developed method was investigated for linearity, accuracy, precision, and lower limit of quantitation, all of which met the commonly accepted criteria for bioanalytical method validation.

  17. [The clinical significance of the measurement of plasma transferrin as a growth factor. II. The changes in various endocrine status].

    Matsubara, M; Odagaki, E; Morioka, T; Nakagawa, K

    1987-05-20

    The clinical significance of the measurement of plasma transferrin (Tf) in patients with hypophysial disorders was reported in our previous papers. In the present study, we determined plasma Tf levels in 55 patients with various endocrine states and considered their clinical significance compared with plasma somatomedin-C (SM-C) levels. Plasma Tf levels decreased significantly in patients with anorexia nervosa (p less than 0.02), hyperthyroidism (p less than 0.05), primary hypothyroidism (p less than 0.05) and Cushing's syndrome (p less than 0.05), while they were elevated significantly in pregnancy (p less than 0.01) or females using estrogens (p less than 0.05). The former two declines were considered a reflection of the malnutritional state of the patients since a significant negative correlation was observed between plasma Tf levels and the percentile deficit from the ideal body weight in patients with anorexia nervosa (p less than 0.01), or between plasma Tf levels and elevated T3 levels which induce hypermetabolism in patients with hyperthyroidism (p less than 0.01). A significant correlation was observed between the SM-C and Tf levels in these subjects (including normal controls and patients with hypophysial disorders) as a whole (r = 0.79, p less than 0.001). These data indicate that plasma Tf is changeable according to the endocrinological and nutritional conditions with good correlation to the SM-C, and it is suggested that Tf also operates as a growth factor in vivo.

  18. Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway

    Schaffert, David Henning; Okholm, Anders Hauge; Sørensen, Rasmus Schøler

    2016-01-01

    DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms....... Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site...... on the origami surface....

  19. GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor and stored in vesicles associated with TGN

    Ralston, E; Ploug, Thorkil

    1996-01-01

    of the constitutive endosomal-lysosomal pathway. To address this question, we have investigated the localization of the endogenous GLUT4 in non-stimulated skeletal myotubes from the cell line C2, by immunofluorescence and immunoelectron microscopy. We have used a panel of antibodies to markers of the Golgi complex...... and in vesicles just beyond, i.e. in the structures that constitute the trans-Golgi network (TGN). In myotubes treated with brefeldin A, the immunofluorescence pattern of GLUT4 is modified, but it differs from both Golgi complex markers and TGN38. Instead, it resembles the pattern of the transferrin receptor...... to the GLUT4-containing tubulo-vesicular elements. In brefeldin A-treated cells, a network of tubules of approximately 70 nm diameter, studded with varicosities, stains for both GLUT4 and transferrin receptor, suggesting that brefeldin A has caused fusion of the transferrin receptor and GLUT4-containing...

  20. Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus.

    Ohara, Nobumasa; Hanyu, Osamu; Hirayama, Satoshi; Nakagawa, Osamu; Aizawa, Yoshifusa; Ito, Seiki; Sone, Hirohito

    2014-02-01

    Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 Å or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state. Excretion of IgG, ceruloplasmin, transferrin, albumin, α2-macroglobulin with a large molecular radius of 88 Å and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio hypertension and nondiabetes mellitus (group hypertension, n = 32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n = 52) and type 2 diabetes mellitus and hypertension (group Both, n =45), and in age-matched controls (n = 72). Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary α2-macroglobulin did not differ among the four groups. These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in

  1. Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe

    Corradini, Elena; Rozier, Molly; Meynard, Delphine; Odhiambo, Adam; Lin, Herbert Y.; Feng, Qi; Migas, Mary C.; Britton, Robert S.; Babitt, Jodie L.; Fleming, Robert E.

    2011-01-01

    Background & Aims HFE and transferrin receptor 2 (TFR2) are each necessary for the normal relationship between body iron status and liver hepcidin expression. In murine Hfe and Tfr2 knockout models of hereditary hemochromatosis (HH), signal transduction to hepcidin via the bone morphogenetic protein 6 (Bmp6)/Smad1,5,8 pathway is attenuated. We examined the effect of dietary iron on regulation of hepcidin expression via the Bmp6/Smad1,5,8 pathway using mice with targeted disruption of Tfr2, Hfe, or both genes. Methods Hepatic iron concentrations and mRNA expression of Bmp6 and hepcidin were compared with wild-type mice in each of the HH models on standard or iron-loading diets. Liver phospho-Smad (P-Smad)1,5,8 and Id1 mRNA levels were measured as markers of Bmp/Smad signaling. Results While Bmp6 expression was increased, liver hepcidin and Id1 expression were decreased in each of the HH models compared with wild-type mice. Each of the HH models also demonstrated attenuated P-Smad1,5,8 levels relative to liver iron status. Mice with combined Hfe/Tfr2 disruption were most affected. Dietary iron loading increased hepcidin and Id1 expression in each of the HH models. Compared with wild-type mice, HH mice demonstrated attenuated (Hfe knockout) or no increases in P-Smad1,5,8 levels in response to dietary iron loading. Conclusions These observations demonstrate that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver BMP6 mRNA or steady-state P-Smad1,5,8 levels. PMID:21745449

  2. Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes. The role of lysosomal mannosidase

    Nok A.J.

    2002-12-01

    Full Text Available Partially purified azanthraquinone (AQ extract from Mitracarpus scaber was coupled to bovine transferrin (Tf using azidophenyl glyoxal (APG. The AQ-APG-Tf conjugate was found to possess an enhanced in vitro trypanocidal activity against Trypanosoma congolense and T. brucei brucei. At low concentrations of 0.39-90 mg/ml, the conjugate diminished the growth of T. congolense and T. b. brucei dose dependently at the logarithmic phase. Both parasites were more sensitive to AQ-APG-Tf than to the free (AQ extract. Growth inhibition on the parasites by the free extract was observed at 20-200 mg/ml. The total activity of the lysosomal enzyme a-mannosidase was reduced in the T. congolense cells treated with AQ-APG-Tf in a dose related pattern. However, the activity of the mannosidase in the T. b. brucei treated cells is less affected. The AQ-APG-Tf is more effective on a mannosidase than free AQ, eight and four fold for T. congolense and T. b. brucei respectively. The results are discussed as regards the potency of using transferrin as suitable drug carrier in the chemotherapy of Human sleeping sickness.

  3. Transferrin-modified liposome promotes α-mangostin to penetrate the blood-brain barrier.

    Chen, Zhi-Lan; Huang, Man; Wang, Xia-Rong; Fu, Jun; Han, Min; Shen, You-Qing; Xia, Zheng; Gao, Jian-Qing

    2016-02-01

    α-Mangostin (α-M) is a polyphenolic xanthone that protects and improves the survival of cerebral cortical neurons against Aβ oligomer-induced toxicity in rats. α-M is a potential candidate as a treatment for Alzheimer's disease (AD). However, the efficacy was limited by the poor penetration of the drug through the blood-brain barrier (BBB). In this study, we modified the α-M liposome with transferrin (Tf) and investigated the intracellular distribution of liposomes in bEnd3 cells. In addition, the transport of α-M across the BBB in the Tf(α-M) liposome group was examined. In vitro studies demonstrated that the Tf(α-M) liposome could cross the BBB in the form of an integrated liposome. Results of the in vivo studies on the α-M distribution in the brain demonstrated that the Tf(α-M) liposome improved the brain delivery of α-M. These results indicated that the Tf liposome is a potential carrier of α-M against AD. The use of α-Mangostin (α-M) as a potential agent to treat Alzheimer's disease (AD) has been reported. However, its use is limited by the poor penetration through the blood brain barrier. The delivery of this agent by transferrin-modified liposomes was investigated by the authors in this study. The positive results could point to a better drug delivery system for brain targeting. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    Jeong, Seung Min, E-mail: smjeong@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Hwang, Sunsook; Seong, Rho Hyun [School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2016-03-11

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  5. Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

    Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi; Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan; Hwu, Yeu-Kuang; Tsai, Din Ping; Chuang, Shih-Yi; Pang, Jong-Hwei S

    2011-01-01

    The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

  6. Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

    Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan [Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China); Hwu, Yeu-Kuang [Institute of Physics, Academia Sinica, Taipei 115, Taiwan (China); Tsai, Din Ping [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Chuang, Shih-Yi; Pang, Jong-Hwei S, E-mail: rsliu@ntu.edu.tw, E-mail: mhsiao@gate.sinica.edu.tw [Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan (China)

    2011-09-30

    The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

  7. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    Jeong, Seung Min; Hwang, Sunsook; Seong, Rho Hyun

    2016-01-01

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  8. Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

    Reuter, Lauri J.; Shahbazi, Mohammad-Ali; Makila, Ermei M.

    2017-01-01

    can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration...... to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of concept for the functionalization...

  9. Influence of carbonate on the complexation of Cm(III) with human serum transferrin studied by time-resolved laser fluorescence spectroscopy (TRLFS)

    Bauer, Nicole; Panak, Petra J.

    2015-01-01

    The complexation of Cm(III) with transferrin is investigated in the pH range from 3.5 to 11.0 in the absence of carbonate and at c(carbonate)(tot) = 25 mM. In the absence of carbonate two Cm(III) transferrin species I and II are formed depending on pH. An increase of the total carbonate concentration favors the formation of the Cm(III) transferrin species II with Cm(III) bound at the Fe(III) binding site of transferrin at significantly lower pH values. The spectroscopic results directly prove that carbonate acts as a synergistic anion for Cm(III) complexation at the binding site of transferrin. At c(carbonate)(tot) = 25 mM the formation of the nonspecific Cm(III) transferrin species I is suppressed completely. Instead, three Cm(III) carbonate species Cm(CO 3 ) + , Cm(CO 3 ) 2 - and Cm(CO 3 ) 3 3- are formed successively with increasing pH. The formation of Cm(III) carbonate species results in a decreased fraction of the Cm(III) transferrin species II at pH ≥ 7.4 which indicates that carbonate complexation is an important competition reaction for Cm(III) transferrin complexation at physiological carbonate concentration. (authors)

  10. Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier

    Johnsen, Kasper Bendix; Larsen, Annette Burkhart; Bruun, Jonas

    2016-01-01

    Brain capillary endothelial cells (BCECs) express transferrin receptors as opposed to endothelial cells of any organ in the remaining body, suggesting that targeting to the transferrin receptors as a reasonable strategy for delivering drugs to the CNS. However, as the intracellular trafficking...

  11. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

    de Swart, Louise; Hendriks, Jan C. M.; van der Vorm, Lisa N.; Cabantchik, Z. Ioav; Evans, Patricia J.; Hod, Eldad A.; Brittenham, Gary M.; Furman, Yael; Wojczyk, Boguslaw; Janssen, Mirian C. H.; Porter, John B.; Mattijssen, Vera E. J. M.; Biemond, Bart J.; MacKenzie, Marius A.; Origa, Raffaella; Galanello, Renzo; Hider, Robert C.; Swinkels, Dorine W.

    2016-01-01

    Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron)

  12. Acute toxicity profile of cadmium revealed by proteomics in brain tissue of Paralichthys olivaceus: Potential role of transferrin in cadmium toxicity

    Zhu Jinyong; Huang Heqing; Bao Xiaodong; Lin Qingmei; Cai Zongwei

    2006-01-01

    An analytical approach using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) separated proteins from the brain tissue of the fish Paralichthys olivaceus. Approximately 600 protein spots were detected from the brain sample when applying 600 μg protein to a 2D-PAGE gel in the pH range 3.5-10.0. Compared to a control sample, significant changes of 24 protein spots were observed in the fish tissue exposed to acute toxicity of seawater cadmium (SCAT) at 10 ppm for 24 h. Among these spots, nine were down-regulated, nine were up-regulated, two showed high expression, and four showed low expression. The collected spots were identified by peptide mass fingerprinting (PMF) and database search, and they were further classified by LOCtree, a hierarchical system of support vector machines which predict their sub-cellular localization. The amount of transferrin expression in brain cells decreased linearly with the increase of SCAT concentration in seawater. Among the 24 proteins identified on a 2D-PAGE gel, 9 demonstrated a synchronous response to acute cadmium, suggesting that they might represent a biomarker profile. Based on their variable levels and trends on the 2D-PAGE gel this protein (likely to be transferrin) suggesting they might be utilized as biomarkers to investigate cadmium pollution levels in seawater and halobios survival, as well as to evaluate the degree of risk of human fatalities. The results indicate that the application of multiple biomarkers has an advantage over a single biomarker for monitoring levels of environmental contamination

  13. Transferrin receptor molecular imaging: targeting for diagnosis and monitoring of gene delivery

    Eun-Mi Kim; Hwan-Jeong Jeong; Jin-Hee Kim; Chang-Guhn Kim

    2004-01-01

    Tc labeled complexes in the tumor two days after administration was visualized fluorescence microscope. Conclusion: Using 99mTc transferrin conjugate, transferrin binding to transferrin receptor on tumor cell could be seen in vivo. Also we certificated the possibility of monitoring whether the Tf-dendrimer gene complex is delivered to the desirous site. (authors)

  14. Kinetic, spectroscopic and chemical modification study of iron release from transferrin; iron(III) complexation to adenosine triphosphate

    Thompson, C.P.

    1985-01-01

    Amino acids other than those that serve as ligands have been found to influence the chemical properties of transferrin iron. The catalytic ability of pyrophosphate to mediate transferrin iron release to a terminal acceptor is largely quenched by modification non-liganded histine groups on the protein. The first order rate constants of iron release for several partially histidine modified protein samples were measured. A statistical method was employed to establish that one non-liganded histidine per metal binding domain was responsible for the reduction in rate constant. These results imply that the iron mediated chelator, pyrophosphate, binds directly to a histidine residue on the protein during the iron release process. EPR spectroscopic results are consistent with this interpretation. Kinetic and amino acid sequence studies of ovotransferrin and lactoferrin, in addition to human serum transferrin, have allowed the tentative assignment of His-207 in the N-terminal domain and His-535 in the C-terminal domain as the groups responsible for the reduction in rate of iron release. The above concepts have been extended to lysine modified transferrin. Complexation of iron(II) to adenosine triphosphate (ATP) was also studied to gain insight into the nature of iron-ATP species present at physiological pH. 31 P NMR spectra are observed when ATP is presented in large excess

  15. 67Ga in transferrin-unbound form is taken up by inflamed liver of mouse treated with CCl4

    Ohkubo, Yasuhito; Sasayama, Akio; Takegahara, Ikumi; Katoh, Shinsuke; Abe, Kenichi; Kohno, Hiroyuki; Kubodera, Akiko.

    1990-01-01

    In order to investigate whether or not transferrin is involved in the uptake of 67 Ga by inflamed liver (acute inflammatory tissues) the uptake of 67 Ga by the liver of mice treated with carbon tetrachloride (CCl 4 ) was studied. The serum GPT value reached its maximum on the 1st day after the CCl 4 treatment. The uptake of 67 Ga by the liver also reached its maximum on the 1st day after the CCl-4 treatment and the amount uptake into inflamed liver was about 6 times that uptaken into normal liver. On the other hand, the uptake of 125 I-transferrin into inflamed liver on the 1st day after CCl 4 treatment was only about 1.6 times that into normal liver. Moreover, cold Fe 3+ decreased the uptake of 67 Ga by normal liver but increased the uptake of 67 Ga by inflamed liver. These results show that transferrin plays an important role in the uptake of 67 Ga by normal liver but not by inflamed liver, i.e. 67 Ga in the transferrin-unbound form is preferentially taken up by inflamed liver. (author)

  16. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  17. Arf6, Rab11 and transferrin receptor define distinct populations of recycling endosomes.

    Kobayashi, Hotaka; Fukuda, Mitsunori

    2013-09-01

    Recycling endosomes are key platforms for endocytic recycling that return internalized molecules back to the plasma membrane. To determine how recycling endosomes perform their functions, searching for proteins and lipids that specifically localized at recycling endosomes has often been performed by colocalization analyses between candidate molecules and conventional recycling endosome markers. However, it remains unclear whether all the conventional markers have identical localizations. Here we report finding that three well-known recycling endosome markers, i.e., Arf6, Rab11 and transferrin receptor (TfR), have different intracellular localizations in PC12 cells. The results of immunofluorescence analyses showed that the signals of endogenous Arf6, Rab11 and TfR in nerve growth factor-stimulated PC12 cells generally differed, although there was some overlapping. Our findings provide new information about recycling endosome markers, and they highlight the heterogeneity of recycling endosomes.

  18. Cross-sectional study of expression of divalent metal transporter-1, transferrin, and hepcidin in blood of smelters who are occupationally exposed to manganese

    Qiyuan Fan

    2016-09-01

    Full Text Available Background Manganese (Mn is widely used in industries including the manufacture of Mn-iron (Fe alloy. Occupational Mn overexposure causes manganism. Mn is known to affect Fe metabolism; this study was designed to test the hypothesis that workers exposed to Mn may have an altered expression of mRNAs encoding proteins in Fe metabolism. Methods Workers occupationally exposed to Mn (n = 71 from a Mn–Fe alloy factory and control workers without Mn-exposure (n = 48 from a pig-iron plant from Zunyi, China, were recruited for this study. Blood samples were collected into Trizol-containing tubes. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis. Metal concentrations were quantified by atomic absorption spectrophotometry. Results Working environment and genetic background of both groups were similar except for marked differences in airborne Mn concentrations (0.18 mg/m3 in Mn–Fe alloy factory vs. 0.0022 mg/m3 in pig-Fe plant, and in blood Mn levels (34.3 µg/L vs. 10.4 µg/L. Mn exposure caused a significant decrease in the expression of divalent metal transporter-1 (DMT1, transferrin (Tf and hepcidin by 58.2%, 68.5% and 61.5%, respectively, as compared to controls, while the expression of transferrin receptor (TfR was unaltered. Linear regression analysis revealed that expressions of DMT1, Tf and hepcidin were inversely correlated with the accumulative Mn exposure; the correlation coefficients (r are −0.47, −0.54, and −0.49, respectively (p < 0.01. Conclusion The data suggest that occupational Mn exposure causes decreased expressions of DMT1, Tf and hepcidin in blood cells; the finding will help understand the mechanism underlying Mn exposure-associated alteration in Fe homeostasis among workers.

  19. Enhanced transferrin receptor expression by proinflammatory cytokines in enterocytes as a means for local delivery of drugs to inflamed gut mucosa.

    Efrat Harel

    Full Text Available Therapeutic intervention in inflammatory bowel diseases (IBDs is often associated with adverse effects related to drug distribution into non-diseased tissues, a situation which attracts a rational design of a targeted treatment confined to the inflamed mucosa. Upon activation of immune cells, transferrin receptor (TfR expression increases at their surface. Because TfR is expressed in all cell types we hypothesized that its cell surface levels are regulated also in enterocytes. We, therefore, compared TfR expression in healthy and inflamed human colonic mucosa, as well as healthy and inflamed colonic mucosa of the DNBS-induced rat model. TfR expression was elevated in the colonic mucosa of IBD patients in both the basolateral and apical membranes of the enterocytes. Increased TfR expression was also observed in colonocytes of the induced colitis rats. To explore the underlying mechanism CaCo-2 cells were treated with various proinflammatory cytokines, which increased both TfR expression and transferrin cellular uptake in a mechanism that did not involve hyper proliferation. These findings were then exploited for the design of targetable carrier towards inflamed regions of the colon. Anti-TfR antibodies were conjugated to nano-liposomes. As expected, iron-starved Caco-2 cells internalized anti-TfR immunoliposomes better than controls. Ex vivo binding studies to inflamed mucosa showed that the anti-TfR immunoliposomes accumulated significantly better in the mucosa of DNBS-induced rats than the accumulation of non-specific immunoliposomes. It is concluded that targeting mucosal inflammation can be accomplished by nano-liposomes decorated with anti-TfR due to inflammation-dependent, apical, elevated expression of the receptor.

  20. Endocytosis of a functionally enhanced GFP-tagged transferrin receptor in CHO cells.

    Qi He

    Full Text Available The endocytosis of transferrin receptor (TfR has served as a model to study the receptor-targeted cargo delivery system for cancer therapy for many years. To accurately evaluate and optically measure this TfR targeting delivery in vitro, a CHO cell line with enhanced green fluorescent protein (EGFP-tagged human TfR was established. A chimera of the hTfR and EGFP was engineered by fusing EGFP to the amino terminus of hTfR. Data were provided to demonstrate that hTfR-EGFP chimera was predominantly localized on the plasma membrane with some intracellular fluorescent structures on CHO cells and the EGFP moiety did not affect the endocytosis property of hTfR. Receptor internalization occurred similarly to that of HepG2 cells expressing wild-type hTfR. The internalization percentage of this chimeric receptor was about 81 ± 3% of wild type. Time-dependent co-localization of hTfR-EGFP and PE-conjugated anti-hTfR mAb in living cells demonstrated the trafficking of mAb-receptor complexes through the endosomes followed by segregation of part of the mAb and receptor at the late stages of endocytosis. The CHO-hTfR cells preferentially took up anti-hTfR mAb conjugated nanoparticles. This CHO-hTfR cell line makes it feasible for accurate evaluation and visualization of intracellular trafficking of therapeutic agents conjugated with transferrin or Abs targeting the hTfRs.

  1. Enhanced expression of transferrin receptor confers UV-resistance in human and monkey cells

    Chen, Zheng; Nomura, Jun; Suzuki, Toshikazu; Suzuki, Nobuo

    2005-01-01

    One of the most intriguing biological subjects is cell-surface molecules that regulate the susceptibility of human cells to cell-killing effects after irradiation with far-ultraviolet light (UV, principally 254 nm wavelength). Human RSa cells have unusual sensitivity to UV-induced cell-killing. We searched for molecules on the cell-surface of RSa cells that were present in different amounts as compared to a variant of these cells, UV r -1 cells, which have increased resistance to UV cell-killing. Among the 21 molecules examined, the amount of transferrin receptor (TfR) protein was found to be 2-fold higher in UV r -1 cells compared with in RSa cells. The amounts of this protein were also higher in the UV-resistant hematopoietic cell lines, CEM6 and Daudi, as compared to the UV-sensitive cell lines, Molt4 and 697. Culturing of UV r -1 cells in a medium containing anti-transferrin antibodies resulted in sensitization of the cells to UV cell-killing as demonstrated by colony formation assay. Similar results were observed by treatment of the cells with TfR siRNA. In contrast, overexpression of TfR protein led to a resistance to UV cell-killing in RSa cells and monkey COS7 cells as demonstrated by both colony formation and apoptosis assay. In TfR-overexpressing cells, reduction of p53 and Bax protein was observed after UV-irradiation. Thus, TfR expression appears to be involved in the regulation of UV-resistance, possibly via modulation of the amount of p53 and Bax protein. (author)

  2. Effects of obesity, total fasting and re-alimentation on L-thyroxine (T4), 3,5,3'-L-triiodothyronine (T3), 3,3',5'-L-triiodothyronine (rT3), thyroxine binding globulin (TBG), cortisol, thyrotrophin, cortisol binding globulin (CBG), transferrin, alpha 2-haptoglobin and complement C'3 in serum.

    Scriba, P C; Bauer, M; Emmert, D; Fateh-Moghadam, A; Hofmann, G G; Horn, K; Pickardt, C R

    1979-08-01

    The effects of total fasting for 31 +/- 10 days followed by re-alimentation with an 800 calorie diet on thyroid function, i.e. T4,T3,rT3,RT3U (resin T3 uptake), and TSH, and on TBG levels in serum were studied sequentially in obese hospitalized patients (N=18). Additionally, cortisol, growth hormone, prolactin, parathyrin and free fatty acids were followed as hormonal and metabolic parameters, respectively. Further, CBG, transferrin, alpha 2-haptoglobin and complement C'3 were measured as representatives of other serum proteins. Results before fasting: T4, T3, TBG, cortisol, CBG, alpha 2-haptoglobin and complement C'3 of the obese patients were elevated when compared with healthy normal weight controls, whereas rT3, T4/TBG ratio, T3/TBG ratio, TSH, coritsol/cbg ratio, growth hormone, prolactin, parathyrin and transferrin of the obese group were normal. RT3U and fT4 index were decreased in the obese patients. Results during fasting: Significant decreases were observed during fasting for the following parameters -- T3, TBG, T3/TBG ratio, transferrin, alpha 2-haptoglobin complement C'3. rT3, T4/TBG ratio, RT3U, fT4 index and FFA increased. T4, tsh response to TRH stimulation, cortisol, CBG, cortisol/cbg ratio, parathyrin, growth hormone and prolactin did not change. Results during re-alimentation: T3, TBG, T3/TBG ratio, TSH response to TRH, transferrin, alpha 2-haptoglobin and complement C'3 increased. Conversely, fT3, RT3U, FFA, cortisol and cortisol/cbg ratio decreased whereas the other parameters did not change. 1) There is no evidence for primary hypothyroidism in obese patients during prolonged fasting and re-alimentation. 2) The rapid decrease of T3 and increase of RT3U after initiation of fasting are not fully explained by the observed slower decreases in TBG. 3) The alterations of T3, rT3 and RT3U resemble in their kinetics the changes in FFA levels. 4) Fasting reduced the levels of only certain serum proteins, interestingly TBG, transferrin, alpha 2

  3. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

    Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

    2017-01-01

    Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibi...... cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain....... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...... not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased...

  4. Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

    Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

    2017-03-07

    The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole

  5. Studies of metal binding by the iron transport protein transferrin using time differential perturbed angular correlation spectroscopy

    Then, G.M.

    1987-01-01

    The binding of the transition metal hafnium to transferrin was studied under various chemical conditions using time differential perturbed γγ angular correlation spectroscopy (TDPAC). Observing the electric quadrupole interaction of the 181 Hf probe nuclei size and symmetry of the electric field gradient induced by the ligands of the metal ions can be determined. The experimental data suggest how homogeneous the binding conditions are and to which extend relaxation phenomena are involved. Due to the excellent time resolution obtained with new BaF 2 detectors the quadrupole coupling parameters of 181 Hf-transferrin could be determined very accurately. Under nearly physiological conditions different binding configurations were quantitatively characterized by spectroscopic means and distinguished with high specificity. (orig./PW) [de

  6. Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box-Behnken design.

    Emami, Jaber; Rezazadeh, Mahboubeh; Sadeghi, Hojjat; Khadivar, Khashayar

    2017-05-01

    The treatment of brain cancer remains one of the most difficult challenges in oncology. The purpose of this study was to develop transferrin-conjugated nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX). PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the impact of various formulation variables were assessed using Box-Behnken design. Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro cytotoxicity of it was investigated against U-87 brain cancer cell line. As a result, 14.1 mg of cholesterol, 18.5 mg of triolein, and 0.5% poloxamer were used to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted formulation were confirmed to be 205.4 ± 11 nm, 25.7 ± 6.22 mV, 91.8 ± 0.5%, 5.38 ± 0.03% and 29.3 h, respectively. Following conjugation of optimized PTX-NLCs with transferrin, coupling efficiency was 21.3 mg transferrin per mmol of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non-significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could potentially be exploited as a delivery system in brain cancer cells.

  7. Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders.

    Ajay Singh

    2011-03-01

    Full Text Available Sporadic Creutzfeldt-Jakob-disease (sCJD is a fatal neurodegenerative condition that escapes detection until autopsy. Recently, brain iron dyshomeostasis accompanied by increased transferrin (Tf was reported in sCJD cases. The consequence of this abnormality on cerebrospinal-fluid (CSF levels of Tf is uncertain. We evaluated the accuracy of CSF Tf, a 'new' biomarker, as a pre-mortem diagnostic test for sCJD when used alone or in combination with the 'current' biomarker total-tau (T-tau. Levels of total-Tf (T-Tf, isoforms of Tf (Tf-1 and Tf-β2, and iron saturation of Tf were quantified in CSF collected 0.3-36 months before death (duration from 99 autopsy confirmed sCJD (CJD+ and 75 confirmed cases of dementia of non-CJD origin (CJD-. Diagnostic accuracy was estimated by non-parametric tests, logistic regression, and receiver operating characteristic (ROC analysis. Area under the ROC curve (AUC, sensitivity, specificity, positive and negative predictive values (PV, and likelihood ratios (LR of each biomarker and biomarker combination were calculated. We report that relative to CJD-, CJD+ cases had lower median CSF T-Tf (125,7093 vs. 217,7893 and higher T-tau (11530 vs. 1266 values. AUC was 0.90 (95% confidence interval (CI, 0.85-0.94 for T-Tf, and 0.93 (95% CI, 0.89-0.97 for T-Tf combined with T-tau. With cut-offs defined to achieve a sensitivity of ∼85%, T-Tf identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1-81.7, positive LR of 3.0 (95% CI, 2.1-4.5, negative LR of 0.2 (95% CI, 0.1-0.3, and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3-94.1, positive LR of 6.8 (95% CI, 3.5-13.1, negative LR of 0.2 (95% CI, 0.1-0.3, positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.

  8. Primary care requests for anaemia chemistry tests in Spain: potential iron, transferrin and folate over-requesting.

    Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Carlos

    2017-09-01

    To study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting. Requests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice. 110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population). The demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs. 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/.

  9. Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria

    Konopka, K.; Romslo, I.; Bergen Univ.

    1981-01-01

    1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein -1 h -1 , or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is depleted, or the experiments are run under anaerobic conditions. Substrate, depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous irons thus formed is available for heme synthesis. (orig.) [de

  10. Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

    Joao Arezes

    Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

  11. Effects of epidermal growth factor, transferrin, and insulin on lipofection efficiency in human lung carcinoma cells.

    Yanagihara, K; Cheng, H; Cheng, P W

    2000-01-01

    Poor transfection efficiency is the major drawback of lipofection. We showed previously that addition of transferrin (TF) to Lipofectin enhanced the expression of a reporter gene in HeLa cells by 120-fold and achieved close to 100% transfection efficiency. The purpose of this study was to determine whether TF and other ligands could improve the efficiency of lipofection in lung carcinoma cells. Confluent A549, Calu3, and H292 cells were transfected for 18 hours with a plasmid DNA (pCMVlacZ) using Lipofectin plus TF, insulin, or epidermal growth factor as the vector. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (light units/microg protein) and the percentage of blue cells following 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside staining. Lipofectin supplemented with epidermal growth factor yielded the largest enhancement of lipofection efficiency (lipofection efficiency in A549 and Calu3 cells but not in H292 cells, whereas TF showed significant lipofection efficiency-enhancing effect in Calu3 and H292 cells but not in A549 cells. The transfection efficiency correlated well with the amounts of DNA delivered to the nucleus as well as the amounts of the receptor. These results indicate that the gene delivery strategy employing ligand-facilitated lipofection can achieve high transfection efficiency in human lung carcinoma cells. In addition, enhancement of the expression of the receptor may be a possible strategy for increasing the efficiency of gene targeting.

  12. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  13. Transferrin coated nanoparticles: study of the bionano interface in human plasma.

    Andrzej S Pitek

    Full Text Available It is now well established that the surface of nanoparticles (NPs in a biological environment is immediately modified by the adsorption of biomolecules with the formation of a protein corona and it is also accepted that the protein corona, rather than the original nanoparticle surface, defines a new biological identity. Consequently, a methodology to effectively study the interaction between nanomaterials and the biological corona encountered within an organism is a key objective in nanoscience for understanding the impact of the nanoparticle-protein interactions on the biological response in vitro and in vivo. Here, we outline an integrated methodology to address the different aspects governing the formation and the function of the protein corona of polystyrene nanoparticles coated with Transferrin by different strategies. Protein-NP complexes are studied both in situ (in human plasma, full corona FC and after washing (hard corona, HC in terms of structural properties, composition and second-order interactions with protein microarrays. Human protein microarrays are used to effectively study NP-corona/proteins interactions addressing the growing demand to advance investigations of the extrinsic function of corona complexes. Our data highlight the importance of this methodology as an analysis to be used in advance of the application of engineered NPs in biological environments.

  14. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier

    Friden, P.M.; Walus, L.R.; Musso, G.F.; Taylor, M.A.; Malfroy, B.; Starzyk, R.M.

    1991-01-01

    Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. The authors have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. This antibody, which was previously shown to bind preferentially to capillary endothelial cells in the brain after intravenous administration, labels the entire cerebrovascular bed in a dose-dependent manner. The initially uniform labeling of brain capillaries becomes extremely punctate ∼ 4 hr after injection, suggesting a time-dependent sequestering of the antibody. Capillary-depletion experiments, in which the brain is separated into capillary and parenchymal fractions, show a time-dependent migration of radiolabeled antibody from the capillaries into the brain parenchyma, which is consistent with the transcytosis of compounds across the blood-brain barrier. Antibody-methotrexate conjugates were tested in vivo to assess the carrier ability of this antibody. Immunohistochemical staining for either component of an OX-26-methotrexate conjugate revealed patterns of cerebrovascular labeling identical to those observed with the unaltered antibody. Accumulation of radiolabeled methotrexate in the brain parenchyma is greatly enhanced when the drug is conjugated to OX-26

  15. Ultrasensitive Sensing Material Based on Opal Photonic Crystal for Label-Free Monitoring of Transferrin.

    Wu, Enqi; Peng, Yuan; Zhang, Xihao; Bai, Jialei; Song, Yanqiu; He, Houluo; Fan, Longxing; Qu, Xiaochen; Gao, Zhixian; Liu, Ying; Ning, Baoan

    2017-02-22

    A new opal photonic crystal (PC) sensing material, allowing label-free detection of transferrin (TRF), is proposed in the current study. This photonic crystal was prepared via a vertical convective self-assembly method with monodisperse microspheres polymerized by methyl methacrylate (MMA) and 3-acrylamidophenylboronic acid (AAPBA). FTIR, TG, and DLS were used to characterize the components and particle size of the monodisperse microspheres. SEM was used to observe the morphology of the PC. The diffraction peak intensity decreases as the TRF concentration increase. This was due to the combination of TRF to the boronic acid group of the photonic crystal. After condition optimization, a standard curve was obtained and the linear range of TRF concentration was from 2 × 10 -3 ng/mL to 200 ng/mL. Measurement of TRF concentration in simulated urine sample was also investigated using the sensing material. The results indicated that the PC provided a cheap, label-free, and easy-to-use alternative for TRF determination in clinical diagnostics.

  16. Chromatographic Monoliths for High-Throughput Immunoaffinity Isolation of Transferrin from Human Plasma

    Irena Trbojević-Akmačić

    2016-06-01

    Full Text Available Changes in protein glycosylation are related to different diseases and have a potential as diagnostic and prognostic disease biomarkers. Transferrin (Tf glycosylation changes are common marker for congenital disorders of glycosylation. However, biological interindividual variability of Tf N-glycosylation and genes involved in glycosylation regulation are not known. Therefore, high-throughput Tf isolation method and large scale glycosylation studies are needed in order to address these questions. Due to their unique chromatographic properties, the use of chromatographic monoliths enables very fast analysis cycle, thus significantly increasing sample preparation throughput. Here, we are describing characterization of novel immunoaffinity-based monolithic columns in a 96-well plate format for specific high-throughput purification of human Tf from blood plasma. We optimized the isolation and glycan preparation procedure for subsequent ultra performance liquid chromatography (UPLC analysis of Tf N-glycosylation and managed to increase the sensitivity for approximately three times compared to initial experimental conditions, with very good reproducibility. This work is licensed under a Creative Commons Attribution 4.0 International License.

  17. Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo

    Wen, Jiexia; Pan, Sumin; Liang, Shuang; Zhong, Zhenyu; He, Ying; Lin, Hongyu; Li, Wenyan; Wang, Liyue; Li, Xiujin; Zhong, Fei

    2013-01-01

    Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo. PMID:24089666

  18. Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo

    Jiexia Wen

    2013-01-01

    Full Text Available Canine parvovirus (CPV disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.

  19. Transgenic HFE-dependent induction of hepcidin in mice does not require transferrin receptor-2.

    Schmidt, Paul J; Fleming, Mark D

    2012-06-01

    Hereditary hemochomatosis (HH) is caused by mutations in several genes, including HFE and transferrin receptor-2 (TFR2). Loss of either protein decreases expression of the iron regulatory hormone hepcidin by the liver, leading to inappropriately high iron uptake from the diet, and resulting in systemic iron overload. In tissue culture, overexpressed HFE and TFR2 physically interact. Hepatocellular overexpression of Hfe in vivo increases hepcidin expression, despite an associated decrease in Tfr2. On this basis, we hypothesized that Tfr2 would not be required for Hfe-dependent up-regulation of hepcidin. We show that hepatocellular overexpression of Hfe in Tfr2(Y245X/Y245X) mice leads to hepcidin induction eventuating in iron deficiency and a hypochromic, microcytic anemia. Furthermore, coimmunoprecipitation studies using liver lysates did not provide evidence for physical interaction between Hfe and Tfr2 in vivo. In conclusion, we demonstrate that Tfr2 is not essential for Hfe-mediated induction of hepcidin expression, supporting the possibility that TFR2 may regulate iron metabolism in an HFE-independent manner. Copyright © 2012 Wiley Periodicals, Inc.

  20. Aluminum access to the brain: A role for transferrin and its receptor

    Roskams, A.J.; Connor, J.R.

    1990-01-01

    The toxicity of aluminum in plant and animal cell biology is well established, although poorly understood. Several recent studies have identified aluminum as a potential, although highly controversial, contributory factor in the pathology of Alzheimer's disease, amyotrophic lateral sclerosis, and dialysis dementia. For example, aluminum has been found in high concentrations in senile plaques and neurofibrillary tangles, which occur in the brains of subjects with Alzheimer's disease. However, a mechanism for the entry of aluminum (Al 3+ ) into the cells of the central nervous system (CNS) has yet to be found. Here the authors describe a possible route of entry for aluminum into the cells of the CNS via the same high-affinity receptor-ligand system that has been postulated for iron (Fe 3 ) aluminum is able to gain access to the central nervous system under normal physiological conditions. Furthermore, these data suggest that the interaction between transferrin and its receptor may function as a general metal ion regulatory system in the CNS, extending beyond its postulated role in iron regulation

  1. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  2. Reference limits and behaviour of serum transferrin receptor in children 6-10 years of age.

    Danise, P; Maconi, M; Morelli, G; Di Palma, A; Rescigno, G; Esposito, C; Avino, D; Talento, B

    2008-08-01

    Serum transferrin receptor (sTfR) originates mostly from erythroblasts and lesser from reticulocytes. The usefulness of sTfR has been implicated in several clinical situations, mainly as a marker of accelerated erythropoiesis or iron deficiency. The assessment of sTfR may be useful in the period of rapid growth during infancy, childhood and adolescence. We evaluated sTfR and the other quantitative and qualitative parameters of the erythropoiesis (Hb, MCV, CHr, Ret-He) and of the iron storage (serum ferritin, sTfR/ferritin index) in a total of 916 children aged 6-10 years. Children were divided into three groups: (A) healthy children, (B) with storage iron deficiency (serum ferritin 3.3). We determined reference intervals by sex and by age in healthy children. sTfR showed a slight but statistically significant age related increase but did not show significant sex differences. We compared sTfR and the other parameters investigated in the three groups of children. sTfR is not a decisive parameter that can be utilized alone in discriminating the border-line situations between normal and pathologic ones but can help in completing the panel of tests in iron deficiency and in thalassaemia Beta trait carriers.

  3. The distribution of iron between the metal-binding sites of transferrin human serum.

    Williams, J; Moreton, K

    1980-02-01

    The Makey & Seal [(1976) Biochim. Biophys. Acta 453, 250--256] method of polyacrylamide-gel electrophoresis in buffer containing 6 M-urea was used to determine the distribution of iron between the N-terminal and C-terminal iron-binding sites of transferrin in human serum. In fresh serum the two sites are unequally occupied; there is preferential occupation of the N-terminal site. On incubation of the serum at 37 degrees C the preference of iron for the N-terminal site becomes more marked. On storage of serum at -15 degrees C the iron distribution changes so that there is a marked preference for the C-terminal site. Dialysis of serum against buffer at pH 7.4 also causes iron to be bound much more strongly by the C-terminal than by the N-terminal site. The original preference for the N-terminal site can be resroted to the dialysed serum by addition of the diffusible fraction.

  4. Using Soluble Transferrin Receptor and Taking Inflammation into Account When Defining Serum Ferritin Cutoffs Improved the Diagnosis of Iron Deficiency in a Group of Canadian Preschool Inuit Children from Nunavik

    Huguette Turgeon O’Brien

    2016-01-01

    Full Text Available The prevalence of iron depletion, iron deficient erythropoiesis (IDE, and iron deficiency anemia (IDA was assessed in preschool Inuit children using soluble transferrin receptor (sTfR and traditional indicators of iron status while disregarding or taking inflammation into account when defining SF cutoffs. Iron depletion was defined as follows: (1 SF 5 mg/L, respectively. IDE corresponded to iron depletion combined with total iron binding capacity > 72 μmol/L and/or transferrin saturation < 16%. Iron depletion and IDE affected almost half of the children when accounting for inflammation, compared to one-third when the SF cutoff was defined regardless of CRP level (P<0.0001. The prevalence of IDE adjusted for inflammation (45.1% was very similar to the prevalence observed when sTfR was used as a sole marker of IDE (47.4%. The prevalence of anemia was 15%. The prevalence of IDA (IDE + hemoglobin < 110 g/L was higher when accounting for than when disregarding inflammation (8.0% versus 6.2%, P=0.083. Using sTfR and different SF cutoffs for children with versus without inflammation improved the diagnosis of iron depletion and IDE. Our results confirm that Inuit children are at particularly high risk for iron deficiency.

  5. Role of Insulin-Transferrin-Selenium in Auricular Chondrocyte Proliferation and Engineered Cartilage Formation in Vitro

    Xia Liu

    2014-01-01

    Full Text Available The goal of this study is to determine the effects of Insulin-Transferrin-Selenium (ITS on proliferation of auricular chondrocytes and formation of engineered cartilage in vitro. Pig auricular monolayer chondrocytes and chondrocyte pellets were cultured in media containing 1% ITS at different concentrations of fetal bovine serum (FBS, 10%, 6%, 2%, 0%, or 10% FBS alone as a control for four weeks. Parameters including cell proliferation in monolayer, wet weight, collagen type I/II/X (Col I, II, X and glycosaminoglycan (GAG expression, GAG content of pellets and gene expression associated with cartilage formation/dedifferentiation (lost cartilage phenotype/hypertrophy within the chondrocyte pellets were assessed. The results showed that chondrocytes proliferation rates increased when FBS concentrations increased (2%, 6%, 10% FBS in ITS supplemented groups. In addition, 1% ITS plus 10% FBS significantly promoted cell proliferation than 10% FBS alone. No chondrocytes grew in ITS alone medium. 1% ITS plus 10% FBS enhanced cartilage formation in terms of size, wet weight, cartilage specific matrices, and homogeneity, compared to 10% FBS alone group. Furthermore, ITS prevented engineered cartilage from dedifferentiation (i.e., higher index of Col II/Col I mRNA expression and expression of aggrecan and hypertrophy (i.e., lower mRNA expression of Col X and MMP13. In conclusion, our results indicated that ITS efficiently enhanced auricular chondrocytes proliferation, retained chondrogenic phenotypes, and promoted engineered cartilage formation when combined with FBS, which is potentially used as key supplementation in auricular chondrocytes and engineered cartilage culture.

  6. Fluorescence imaging of bombesin and transferrin receptor expression is comparable to 18F-FDG PET in early detection of sorafenib-induced changes in tumor metabolism.

    Jen-Chieh Tseng

    noticeable changes in tumor size. For comparison, two FLI probes, BombesinRSense™ 680 (BRS-680 and Transferrin-Vivo™ 750 (TfV-750, were assessed for their potential in metabolic imaging. Metabolically active cancer cells are known to have elevated bombesin and transferrin receptor levels on the surface. In excellent agreement with PET imaging, the BRS-680 imaging showed 40% and 79% inhibition on days 2 and 3, respectively, and the TfV-750 imaging showed 65% inhibition on day 3. In both cases, no significant reduction in tumor volume or BLI signal was observed during the first 3 days of treatment. These results suggest that metabolic FLI has potential preclinical application as an additional method for detecting drug-induced metabolic changes in tumors.

  7. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma.

    Johnsen, Kasper Bendix; Burkhart, Annette; Melander, Fredrik; Kempen, Paul Joseph; Vejlebo, Jonas Bruun; Siupka, Piotr; Nielsen, Morten Schallburg; Andresen, Thomas Lars; Moos, Torben

    2017-09-04

    Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain.

  8. A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

    Yang, Zhaogang; Yu, Bo; Zhu, Jing; Huang, Xiaomeng; Xie, Jing; Xu, Songlin; Yang, Xiaojuan; Wang, Xinmei; Yung, Bryant C.; Lee, L. James; Lee, Robert J.; Teng, Lesheng

    2014-07-01

    The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.

  9. Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

    Jason T Kaelber

    Full Text Available Parvoviruses exploit transferrin receptor type-1 (TfR for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host.

  10. Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

    Kaelber, Jason T; Demogines, Ann; Harbison, Carole E; Allison, Andrew B; Goodman, Laura B; Ortega, Alicia N; Sawyer, Sara L; Parrish, Colin R

    2012-01-01

    Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host.

  11. The transferrin receptor of Actinobacillus pleuropneumoniae: Quantitation of expression and structural characterization using a peptide-specific monoclonal antibody

    Bøg, Yang S.; Andresen, Lars Ole; Bastholm, L.

    2001-01-01

    transferrin. This complex was studied using a monoclonal antibody (Mab 1.48) raised against a synthetic peptide corresponding to a hydrophilic domain of Tbp2 common to several A. pp serotypes. The antibody reacted specifically with a 60-70 kDa Tbp2-antigen found in all serotypes of A. pp obtained from iron...... expressing Tbp2 and in wild type A. pp grown under iron restricted conditions. The subcellular location of Tbp2 in A. pp was studied by immunoelectron microscopy using the Mab 1.48. Interestingly, all antibody binding was found inside the A. pp cells, while Tbp2 expressed in recombinant E. coli was found...

  12. Diagnosis of protein-losing gastroenteropathy by 111In-transferrin scanning and fecal excretion test

    Urita, Yoshihisa

    1991-01-01

    A total of 12 patients with gastroenteropathy were studied for possible protein loss. The underlying diseases were intestinal lymphangiectasia, ulcerative colitis and Crohn's disease in 2 patients each; and Menetrier's disease, Cronkhite-Canada syndrome, postgastrectomy syndrome, severe atrophic gastritis, gastric cancer and gastroenteropathy of unknown origin in one patient each. The controls were four healthy volunteers and 9 patients with benign disease not accompanied by lesions in the digestive tract and protein loss, 111 In-transferrin (Tf) was prepared by incubating 2-3 mCi of 111 In-chloride with 15-20 ml of each patient's plasma in a sterilized vial at room temperature for 1 hour. After i.v. injection of 111 In-Tf, the patients were scanned at given intervals of time for 72 hours to localize protein loss. Seventy-two hour fecal 111 In-Tf excretion was also measured. 111 In-Tf was detected in the feces of all patients. The recovery rate in the patient group was 7.95±3.65%, being significantly higher than 0.48±0.26% in the control group. However, 111 In-Tf scanning showed the site of protein loss only in 6 patients. Negative scan in six other patients was thought to be associated with extensive inflammation and severe diarrhea. Five of the 12 patients were observed before and after treatment. A decrease in fecal 111 In-Tf excretion with clinical improvement was noted in the 5 patients after treatment. The site of protein loss could be demonstrated in 3 of the 5 patients before treatment. Its site in 1 of the 3 patients was the small intestine. However, accumulation of 111 In-Tf was found there in the 3 patients after treatment. The site of protein loss in one of three patients was the small intestine. 111 In-Tf scanning is particularly useful when the small intestine is involved, because surgery is contraindicated in this case. Fecal 111 In-Tf excretion test is mandatory when the site of protein loss cannot be imaged. (author)

  13. Metal retention in human transferrin: consequences of solvent composition in analytical sample preparation methods.

    Quarles, C Derrick; Randunu, K Manoj; Brumaghim, Julia L; Marcus, R Kenneth

    2011-10-01

    The analysis of metal-binding proteins requires careful sample manipulation to ensure that the metal-protein complex remains in its native state and the metal retention is preserved during sample preparation or analysis. Chemical analysis for the metal content in proteins typically involves some type of liquid chromatography/electrophoresis separation step coupled with an atomic (i.e., inductively coupled plasma-optical emission spectroscopy or -mass spectrometry) or molecular (i.e., electrospray ionization-mass spectrometry) analysis step that requires altered-solvent introduction techniques. UV-VIS absorbance is employed here to monitor the iron content in human holo-transferrin (Tf) under various solvent conditions, changing polarity, pH, ionic strength, and the ionic and hydrophobic environment of the protein. Iron loading percentages (i.e. 100% loading equates to 2 Fe(3+):1 Tf) were quantitatively determined to evaluate the effect of solvent composition on the retention of Fe(3+) in Tf. Maximum retention of Fe(3+) was found in buffered (20 mM Tris) solutions (96 ± 1%). Exposure to organic solvents and deionized H(2)O caused release of ~23-36% of the Fe(3+) from the binding pocket(s) at physiological pH (7.4). Salt concentrations similar to separation conditions used for ion exchange had little to no effect on Fe(3+) retention in holo-Tf. Unsurprisingly, changes in ionic strength caused by additions of guanidine HCl (0-10 M) to holo-Tf resulted in unfolding of the protein and loss of Fe(3+) from Tf; however, denaturing and metal loss was found not to be an instantaneous process for additions of 1-5 M guanidinium to Tf. In contrast, complete denaturing and loss of Fe(3+) was instantaneous with ≥6 M additions of guanidinium, and denaturing and loss of iron from Tf occurred in parallel proportions. Changes to the hydrophobicity of Tf (via addition of 0-14 M urea) had less effect on denaturing and release of Fe(3+) from the Tf binding pocket compared to changes

  14. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

    Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

    2017-01-01

    Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing...... the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we...... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...

  15. Loss of circulating 67Ga-transferrin due to its accumulation in malignant tumors of the rat and its relation to the synthesis of hemoglobin

    Kratzer, J.

    1981-01-01

    Taking into account earlier findings of other study groups, the author draws the following conclusions: 1. The elimination of 67 Ga-labelled transferrin from the blood of tumor carrier rats is accelerated as compared to normal. The acceleration is the more marked the greater the tumor mass and the higher its proliferation speed are. 2. The eliminated 67 Ga transferrin is detectable in the tumor by scintiscanning, and its retention increases concurrently with the tumor proliferation rate. 3. These tumor-dependent losses of transferrin entail a perturbation of reticulocytal Fe utilization and cause anemia, which is again aggravated as the tumor mass and its malignant nature increase. 4. If the tumor can be eliminated by therapy, the anemia disappears completely. (orig./MG) [de

  16. Transferrin-loaded nido-carborane liposomes. Synthesis and intracellular targeting to solid tumors for boron neutron capture therapy

    Nakamura, Hiroyuki; Miyajima, Yusuke; Kuwata, Yasuhiro; Maruyama, Kazuo; Masunaga, Shinichiro; Ono, Koji

    2006-01-01

    The boron ion cluster lipids, as a double-tailed boron lipid synthesized from heptadecanol, formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO 2 H moieties of PEG-CL liposomes. The biodistribution of Tf-PEG-CL liposomes showed that Tf-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor:blood concentration ratio. A 10 B concentration of 22 ppm in tumor tissues was achieved by the injection of Tf-PEG-CL liposome at 7.2 mg/kg body weight 10 B in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf-PEG-CL liposomes; one of them even survived for 52 days after BNCT. (author)

  17. α-Taxilin interacts with sorting nexin 4 and participates in the recycling pathway of transferrin receptor.

    Hiroshi Sakane

    Full Text Available Membrane traffic plays a crucial role in delivering proteins and lipids to their intracellular destinations. We previously identified α-taxilin as a binding partner of the syntaxin family, which is involved in intracellular vesicle traffic. α-Taxilin is overexpressed in tumor tissues and interacts with polymerized tubulin, but the precise function of α-taxilin remains unclear. Receptor proteins on the plasma membrane are internalized, delivered to early endosomes and then either sorted to the lysosome for degradation or recycled back to the plasma membrane. In this study, we found that knockdown of α-taxilin induced the lysosomal degradation of transferrin receptor (TfnR, a well-known receptor which is generally recycled back to the plasma membrane after internalization, and impeded the recycling of transferrin. α-Taxilin was immunoprecipitated with sorting nexin 4 (SNX4, which is involved in the recycling of TfnR. Furthermore, knockdown of α-taxilin decreased the number and length of SNX4-positive tubular structures. We report for the first time that α-taxilin interacts with SNX4 and plays a role in the recycling pathway of TfnR.

  18. Structural and functional consequences of binding site mutations in transferrin: crystal structures of the Asp63Glu and Arg124Ala mutants of the N-lobe of human transferrin.

    Baker, Heather M; He, Qing-Yu; Briggs, Sara K; Mason, Anne B; Baker, Edward N

    2003-06-17

    Human transferrin is a serum protein whose function is to bind Fe(3+) with very high affinity and transport it to cells, for delivery by receptor-mediated endocytosis. Structurally, the transferrin molecule is folded into two globular lobes, representing its N-terminal and C-terminal halves, with each lobe possessing a high-affinity iron binding site, in a cleft between two domains. Central to function is a highly conserved set of iron ligands, including an aspartate residue (Asp63 in the N-lobe) that also hydrogen bonds between the two domains and an arginine residue (Arg124 in the N-lobe) that binds an iron-bound carbonate ion. To further probe the roles of these residues, we have determined the crystal structures of the D63E and R124A mutants of the N-terminal half-molecule of human transferrin. The structure of the D63E mutant, determined at 1.9 A resolution (R = 0.245, R(free) = 0.261), showed that the carboxyl group still binds to iron despite the larger size of the Glu side chain, with some slight rearrangement of the first turn of alpha-helix residues 63-72, to which it is attached. The structure of the R124A mutant, determined at 2.4 A resolution (R = 0.219, R(free) = 0.288), shows that the loss of the arginine side chain results in a 0.3 A displacement of the carbonate ion, and an accompanying movement of the iron atom. In both mutants, the iron coordination is changed slightly, the principal change being in each case a lengthening of the Fe-N(His249) bond. Both mutants also release iron more readily than the wild type, kinetically and in terms of acid lability of iron binding. We attribute this to more facile protonation of the synergistically bound carbonate ion, in the case of R124A, and to strain resulting from the accommodation of the larger Glu side chain, in the case of D63E. In both cases, the weakened Fe-N(His) bond may also contribute, consistent with protonation of the His ligand being an early intermediate step in iron release, following the

  19. Transferrin-mediated PEGylated nanoparticles for delivery of DNA/PLL

    Gu Wangwen; Xu Zhenghong; Gao Yu; Chen Lingli; Li Yaping

    2006-01-01

    The purpose of this work was to determine the stability of pDNA/poly(L-lysine) complex (DNA/PLL) during microencapsulation, prepare transferrin (TF) conjugated PEGylated nanoparticles (TF-PEG-NP) loading DNA/PLL, and assess its physicochemical characteristics and in vitro transfection efficiency. The DNA/PLL was prepared by mixing plasmid DNA (pDNA) in deionized water with various amounts of PLL. PEGylated nanoparticles (PEG-NP) loading DNA/PLL were prepared by a water-oil-water double emulsion solvent evaporation technique. TF-PEG-NP was prepared by coupling TF with PEG-NP. The physicochemical characteristics of TF-PEG-NP and in vitro transfection efficiency on K562 cells were measured. The results showed that free pDNA reserved its double supercoiled form (dsDNA) for only on average 25.7% after sonification, but over 70% of dsDNA was reserved after pDNA was contracted with PLL. The particle size range of TF-PEG-NP loading DNA/PLL was 150-450 nm with entrapment efficiency over 70%. TF-PEG-NP exhibited the low burst effect (<10%) within 1 day. After the first phase, DNA/PLL displayed a sustained release. The amount of cumulated DNA/PLL release from TF-PEG-NP with 2% polymer over 7 days was 85.4% for DNA/PLL (1:0.3 mass ratio), 59.8% and 43.1% for DNA/PLL (1:0.6) and DNA/PLL (1:1.0), respectively. To TF-PEG-NP loading DNA/PLL without chloroquine, the percentage of EGFP expressing cells was 28.9% for complexes consisting of DNA/PLL (1:0.3), 38.5% and 39.7% for DNA/PLL (1:0.6) and DNA/PLL (1:1.0), respectively. In TF-PEG-NP loading DNA/PLL with chloroquine, more cells were transfected, the percentage of positive cells was 37.6% (DNA/PLL, 1:0.3), 47.1% (DNA/PLL, 1:0.6) and 45.8% (DNA/PLL, 1:1.0), which meant that the transfection efficiency of pDNA was increased by over 50 times when PLL and TF-PEG-NP were jointly used as a plasmid DNA carrier, in particular, the maximal percentage of positive cells (47.1%) from TF-PEG-NP loading DNA/PLL (1:0.6) was about 70 times the

  20. A Low-Molecular-Weight Ferroxidase Is Increased in the CSF of sCJD Cases: CSF Ferroxidase and Transferrin as Diagnostic Biomarkers for sCJD

    Haldar, Swati; Beveridge, ’Alim J.; Wong, Joseph; Singh, Ajay; Galimberti, Daniela; Borroni, Barbara; Zhu, Xiongwei; Blevins, Janis; Greenlee, Justin; Perry, George; Mukhopadhyay, Chinmay K.; Schmotzer, Christine

    2013-01-01

    Abstract Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are surrogate in nature, and provide suboptimal sensitivity and specificity. Results: We report that CJD-associated brain iron dyshomeostasis is reflected in the cerebrospinal fluid (CSF), providing disease-specific diagnostic biomarkers. Analysis of 290 premortem CSF samples from confirmed cases of CJD, Alzheimer's disease, and other dementias (DMs), and 52 non-DM (ND) controls revealed a significant difference in ferroxidase (Frx) activity and transferrin (Tf) levels in sporadic Creutzfeldt-Jakob disease (sCJD) relative to other DM and ND controls. A combination of CSF Frx and Tf discriminated sCJD from other DMs with a sensitivity of 86.8%, specificity of 92.5%, accuracy of 88.9%, and area-under-the receiver-operating-characteristic (ROC) curve of 0.94. This combination provided a similar diagnostic accuracy in discriminating CJD from rapidly progressing cases who died within 6 months of sample collection. Surprisingly, ceruloplasmin and amyloid precursor protein, the major brain Frxs, displayed minimal activity in the CSF. Most of the Frx activity was concentrated in the <3-kDa fraction in normal and diseased CSF, and resisted heat and proteinase-K treatment. Innovation: (i) A combination of CSF Frx and Tf provides disease-specific premortem diagnostic biomarkers for sCJD. (ii) A novel, nonenzymatic, nonprotein Frx predominates in human CSF that is distinct from the currently known CSF Frxs. Conclusion: The underlying cause of iron imbalance is distinct in sCJD relative to other DMs associated with the brain iron imbalance. Thus, change in the CSF levels of iron-management proteins can provide disease-specific biomarkers and insight into the cause of iron imbalance in neurodegenerative conditions. Antioxid. Redox Signal. 19, 1662–1675. PMID:23379482

  1. In Vitro and In Vivo Effect of HPMA Copolymer-bound Doxorubicin Targeted to Transferrin Receptor of B-cell Lymphoma 38C13

    Kovář, Marek; Strohalm, Jiří; Ulbrich, Karel; Říhová, Blanka

    2002-01-01

    Roč. 10, č. 1 (2002), s. 23-30 ISSN 1061-186X Institutional research plan: CEZ:AV0Z5020903 Keywords : targeting * transferrin * hpma copolymer Subject RIV: EC - Immunology Impact factor: 2.045, year: 2002

  2. N-glycan structures of human transferrin produced by Lymantria dispar (gypsy moth)cells using the LdMNPV expression system

    One Choi; Noboru Tomiya; Jung H. Kim; James M. Slavicek; Michael J. Betenbaugh; Yuan C. Lee

    2003-01-01

    N-glycan structures of recombinant human serum transferrin (hTf) expressed by Lymantria dispar (gypsy moth) 652Y cells were determined. The gene encoding hTf was incorporated into a Lymantria dispar nucleopolyhedrovirus (LdMNPV) under the control of the polyhedrin promoter. This virus was then...

  3. In vitro isotopic determination of diffusion volumes by transferrin labelled with indium 111. study of the correlation with SARI 125; Determination isotopique in vitro de volumes de diffusion par la transferrine marquee a l'indium 111. Etude de la correlation avec la SARI 125

    Porot, C.L. [CHU Jean-Minjoz, Service de medecine nucleaire, 25 - Besancon (France); Angoue, O.R. [CHU Jean-Minjoz, laboratoire de biophysique et statistiques, 25 - Besancon (France); Berthetc, L.O. [CHU Jean-Minjoz, 25 - Besancon (France); Ungureanu, C.O.; Boulahdour, H.A.

    2010-07-01

    Serum albumin labeled with iodine 125 (S.A.R.I. 125) is the reference tracer used in measuring isotopic plasma volume. It has been causing a suspension of manufacturing leading to a supply disruption and resulting in the search for an alternative to measure plasma volume under consideration for measuring blood volume. Plasma transferrin labeled with indium-111 (Tf-{sup 111}In) is a potentially useful marker. To this end, we assessed the level of activity to be administered to determine a volume of distribution. The study of the correlation between the volume of distribution values obtained with S.A.R.I. 125 and Tf-{sup 111}In was then performed. Tf is an autologous protein which the labelling is easy and stable. Tf-{sup 111}In is a valid alternative to the S.A.R.I. 125 for measuring the plasma volume. The activity required for this examination shall not exceed 100 micro curies. (N.C.)

  4. Molecular studies of Callithrix pygmaea (Primates, Platyrrhini based on transferrin intronic and ND1 regions: implications for taxonomy and conservation

    Tagliaro Claudia Helena

    2000-01-01

    Full Text Available Traditional classifications of Platyrrhini monkeys, based mainly on morphological features, are being contested by recent molecular data. The subfamily Callitrichinae (Platyrrhini, Primates consists of a diverse group of species, many of them considered endangered. Our analysis of two DNA regions, a mtDNA gene (ND1 and a nuclear gene (intronic regions of the transferrin gene, suggests that Callithrix pygmaea may have sufficient variability to justify the existence of subspecies or even separate species. Phylogenetic dendrograms based on the ND1 region show that this species is more closely related to Amazonian than to Atlantic forest marmosets. These results reopen the discussion about diversity and conservation programs based exclusively on traditional classifications.

  5. Molecular mass spectrometry in metallodrug development: A case of mapping transferrin-mediated transformations for a ruthenium(III) anticancer drug

    Jarosz, Maciej [Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw (Poland); Matczuk, Magdalena, E-mail: mmatczuk@ch.pw.edu.pl [Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw (Poland); Pawlak, Katarzyna [Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw (Poland); Timerbaev, Andrei R. [Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, Kosygin St. 19, 119991 Moscow (Russian Federation)

    2014-12-03

    Highlights: • Extra- and intra-cellular interactions of Ru(III) anticancer drug candidate. • ESI-TOF-MS mapping of the ruthenium species bound to transferring. • ESI-QqQ-MS identification of released Ru species under cytosol simulated conditions. - Abstract: Electrospray ionization mass spectrometry (ESI-MS) techniques have been used to characterize the speciation of a Ru(III) anticancer drug, indazolium trans-[tetrachloridobis(1H-indazole) ruthenate(III)], upon its binding to transferrin and the impact of cellular reducing components on drug–transferrin adducts. Using time-of-flight ESI-MS, the polymorphism of apo- (iron-free) and holo-form (iron-saturated) of the protein was confirmed. While the ruthenium moieties bound to each of five isoforms under simulated extracellular conditions are essentially identical in numbers for apo- and holo-transferrin, distinct differences were found in the composition of Ru(III) species attached to either of the protein forms, which are dominated by differently coordinated aquated complexes. On the other hand, at least one of the Ru-N bonds in metal-organic framework remains intact even after prolonged interaction with the protein. Triple quadrupole tandem ESI-MS measurements demonstrated that the ruthenium species released from drug adducts with holo-transferrin in simulated cancer cytosol are underwent strong ligand exchange (as compared to the protein-bound forms) but most strikingly, they contain the metal center in the reduced Ru(II) state. In vitro probing the extra- and intracellular interactions of promising Ru(III) drug candidate performed by ESI-MS is thought to shed light on the transportation to tumor cells by transferrin and on the activation to more reactive species by the reducing environment of solid tumors.

  6. Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody.

    Pardridge, William M

    2015-02-01

    Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG-neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG-avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials.

  7. Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection

    Kumar, Vijay; Boddeti, Dilip K.; Evans, Scott G.; Roesch, Frank; Howman-Giles, Robert

    2011-01-01

    Introduction: 67 Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether 68 Ga-apo-transferrin ( 68 Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection. Methods: An infection was induced in male Wistar rats by injecting 5x10 5 CFU units of Staphyococcus aureus in the right thigh muscle. 68 Ga-TF was synthesized by mixing 68 GaCl 3 with apo-transferrin (TF, 2 mg) in sodium carbonate (0.1 M, pH 7.0) and incubating at 40 o C for 1 h. Animals were injected with 10-15 MBq of 68 Ga-TF containing approximately 0.2 mg TF and imaged at different time intervals using Siemens Biograph PET-CT. Results: When 68 Ga-TF were injected in the infected rats, the infection lesion was detectable within 20 min post injection. The biodistribution showed the uptake at the lesion increased with time as shown by significantly increased standard uptake values for up to 4 h post injection. There was a considerable decrease in the background activity during the same period of study, giving higher target-to-muscle ratios. Blood pool activity at 3 h post injection was insignificant. 68 GaCl 3 (when not conjugated to TF) did not localize at the infection lesion up to 120 min post injection. Conclusion: The preliminary results suggest that 68 Ga-TF is capable of detecting S. aureus infection in the rat model, within an hour after intravenous injection.

  8. Effects of hemochromatosis and transferrin gene mutations on peripheral iron dyshomeostasis in Mild Cognitive Impairment and Alzheimer’s and Parkinson’s diseases

    Stefania eMariani

    2013-08-01

    Full Text Available Deregulation of iron metabolism has been observed in patients with neurodegenerative diseases. We have carried out a molecular analysis investigating the interaction between iron specific gene variants [transferrin (TF, P589S, hemochromatosis (HFE C282Y and H63D], iron biochemical variables [iron, Tf, ceruloplasmin (Cp, Cp:Tf ratio and % of Tf saturation (% Tf-sat] Impairment (MCI, 78 Parkinson’s disease (PD patients and 139 healthy controls to investigate mechanisms of iron regulation or toxicity. No difference in genetic variant distributions between patients and controls was found in our Italian sample, but the stratification for the APOE e4 allele revealed that among the APOE e4 carriers was higher the frequency of those carriers of at least a mutated TF P589S allele. Decreased Tf in both AD and MCI and increased Cp:Tf ratio in AD vs. controls were detected. A multinomial logistic regression model revealed that increased iron and Cp:Tf ratio and being man instead of woman increased the risk of having PD, that increased values of Cp:Tf ratio corresponded to a 4-fold increase of the relative risk of having MCI, while higher Cp levels were protective for PD and MCI. Our study has some limitations: the small size of the sample, one ethnic group considered, the rarity of some alleles which prevent the statistical power of some genetic analysis. Even though they need confirmation in larger cohorts, our data suggest the hypothesis that deregulation of iron metabolism, in addition to other factors, has some effect on the PD disease risk.

  9. Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin.

    Latour, Chloé; Besson-Fournier, Céline; Meynard, Delphine; Silvestri, Laura; Gourbeyre, Ophélie; Aguilar-Martinez, Patricia; Schmidt, Paul J; Fleming, Mark D; Roth, Marie-Paule; Coppin, Hélène

    2016-01-01

    Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor-2 (TfR2), and hemojuvelin (HJV) genes. However, it is still not clear whether these molecules intersect in vivo with bone morphogenetic protein 6 (BMP6)/mothers against decapentaplegic (SMAD) homolog signaling, the main pathway up-regulating hepcidin expression in response to elevated hepatic iron. To answer this question, we produced double knockout mice for Bmp6 and β2-microglobulin (a surrogate for the loss of Hfe) and for Bmp6 and Tfr2, and we compared their phenotype (hepcidin expression, Bmp/Smad signaling, hepatic and extrahepatic tissue iron accumulation) with that of single Bmp6-deficient mice and that of mice deficient for Hjv, alone or in combination with Hfe or Tfr2. Whereas the phenotype of Hjv-deficient females was not affected by loss of Hfe or Tfr2, that of Bmp6-deficient females was considerably worsened, with decreased Smad5 phosphorylation, compared with single Bmp6-deficient mice, further repression of hepcidin gene expression, undetectable serum hepcidin, and massive iron accumulation not only in the liver but also in the pancreas, the heart, and the kidneys. These results show that (1) BMP6 does not require HJV to transduce signal to hepcidin in response to intracellular iron, even if the loss of HJV partly reduces this signal, (2) another BMP ligand can replace BMP6 and significantly induce hepcidin expression in response to extracellular iron, and (3) BMP6 alone is as efficient at inducing hepcidin as the other BMPs in association with the HJV/HFE/TfR2 complex; they provide an explanation for the compensatory effect of BMP6 treatment on the molecular defect underlying Hfe hemochromatosis in mice. © 2015 by the American Association for the Study of Liver Diseases.

  10. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells.

    Chang, Jiang; Paillard, Archibald; Passirani, Catherine; Morille, Marie; Benoit, Jean-Pierre; Betbeder, Didier; Garcion, Emmanuel

    2012-06-01

    Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.

  11. The Use of Soluble Transferrin Receptor in the Detection of rHuEPO abuse in Sports

    Donovan McGrowder

    2010-01-01

    Full Text Available Erythropoietin (EPO increases the number of circulating erythrocytes and muscle oxygenation. The recombinant forms of EPO have indiscriminately been used by athletes, mainly in endurance sports to increase their erythrocytes concentration, thus generating a better delivery of oxygen to the muscle tissue. The administration of recombinant human erythropoietin (rHuEPO except for therapeutic use was prohibited by the International Olympic Committee (IOC and its unauthorized use considered as doping. In the last few years, a number of studies using parameters indicative of accelerated erythropoiesis have investigated a number of indirect methods for the detection of rHuEPO abuse. No single indirect marker has been found that can satisfactorily demonstrated rHuEPO misuse. Soluble transferrin receptor (sTfR is a new marker of iron status and erythropoietic activity. It has been included in multivariable blood testing models for the detection of performance enhancing EPO abuse in sports. Indirect markers of altered erythropoiesis give reliable evidence of current or discontinued rHuEPO usage. This review describes the physical, biological and pharmacokinetic properties of endogenous EPO and its recombinant form. It also discusses the available strategies for the detection of rHuEPO abuse in sports, involving the use of sTfR concentration directly or in mathematical multivariate models.

  12. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Jain, Aviral, E-mail: draviraljain@gmail.com; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi [Adina Institute of Pharmaceutical Sciences, Pharmaceutics Research Laboratory, Department of Pharmaceutics (India)

    2013-03-15

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 {+-} 3.22 nm with entrapment efficiency of 69.83 {+-} 2.52 and 249 {+-} 2.61 nm with entrapment efficiency decreased to 64.21 {+-} 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  13. Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier.

    Ghadiri, Maryam; Vasheghani-Farahani, Ebrahim; Atyabi, Fatemeh; Kobarfard, Farzad; Mohamadyar-Toupkanlou, Farzaneh; Hosseinkhani, Hossein

    2017-10-01

    Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017. © 2017 Wiley Periodicals, Inc.

  14. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Jain, Aviral; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi

    2013-03-01

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 ± 3.22 nm with entrapment efficiency of 69.83 ± 2.52 and 249 ± 2.61 nm with entrapment efficiency decreased to 64.21 ± 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  15. A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

    Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

    2012-05-01

    A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

    Gao W

    2017-02-01

    Full Text Available Wei Gao,1 Guihua Ye,1 Xiaochuan Duan,1 Xiaoying Yang,1 Victor C Yang1,2 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics, School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA Abstract: The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR. To overcome multidrug resistance (MDR and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep. First, the polymers poly(l-histidine-coupled polyethylene glycol-2000 (PHIS-PEG2000 and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG2000 were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2000 or 7pep-DSPE-PEG2000 (7-pep HD micelles. The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX, the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr, which attributed to the synergistic effect of poly(l-histidine-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the targetability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug

  17. Intracellular targeting of mercaptoundecahydrododecaborate (BSH) to malignant glioma by transferrin-PEG liposomes for boron neutron capture therapy (BNCT)

    Doi, Atsushi; Miyatake, Shin-ichi; Iida, Kyouko

    2006-01-01

    Malignant glioma is one of the most difficult tumor to control with usual therapies. In our institute, we select boron neutron capture therapy (BNCT) as an adjuvant radiation therapy after surgical resection. This therapy requires the selective delivery of high concentration of 10 B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10 B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10 B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10 B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10 B/ml derived from each BDS by inductively coupled plasma atomic emission spectrometry (ICP-AES). In vivo, human U87Δ glioma-bearing nude mice were administered with each BDS (35mg 10 B/kg) intravenously. We analyzed 10 B concentration of tumor, normal brain and blood by ICP-AES. The TF-PEG liposome-BSH showed higher absolute concentration more than the other BDS. Moreover, TF-PEG liposome-BSH decreased 10 B concentration in blood and normal tissue while it maintained high 10 B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10 B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10 B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

  18. Elevated temperature inhibits recruitment of transferrin-positive vesicles and induces iron-deficiency genes expression in Aiptasia pulchella host-harbored Symbiodinium.

    Song, Po-Ching; Wu, Tsung-Meng; Hong, Ming-Chang; Chen, Ming-Chyuan

    2015-10-01

    Coral bleaching is the consequence of disruption of the mutualistic Cnidaria-dinoflagellate association. Elevated seawater temperatures have been proposed as the most likely cause of coral bleaching whose severity is enhanced by a limitation in the bioavailability of iron. Iron is required by numerous organisms including the zooxanthellae residing inside the symbiosome of cnidarian cells. However, the knowledge of how symbiotic zooxanthellae obtain iron from the host cells and how elevated water temperature affects the association is very limited. Since cellular iron acquisition is known to be mediated through transferrin receptor-mediated endocytosis, a vesicular trafficking pathway specifically regulated by Rab4 and Rab5, we set out to examine the roles of these key proteins in the iron acquisition by the symbiotic Symbiodinium. Thus, we hypothesized that the iron recruitments into symbiotic zooxanthellae-housed symbiosomes may be dependent on rab4/rab5-mediated fusion with vesicles containing iron-bound transferrins and will be retarded under elevated temperature. In this study, we cloned a novel monolobal transferrin (ApTF) gene from the tropical sea anemone Aiptasia pulchella and confirmed that the association of ApTF with A. pulchella Rab4 (ApRab4) or A. pulchella Rab5 (ApRab5) vesicles is inhibited by elevated temperature through immunofluorescence analysis. We confirmed the iron-deficient phenomenon by demonstrating the induced overexpression of iron-deficiency-responsive genes, flavodoxin and high-affinity iron permease 1, and reduced intracellular iron concentration in zooxanthellae under desferrioxamine B (iron chelator) and high temperature treatment. In conclusion, our data are consistent with algal iron deficiency being a contributing factor for the thermal stress-induced bleaching of symbiotic cnidarians. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Total and cause-specific mortality by elevated transferrin saturation and hemochromatosis genotype in individuals with diabetes - two general population studies

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Tybjærg-Hansen, Anne

    2013-01-01

    ObjectiveMortality is increased in patients with hereditary hemochromatosis, in individuals from the general population with increased transferrin saturation(TS), and also in patients with diabetes type 1 and increased TS from a highly specialised diabetes clinic. Thus, we have recommended targeted...... and hemochromatosis genotype(HFE) C282Y/C282Y in individuals with diabetes(type 1,N=118;type 2,N=3228;total,N=3346).ResultsThe cumulative survival was reduced in individuals with diabetes with TS≥50% vs....

  20. Diagnosis of protein-losing gastroenteropathy by sup 111 In-transferrin scanning and fecal excretion test

    Urita, Yoshihisa (Toho Univ., Tokyo (Japan). School of Medicine)

    1991-10-01

    A total of 12 patients with gastroenteropathy were studied for possible protein loss. The underlying diseases were intestinal lymphangiectasia, ulcerative colitis and Crohn's disease in 2 patients each and Menetrier's disease, Cronkhite-Canada syndrome, postgastrectomy syndrome, severe atrophic gastritis, gastric cancer and gastroenteropathy of unknown origin in one patient each. The controls were four healthy volunteers and 9 patients with benign disease not accompanied by lesions in the digestive tract and protein loss {sup 111}In-transferrin Tf was prepared by incubating 2-3 mCi of {sup 111}In-chloride with 15-20 ml of each patient's plasma in a sterilized vial at room temperature for 1 hour. After iv injection of {sup 111}In-Tf the patients were scanned at given intervals of time for 72 hours to localize protein loss. Seventy-two hour fecal {sup 111}In-Tf excretion was also measured. {sup 111}In-Tf was detected in the feces of all patients. The recovery rate in the patient group was 7.95{+-}3.65%, being significantly higher than 0.48{+-}0.26% in the control group. However {sup 111}In-Tf scanning showed the site of protein loss only in 6 patients. Negative scan in six other patients was thought to be associated with extensive inflammation and severe diarrhea. Five of the 12 patients were observed before and after treatment. A decrease in fecal {sup 111}In-Tf excretion with clinical improvement was noted in the 5 patients after treatment. The site of protein loss could be demonstrated in 3 of the 5 patients before treatment. Its site in 1 of the 3 patients was the small intestine. However accumulation of {sup 111}In-Tf was found there in the 3 patients after treatment. The site of protein loss in 1 of 3 patients was the small intestine. {sup 111}In-Tf scanning is particularly useful when the small intestine is involved, because surgery is contraindicated in this case. Fecal {sup 111}In-Tf excretion test is mandatory when the site of protein loss

  1. TIBC, UIBC and Transferrin

    ... circulating and stored iron may eventually lead to iron deficiency anemia (decreased hemoglobin and hematocrit , smaller and paler red ... results of each can help identify iron deficiency, iron deficiency anemia, or too much iron in the body (overload). ...

  2. Expression of the amino-terminal half-molecule of human serum transferrin in cultured cells and characterization of the recombinant protein

    Funk, W.D.; MacGillivray, R.T.A.; Mason, A.B.; Brown, S.A.; Woodworth, R.C.

    1990-01-01

    A human liver cDNA library was screened with a synthetic oligonucleotide, complementary to the 5' region of human transferrin mRNA, as a hybridization probe. The full-length human cDNA clone isolated from this screen contained part of the 5' untranslated region, the complete coding region for the signal peptide and the two lobes of transferrin, the 3' untranslated region, and a poly(A) tail. By use of oligonucleotide-directed mutagenesis in vitro, two translational stop codons and a HindIII site were introduced after the codon for Asp-337. This fragment was inserted into two different expression vectors that were then introduced into Escherichia coli. As judged by NaDodSO 4 -polyacrylamide gel electrophoresis and Western blot analysis, however, recombinant hTF/2N was undetectable in bacteria transformed by these plasmids. Concurrently, the authors developed a plasmid vector for the expression of recombinant hTF/2N in eukaryotic cells. The recombinant hTF/2N appeared to behave identically with the proteolytically derived half-molecule, but to show a higher degree of monodispersity than the latter protein. Addition of m-fluorotyrosine to the culture medium resulted in random incorporation of this amino acid into cellular protein in lieu of tyrosine. Purified recombinant 19 F-Tyr hTF/2N gave four well-resolved 19 F NMR resonances of 20-40 Hz line width, two with suggestions of shoulders

  3. Fabrication of transferrin functionalized gold nanoclusters/graphene oxide nanocomposite for turn-on near-infrared fluorescent bioimaging of cancer cells and small animals.

    Wang, Yong; Chen, Jia-Tong; Yan, Xiu-Ping

    2013-02-19

    Transferrin (Tf)-functionalized gold nanoclusters (Tf-AuNCs)/graphene oxide (GO) nanocomposite (Tf-AuNCs/GO) was fabricated as a turn-on near-infrared (NIR) fluorescent probe for bioimaging cancer cells and small animals. A one-step approach was developed to prepare Tf-AuNCs via a biomineralization process with Tf as the template. Tf acted not only as a stabilizer and a reducer but also as a functional ligand for targeting the transferrin receptor (TfR). The prepared Tf-AuNCs gave intense NIR fluorescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The assembly of Tf-AuNCs and GO gave the Tf-AuNCs/GO nanocomposite, a turn-on NIR fluorescent probe with negligible background fluorescence due to the super fluorescence quenching property of GO. The NIR fluorescence of the Tf-AuNCs/GO nanocomposite was effectively restored in the presence of TfR, due to the specific interaction between Tf and TfR and the competition of TfR with the GO for the Tf in Tf-AuNCs/GO composite. The developed turn-on NIR fluorescence probe offered excellent water solubility, stability, and biocompatibility, and exhibited high specificity to TfR with negligible cytotoxicity. The probe was successfully applied for turn-on fluorescent bioimaging of cancer cells and small animals.

  4. Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

    Nagai, Kentaro; Nakahata, Shingo; Shimosaki, Shunsuke; Tamura, Tomohiro; Kondo, Yuudai; Baba, Takashi; Taki, Tomohiko; Taniwaki, Masafumi; Kurosawa, Gene; Sudo, Yukio; Okada, Seiji; Sakoda, Sumio; Morishita, Kazuhiro

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC

  5. Rapid screening of transferrin-binders in the flowers of Bauhinia blakeana Dunn by on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-transferrin-fluorescence detection system.

    Liu, Meixian; Dong, Jing; Lin, Zongtao; Niu, Yanyan; Zhang, Xiaotian; Jiang, Haixiu; Guo, Ning; Li, Wei; Wang, Hong; Chen, Shizhong

    2016-06-10

    Transferrin (Transferrin, TRF, TF) has drawn increasing attention in cancer therapy due to its potential applications in drug delivery. TF receptor, highly expressed in tumor cells, recognizes and transports Fe(3+)-TF into cells to release iron into cytoplasm. Thus, discovering TF-binding compounds has become an active research area and is of great importance for target therapy. In this study, an on-line analysis method was established for screening TF-binding compounds from the flowers of Bauhinia blakeana Dunn using a high-performance liquid chromatography-diode-array detector-multi-stage mass spectrometry-transferrin-fluorescence detector (HPLC-DAD-MS(n)-TF-FLD) method. As a result, 33 of 80 identified or tentatively characterized compounds in the sample were TF-binding active. Twenty-five flavonol glycosides and eight phenolic acids were identified as TF-binders. Twelve of these active compounds together with six standard compounds were used to study the dose-response effects and structure-activity relationships of flavonoids and phenolic acids. The method was validated by vitexin with a good linearity in the range of concentrations used in the study. The limit of detection for vitexin was 0.1596 nmol. Our study indicated that the established method is simple, rapid and sensitive for screening TF-binding active compounds in the extract of Bauhinia blakeana Dunn, and therefore is important for discovering potential anti-cancer ingredients from complex samples for TF related drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Identification of Tumor Antigen AF20 as Glycosylated Transferrin Receptor 1 in Complex with Heat Shock Protein 90 and/or Transporting ATPase.

    Jason M Shapiro

    Full Text Available We previously isolated AF20, a murine monoclonal antibody that recognizes a cell surface glycoprotein of approximately 90-110 kDa. The AF20 antigen is specifically expressed in human hepatoma and colon cancer cell lines, and thus could serve as a cancer biomarker. To uncover the molecular identity of the AF20 antigen, a combination of ion-exchange chromatography, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis was employed to purify the AF20 antigen followed by trypsin digestion and mass spectrometry. Surprisingly, three host proteins were thus purified from human hepatoma and colon cancer cell lines: transferrin receptor 1 (TFR1, heat shock protein 90 (HSP90, and Na+/K+ ATPase or Mg++ ATPase. Co-immunoprecipitation followed by Western blot analysis confirmed interaction among the three proteins. However, only the cDNA encoding TFR1 conferred strong cell surface staining by the AF20 antibody following its transient transfection into a cell line lacking endogenous AF20. In support of the molecular identity of AF20 as TFR1, diferric but not iron-free transferrin could prevent AF20 antigen-antibody interaction during immunoprecipitation. Moreover, very similar patterns of AF20 and TFR1 overexpression was documented in colon cancer tissues. In conclusion, AF20 is glycosylated TFR1. This finding could explain the molecular structure of AF20, its cell surface localization, as well as overexpression in cancer cells. Glycosylated TFR1 should serve as a usefulness target for anti-cancer therapy, or a vehicle for delivery of anti-tumor drugs with high affinity and specificity. The biological significance of the complex formation between TFR1, HSP90, and/or transporting ATPase warrants further investigation.

  7. 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

    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.

  8. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

    Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

    2011-11-01

    Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

  9. Performance of a commercial Chicken-Ovo-transferrin-ELISA on the serum of brown layer chickens infected with Gallibacterium anatis and Streptococcus zooepidemicus

    Roy, Krisna; Kjelgaard-Hansen, Mads; Pors, Susanne Elisabeth

    2014-01-01

    To evaluate Ovo-transferrin (OTF), a positive acute-phase protein in chickens, as a diagnostic biomarker of selected bacterial infections we checked the performance of a commercial Chicken-OTF-ELISA (ICL, Inc., Portland, OR, USA) by analytical and overlap performances using two groups of serum sa......-infected birds) were >6.4, >3.8 to 6.7, >3.5 to...

  10. Determination of bone blood supply with /sup 99m/Tc red blood cells and /sup 113m/In transferrin in fractures of femoral neck: concise communication

    Kempi, V.; Sandegard, J.

    1982-05-01

    The uptake of in vivo labeled /sup 99m/Tc RBCs and /sup 113/In transferrin was studied in femoral bone of 21 patients who had recent operations for fracture of the femoral neck. Femoral bone biopsies and blood samples were obtained during the operation. The activity values for bone biopsies, erythrocytes, and serum were determined, and the uptake ratios between bone and erythrocyte cpm/g and between bone and serum were calculated. Biopsy samples were taken from the femoral head in 21 cases and from the trochanteric region in 14. The activity ratios for the two tracers correlated well: r . 0.94 for femoral head biopsies (P less than 0.001) and r . 0.98 for samples from the trochanteric region (P less than 0.001). Thus, the procedures are interchangeable and either may be valuable in assessing bone blood supply. An additional patient, studied only with /sup 99m/Tc RBCs, had a subsequent operation for nonunion of a fracture. Samples of both cancellous and cortical bone were obtained from the removed head. The activity ratios for the two types of bone tissue differed significantly (P . 0.02).

  11. Determination of bone blood supply with /sup 99m/Tc red blood cells and /sup 113m/In transferrin in fractures of femoral neck: concise communication

    Kempi, V.; Sandegard, J.

    1982-01-01

    The uptake of in vivo labeled /sup 99m/Tc RBCs and 113 In transferrin was studied in femoral bone of 21 patients who had recent operations for fracture of the femoral neck. Femoral bone biopsies and blood samples were obtained during the operation. The activity values for bone biopsies, erythrocytes, and serum were determined, and the uptake ratios between bone and erythrocyte cpm/g and between bone and serum were calculated. Biopsy samples were taken from the femoral head in 21 cases and from the trochanteric region in 14. The activity ratios for the two tracers correlated well: r . 0.94 for femoral head biopsies (P less than 0.001) and r . 0.98 for samples from the trochanteric region (P less than 0.001). Thus, the procedures are interchangeable and either may be valuable in assessing bone blood supply. An additional patient, studied only with /sup 99m/Tc RBCs, had a subsequent operation for nonunion of a fracture. Samples of both cancellous and cortical bone were obtained from the removed head. The activity ratios for the two types of bone tissue differed significantly

  12. Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma.

    Xie, Yuran; Kim, Na Hyung; Nadithe, Venkatareddy; Schalk, Dana; Thakur, Archana; Kılıç, Ayşe; Lum, Lawrence G; Bassett, David J P; Merkel, Olivia M

    2016-05-10

    Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Interaction between holo transferrin and HSA-PPIX complex in the presence of lomefloxacin: An evaluation of PPIX aggregation in protein-protein interactions

    Sattar, Zohreh; Iranfar, Hediye; Asoodeh, Ahmad; Saberi, Mohammad Reza; Mazhari, Mahboobeh; Chamani, Jamshidkhan

    2012-11-01

    Human serum albumin (HSA) and holo transferrin (TF) are two serum carrier proteins that are able to interact with each other, thereby altering their binding behavior toward their ligands. During the course of this study, the interaction between HSA-PPIX and TF, in the presence and absence of lomefloxacin (LMF), was for the first time investigated using different spectroscopic and molecular modeling techniques. Fluorescence spectroscopy experiments were performed in order to study conformational changes of proteins. The RLS technique was utilized to investigate the effect of LMF on J-aggregation of PPIX, which is the first report of its kind. Our findings present clear-cut evidence for the alteration of interactions between HSA and TF in the presence of PPIX and changes in drug-binding to HSA and HSA-PPIX complex upon interaction with TF. Moreover, molecular modeling studies suggested that the binding site for LMF became switched in the presence of PPIX, and that LMF bound to the site IIA of HSA. The obtained results should give new insight into research in this field and may cast some light on the dynamics of drugs in biological systems.

  14. Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells

    Wang Enxiu; Obeng-Adjei, Nyamekye; Ying Qihua; Meertens, Laurent; Dragic, Tanya; Davey, Robert A.; Ross, Susan R.

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-with of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment

  15. Performance of a commercial Chicken-Ovo-transferrin-ELISA on the serum of brown layer chickens infected with Gallibacterium anatis and Streptococcus zooepidemicus.

    Roy, Krisna; Kjelgaard-Hansen, Mads; Pors, Susanne Elisabeth; Christensen, Jens Peter; Biswas, Paritosh Kumar; Bojesen, Anders Miki

    2014-01-01

    To evaluate Ovo-transferrin (OTF), a positive acute-phase protein in chickens, as a diagnostic biomarker of selected bacterial infections we checked the performance of a commercial Chicken-OTF-ELISA (ICL, Inc., Portland, OR, USA) by analytical and overlap performances using two groups of serum samples obtained from 26 Gallibacterium anatis-infected and 20 Streptococcus zooepidemicus-infected brown layer chickens. In addition, sera from 14 apparently healthy and 19 negative control chickens were analysed in the Gallibacterium group whereas sera from 20 healthy and 11 negative control chickens from the Streptococcus group were analysed. All calibration curves revealed high coefficients of determination (≥ 0.97) between optical density (OD 450nm) and concentrations of OTF (mg/ml). OTF concentrations in high, medium and low pools (made of sera from a combination of infected and/or non-infected birds) were >6.4, >3.8 to 6.7, >3.5 to chickens (Gallibacterium, 4.4 ± 0.3 mg/ml; Streptococcus, 3.2 ± 0.4 mg/ml) compared with negative controls (1.7 ± 0.1 mg/ml) (P Chicken-OTF-ELISA can be used to measure reproducible serum OTF concentrations in brown layer chickens as a response to G. anatis infections, whereas an adjustment of dilution process is proposed to optimize to use in S. zooepidemicus-infected chickens.

  16. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs

    Masanori Yoshinaga

    2017-05-01

    Full Text Available Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1, has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1−/− mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.

  17. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs.

    Yoshinaga, Masanori; Nakatsuka, Yoshinari; Vandenbon, Alexis; Ori, Daisuke; Uehata, Takuya; Tsujimura, Tohru; Suzuki, Yutaka; Mino, Takashi; Takeuchi, Osamu

    2017-05-23

    Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1 -/- mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia

    Balasubramanian S

    2014-01-01

    Full Text Available Sivakumar Balasubramanian,1 Aswathy Ravindran Girija,1 Yutaka Nagaoka,1 Seiki Iwai,1 Masashi Suzuki,1 Venugopal Kizhikkilot,2 Yasuhiko Yoshida,1 Toru Maekawa,1 Sakthikumar Dasappan Nair1 1Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan; 2Department of Respiratory Medicine, Sooriya Hospital, Chennai, India Abstract: The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU] and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes by initiating early and late apoptosis. Keywords: nanotechnology, curcumin, 5FU, folate, transferrin, PLGA nanoparticle, magnetic hyperthermia

  19. Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity

    Check, I.J.; Kidd, M.R.; Staton, G.W. Jr.

    1986-01-01

    BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Ten patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis

  20. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy.

    Seki, Masafumi; Iwakawa, Jun; Cheng, Helen; Cheng, Pi-Wan

    2002-04-10

    We previously reported that supplementation of a cationic liposome with transferrin (Tf) greatly enhanced lipofection efficiency (P.-W. Cheng, Hum. Gene Ther. 1996;7:275-282). In this study, we examined the efficacy of p53 and PTEN tumor suppressor gene therapy in a mouse xenograft model of human prostate PC-3 carcinoma cells, using a vector consisting of dimyristoyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE)-cholesterol (DC) and Tf. When the volume of the tumors grown subcutaneously in athymic nude mice reached 50-60 mm(3), three intratumoral injections of the following four formulations were performed during week 1 and then during week 3: (1) saline, (2) DC + Tf + pCMVlacZ, (3) DC + Tf + pCMVPTEN, and (4) DC + Tf + pCMVp53 (standard formulation). There was no significant difference in tumor volume and survival between group 1 and group 2 animals. As compared with group 1 controls, group 3 animals had slower tumor growth during the first 3 weeks but thereafter their tumor growth rate was similar to that of the controls. By day 2 posttreatment, group 4 animals had significantly lower tumor volume relative to initial tumor volume as well as controls at the comparable time point. Also, animals treated with p53 survived longer. Treatment with DC, Tf, pCMVp53, DC + pCMVp53, or Tf + pCMVp53 had no effect on tumor volume or survival. Expression of p53 protein and apoptosis were detected in tumors treated with the standard formulation, thus associating p53 protein expression and apoptosis with efficacy. However, p53 protein was expressed in only a fraction of the tumor cells, suggesting a role for bystander effects in the efficacy of p53 gene therapy. We conclude that intratumoral gene delivery by a nonviral vector consisting of a cationic liposome and Tf can achieve efficacious p53 gene therapy of prostate cancer.

  1. The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge.

    Thom, R E; Elmore, M J; Williams, A; Andrews, S C; Drobniewski, F; Marsh, P D; Tree, J A

    2012-05-02

    Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Revisiting nanoparticle technology for blood-brain barrier transport: Unfolding at the endothelial gate improves the fate of transferrin receptor-targeted liposomes.

    Johnsen, Kasper Bendix; Moos, Torben

    2016-01-28

    An unmet need exists for therapeutic compounds to traverse the brain capillary endothelial cells that denote the blood-brain barrier (BBB) to deliver effective treatment to the diseased brain. The use of nanoparticle technology for targeted delivery to the brain implies that targeted liposomes encapsulating a drug of interest will undergo receptor-mediated uptake and transport through the BBB with a subsequent unfolding of the liposomal content inside the brain, hence revealing drug release to adjacent drug-demanding neurons. As transferrin receptors (TfRs) are present on brain capillary endothelial, but not on endothelial cells elsewhere in the body, the use of TfR-targeted liposomes - colloidal particulates with a phospholipid bilayer membrane - remains the most relevant strategy to obtain efficient drug delivery to the brain. However, many studies have failed to provide sufficient quantitative data to proof passage of the BBB and significant appearance of drugs inside the brain parenchyma. Here, we critically evaluate the current evidence on the use of TfR-targeted liposomes for brain drug delivery based on a thorough investigation of all available studies within this research field. We focus on issues with respect to experimental design and data analysis that may provide an explanation to conflicting reports, and we discuss possible explanations for the current lack of sufficient transcytosis across the BBB for implementation in the design of TfR-targeted liposomes. We finally provide a list of suggestions for strategies to obtain substantial uptake and transport of drug carriers at the BBB with a concomitant transport of therapeutics into the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The monotony of transferrin and esterase electrophoretic patterns in pirarucu, Arapaima gigas (Schinz, 1822) from Santa Cruz Lake, Tefé River, Amazonas, Brazil.

    Teixeira, A S

    2008-05-07

    Starch gel electrophoresis was used for examining the transferrin gene locus (Tf) and two esterase gene loci (Est-1 and Est-D1) of a pirarucu (Arapaima gigas) population sample collected from Santa Cruz Lake, Tefé River, Amazonas, Brazil. The Tf locus was tentatively classified as being polymorphic, showing two double-banded patterns (Tf(12) and Tf(22)) of the three theoretically expected ones (Tf(11), Tf(12) and Tf(22)), presumably controlled by two co-dominant alleles, Tf(1) and Tf(2). The monotony detected in pirarucu Tf locus genotypes showing a very high proportion of the double-banded heterozygote pattern Tf(12) (95% of the sampled individuals) may indicate the possibility of their having come from representatives of the same brood begotten by a pair of fish, where a single-banded Tf(11) homozygote pattern male would have crossed with a single-banded Tf(22) homozygote pattern female, or vice versa. One zone of electrophoretic activity was detected in esterase, presumably controlled by a monomorphic Est-1 locus with the fixed allele Est-1(1) where all individuals showed the single-banded Est-1(11) homozygote pattern. Esterase-D also displayed one zone of electrophoretic activity, presumably controlled by a monomorphic Est-D1 locus with a fixed allele Est-D1(1) where all individuals revealed the single-banded Est-D1(11) genotype pattern. The monotony comprised by single-banded genotype patterns in both esterase systems tested may also indicate the possibility of the individuals from the sample examined having come from representatives of the same brood begotten by a pair of fish with both the male and female having the same genotypes.

  4. Use of Spectroscopic, Zeta Potential and Molecular Dynamic Techniques to Study the Interaction between Human Holo-Transferrin and Two Antagonist Drugs: Comparison of Binary and Ternary Systems

    Mohammad Reza Saberi

    2012-03-01

    Full Text Available For the first time, the binding of ropinirole hydrochloride (ROP and aspirin (ASA to human holo-transferrin (hTf has been investigated by spectroscopic approaches (fluorescence quenching, synchronous fluorescence, time-resolved fluorescence, three-dimensional fluorescence, UV-vis absorption, circular dichroism, resonance light scattering, as well as zeta potential and molecular modeling techniques, under simulated physiological conditions. Fluorescence analysis was used to estimate the effect of the ROP and ASA drugs on the fluorescence of hTf as well as to define the binding and quenching properties of binary and ternary complexes. The synchronized fluorescence and three-dimensional fluorescence spectra demonstrated some micro-environmental and conformational changes around the Trp and Tyr residues with a faint red shift. Thermodynamic analysis displayed the van der Waals forces and hydrogen bonds interactions are the major acting forces in stabilizing the complexes. Steady-state and time-resolved fluorescence data revealed that the fluorescence quenching of complexes are static mechanism. The effect of the drugs aggregating on the hTf resulted in an enhancement of the resonance light scattering (RLS intensity. The average binding distance between were computed according to the forster non-radiation energy transfer theory. The circular dichroism (CD spectral examinations indicated that the binding of the drugs induced a conformational change of hTf. Measurements of the zeta potential indicated that the combination of electrostatic and hydrophobic interactions between ROP, ASA and hTf formed micelle-like clusters. The molecular modeling confirmed the experimental results. This study is expected to provide important insight into the interaction of hTf with ROP and ASA to use in various toxicological and therapeutic processes.

  5. Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

    Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

    2000-01-01

    The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

  6. Effect of Fibroblast Growth Factor 2 (FGF2 and Insulin Transferrin Selenium (ITS on In Vitro Maturation, Fertilization and Embryo Development in Sheep

    Sukanta Mondal

    2015-08-01

    Full Text Available The present study evaluated the effect of fibroblast growth factor 2 (FGF2 and insulin-transferrin-selenium (ITS to the in vitro maturation and embryo culture media on ovine oocyte maturation, cleavage and embryo development. Oocytes having more than five layers of unexpanded cumulus cells and granular homogenous ooplasm were cultured into 50 μL droplets of eight different culture systems: (i TCM-199 (Tissue Culture Medium-199; (ii TCM-199+10 ng/mL FGF2; (iii TCM-199+20 ng/mL FGF2; (iv TCM-199+30 ng/mL FGF2; (v TCM-199+10 ng/mL ITS; (vi TCM-199+20 ng/mL ITS; (vii TCM-199+30 ng/mL ITS and (viii TCM-199+20 ng/mL ITS+20 ng/mL FGF2 in a CO2 incubator at 38.50C for 24 h. All the oocyte culture media were supplemented with 10% FBS, FSH (10 μg/mL and gentamicin (50 µg/mL. The maturation rate was assessed based on the degree of expansion of cumulus cells and identifying first polar body extrusion into perivitelline space. The matured oocytes were inseminated with 1 to 2 million spermatozoa/mL in Brackett and Oliphant medium and the cleavage rate was checked after 42-48 h post insemination and further cultured for 6-7 days. Maturation and cleavage rates were significantly higher (P<0.05 in the oocytes cultured in TCM-199 +10% FBS+FSH (10 μg/mL supplemented with both 20 ng/mL ITS and 20 ng/mL FGF2 as compared to the control. It was concluded that the supplementation of ITS and FGF2 in maturation medium was beneficial for improving maturation and cleavage rates of sheep oocytes. The addition of ITS and FGF2 in embryo culture medium did not improve the development of sheep embryos.

  7. A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

    Feng, Liuxing, E-mail: fenglx@nim.ac.cn; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

    2015-07-16

    Highlights: • Species-unspecific ID-PAGE-LA-ICP-MS was used to quantify Alb and Tf in human serum. • Addition methods of species-unspecific {sup 34}S spike were evaluated. • Isotope change conditions were investigated to reach satisfactory “isotope equilibration”. • Human serum CRM (ERM-DA470k/IFCC) was used to validate the new arrangements. • The developed method offers potential for accurate quantification of protein by ID-PAGE-LA-ICP-MS. - Abstract: Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with {sup 34}S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and {sup 34}S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m{sub sp}/m{sub sam}) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation

  8. Role of ARF6 in internalization of metal-binding proteins, metallothionein and transferrin, and cadmium-metallothionein toxicity in kidney proximal tubule cells

    Wolff, Natascha A.; Lee, Wing-Kee; Abouhamed, Marouan; Thevenod, Frank

    2008-01-01

    Filtered metal-protein complexes, such as cadmium-metallothionein-1 (CdMT-1) or transferrin (Tf) are apically endocytosed partly via megalin/cubilin by kidney proximal tubule (PT) cells where CdMT-1 internalization causes apoptosis. Small GTPase ARF (ADP-ribosylation factor) proteins regulate endocytosis and vesicular trafficking. We investigated roles of ARF6, which has been shown to be involved in internalization of ligands and endocytic trafficking in PT cells, following MT-1/CdMT-1 and Tf uptake by PT cells. WKPT-0293 Cl.2 cells derived from rat PT S1 segment were transfected with hemagglutinin-tagged wild-type (ARF6-WT) or dominant negative (ARF6-T27N) forms of ARF6. Using immunofluorescence, endogenous ARF6 was associated with the plasma membrane (PM) as well as juxtanuclear and co-localized with Rab5a and Rab11 involved in early and recycling endosomal trafficking. Immunofluorescence staining of megalin showed reduced surface labelling in ARF6 dominant negative (ARF6-DN) cells. Intracellular Alexa Fluor 546-conjugated MT-1 uptake was reduced in ARF6-DN cells and CdMT-1 (14.8 μM for 24 h) toxicity was significantly attenuated from 27.3 ± 3.9% in ARF6-WT to 11.1 ± 4.0% in ARF6-DN cells (n = 6, P < 0.02). Moreover, reduced Alexa Fluor 546-conjugated Tf uptake was observed in ARF-DN cells (75.0 ± 4.6% versus 3.9 ± 3.9% of ARF6-WT cells, n = 3, P < 0.01) and/or remained near the PM (89.3 ± 5. 6% versus 45.2 ± 14.3% of ARF6-WT cells, n = 3, P < 0.05). In conclusion, the data support roles for ARF6 in receptor-mediated endocytosis and trafficking of MT-1/Tf to endosomes/lysosomes and CdMT-1 toxicity of PT cells

  9. A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

    Feng, Liuxing; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

    2015-01-01

    Highlights: • Species-unspecific ID-PAGE-LA-ICP-MS was used to quantify Alb and Tf in human serum. • Addition methods of species-unspecific 34 S spike were evaluated. • Isotope change conditions were investigated to reach satisfactory “isotope equilibration”. • Human serum CRM (ERM-DA470k/IFCC) was used to validate the new arrangements. • The developed method offers potential for accurate quantification of protein by ID-PAGE-LA-ICP-MS. - Abstract: Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with 34 S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and 34 S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m sp /m sam ) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation process. Moreover, the

  10. The importance of the stem cell marker prominin-1/CD133 in the uptake of transferrin and in iron metabolism in human colon cancer Caco-2 cells.

    Erika Bourseau-Guilmain

    Full Text Available As the pentaspan stem cell marker CD133 was shown to bind cholesterol and to localize in plasma membrane protrusions, we investigated a possible function for CD133 in endocytosis. Using the CD133 siRNA knockdown strategy and non-differentiated human colon cancer Caco-2 cells that constitutively over-expressed CD133, we provide for the first time direct evidence for a role of CD133 in the intracellular accumulation of fluorescently labeled extracellular compounds. Assessed using AC133 monoclonal antibody, CD133 knockdown was shown to improve Alexa488-transferrin (Tf uptake in Caco-2 cells but had no impact on FITC-dextran or FITC-cholera-toxin. Absence of effect of the CD133 knockdown on Tf recycling established a role for CD133 in inhibiting Tf endocytosis rather than in stimulating Tf exocytosis. Use of previously identified inhibitors of known endocytic pathways and the positive impact of CD133 knockdown on cellular uptake of clathrin-endocytosed synthetic lipid nanocapsules supported that CD133 impact on endocytosis was primarily ascribed to the clathrin pathway. Also, cholesterol extraction with methyl-β-cyclodextrine up regulated Tf uptake at greater intensity in the CD133(high situation than in the CD133(low situation, thus suggesting a role for cholesterol in the inhibitory effect of CD133 on endocytosis. Interestingly, cell treatment with the AC133 antibody down regulated Tf uptake, thus demonstrating that direct extracellular binding to CD133 could affect endocytosis. Moreover, flow cytometry and confocal microscopy established that down regulation of CD133 improved the accessibility to the TfR from the extracellular space, providing a mechanism by which CD133 inhibited Tf uptake. As Tf is involved in supplying iron to the cell, effects of iron supplementation and deprivation on CD133/AC133 expression were investigated. Both demonstrated a dose-dependent down regulation here discussed to the light of transcriptional and post

  11. Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

    Zheng, Y; Gao, L; Wang, D; Zang, D

    2017-08-01

    The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models.

    Aya Sugyo

    Full Text Available Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR, is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT with 90Y-TSP-A01 in pancreatic cancer mouse models.TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2 was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02 were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted.MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced.90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further

  13. Serum levels of iron in Sør-Varanger, Northern Norway--an iron mining municipality.

    Broderstad, Ann R; Smith-Sivertsen, Tone; Dahl, Inger Marie S; Ingebretsen, Ole Christian; Lund, Eiliv

    2006-12-01

    The purpose of this study was to investigate iron status in a population with a high proportion of miners in the northernmost part of Norway. Cross-sectional, population-based study performed in order to investigate possible health effects of pollution in the population living on both sides of the Norwegian-Russian border. All individuals living in the community of Sør-Varanger were invited for screening in 1994. In 2000, blood samples from 2949 participants (response rate 66.8 %), age range 30-69 years, were defrosted. S-ferritin and transferrin saturation were analysed in samples from 1548 women and 1401 men. About 30 % (n = 893) were employed in the iron mining industry, 476 of whom were miners and 417 had other tasks in the company. Type and duration of employment and time since last day of work at the company were used as indicators of exposure. Both s-ferritin levels and transferrin saturation were higher in men than in women. S-ferritin increased with increasing age in women, while the opposite was true for men. Iron deficiency occurred with higher frequencies in women (16 %) than in men (4 %). Iron overload was uncommon in both sexes. Adjustment for smoking and self-reported pulmonary diseases did not show any effect on iron levels. Miners had non-significant higher mean s-ferritin and transferrin saturation than non-miners. Neither duration, nor time since employment in the mine, had any impact on iron status. Our analyses did not show any associations between being a miner in the iron mining industry and serum iron levels compared to the general population.

  14. Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.

    McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min; Loguinov, Alex; Valore, Erika; Hui, Simon T; Jung, Grace; Zhou, Jie; Lusis, Aldons J; Fuqua, Brie; Ganz, Tomas; Nemeth, Elizabeta; Vulpe, Chris D

    2017-11-01

    Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin ( Hamp1 ) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least

  15. Hemoglobin levels in normal Filipino pregnant women.

    Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

    1981-09-01

    The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

  16. Anemia in kidney transplants without erythropoietic agents: levels of erythropoietin and iron parameters.

    Florit, E A; Hadad, F; Rodriguez Cubillo, B; De la Flor, J C; Valga, F; Perez Flores, I; Calvo Romero, N; Valero San Cecilio, R; Barrientos Guzman, A; Sanchez Fructuoso, A

    2012-11-01

    To study the association between hemoglobin, endogenous erythropoietin (EPO) levels and ferric parameters in kidney recipients not treated with EPO-stimulating agents. Transverse study of 219 kidney transplant outpatients. The median time after transplantation was 54 months (P(25-75), 23-107). We assessed blood counts, ferric parameters, EPO levels, renal function (MDRD-4), and adjuvant treatment. We performed a linear regression analysis to predict hemoglobin. Median EPO values were 14.05 mUI/mL (P(25-75) = 10.2-19.7). Applying the formulas described by Beguin, kidney transplant recipients showed a low observed/expected ratio of erythropoietin and of transferrin. Considering anemia to be an hemoglobin of calculate hemoglobin was: hemoglobin = 11829-0909 log (EPG level) - 0455 (if female) + 0.010 0.013 transferrin + 0.013 creatinine clearance (r = .424, P < .001). Treatment with ACEI and/or ARBs seemed to produce a defect in the synthesis of EPO, while those treated with mTORi, a hyporesponsive state. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Biomarker-Based Approaches for Assessing Alcohol Use Disorders

    Onni Niemelä

    2016-01-01

    Full Text Available Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders.

  18. Utilidad en el post parto de la determinación de protoporfirina eritrocitaria y su relación con el receptor soluble de transferrina Usefulness of erythrocyte protoporphyrin test in the puerperium compared to the soluble transferrin receptor

    Silvia H. Langini

    2004-08-01

    Full Text Available Se estudió, en 77 puérperas, la relación entre la protoporfirina eritrocitaria (PE, la ferritina sérica (FS, el receptor soluble de transferrina (RsT y los indicadores hematológicos utilizados en la rutina clínica. En sangre venosa se determinó: Hematocrito (Hto, Hemoglobina (Hb, recuento de glóbulos rojos (GR y glóbulos blancos (GB (contador electrónico MEGA; PE (Piomelli; en suero: RsT (ELISA, Orion Diagnostica, FS (ELISA, IMx Ferritina, Abbott y Proteína C-Reactiva (PCR- Látex, Wiener lab. Se analizaron sensibilidad (S, especificidad (E y puntos de corte mediante el modelo ROC (Receiver Operating Characteristics, considerando como gold standard el RsT. Los resultados (media ± DE fueron: Hto (% 35 ± 5; Hb (g/l 113 ± 18; GRx10³/mm³ 3 893 ± 489; VCM (fL 90 ± 6; GB/mm³ 9 543 ± 2.669; PE (µg/dl GR 46 ± 39; RsT (mg/l 4.7 ± 2.8; FS (µg/l 26 ± 31; PCR (Pos/Neg 72/5. La PE no correlacionó con FS, pero sí con el RsT (r=0.323, p=0.007. La S y E de la FS fueron de 83% y 63%, respectivamente, para un punto de corte de 25 µg/l; para la PE la S fue de 38% y la E de 90% para un punto de corte de 53 µg/dl GR. Estos resultados sugieren que ese punto de corte en el puerperio, permitiría detectar con un bajo costo un mayor porcentaje de mujeres (16% en nuestro estudio que presentan deficiencia de Fe pese a sus valores normales de hemoglobina.Erythrocyte protoporphyrin (EP, serum ferritin (SF, soluble transferrin receptor (sTfR and routine hematological laboratory tests were studied in 77 women 24 h post-partum, assisted at Paroissien Hospital (in Buenos Aires Province. Hematocrite (Hct, hemoglobin (Hb, red blood cells (RBC and white blood cells (WBC were determined using an electronic counter (Mega; EP by Piomelli’s; SF by ELISA (IMx Ferritina, Abbott; sTfR by ELISA (Orion Diagnostica and C-Reactive Protein (PCR-Latex, Wiener lab. All determinations were made in fasting blood samples. Statistical analysis (Receiver Operating

  19. Urinary hepcidin level as an early predictor of iron deficiency in children: A case control study

    Gharib Amal F

    2011-08-01

    Full Text Available Abstract Background The ideal screening test would be capable of identifying iron deficiency in the absence of anemia. We tried to detect role of urinary hepcidin-25 level in early prediction of iron deficiency in children. Methods This is a case control study performed on 100 children in Hematology Unit of Pediatric Department, Zagazig University Hospital, Egypt. Our study included 25 cases of iron deficiency (ID stage-1 (iron depletion, 25 cases ID stage-2 (iron-deficient erythropoiesis, 25 cases ID stage-3 (iron deficiency anemia and 25 healthy children as a control group. Estimation of iron status parameters was done. Urinary hepcidin-25 level was detected. Results Urinary hepcidin-25 level was significantly lower in all stages of iron deficiency than in control group, more significant reduction in its level was observed with the progress in severity of iron deficiency. Urinary hepcidin showed significant positive correlation with hemoglobin, mean corpuscular volume, hematocrit value, serum iron and ferritin and transferrin saturation. In contrary, it showed significant negative correlation with serum transferrin and total iron binding capacity. Urinary hepcidin at cutoff point ≤0.94 nmol/mmol Cr could Predict ID stage-1 with sensitivity 88% and specificity 88%. Cutoff point ≤0.42 nmol/mmol Cr could predict ID stage-2 with sensitivity 96% and specificity 92%. Cutoff point ≤0.08 nmol/mmol Cr could Predict ID stage-3 with Sensitivity 96% and specificity 100%. Conclusions We can conclude that detection of urinary hepcidin-25 level was a simple and non invasive test and could predict iron deficiency very early, before appearance of hematological affections.

  20. Plasma iron levels appraised 15 days after spinal cord injury in a limb movement animal model.

    Reis, F M; Esteves, A M; Tufik, S; de Mello, M T

    2011-03-01

    Experimental, controlled trial. The purpose of this study was to evaluate plasma iron and transferrin levels in a limb movement animal model with spinal cord injury (SCI). Universidade Federal de São Paulo, Departamento de Psicobiologia. In all, 72 male Wistar rats aged 90 days were divided into four groups: (1) acute SCI (1 day, SCI1), (2) 3 days post-SCI (SCI3), (3) 7 days post-SCI (SCI7) and (4) 15 days post-SCI (SCI15). Each of these groups had corresponding control (CTRL) and SHAM groups. Plasma iron and transferrin levels of the different groups were analyzed using a one-way analysis of variance (ANOVA) followed by Tukey's test. We found a significant reduction in iron plasma levels after SCI compared with the CTRL group: SCI1 (CTRL: 175±10.58 μg dl(-1); SCI: 108.28±11.7 μg dl(-1)), SCI3 (CTRL: 195.5±11.00 μg dl(-1); SCI: 127.88±12.63 μg dl(-1)), SCI7 (CTRL: 186±2.97 μg dl(-1); SCI: 89.2±15.39 μg dl(-1)) and SCI15 (CTRL: 163±5.48 μg dl(-1); SCI: 124.44±10.30 μg dl(-1)) (P<0.05; ANOVA). The SHAM1 group demonstrated a reduction in iron plasma after acute SCI (CTRL: 175±10.58 μg dl(-1); SHAM: 114.60±7.81 μg dl(-1)) (P<0.05; ANOVA). Reduced iron metabolism after SCI may be one of the mechanisms involved in the pathogenesis of sleep-related movement disorders.

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

    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/.

  2. Lathe leveler

    Lovelady, III, Michael W.J.

    2018-03-06

    A lathe leveler for centering a cutting tool in relation to a cylindrical work piece includes a first leveling arm having a first contact point disposed adjacent a distal end of the first leveling arm, a second leveling arm having a second contact point disposed adjacent a distal end of the second leveling arm, a leveling gage, and a leveling plate having a cutting tool receiving surface positioned parallel to a horizontal axis of the leveling gage and on a same plane as a midpoint of the first contact point and the second contact point. The leveling arms and leveling plate are dimensioned and configured such that the cutting tool receiving surface is centered in relation to the work piece when the first and second contact points are in contact with one of the inner surface and outer surface of the cylindrical work piece and the leveling gage is centered.

  3. High dose ESAs are associated with high iPTH levels in hemodialysis patients with end-stage kidney disease: a retrospective analysis

    Lan eChen

    2015-11-01

    Full Text Available Objective: Anemia and secondary hyperparathyroidism are the two most common complications associated with chronic kidney disease (CKD. Erythropoiesis-stimulating agents (ESAs are widely used in the management of anemia in hemodialysis patients. A reverse correlation has been established between hyperparathyroidism and hemoglobin levels. The aim of this retrospective study is to evaluate the relationship of high dose ESAs and hyperparathyroidism in hemodialysis patients with anemia. Methods: A total of 240 uremic patients maintained on regular hemodialysis were enrolled into this study. Among them, 142 patients were treated with Epiao® (epoetin-alfa and 98 patients were treated with Recormon® (epoetin-beta. The target hemoglobin concentration was 110-130 g/L. Laboratory measurements including hemoglobin, calcium, phosphorus, albumin, intact-parathyroid hormone (iPTH, serum ferritin and transferrin saturation were collected. Results: Hemoglobin concentration increased as iPTH level decreased by stratification. However, no significant association between anemia and calcium or phosphorus level was found. Patients with iPTH levels within 150-300 pg/mL had the highest levels of hemoglobin, serum ferritin and transferrin saturation. Patients treated with Recormon and Epiao had similar hemoglobin concentrations. However, the dose of Recormon for anemia treatment was significantly less than that the dose of Epiao (P<0.05. The level of iPTH in the Recormon group was significantly lower than in the Epiao group. In patients with hemoglobin levels between 110-130 g/L (P<0.05, iPTH level was found to be significantly lower in patients treated with lower doses of ESAs than in patients treated with higher doses of ESAs, no matter which ESA was used (Recormon or Epiao, P<0.05. Conclusions: The dose of ESAs might be positively associated with iPTH level, suggesting that a reasonable hemoglobin target can be achieved by using the lowest possible ESA dose.

  4. Cortisol level

    ... enable JavaScript. The cortisol blood test measures the level of cortisol in the blood. Cortisol is a ... in the morning. This is important, because cortisol level varies throughout the day. You may be asked ...

  5. Triglyceride level

    ... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, please enable JavaScript. The triglyceride level is a blood test to measure the amount ...

  6. Level 1 - level 2 interface

    Boneham, P.

    2003-01-01

    The Plant Damage States (PDS) are the starting point for the level 2 analysis. A PDS is group of core damage sequences that are expected to have similar severe accident progressions. In this paper an overview of Level 1/Level 2 interface, example PDS parameters, example PDS definitions using codes and example Bridge Tree are presented. PDS frequency calculation (identification of sequences for each PDS in level 1,split some CD sequences which have different level 2 progressions), code calculations providing support for grouping decisions and timings as well as PDS frequencies and definitions input to level 2 are also discussed

  7. Level densities

    Ignatyuk, A.V.

    1998-01-01

    For any applications of the statistical theory of nuclear reactions it is very important to obtain the parameters of the level density description from the reliable experimental data. The cumulative numbers of low-lying levels and the average spacings between neutron resonances are usually used as such data. The level density parameters fitted to such data are compiled in the RIPL Starter File for the tree models most frequently used in practical calculations: i) For the Gilber-Cameron model the parameters of the Beijing group, based on a rather recent compilations of the neutron resonance and low-lying level densities and included into the beijing-gc.dat file, are chosen as recommended. As alternative versions the parameters provided by other groups are given into the files: jaeri-gc.dat, bombay-gc.dat, obninsk-gc.dat. Additionally the iljinov-gc.dat, and mengoni-gc.dat files include sets of the level density parameters that take into account the damping of shell effects at high energies. ii) For the backed-shifted Fermi gas model the beijing-bs.dat file is selected as the recommended one. Alternative parameters of the Obninsk group are given in the obninsk-bs.dat file and those of Bombay in bombay-bs.dat. iii) For the generalized superfluid model the Obninsk group parameters included into the obninsk-bcs.dat file are chosen as recommended ones and the beijing-bcs.dat file is included as an alternative set of parameters. iv) For the microscopic approach to the level densities the files are: obninsk-micro.for -FORTRAN 77 source for the microscopical statistical level density code developed in Obninsk by Ignatyuk and coworkers, moller-levels.gz - Moeller single-particle level and ground state deformation data base, moller-levels.for -retrieval code for Moeller single-particle level scheme. (author)

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

    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

  9. Iron stores and obesity are negatively associated with ovarian volume and anti-Müllerian hormone levels in women with polycystic ovary syndrome.

    Yang, Jehn-Hsiahn; Chou, Chia-Hung; Yang, Wei-Shiung; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

    2015-12-01

    Obesity and insulin resistance are associated with increased iron stores, but have conflicting effects on ovarian reserve in women with polycystic ovary syndrome (PCOS). Iron-catalyzed oxidative stress might be detrimental to ovarian tissue and granulosa cell function. In this study we determined the association between body iron stores, obesity, and ovarian reserve in women with PCOS. One hundred and fifty-six women diagnosed with PCOS according to Rotterdam criteria and 30 normoweight healthy control women were enrolled in this cross-sectional study. Ovarian volume, total antral follicle count, and the anti-Müllerian hormone (AMH) level were measured as an indicator of ovarian reserve. Ferritin and transferrin-bound iron levels were significantly higher in women with PCOS than normoweight controls. Obese women with PCOS had higher ferritin levels (p = 0.006), but lower AMH levels (p ovarian volume were inversely related to the ferritin level, homeostasis model assessment of insulin resistance, and body mass index in women with PCOS. Body mass index and ferritin level remained significantly correlated with a lower AMH level and reduced ovarian volume, respectively, after considering other confounding variables. An elevated ferritin level and obesity were negatively associated with ovarian volume and the AMH level, respectively, in women with PCOS. Copyright © 2015. Published by Elsevier B.V.

  10. Expression of Hepcidin and Growth Differentiation Factor 15 (GDF-15 Levels in Thalassemia Patients with Iron Overload and Positive Anti Hepatitis C Virus

    Nuri Dyah Indrasari

    2016-09-01

    Full Text Available Background: Thalassemia patients who undergo life-long recurrent blood transfusion will experience iron overload in various organs including the liver and possibly suffer from chronic hepatitis C infection which may lead to liver impairment. The liver produces hepcidin, a hormone which plays role in the regulation of iron level in the blood. Various factors may influence hepcidin level in the blood. Chronic hepatitis C causes iron overload and liver impairment. Liver impairment and haemolytic anaemia due to haemoglobinopathy will suppress hepcidin production. Anaemia stimulates growth differentiation factor 15 (GDF-15 to increase erythropoiesis and suppress hepcidin production. Iron overload causes increase in hepcidin level. Presence of factors which decrease or increase hepcidin production will express various levels of hepcidin. This study aimed to identify the expression of hepcidin and GDF-15 levels in thalassemia patients with iron overload and positive anti-HCV. Information on hepcidin and GDF-15 levels are beneficial in the management of iron overload in thalassemia with positive anti-HCV. Method: This study was a descriptive analytic study in thalassemia patients who had received recurrent blood transfusion ≥ 12 times, suffered from iron overload (transferrin saturation > 55% and ferritin > 1,000 ng/mL, which consisted of 31 individuals with positive anti-HCV and 27 individuals with negative anti-HCV. This study was performed in Thalassemia Centre Department of Child Health and Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, in October 2011–January 2012. Serum hepcidin and GDF-15 examinations were performed using enzyme-linked immunosorbent assay (ELISA method. Aspartate aminotransferase (AST and alanine aminotransferase (ALT examinations were performed using colorimetry method. Data on ferritin and transferrin saturation were obtained from medical records in the last 3

  11. Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

    Aranda, Nuria; Bedmar, Cristina; Arija, Victoria; Jardí, Cristina; Jimenez-Feijoo, Rosa; Ferré, Natalia; Tous, Monica

    2018-06-01

    The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

  12. Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

    Kayaalti, Zeliha, E-mail: kayaalti@ankara.edu.tr [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Kaya-Akyüzlü, Dilek [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Söylemez, Esma [Ankara University, Institute of Forensic Sciences, Ankara (Turkey); Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat (Turkey); Söylemezoğlu, Tülin [Ankara University, Institute of Forensic Sciences, Ankara (Turkey)

    2015-07-15

    Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother–placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR–RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods. - Highlights: • Mothers with H63D gene variants have higher lead levels of their newborn's umbilical cord blood. • Unborn child of women with HD+DD genotypes may be at increased risk of internal exposure to lead. • Maternal HFE status may have an effect on increased placenta, maternal and cord blood lead levels.

  13. Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

    Kayaalti, Zeliha; Kaya-Akyüzlü, Dilek; Söylemez, Esma; Söylemezoğlu, Tülin

    2015-01-01

    Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother–placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR–RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods. - Highlights: • Mothers with H63D gene variants have higher lead levels of their newborn's umbilical cord blood. • Unborn child of women with HD+DD genotypes may be at increased risk of internal exposure to lead. • Maternal HFE status may have an effect on increased placenta, maternal and cord blood lead levels.

  14. Morbidity and immunological tests in miners working in mines with low ionizing radiation level

    Wagner, V.; Skokanova, V.; Skokanova, K.; Wagnerova, M.; Heribanova, A.; Riha, M.

    1984-01-01

    The total count of morbidity and prevalence of upper respiratory tract diseases (RTD) were studied in 210 miners working in shale mines with a low level of ionizing radiation with respect to their smoking habits. After one and a half years of observation tests of humoral immunity in the blood serum and saliva (immunoglobulins G, A, M and sIA) and tests of non-specific indices (alpha 2 macroglobulin (A 2M), transferrin, lysozyme) were performed. The number of healthy non-smokers reached 41.3% whereas the number of healthy smokers was only 26.5% (P<0.05). The greater was the number of diseases in single subjects, the greater was the difference between smokers and non-smokers (P<0.005). The difference between RTD morbidity of smokers and non-smokers was not significant in the subgroup of miners employed less than 10 years but the duration of employment raised the value significantly (P<0.002) in disfavour of smokers. The difference between smokers and non-smokers is emphasized in ageing. The mean levels of immunoglobulins (IgG, IgA, IgM) were significantly higher in healthy non-smokers in comparison with other miners; this is also stressed by distribution analysis. The distribution of A 2M values also significantly differed in the subgroup of healthy non-smokers compared with other miners. Highly significant differences were found between healthy non-smokers and other miners using discrimination analysis of coupled tests. In contrast to that, the level of A 2M was in inverse relationship to the levels of Ig; in the subgroup of healthy non-smokers low levels of A 2M correlated with high levels of Ig of all three classes. The results are discussed from the point of view of the smokers' habits, the duration of employment in the mine, the age of the miners and the presumed genetical factors

  15. Positive Association of Vitamin E Supplementation with Hemoglobin Levels in Mildly Anemic Healthy Pakistani Adults.

    Jilani, Tanveer; Azam, Iqbal; Moiz, Bushra; Mehboobali, Naseema; Perwaiz Iqbal, Mohammad

    2015-01-01

    Hemoglobin levels slightly below the lower limit of normal are common in adults in the general population in developing countries. A few human studies have suggested the use of antioxidant vitamins in the correction of mild anemia. The objective of the present study was to investigate the association of vitamin E supplementation in mildly anemic healthy adults with post-supplemental blood hemoglobin levels in the general population of Karachi, Pakistan. In a single-blinded and placebo-controlled randomized trial, 124 mildly anemic subjects from the General Practitioners' Clinics and personnel of the Aga Khan University were randomized into intervention (n = 82) and control (n = 42) group. In the intervention group, each subject was given vitamin E (400 mg) everyday for a period of three months, while control group subjects received a placebo. Eighty six subjects completed the trial. Fasting venous blood was collected at baseline and after three months of supplementation. Hemoglobin levels and serum/plasma concentrations of vitamin E, vitamin B12, folate, ferritin, serum transferrin receptor (sTfR), glucose, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, creatinine, total-antioxidant-status and erythropoietin were measured and analyzed using repeated measures ANOVA and multiple linear regression. The adjusted regression coefficients (β) and standard error [SE(β)] of the significant predictors of post-supplemental hemoglobin levels were serum concentration of vitamin E (0.983[0.095]), gender (- 0.656[0.244]), sTfR (- 0.06[0.02]) and baseline hemoglobin levels (0.768[0.077]). The study showed a positive association between vitamin E supplementation and enhanced hemoglobin levels in mildly anemic adults.

  16. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-02-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. Copyright© Ferrata Storti Foundation.

  17. Is there an association between Vitamin D level and inflammatory markers in hemodialysis patients? A cross-sectional study

    Syed Atif Mohiuddin

    2016-01-01

    Full Text Available Vitamin D deficiency is very prevalent among the patients with end-stage renal disease. The etiology of this is multifactorial, including nutritional deficiency, insufficient expo- sure to sunlight, race, obesity and not the least, impaired Vitamin D synthesis and metabolism in chronic kidney disease patients. We hypothesized that lower Vitamin D level will be associated with higher inflammatory burden and low immunological response to hepatitis B vaccination in hemodialysis (HD population. The study was carried out in March 2013 among 100 HD patients who were identified to be eligible for the study. This was a cross-sectional study analyzing the relationship between Vitamin D level and inflammatory markers in HD patients. A relationship between Vitamin D level and markers of mineral bone disorder was also analyzed. We also analyzed the relationship between Vitamin D level and hemoglobin and erythropoietin dosage. Hemoglobin, transferrin saturation, and erythropoietin dose were used to study the relationship between Vitamin D and markers of anemia. Antibodies to hepatitis B surface antigen were measured to study the response between Vitamin D level and immune response to hepatitis B vaccine. Vitamin D levels were significantly lower in females compared to males (P = 0.009 and diabetics compared to non-diabetics (P = 0.02. No significant association was observed between Vitamin D levels with immune response to hepatitis B vaccine (P = 0.89, C-reactive protein (P = 0.19, serum albumin (P = 0.17, hemoglobin level (P = 0.18, and erythropoietin requirement (P = 0.87, parathyroid hormone (PTH levels (P = 0.57, calcium levels (P = 0.79 and phosphate level (P = 0.1.

  18. Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners

    Aya Ishibashi

    2017-03-01

    Full Text Available Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February and during an intensified training period (INT; late of August to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT (p < 0.05. Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW (p < 0.05. Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW (p < 0.05. In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron.

  19. Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

    Seyed Ali Mousavi

    2015-01-01

    Full Text Available Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L baseline hemoglobin were compared with those with lower (<138 g/L baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations.

  20. Serum Ferritin Levels Are Lower in Children With Tic Disorders Compared with Children Without Tics: A Cross-Sectional Study.

    Avrahami, Matan; Barzilay, Ran; HarGil, Miki; Weizman, Abraham; Watemberg, Nathan

    2017-03-01

    Alteration in peripheral iron indices has been reported in a number of movement disorders, particularly Parkinson's disease. We hypothesized that iron stores may be diminished in children at an early stage of tic disorder. Using data retrieved from electronic medical records, we compared serum ferritin levels, an indicator of body iron store balance, in drug-naive children diagnosed for the first time with tic disorder (study group; N = 47, 32 boys/15 girls, aged 8.66 ± 3.17 years) compared to age- and sex-matched children with headaches (comparison group, n = 100, 62 boys/38 girls, aged 9.51 ± 3.15 years) treated in the same pediatric neurological clinic. Mean serum ferritin levels were significantly lower (-32%, p = 0.01) in the tic disorder group compared to the headache group. No significant differences were detected in circulatory hemoglobin, iron, transferrin, and platelet count between the two groups. Our findings suggest that body iron stores may be reduced in children with recent-onset tic disorder.

  1. Comparison of nutritional status and inflammatory stress levels after gastric cancer patients with chemotherapy received palonosetron hydrochloride injection and tropisetron

    Wei Zheng

    2017-01-01

    Full Text Available Objective: To study the nutritional status and inflammatory stress levels after gastric cancer patients with chemotherapy received palonosetron and tropisetron. Methods: 94 patients with advanced gastric cancer undergoing FOLFOX4 intravenous chemotherapy in our hospital between May 2014 and March 2016 were selected and randomly divided into observation group (n=47 and control group (n=47 who received palonosetron and tropisetron for chemotherapy anti-emesis respectively. After four cycles of chemotherapy, serum samples were collected from two groups of patients to determine nutritional status, inflammatory reaction and stress reaction indexes. Results: After four cycles of chemotherapy, serum albumin (ALB, prealbumin (PAB, transferrin (TFN, immunoglobulin A (IgA, IgG and IgM content of observation group were significantly higher than those of control group (P<0.05. After four cycles of chemotherapy, serum Keap1 content of observation group was significantly higher than that of control group (P<0.05, while Nrf2, ARE, NQO1, HO-1, interferon-γ (IFN-γ, tumor necrosis factor α (TNF-α, interleukin-4 (IL-4 and IL-10 content were significantly lower than those of control group (P<0.05. Conclusions: Palonosetron has better antiemetic effect than tropisetron for gastric cancer patients with chemotherapy, and after chemotherapy, the nutritional status is better and the inflammatory stress level is lighter.

  2. Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

    Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

    2015-01-01

    Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

  3. Differences in micronucleus frequency and acrylamide adduct levels with hemoglobin between vegetarians and non-vegetarians.

    Kotova, Natalia; Frostne, Cecilia; Abramsson-Zetterberg, Lilianne; Tareke, Eden; Bergman, Rolf; Haghdoost, Siamak; Paulsson, Birgit; Törnqvist, Margareta; Segerbäck, Dan; Jenssen, Dag; Grawé, Jan

    2015-10-01

    Nutrients and food constituents can prevent or contribute to genotoxicity. In this study, the possible influence of a vegetarian/non-vegetarian diet on genotoxic effects was investigated in 58 non-smoking healthy vegetarians (V) and non-vegetarians (NV), age 21-37 years from the Stockholm area in Sweden. Physical activity and dietary habits were similar in both groups, with the exception of the intake of meat and fish. Using flow cytometry, we determined the formation of micronuclei (MN) in transferrin-positive immature peripheral blood reticulocytes (Trf-Ret) (Total: n = 53; V: n = 27; NV: n = 26). Dietary exposure to acrylamide was measured through hemoglobin (Hb) adducts in peripheral erythrocytes (Total: n = 53; V: n = 29; NV: n = 24). Hb adducts of both acrylamide and its genotoxic metabolite glycidamide were monitored as a measure of the corresponding in vivo doses. Our data demonstrated that compared with the non-vegetarians, the vegetarians exhibited lower frequencies of MN (fMN) in the Trf-Ret (p vegetarians and non-vegetarians. Furthermore, there were no significant relationships between the adduct levels and fMN in the individuals. The ratio of the Hb adduct levels from glycidamide and acrylamide, however, showed a significant difference (p vegetarian diet might be beneficial in lowering genomic instability in healthy individuals. The measured Hb adduct levels indicate that the total intake of acrylamide does not differ between the two studied groups and does not contribute to the observed difference in fMN, although an influence of the diet on the metabolic rates of acrylamide was indicated. In addition, the observed significant difference in the background fMN in the two groups demonstrated that the MN analysis method has a sensitivity applicable to the biomonitoring of human lifestyle factors.

  4. Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk-driving among previously convicted drunk-driving offenders: results from the recidivism of alcohol-impaired driving (ROAD) study.

    Maenhout, Thomas M; Poll, Anneleen; Vermassen, Tijl; De Buyzere, Marc L; Delanghe, Joris R

    2014-01-01

    In several European countries, drivers under the influence (DUI), suspected of chronic alcohol abuse are referred for medical and psychological examination. This study (the ROAD study, or Recidivism Of Alcohol-impaired Driving) investigated the usefulness of indirect alcohol biomarkers for predicting drunk-driving recidivism in previously convicted drunk-driving offenders. The ROAD study is a prospective study (2009-13) that was performed on 517 randomly selected drivers in Belgium. They were convicted for drunk-driving for which their licence was confiscated. The initial post-arrest blood samples were collected and analysed for percentage carbohydrate-deficient transferrin (%CDT), transaminsase activities [alanine amino transferase (ALT), aspartate amino transferase (AST)], gamma-glutamyltransferase (γGT) and red cell mean corpuscular volume (MCV). The observation time for each driver was 3 years and dynamic. A logistic regression analysis revealed that ln(%CDT) (P drunk-driving. The ROAD index (which includes ln(%CDT), ln(γGT), -ln(ALT) and the sex of the driver) was calculated and had a significantly higher area under the receiver operator characteristic curve (0.71) than the individual biomarkers for drunk-driving recidivism. Drivers with a high risk of recidivating (ROAD index ≥ 25%; third tertile) could be distinguished from drivers with an intermediate risk (16% ≤ ROAD index drunk-driving. The association with gamma-glutamyltransferase, alanine amino transferase and the sex of the driver could have additional value for identifying drunk-drivers at intermediate risk of recidivism. Non-specific indirect alcohol markers, such as alanine amino transferase, gamma-glutamyltransferase, aspartate amino transferase and red cell mean corpuscular volume have minimal added value to % carbohydrate-deficient transferrin for distinguishing drunk drivers with a low or high risk of recidivism. © 2013 Society for the Study of Addiction.

  5. Changes in serum iron, total iron binding capacity and transferrin ...

    Background: Iron is a vital constituent of cells but in excess may be harmful and is associated with a raised risk for some malignant diseases including breast cancer. We aimed to study changes in iron profile in Sudanese females newly diagnosed with breast cancer. Methods: A case- control study in which serum iron, Total ...

  6. Soluble Transferrin Receptor - A Marker For Iron Deficiency; A Review

    Parameters for measuring iron deficiency have been established for decades and have served clinicians in the management of this nutritional disorder. The bone marrow still remains the gold standard in the final diagnosis of iron deficiency. However, researchers have been able to identify the dominating role of the ...

  7. Sea level change

    Church, J.A.; Clark, P.U.; Cazenave, A.; Gregory, J.M.; Jevrejeva, S.; Levermann, A.; Merrifield, M.A.; Milne, G.A.; Nerem, R.S.; Nunn, P.D.; Payne, A.J.; Pfeffer, W.T.; Stammer, D.; Unnikrishnan, A.S.

    This chapter considers changes in global mean sea level, regional sea level, sea level extremes, and waves. Confidence in projections of global mean sea level rise has increased since the Fourth Assessment Report (AR4) because of the improved...

  8. The Influence of Tobacco Smoke on Protein and Metal Levels in the Serum of Women during Pregnancy.

    Marta Wrześniak

    Full Text Available Tobacco smoking by pregnant women has a negative effect on fetal development and increases pregnancy risk by changing the oxidative balance and microelements level. Smoking affects the concentration, structure and function of proteins, potentially leading to various negative effects on pregnancy outcomes.The influence of tobacco smoke on key protein fractions in smoking and non-smoking healthy pregnant women was determined by capillary electrophoresis (CE. Concentrations of the proteins α1-antitrypsin, α1-acid glycoprotein, α2-macroglobulin and transferrin were determined by ELISA tests. Total protein concentration was measured by the Biuret method. Smoking status was established by cotinine levels. Cadmium (Cd and Zinc (Zn concentrations were determined by flame atomic absorption spectrometry and the Zn/Cd ratio was calculated based on these numbers. Smoking women had a 3.7 times higher level of Cd than non-smoking women. Zn levels decreased during pregnancy for all women. The Zn/Cd ratio was three times lower in smoking women. The differences between the changes in the protein profile for smoking and non-smoking women were noted. Regarding proteins, α1-antitrypsin and α2-macroglobulin levels were lower in the non-smoking group than in the smoking group and correlated with Cd levels (r = -0.968, p = 0.032 for non-smokers; r = -0.835, p = 0.019 for smokers. Zn/Cd ratios correlated negatively with α1-, α2- and β-globulins.Exposure to tobacco smoke increases the concentration of Cd in the blood of pregnant women and may lead to an elevated risk of pregnancy disorders. During pregnancy alter concentrations of some proteins. The correlation of Cd with proteins suggests that it is one of the causes of protein aberrations.

  9. Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.

    Konstantinos Gkouvatsos

    Full Text Available Hemojuvelin (Hjv is a bone morphogenetic protein (BMP co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.

  10. Modulating antibody affinity towards the transferrin receptor to increase brain uptake of anti-transferrin receptor antibody targeted gold nanoparticles

    Johnsen, Kasper Bendix; Bak, Martin; Melander, Fredrik

    2017-01-01

    by silver enhancement and light microscopy. Electron microscopy showed that the particles had been efficiently endocytosed into the endothelial cells of the BBB. A small fraction of particles could also be detected in the brain parenchyma, which was underscored by measuring the gold content in brain...

  11. Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with β-thalassemia major.

    Mirlohi, Maryam Sadat; Yaghooti, Hamid; Shirali, Saeed; Aminasnafi, Ali; Olapour, Samaneh

    2018-04-01

    The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

  12. Guidance levels, achievable doses and expectation levels

    Li, Lianbo; Meng, Bing

    2002-01-01

    The National Radiological Protection Board (NRPB), the International Atomic Energy Agency (IAEA) and the Commission of the European Communities (CEC) published their guidance levels and reference doses for typical X-ray examination and nuclear medicine in their documents in 1993, 1994 and 1996 respectively. From then on, the concept of guidance levels or reference doses have been applied to different examinations in the field of radiology and proved to be effective for reduction of patient doses. But the guidance levels or reference doses are likely to have some shortcomings and can do little to make further reduction of patient dose in the radiology departments where patient dose are already below them. For this reason, the National Radiological Protection Board (NRPB) proposed a concept named achievable doses which are based on the mean dose observed for a selected sample of radiology departments. This paper will review and discuss the concept of guidance levels and achievable doses, and propose a new concept referred to as Expectation Levels that will encourage the radiology departments where patient dose are already below the guidance levels to keep patient dose as low as reasonably achievable. Some examples of the expectation levels based on the data published by a few countries are also illustrated in this paper

  13. Correlation between plasma homocysteine levels and craving in alcohol dependent stabilized patients.

    Coppola, Maurizio; Mondola, Raffaella

    2018-06-01

    Homocysteine is a sulfur amino acid strictly related with alcohol consumption. In alcoholics, hyperhomocysteinemia can increase the risk of various alcohol-related disorders such as: brain atrophy, epileptic seizures during withdrawal, and mood disorders. To evaluate the correlation among serum homocysteine concentrations, craving, hazardous and harmful patterns of alcohol consumption in patients stabilized for withdrawal symptoms. Participants were adult outpatients accessed at the Addiction Treatment Unit. Alcoholism was assessed using the following tools: Mini-International Neuropsychiatric Interview Plus (MINI Plus), Alcohol Use Disorder Identification test (AUDIT), Visual Analogic Scale for craving (VAS). Furthermore, during the first visit a blood sample was taken from all patients to measure the plasma concentration of both homocysteine and Carboxy Deficient Transferrin (CDT). Differences between groups in socio-demographic and clinical characteristics were analyzed using the t-test and the Mann-Whitney's U test for normally and non-normally distributed data, respectively. Correlation between clinical scale scores and plasma concentration of homocysteine and CDT was evaluated using the Pearson's correlation coefficient and the Kendall's Tau-b bivariate correlation coefficient for normally and non-normally distributed data, respectively. Our study included 92 patients. No difference was found in socio-demographic characteristics between groups. The group with high homocysteine had higher prevalence of mood disorders (p correlation with both VAS score (p correlated with alcoholism in a bidirectional manner because its level appears to be related with alcohol degree, but simultaneously, hyperhomocysteinemia could enhance the alcohol consumption increasing the severity of craving in a circular self reinforcing mechanism. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  14. Readability versus Leveling.

    Fry, Edward

    2002-01-01

    Shows some similarities and differences between readability formulas and leveling procedures and reports some current large-scale uses of readability formulas. Presents a dictionary definition of readability and leveling, and a history and background of readability and leveling. Discusses what goes into determining readability and leveling scores.…

  15. STUDY OF SERUM HAPTOGLOBIN LEVEL AND ITS RELATION TO ERYTHROPOIETIC ACTIVITY IN BETA THALASSEMIA CHILDREN .

    Seham Ragab

    2015-02-01

    Full Text Available Background  :Serum haptoglobin (Hp is a reliable marker for hemolysis regardless the inflammatory state.  Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV infection and iron load in β-thalassemia children. Methods: Twenty  two β-thalassemia major (TM ,20 β-thalassemia  intermedia (TI children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp  and transferrin receptor  levels (sTfR  (by ELISA , alanine aminotransferase (ALT and  aspartate aminotransferase (AST  (by colorimetric method were assayed. Markers of hepatitis C virus  (HCV  were done by PCR. Results:  The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl , 8.6 ±0.72 (mg/dl  and 122  ± 18.5(mg/dl   for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001  with significant lower level in TM compared to TI  children ( P= 0.034  .Significant inverse correlations were  found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI as well as among HCV infected children. STfR   was the only significant independent predictor for  serum Hp level (t= -5.585 , P<0.0001 . Among  HCV infected patients , no significant correlation was found between serum Hp and serum transaminases  .Conclusion:  Serum Hp depletion in thalassemia had significant relation to disease severity and correlated   well with their erythropoietic activity, as assessed by the measurement of  sTfR without significant relation  HCV infection . Large sample  multicenter studies are  recommended.

  16. Data analysis at Level-1 Trigger level

    Wittmann, Johannes; Aradi, Gregor; Bergauer, Herbert; Jeitler, Manfred; Wulz, Claudia; Apanasevich, Leonard; Winer, Brian; Puigh, Darren Michael

    2017-01-01

    With ever increasing luminosity at the LHC, optimum online data selection is getting more and more important. While in the case of some experiments (LHCb and ALICE) this task is being completely transferred to computer farms, the others - ATLAS and CMS - will not be able to do this in the medium-term future for technological, detector-related reasons. Therefore, these experiments pursue the complementary approach of migrating more and more of the offline and High-Level Trigger intelligence into the trigger electronics. This paper illustrates how the Level-1 Trigger of the CMS experiment and in particular its concluding stage, the Global Trigger, take up this challenge.

  17. Serum erythropoietin level in anemic and non-anemic nephrotic children with normal kidney functions

    Moustafa, A.M.E.; Moawad, A.T.; Gad, A.A.; Ahmed, S.M.

    2005-01-01

    Nephrotic syndrome (NS) is associated with a significant alteration in protein metabolism. While lowering the concentration of certain proteins, the disease often raises the level of certain other proteins. The current study aimed to investigate the serum erythropoietin (EPO) levels in children with NS either anemic or non-anemic and to compare them to children with iron deficiency anemia (IDA) and healthy controls with normal hemoglobin level (NHB). Sixteen nephrotic children with anemia (NS-A) and 15 nephrotic children with normal hemoglobin level (NS-NHB) were examined and compared with 10 children with iron deficiency anemia (IDA) and 10 healthy controls (NHB). Circulating serum EPO levels, blood indices and iron status were measured in nephrotic patients with anemia (NS-A) and compared to those nephrotic patients with normal HE (NS-NHB). Most NS-A children were steroid resistant. The NS-A children showed greater EPO levels than those without anemia (21.01 ±4.02 mlU/ml versus 9.18 ± 0.79 mlU/ml; P < 0.001) but their response to treatment of anemia was inappropriately low when compared to IDA (EPO 96.9 ±4.9 mlU/ml) despite similar HB concentration. A significant positive correlation was observed between serum EPO and serum albumin in NS-A (r = 0.84, P < 0.001) and in NS-NHB group (r = 0.89, P < 0.001). Moreover, a significant positive correlation was observed between serum EPO and HB in the nephrotic groups indicating a blunted EPO response to anemia in NS-A (r 0.63, P < 0.05) and in NS-NHB group (r = 0.80, P < 0.001). In conclusion, anemia is a common feature of NS and is present even before the worsening of kidney function. Depletion of the iron stores due to loss of iron and transferrin in urine due to massive proteinurea may contribute to the development of anemia, but it was found that iron replacement was ineffective alone

  18. Low magnesium level

    Low magnesium level is a condition in which the amount of magnesium in the blood is lower than normal. The medical ... that convert or use energy ( metabolism ). When the level of magnesium in the body drops below normal, ...

  19. Beyond level planarity

    Angelini, P.; Da Lozzo, G.; Di Battista, G.; Frati, F.; Patrignani, M.; Rutter, I.; Hu, Y.; Nöllenburg, M.

    2016-01-01

    In this paper we settle the computational complexity of two open problems related to the extension of the notion of level planarity to surfaces different from the plane. Namely, we show that the problems of testing the existence of a level embedding of a level graph on the surface of the rolling

  20. Liquid metal level measurement

    Hale, J.C.; Leyland, K.S.

    1982-01-01

    A liquid metal level indicator is described which can be used to measure, in a stainless steel tank, the level of a nuclear reactor coolant such as sodium. The instrument, which is based on the eddy current induction effect, gives readings over substantially the full depth of the tank and indicates the sense of change of level. (U.K.)

  1. Screening for At-Risk Drinking in a Population Reporting Symptoms of Depression: A Validation of the AUDIT, AUDIT-C, and AUDIT-3.

    Levola, Jonna; Aalto, Mauri

    2015-07-01

    Excessive alcohol use is common in patients presenting with symptoms of depression. The aim of this study was to evaluate how the Alcohol Use Disorders Identification Test (AUDIT) and its most commonly used abbreviated versions perform in detecting at-risk drinking among subjects reporting symptoms of depression. A subsample (n = 390; 166 men, 224 women) of a general population survey, the National FINRISK 2007 Study, was used. Symptoms of depression were measured with the Beck Depression Inventory-Short Form and alcohol consumption with the Timeline Follow-back (TLFB). At-risk drinking was defined as ≥280 g weekly or ≥60 g on at least 1 occasion in the previous 28 days for men, 140 and 40 g, respectively, for women. The AUDIT, AUDIT-C, and AUDIT-3 were tested against the defined gold standard, that is, alcohol use calculated from the TLFB. An optimal cutoff was designated as having a sensitivity and specificity of over 0.75, with emphasis on specificity. The AUDIT and its abbreviations were compared with carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase. At-risk drinking was common. The AUDIT and AUDIT-C performed quite consistently. Optimal cutoffs for men were ≥9 for the AUDIT and ≥6 for AUDIT-C. The optimal cut-offs for women with mild symptoms of depression were ≥5 for the AUDIT and ≥4 for AUDIT-C. Optimal cutoffs could not be determined for women with moderate symptoms of depression (specificity AUDIT. The AUDIT-3 failed to perform in women, but in men, a good level of sensitivity and specificity was reached at a cutoff of ≥2. With standard threshold values, the biochemical markers demonstrated very low sensitivity (9 to 28%), but excellent specificity (83 to 98%). Screening for at-risk drinking among patients presenting with symptoms of depression using the full AUDIT is recommended, although the AUDIT-C performed almost equally well. Cut-offs should be adjusted according to gender, but not according to the severity

  2. Precision contact level gauge

    Krejci, M.; Pilat, M.; Stulik, P.

    1977-01-01

    Equipment was developed measuring the heavy water level in the TR-0 reactor core within an accuracy of several hundredths of a millimeter in a range of around 3.5 m and at a temperature of up to 90 degC. The equipment uses a vibrating needle contact as a high sensitivity level gauge and a servomechanical system with a motion screw carrying the gauge for monitoring and measuring the level in the desired range. The advantage of the unique level gauge consists in that that the transducer converts the measured level position to an electric signal, ie., pulse width, with high sensitivity and without hysteresis. (Kr)

  3. High-level verification

    Lerner, Sorin; Kundu, Sudipta

    2011-01-01

    Given the growing size and heterogeneity of Systems on Chip (SOC), the design process from initial specification to chip fabrication has become increasingly complex. This growing complexity provides incentive for designers to use high-level languages such as C, SystemC, and SystemVerilog for system-level design. While a major goal of these high-level languages is to enable verification at a higher level of abstraction, allowing early exploration of system-level designs, the focus so far for validation purposes has been on traditional testing techniques such as random testing and scenario-based

  4. Multi-Level Model

    Constanta Nicoleta BODEA

    2008-01-01

    Full Text Available Is an original paper, which contains a hierarchical model with three levels, for determining the linearized non-homogeneous and homogeneous credibility premiums at company level, at sector level and at contract level, founded on the relevant covariance relations between the risk premium, the observations and the weighted averages. We give a rather explicit description of the input data for the multi- level hierarchical model used, only to show that in practical situations, there will always be enough data to apply credibility theory to a real insurance portfolio.

  5. Sea level report

    Schwartz, M.L.

    1979-01-01

    Study of Cenozoic Era sea levels shows a continual lowering of sea level through the Tertiary Period. This overall drop in sea level accompanied the Pleistocene Epoch glacio-eustatic fluctuations. The considerable change of Pleistocene Epoch sea level is most directly attributable to the glacio-eustatic factor, with a time span of 10 5 years and an amplitude or range of approximately 200 m. The lowering of sea level since the end of the Cretaceous Period is attributed to subsidence and mid-ocean ridges. The maximum rate for sea level change is 4 cm/y. At present, mean sea level is rising at about 3 to 4 mm/y. Glacio-eustacy and tectono-eustacy are the parameters for predicting sea level changes in the next 1 my. Glacio-eustatic sea level changes may be projected on the basis of the Milankovitch Theory. Predictions about tectono-eustatic sea level changes, however, involve predictions about future tectonic activity and are therefore somewhat difficult to make. Coastal erosion and sedimentation are affected by changes in sea level. Erosion rates for soft sediments may be as much as 50 m/y. The maximum sedimentation accumulation rate is 20 m/100 y

  6. System level ESD protection

    Vashchenko, Vladislav

    2014-01-01

    This book addresses key aspects of analog integrated circuits and systems design related to system level electrostatic discharge (ESD) protection.  It is an invaluable reference for anyone developing systems-on-chip (SoC) and systems-on-package (SoP), integrated with system-level ESD protection. The book focuses on both the design of semiconductor integrated circuit (IC) components with embedded, on-chip system level protection and IC-system co-design. The readers will be enabled to bring the system level ESD protection solutions to the level of integrated circuits, thereby reducing or completely eliminating the need for additional, discrete components on the printed circuit board (PCB) and meeting system-level ESD requirements. The authors take a systematic approach, based on IC-system ESD protection co-design. A detailed description of the available IC-level ESD testing methods is provided, together with a discussion of the correlation between IC-level and system-level ESD testing methods. The IC-level ESD...

  7. Gamma spectrometry; level schemes

    Blachot, J.; Bocquet, J.P.; Monnand, E.; Schussler, F.

    1977-01-01

    The research presented dealt with: a new beta emitter, isomer of 131 Sn; the 136 I levels fed through the radioactive decay of 136 Te (20.9s); the A=145 chain (β decay of Ba, La and Ce, and level schemes for 145 La, 145 Ce, 145 Pr); the A=47 chain (La and Ce, β decay, and the level schemes of 147 Ce and 147 Pr) [fr

  8. Nuclear Level Densities

    Grimes, S.M.

    2005-01-01

    Recent research in the area of nuclear level densities is reviewed. The current interest in nuclear astrophysics and in structure of nuclei off of the line of stability has led to the development of radioactive beam facilities with larger machines currently being planned. Nuclear level densities for the systems used to produce the radioactive beams influence substantially the production rates of these beams. The modification of level-density parameters near the drip lines would also affect nucleosynthesis rates and abundances

  9. Levels of safety

    Povyakalo, A.A.

    1996-01-01

    When speaking about danger of catastrophe, it is the first level of danger. Its absence is the first level of safety. When speaking about danger of danger of catastrophe, it is the second level of danger. Its absence is the second level of safety. The paper proposes the way to formalize these ideas and use formal models to construct the states-and-event scale for a given object. The proposed approach can be applied to objects of different nature. The states-and-events scale may be used for transformation of initial objectives state-and-transitions graph to reduce bad classes of states

  10. Tiltmeter leveling mechanism

    Hunter, Steven L.; Boro, Carl O.; Farris, Alvis

    2002-01-01

    A tiltmeter device having a pair of orthogonally disposed tilt sensors that are levelable within an inner housing containing the sensors. An outer housing can be rotated to level at least one of the sensor pair while the inner housing can be rotated to level the other sensor of the pair. The sensors are typically rotated up to about plus or minus 100 degrees. The device is effective for measuring tilts in a wide range of angles of inclination of wells and can be employed to level a platform containing a third sensor.

  11. Standard Industry Fare Level

    Department of Transportation — Standard Industry Fare Level was establish after airline deregulation to serve as the standard against which a statutory zone of operating expense reasonableness was...

  12. PEP liquid level system

    Lauritzen, T.; Sah, R.C.

    1981-03-01

    A liquid level system has been installed in the accelerator housing of the PEP storage ring. This instrument spans the entire 2.2 km circumference of the PEP project, and over one hundred readouts provide reference elevations which are used for the accurate alignment of accelerator components. The liquid level has proven to be extremely precise (+-0.10 mm) and quick to use, and it has contributed to the accurate alignment of PEP before beam turn-on. Since the liquid level readouts are rigidly attached to the accelerator housing, the liquid level has been a convenient means to monitor the settling of the accelerator housing

  13. Reference handbook: Level detectors

    1990-01-01

    The purpose of this handbook is to provide Rocky Flats personnel with the information necessary to understand level measurement and detection. Upon completion of this handbook you should be able to do the following: List three reasons for measuring level. Describe the basic operating principles of the sight glass. Demonstrate proper techniques for reading a sight glass. Describe the basic operating principles of a float level detector. Describe the basic operating principles of a bubbler level indicating system. Explain the differences between a wet and dry reference leg indicating system, and describe how each functions. This handbook is designed for use by experienced Rocky Flats operators to reinforce and improve their current knowledge level, and by entry-level operators to ensure that they possess a minimum level of fundamental knowledge. Level Detectors is applicable to many job classifications and can be used as a reference for classroom work or for self-study. Although this reference handbook is by no means all-encompassing, you will gain enough information about this subject area to assist you in contributing to the safe operation of Rocky Flats Plant

  14. Authentication Assurance Levels

    Kouzes, Richard T.; Cash, James R.; Devaney, David M.; Geelhood, Bruce D.; Hansen, Randy R.; Melton, Ronald B.; Pitts, W. Karl

    2002-01-01

    This Common Criteria approach has been applied to create a definition of Authentication Assurance Levels that can quantify the level of assurance reached for a system subject to a set of authentication procedures. The arms-control authentication application of the Common Criteria expands on more typical information security evaluations in that it must contend with information barriers and preclude sophisticated intentional subversion attempts.

  15. Raised IL-6 Levels

    user

    Cardiovascular Associated Complications in HIV. Positive Zambians before ... compare plasma levels of IL-6 in HIV positive and. HIV negative .... cancer. Results from this study showed that IL-6 levels in. HIV positive ART naive individuals were significantly higher than in the HIV positive individuals on ART. Our findings ...

  16. Low level waste repositories

    Hill, P.R.H.; Wilson, M.A.

    1983-11-01

    Factors in selecting a site for low-level radioactive waste disposal are discussed. South Australia has used a former tailings dam in a remote, arid location as a llw repository. There are also low-level waste disposal procedures at the Olympic Dam copper/uranium project

  17. Definition of Virtual Levels.

    Shore, Bruce W.

    1979-01-01

    Presents an examination of graphical displays of solutions to time-dependent Schrodinger equation modeling a laser-excited three-level atom. It suggests that an energy level may be regarded as virtual when it is detuned from resonance by more than two Rabi frequencies. (Author/HM)

  18. Levels of Literary Meaning

    Klausen, Søren Harnow

    2017-01-01

    I argue that intentionalist theories of meaning and interpretation, like those of Hirsch and Juhl, have been insufficiently attentive to the different levels of authorial intention that are operative in literary works. By countenancing intentions on different levels – ranging from simple semantic...

  19. Arctic Sea Level Reconstruction

    Svendsen, Peter Limkilde

    Reconstruction of historical Arctic sea level is very difficult due to the limited coverage and quality of tide gauge and altimetry data in the area. This thesis addresses many of these issues, and discusses strategies to help achieve a stable and plausible reconstruction of Arctic sea level from...... 1950 to today.The primary record of historical sea level, on the order of several decades to a few centuries, is tide gauges. Tide gauge records from around the world are collected in the Permanent Service for Mean Sea Level (PSMSL) database, and includes data along the Arctic coasts. A reasonable...... amount of data is available along the Norwegian and Russian coasts since 1950, and most published research on Arctic sea level extends cautiously from these areas. Very little tide gauge data is available elsewhere in the Arctic, and records of a length of several decades,as generally recommended for sea...

  20. A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

    Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

    2018-05-10

    The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

  1. Contemporary Arctic Sea Level

    Cazenave, A. A.

    2017-12-01

    During recent decades, the Arctic region has warmed at a rate about twice the rest of the globe. Sea ice melting is increasing and the Greenland ice sheet is losing mass at an accelerated rate. Arctic warming, decrease in the sea ice cover and fresh water input to the Arctic ocean may eventually impact the Arctic sea level. In this presentation, we review our current knowledge of contemporary Arctic sea level changes. Until the beginning of the 1990s, Arctic sea level variations were essentially deduced from tide gauges located along the Russian and Norwegian coastlines. Since then, high inclination satellite altimetry missions have allowed measuring sea level over a large portion of the Arctic Ocean (up to 80 degree north). Measuring sea level in the Arctic by satellite altimetry is challenging because the presence of sea ice cover limits the full capacity of this technique. However adapted processing of raw altimetric measurements significantly increases the number of valid data, hence the data coverage, from which regional sea level variations can be extracted. Over the altimetry era, positive trend patterns are observed over the Beaufort Gyre and along the east coast of Greenland, while negative trends are reported along the Siberian shelf. On average over the Arctic region covered by satellite altimetry, the rate of sea level rise since 1992 is slightly less than the global mea sea level rate (of about 3 mm per year). On the other hand, the interannual variability is quite significant. Space gravimetry data from the GRACE mission and ocean reanalyses provide information on the mass and steric contributions to sea level, hence on the sea level budget. Budget studies show that regional sea level trends over the Beaufort Gyre and along the eastern coast of Greenland, are essentially due to salinity changes. However, in terms of regional average, the net steric component contributes little to the observed sea level trend. The sea level budget in the Arctic

  2. Nuclear level density

    Cardoso Junior, J.L.

    1982-10-01

    Experimental data show that the number of nuclear states increases rapidly with increasing excitation energy. The properties of highly excited nuclei are important for many nuclear reactions, mainly those that go via processes of the compound nucleus type. In this case, it is sufficient to know the statistical properties of the nuclear levels. First of them is the function of nuclear levels density. Several theoretical models which describe the level density are presented. The statistical mechanics and a quantum mechanics formalisms as well as semi-empirical results are analysed and discussed. (Author) [pt

  3. Measuring Your Fitness Level

    ... online calculator. If you'd rather do the math yourself, divide your weight in pounds by your ... Human Services recommends one of the following activity levels for adult fitness and health benefits: 150 minutes ...

  4. Three Levels of Semiosis

    Alrøe, Hugo Fjelsted

    2016-01-01

    This paper presents a second-order semiotic framework for ontological levels, which is based on the structure of semiosis in a more fundamental way than other existing approaches to semiotic levels. Building on the key semiotic concept of representation, three levels are posited: (1) non- or proto......-semiotic processes, without representation, such as physical or causal processes, (2) semiotic processes, with representation, such as the processes of life and cognition, and (3) second-order semiotic processes, with representation of representation, such as self-conscious and self-reflexive communicative processes....... This semiotic framework for ontological levels is compared with recent discussions of different ontological kinds of kinds such as indifferent and interactive kinds. This leads to the distinction between not two, but three kinds of kinds: indifferent, adaptive and reflexive kinds, of which the last two hitherto...

  5. Water Level Station History

    National Oceanic and Atmospheric Administration, Department of Commerce — Images contain station history information for 175 stations in the National Water Level Observation Network (NWLON). The NWLON is a network of long-term,...

  6. Projecting future sea level

    Cayan, Daniel R.; Bromirski, Peter; Hayhoe, Katharine; Tyree, Mary; Dettinger, Mike; Flick, Reinhard

    2006-01-01

    California’s coastal observations and global model projections indicate that California’s open coast and estuaries will experience increasing sea levels over the next century. Sea level rise has affected much of the coast of California, including the Southern California coast, the Central California open coast, and the San Francisco Bay and upper estuary. These trends, quantified from a small set of California tide gages, have ranged from 10–20 centimeters (cm) (3.9–7.9 inches) per century, quite similar to that estimated for global mean sea level. So far, there is little evidence that the rate of rise has accelerated, and the rate of rise at California tide gages has actually flattened since 1980, but projections suggest substantial sea level rise may occur over the next century. Climate change simulations project a substantial rate of global sea level rise over the next century due to thermal expansion as the oceans warm and runoff from melting land-based snow and ice accelerates. Sea level rise projected from the models increases with the amount of warming. Relative to sea levels in 2000, by the 2070–2099 period, sea level rise projections range from 11–54 cm (4.3–21 in) for simulations following the lower (B1) greenhouse gas (GHG) emissions scenario, from 14–61 cm (5.5–24 in) for the middle-upper (A2) emission scenario, and from 17–72 cm (6.7–28 in) for the highest (A1fi) scenario. In addition to relatively steady secular trends, sea levels along the California coast undergo shorter period variability above or below predicted tide levels and changes associated with long-term trends. These variations are caused by weather events and by seasonal to decadal climate fluctuations over the Pacific Ocean that in turn affect the Pacific coast. Highest coastal sea levels have occurred when winter storms and Pacific climate disturbances, such as El Niño, have coincided with high astronomical tides. This study considers a range of projected future

  7. High potassium level

    ... level is very high, or if you have danger signs, such as changes in an ECG . Emergency ... Seifter JL. Potassium disorders. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  8. Technology Readiness Level Guidebook

    2017-09-01

    This guidebook provides the necessary information for conducting a Technology Readiness Level (TRL) Assessment. TRL Assessments are a tool for determining the maturity of technologies and identifying next steps in the research process. This guidebook...

  9. Low potassium level

    ... treat and prevent low level of potassium. These foods include: Avocados Baked potato Bananas Bran Carrots Cooked lean beef Milk Oranges Peanut butter Peas and beans Salmon Seaweed Spinach Tomatoes Wheat germ

  10. Low level waste disposal

    Barthoux, A.

    1985-01-01

    Final disposal of low level wastes has been carried out for 15 years on the shallow land disposal of the Manche in the north west of France. Final participant in the nuclear energy cycle, ANDRA has set up a new waste management system from the production center (organization of the waste collection) to the disposal site including the setting up of a transport network, the development of assessment, additional conditioning, interim storage, the management of the disposal center, records of the location and characteristics of the disposed wastes, site selection surveys for future disposals and a public information Department. 80 000 waste packages representing a volume of 20 000 m 3 are thus managed and disposed of each year on the shallow land disposal. The disposal of low level wastes is carried out according to their category and activity level: - in tumuli for very low level wastes, - in monoliths, a concrete structure, of the packaging does not provide enough protection against radioactivity [fr

  11. Lead levels - blood

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  12. Lake Level Reconstructions

    National Oceanic and Atmospheric Administration, Department of Commerce — Records of past lake levels, mostly related to changes in moisture balance (evaporation-precipitation). Parameter keywords describe what was measured in this data...

  13. Liquid level controller

    Mangus, J.D.; Redding, A.H.

    1975-01-01

    A system for maintaining two distinct sodium levels within the shell of a heat exchanger having a plurality of J-shaped modular tube bundles each enclosed in a separate shell which extends from a common base portion. A lower liquid level is maintained in the base portion and an upper liquid level is maintained in the shell enwrapping the long stem of the J-shaped tube bundles by utilizing standpipes with a notch at the lower end which decreases in open area the distance from the end of the stand pipe increases and a supply of inert gas fed at a constant rate to produce liquid levels, which will remain generally constant as the flow of liquid through the vessel varies

  14. Fission level densities

    Maslov, V.M.

    1998-01-01

    Fission level densities (or fissioning nucleus level densities at fission saddle deformations) are required for statistical model calculations of actinide fission cross sections. Back-shifted Fermi-Gas Model, Constant Temperature Model and Generalized Superfluid Model (GSM) are widely used for the description of level densities at stable deformations. These models provide approximately identical level density description at excitations close to the neutron binding energy. It is at low excitation energies that they are discrepant, while this energy region is crucial for fission cross section calculations. A drawback of back-shifted Fermi gas model and traditional constant temperature model approaches is that it is difficult to include in a consistent way pair correlations, collective effects and shell effects. Pair, shell and collective properties of nucleus do not reduce just to the renormalization of level density parameter a, but influence the energy dependence of level densities. These effects turn out to be important because they seem to depend upon deformation of either equilibrium or saddle-point. These effects are easily introduced within GSM approach. Fission barriers are another key ingredients involved in the fission cross section calculations. Fission level density and barrier parameters are strongly interdependent. This is the reason for including fission barrier parameters along with the fission level densities in the Starter File. The recommended file is maslov.dat - fission barrier parameters. Recent version of actinide fission barrier data obtained in Obninsk (obninsk.dat) should only be considered as a guide for selection of initial parameters. These data are included in the Starter File, together with the fission barrier parameters recommended by CNDC (beijing.dat), for completeness. (author)

  15. Changing Sea Levels

    Pugh, David

    2004-04-01

    Flooding of coastal communities is one of the major causes of environmental disasters world-wide. This textbook explains how sea levels are affected by astronomical tides, weather effects, ocean circulation and climate trends. Based on courses taught by the author in the U.K. and the U.S., it is aimed at undergraduate students at all levels, with non-basic mathematics being confined to Appendices and a website http://publishing.cambridge.org/resources/0521532183/.

  16. Float level indicator

    Grishchuk, M.Kh.; Laptev, A.G.; Pashkov, V.A.

    1980-01-01

    Specially developed level indicator is suggested with differential to-transformer converter of the float motion, operating in line with a movable electronic block, intended for indicating the level of the dissociating nitrogen tetroxide liquid phase. On the basis of the indicator elements the device is realized to measure the time of calibrated volume fillino. in by liquid nitrogen tetroxide in steady state operation of the experimental bench-marks [ru

  17. Contemporary sea level rise.

    Cazenave, Anny; Llovel, William

    2010-01-01

    Measuring sea level change and understanding its causes has considerably improved in the recent years, essentially because new in situ and remote sensing observations have become available. Here we report on most recent results on contemporary sea level rise. We first present sea level observations from tide gauges over the twentieth century and from satellite altimetry since the early 1990s. We next discuss the most recent progress made in quantifying the processes causing sea level change on timescales ranging from years to decades, i.e., thermal expansion of the oceans, land ice mass loss, and land water-storage change. We show that for the 1993-2007 time span, the sum of climate-related contributions (2.85 +/- 0.35 mm year(-1)) is only slightly less than altimetry-based sea level rise (3.3 +/- 0.4 mm year(-1)): approximately 30% of the observed rate of rise is due to ocean thermal expansion and approximately 55% results from land ice melt. Recent acceleration in glacier melting and ice mass loss from the ice sheets increases the latter contribution up to 80% for the past five years. We also review the main causes of regional variability in sea level trends: The dominant contribution results from nonuniform changes in ocean thermal expansion.

  18. Water level indicator

    Murase, Michio; Araki, Hidefumi.

    1996-01-01

    A difference of pressure between a standard pressure conduit in communication with a gas phase of a reactor pressure vessel and a water level pressure conduit in communication with a liquid phase of the pressure vessel is detected by a pressure difference gage. A communication pipe and a standard level vessel are disposed between the pressure vessel and the standard pressure conduit, and a standard liquid surface on the side of the standard pressure conduit is formed in the standard level vessel. A gas releaser is disposed to the gas phase portion of the standard level vessel. The gas releaser equipment is constituted by a porous material, a permeation membrane and a gas exhaustion hole. The gas phase of the standard level vessel is divided by a partition plate into a first gas phase being in contact with a connection portion with the communication pipe and a second gas phase in contact with the gas releaser. A gas flow channel hole and a condensate descending hole are disposed to the partition plate. Since incondensible gases accumulated to the standard level vessel are effectively exhausted, the incondensible gases are prevented from being dissolved into liquid. (I.N.)

  19. 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.

    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.

  20. Transmutations across hierarchical levels

    O'Neill, R.V.

    1977-01-01

    The development of large-scale ecological models depends implicitly on a concept known as hierarchy theory which views biological systems in a series of hierarchical levels (i.e., organism, population, trophic level, ecosystem). The theory states that an explanation of a biological phenomenon is provided when it is shown to be the consequence of the activities of the system's components, which are themselves systems in the next lower level of the hierarchy. Thus, the behavior of a population is explained by the behavior of the organisms in the population. The initial step in any modeling project is, therefore, to identify the system components and the interactions between them. A series of examples of transmutations in aquatic and terrestrial ecosystems are presented to show how and why changes occur. The types of changes are summarized and possible implications of transmutation for hierarchy theory, for the modeler, and for the ecological theoretician are discussed

  1. Optimal Levels of Embeddedness

    Andersen, Kristina Vaarst

    Co-location of industry professionals often leads to development of collaboration networks, and multiple studies have emphasized the benefits of embedded collaboration. Due to higher levels of trust, embedded collaboration reduces transaction costs and facilitates ready knowledge exchanged. Other...... on regional level data on co-location of knowledge workers, workplaces, and cultural amenities. Two papers build on individual level data from the Danish film industry. The first paper analyses why the importance of co-location differs between groups of knowledge workers and aim to explain centralization...... in localized collaboration networks is so essential, it affects location choices. The second paper challenges the proposition of embeddedness as an absolute term through an analysis of costs and benefits of embeddedness in an industry network. The results show that the association between embeddedness...

  2. Caribbean Sea Level Network

    von Hillebrandt-Andrade, C.; Crespo Jones, H.

    2012-12-01

    Over the past 500 years almost 100 tsunamis have been observed in the Caribbean and Western Atlantic, with at least 3510 people having lost their lives to this hazard since 1842. Furthermore, with the dramatic increase in population and infrastructure along the Caribbean coasts, today, millions of coastal residents, workers and visitors are vulnerable to tsunamis. The UNESCO IOC Intergovernmental Coordination Group for Tsunamis and other Coastal Hazards for the Caribbean and Adjacent Regions (CARIBE EWS) was established in 2005 to coordinate and advance the regional tsunami warning system. The CARIBE EWS focuses on four areas/working groups: (1) Monitoring and Warning, (2) Hazard and Risk Assessment, (3) Communication and (4) Education, Preparedness and Readiness. The sea level monitoring component is under Working Group 1. Although in the current system, it's the seismic data and information that generate the initial tsunami bulletins, it is the data from deep ocean buoys (DARTS) and the coastal sea level gauges that are critical for the actual detection and forecasting of tsunamis impact. Despite multiple efforts and investments in the installation of sea level stations in the region, in 2004 there were only a handful of sea level stations operational in the region (Puerto Rico, US Virgin Islands, Bermuda, Bahamas). Over the past 5 years there has been a steady increase in the number of stations operating in the Caribbean region. As of mid 2012 there were 7 DARTS and 37 coastal gauges with additional ones being installed or funded. In order to reach the goal of 100 operational coastal sea level stations in the Caribbean, the CARIBE EWS recognizes also the importance of maintaining the current stations. For this, a trained workforce in the region for the installation, operation and data analysis and quality control is considered to be critical. Since 2008, three training courses have been offered to the sea level station operators and data analysts. Other

  3. Seismic Level 2 PSA

    Dirksen, Gerben; Pellissetti, Manuel; Duncan-Whiteman, Paul

    2014-01-01

    For most external events, the calculation of the core damage frequency (CDF) in Level 1 PSA is sufficient to be able to show that the contribution of the event to the plant risk is negligible. However, it is not sufficient to compare the CDF due to the external event to the total plant CDF; instead the Level 1 PSA result for the event should be compared to the large early release frequency (LERF), or alternatively arguments should be given why the CDF from the external event will not contribute mostly to LERF. For seismic events in particular, it can often not be easily excluded that sequences leading to core damage would not also result in LERF. Since the confinement function is one of the most essential functions for Level 2 PSA, special care must be taken of the containment penetrations. For example systems with containment penetrations that are normally closed during operation or are designed to withstand more than the maximum containment pressure are normally screened out in the Level 2 PSA for the containment isolation function, however the possibility of LOCA in such systems due to an earthquake may nevertheless lead to containment bypass. Additionally, the functionality of passive features may be compromised in case of a beyond design earthquake. In the present paper, we present crucial ingredients of a methodology for a Level 2 seismic PSA. This methodology consists of the following steps: Extension of the seismic equipment list (SEL) to include Level 2 PSA relevant systems (e.g. containment isolation system, features for core melt stabilization, hydrogen mitigation systems), Determination of the systems within the existing SEL with increased demands in case of severe accidents, Determination of essential components for which a dedicated fragility analysis needs to be performed. (author)

  4. Street level society

    Vinum, Christine; Nissen, Morten

    2006-01-01

    This paper aims to reflect on research findings from different empirical studies of social work with young drug users and socially excluded young people in Copenhagen. In the paper we account for historical changes in social policy and interventions into young people's drug taking in Copenhagen......, and partly from the decentralizing and specializing efforts characteristic of the Danish welfare state and its institutions. We discuss a general turn towards street level interventions to address the problems of social exclusion, as well as different attempts to create what we term street level heterotopias...

  5. Level width broadening effect

    Zhang Jingshang

    2003-01-01

    In file-6 for double-differential cross sections, the level width broadening effect should be taken into account properly due to Heisenberg' uncertainty. Besides level width broadening effect, the energy resolution in the measurements is also needed in fitting measurement procedure. In general, the traditional normal Gaussian expansion is employed. However, to do so in this way the energy balance could not be held. For this reason, the deformed Gaussian expansion functions with exponential form for both the single energy point and continuous spectrum are introduced, with which the normalization and energy balance conditions could be held exactly in the analytical form. (author)

  6. Middle Level Learning.

    Wyman, Richard M., Jr.; Young, Katherine A.; Sliger, Bruce; Kafi, Patricia; Singer, Alan; Lamme, Linda Leonard

    1998-01-01

    Presents five brief articles related to middle-level learning. The articles are, "Using Children's Diaries to Teach the Oregon Trail"; "Living the Geography of Joseph and Temperance Brown"; "The ABCs of Small Grant Acquisition for Social Studies"; "Isomo Loruko: The Yoruba Naming Ceremony"; and "Child…

  7. New level of structure

    Greenberg, O.W.

    1985-01-01

    In the standard model of matter, ther are five stages of compositeness- molecules, atoms, nuclei, nucleons, and quarks and leptons-but we are beginning to see regularities at the fifth layer that may point to a deeper, sixth level of structure

  8. Reliability and code level

    Kasperski, M.; Geurts, C.P.W.

    2005-01-01

    The paper describes the work of the IAWE Working Group WBG - Reliability and Code Level, one of the International Codification Working Groups set up at ICWE10 in Copenhagen. The following topics are covered: sources of uncertainties in the design wind load, appropriate design target values for the

  9. Organotin levels in seafood

    Belfroid, A.C.; Purperhart, M.; Ariese, F.

    2000-01-01

    Tolerable average residue levels (TARL) for tributylin (TBT) in seafood products were calculated based on the tolerable daily intake (TDI) of TBT and the seafood consumption of the average consumer in various countries. Data from the literature show that these TARLs in seafood are exceeded in one or

  10. 55Co level properties

    Lodin, G.; Nilsson, L.; Erlandsson, B.; Lyttkens, J.

    1975-01-01

    The decay pf low-lying levels in 55 Co has been studied by means of the 54 Fe(d,nγ) 55 Co reaction. Neutron energies were determined by time-of-flight techniques using a pulsed incident beam and a large liquid scintillator. Gamma rays in coincidence with neutrons were detected by a Ge(Li)spectrometer, Three levels at 4720.8+-0.6, 4747.1+-0.6 and 5172.4+-0.6 keV were strongly populated. The 4720 and 5172 keV levels have earlier been identified as the isobaric analogues of the 55 Fe ground state and first excited state. On the basis of a comparison of the present results with previous particle-transfer reaction studies it is suggested that the ground state analogue is split into the 4720 and 4747 keV levels. A study of excitation functions of 54 Fe(d,n)transitions at incident deuteron energies between 5.0 and 6.0 MeV show that the spectroscopic strengths obtained from (d,n) experiments in this mass region at these energies depend strongly on the incident energy. (Auth.)

  11. Implementing Modular A Levels.

    Holding, Gordon

    This document, which is designed for curriculum managers at British further education (FE) colleges, presents basic information on the implementation and perceived benefits of the General Certificate of Education (GCE) modular A (Advanced) levels. The information was synthesized from a survey of 12 FE colleges that introduced the modular A levels…

  12. Levels of valence

    Vera eShuman

    2013-05-01

    Full Text Available The distinction between the positive and the negative is fundamental in our emotional life. In appraisal theories, in particular in the component process model of emotion (Scherer, 1984, 2010, qualitatively different types of valence are proposed based on appraisals of (unpleasantness, goal obstructiveness/conduciveness, low or high power, self- (incongruence, and moral badness/goodness. This multifaceted conceptualization of valence is highly compatible with the frequent observation of mixed feelings in real life. However, it seems to contradict the one-dimensional conceptualization of valence often encountered in psychological theories, and the notion of valence as a common currency used to explain choice behavior. Here, we propose a framework to integrate the seemingly disparate conceptualizations of multifaceted valence and one-dimensional valence by suggesting that valence should be conceived at different levels, micro and macro. Micro-valences correspond to qualitatively different types of evaluations, potentially resulting in mixed feelings, whereas one-dimensional macro-valence corresponds to an integrative common currency to compare alternatives for choices. We propose that conceptualizing levels of valence may focus research attention on the mechanisms that relate valence at one level (micro to valence at another level (macro, leading to new hypotheses and addressing various concerns that have been raised about the valence concept, such as the valence-emotion relation.

  13. Levels of Valence

    Shuman, Vera; Sander, David; Scherer, Klaus R.

    2013-01-01

    The distinction between the positive and the negative is fundamental in our emotional life. In appraisal theories, in particular in the component process model of emotion (Scherer, 1984, 2010), qualitatively different types of valence are proposed based on appraisals of (un)pleasantness, goal obstructiveness/conduciveness, low or high power, self-(in)congruence, and moral badness/goodness. This multifaceted conceptualization of valence is highly compatible with the frequent observation of mixed feelings in real life. However, it seems to contradict the one-dimensional conceptualization of valence often encountered in psychological theories, and the notion of valence as a common currency used to explain choice behavior. Here, we propose a framework to integrate the seemingly disparate conceptualizations of multifaceted valence and one-dimensional valence by suggesting that valence should be conceived at different levels, micro and macro. Micro-valences correspond to qualitatively different types of evaluations, potentially resulting in mixed feelings, whereas one-dimensional macro-valence corresponds to an integrative “common currency” to compare alternatives for choices. We propose that conceptualizing levels of valence may focus research attention on the mechanisms that relate valence at one level (micro) to valence at another level (macro), leading to new hypotheses, and addressing various concerns that have been raised about the valence concept, such as the valence-emotion relation. PMID:23717292

  14. Higher-level Innovization

    Bandaru, Sunith; Tutum, Cem Celal; Deb, Kalyanmoy

    2011-01-01

    we introduce the higher-level innovization task through an application of a manufacturing process simulation for the Friction Stir Welding (FSW) process where commonalities among two different Pareto-optimal fronts are analyzed. Multiple design rules are simultaneously deciphered from each front...

  15. Guideline level-3 PSA

    Roelofsen, P.M.; Van der Steen, J.

    1993-09-01

    For several applications of radioactive materials calculations must be executed to determine the radiation risk for the population. A guideline for the risk calculation method of two main sources: nuclear power plants, and other intended and unintended activities with radioactive materials, is given. The standards, recommendations and regulations in this report concern mainly the analysis of the radiological (external) consequences of nuclear power plant accidents, classified as level-3 PSA (Probabilistic Safety Analysis). Level-3 PSA falls within the scales 5-7 of the International Nuclear Event Scale (INES). The standards, etc., focus on the risks for groups of people and the so-called maximum individual risk. In chapter two the standards and regulations are formulated for each part of level-3 PSA: the source term spectrum, atmospheric distribution and deposition, exposure to radiation doses and calculation of radiation doses, dose-response relationships, measures to reduce the effect of radiation doses, design basis accidents, and finally uncertainty analysis. In chapter four, modelled descriptions are given of the standards and regulations, which could or should be used in a calculation program in case of level-3 PSA. In chapter three the practical execution of a probabilistic consequences analysis, the collection of input data and the presentation of the results are dealt with. 2 figs., 14 tabs., 64 refs

  16. General Algorithm (High level)

    First page Back Continue Last page Overview Graphics. General Algorithm (High level). Iteratively. Use Tightness Property to remove points of P1,..,Pi. Use random sampling to get a Random Sample (of enough points) from the next largest cluster, Pi+1. Use the Random Sampling Procedure to approximate ci+1 using the ...

  17. Liquid level detector

    Dean, A.P.; Pendleton, J.R.

    1982-01-01

    A device is described for locating the level of the liquid metal in a sodium cooled nuclear reactor by using a movable probe equipped to signal a phase change with null on arrival at the interface between two conductively differing media. (U.K.)

  18. Low-level effects

    Devine, R.T.; Chaput, R.L.

    1987-01-01

    Risk assignments can be made to given practices involving exposure to radiation, because sufficient data are available for the effects of high-dose, low-LET radiation and because sufficient exists in the methods of extrapolation to low doses and low dose rates. The confidence in the extrapolations is based on the fact that the risk is not expected to be overestimated, using the assumptions made (as opposed to the possibility that the extrapolations represent an accurate estimate of the risk). These risk estimates have been applied to the selection of permissible exposure levels, to show that various amounts of radiation involve no greater risk to the worker than the risk expected in another industry that is generally considered safe. The setting of standards for protection from exposure to low levels of ionizing radiation is made by expert committees at the national and international levels who weigh social factors as well as scientific factors. Data on low-level effects may be applied when assigning a ''probability of causation'' to a certain exposure of radiation. This has become a prominent method for arriving at an equitable award for damages caused by such exposure. The generation of these tables requires as many (if not more) social and political considerations as does the setting up of protection criteria. It is impossible to extract a purely scientific conclusion solely from the protection standards and other legal decisions. Sufficient information exists on low-LET radiation that safety standards for exposure can be rationally (if not scientifically) agreed upon

  19. Low-level radiation

    Myers, D.K.

    1982-05-01

    It is known that the normal incidence of cancer in human populations is increased by exposure to moderately high doses of ionizing radiation. At background radiation levels or at radiation levels which are 100 times greater, the potential health risks are considered to be directly proportional to the total accumulated dose of radiation. Some of the uncertainties associated with this assumption and with the accepted risk estimates have been critically reviewed in this document. The general scientific consensus at present suggests that the accepted risk estimates may exaggerate the actual risk of low levels of sparsely ionizing radiations (beta-, gamma- or X-rays) somewhat but are unlikely to overestimate the actual risks of densely ionizing radiations (fast neutrons, alpha-particles). At the maximum permissible levels of exposure for radiation workers in nuclear power stations, the potential health hazards in terms of life expectancy would be comparable to those encountered in transportation and public utilities or in the construction industry. At the average radiation exposures received by these workers in practice, the potential health hazards are similar to those associated with safe categories of industries. Uranium mining remains a relativly hazardous occupation. In terms of absolute numbers, the genetic hazards, which are less well established, are thought to be smaller than the carcinogenic hazards of radiation when only the first generation is considered but to be of the same order of magnitude as the carcinogenic hazards when the total number of induced genetic disorders is summed over all generations

  20. Levels of Literacy.

    Nettle, Keith

    Democracy in western countries now depends on literacy at every level: censuses by which governments can plan for the future; elections which are the cornerstone of democratic choice; local meetings which have agendas and minutes--the whole apparatus of social living is organized and recorded through literacy. This paper is concerned with how…

  1. Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure.

    Andrew D Govus

    Full Text Available To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass and iron parameters after 2-4 weeks of moderate altitude exposure.Hematological data collected from 178 athletes (98 males, 80 females exposed to moderate altitude (1,350-3,000 m were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII and blood iron parameters [ferritin and transferrin saturation (TSAT].Altitude exposure (mean ± s: 21 ± 3 days increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d = -2.87 [-3.88, -1.66].Oral iron supplementation during 2-4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores.

  2. Transferin concentration and location during formation of chick retina: developmental correlates

    Zeevalk, G.D.; Hyndman, A.G.

    1988-01-01

    The amount of transferrin in chick retina was measured during development and compared to transferrin location seen immunocytochemically. Between embryonic day 6 (E6), and 5 days post hatching, two periods occur in which transferrin concentrations rise sharply and decline. During the first, transferrin concentration rises 5-fold between E6 and 10, then rapidly declines by E14. A second increase begins on E17 and peaks by E19-20. Immunocytochemical findings demonstrate that during the first rise in concentration, transferrin is located primarily in neuritic layers. Later in development, when levels again increase, newly forming photoreceptor outer segments are strongly transferrin positive. These findings are discussed in light of developmental events occurring during retinal maturation (author)

  3. Identification of platform levels

    Mortensen, Niels Henrik

    2005-01-01

    reduction, ability to launch a wider product portfolio without increasing resources and reduction of complexity within the whole company. To support the multiple product development process, platform based product development has in many companies such as Philips, VW, Ford etc. proven to be a very effective...... product development in one step and therefore the objective of this paper is to identify levels of platform based product development. The structure of this paper is as follows. First the applied terminology for platforms will be briefly explained and then characteristics between single and multi product...... development will be examined. Based on the identification of the above characteristics five platform levels are described. The research presented in this paper is a result of MSc, Ph.D projects at the Technical University of Denmark and consultancy projects within the organisation of Institute of Product...

  4. Tree-level formalism

    Brandhuber, Andreas; Spence, Bill; Travaglini, Gabriele

    2011-01-01

    We review two novel techniques used to calculate tree-level scattering amplitudes efficiently: MHV diagrams, and on-shell recursion relations. For the MHV diagrams, we consider applications to tree-level amplitudes and focus in particular on the N=4 supersymmetric formulation. We also briefly describe the derivation of loop amplitudes using MHV diagrams. For the recursion relations, after presenting their general proof, we discuss several applications to massless theories with and without supersymmetry, to theories with massive particles, and to graviton amplitudes in general relativity. This article is an invited review for a special issue of Journal of Physics A: Mathematical and Theoretical devoted to 'Scattering amplitudes in gauge theories'. (review)

  5. High level nuclear wastes

    Lopez Perez, B.

    1987-01-01

    The transformations involved in the nuclear fuels during the burn-up at the power nuclear reactors for burn-up levels of 33.000 MWd/th are considered. Graphs and data on the radioactivity variation with the cooling time and heat power of the irradiated fuel are presented. Likewise, the cycle of the fuel in light water reactors is presented and the alternatives for the nuclear waste management are discussed. A brief description of the management of the spent fuel as a high level nuclear waste is shown, explaining the reprocessing and giving data about the fission products and their radioactivities, which must be considered on the vitrification processes. On the final storage of the nuclear waste into depth geological burials, both alternatives are coincident. The countries supporting the reprocessing are indicated and the Spanish programm defined in the Plan Energetico Nacional (PEN) is shortly reviewed. (author) 8 figs., 4 tabs

  6. Acceptable noise level

    Olsen, Steen Østergaard; Nielsen, Lars Holme; Lantz, Johannes

    2012-01-01

    The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjects...... using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli....

  7. Service Level Status

    Lopienski, S

    2007-01-01

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them.

  8. Liquid Level Sensing System

    Korman, Valentin (Inventor); Wiley, John T. (Inventor); Duffell, Amanda G. (Inventor)

    2014-01-01

    A liquid level sensing system includes waveguides disposed in a liquid and distributed along a path with a gap between adjacent waveguides. A source introduces electromagnetic energy into the waveguides at a first end of the path. A portion of the electromagnetic energy exits the waveguides at a second end of the path. A detector measures the portion of the electromagnetic energy exiting the second end of the path.

  9. Level up Book Club

    LaGarde, Jennifer; Winner, Matthew C.

    2012-01-01

    Like all great ideas, Level Up Book Club grew out of a genuine need, the spontaneous firing of a few brain sparks, and the kind of luck that comes from being "in the right place at the right time." By mid-June 2011 the authors were already "bona fide" wonder twins--two educators who, although they'd never met, had stumbled upon each other through…

  10. Current level detector

    Kerns, C.R.

    1977-01-01

    A device is provided for detecting the current level of a dc signal. It includes an even harmonic modulator to which a reference ac signal is applied. The unknown dc signal acts on the reference ac signal so that the output of the modulator includes an even harmonic whose amplitude is proportional to the unknown dc current. The device may be used to provide overcurrent protection for proportional wire chambers

  11. Acceptable noise level

    Olsen, Steen Østergaard; Nielsen, Lars Holme; Lantz, Johannes

    2012-01-01

    The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjec...... using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli....

  12. Multi-level spondylolysis.

    Hersh, David S; Kim, Yong H; Razi, Afshin

    2011-01-01

    The incidence of isthmic spondylolysis is approximately 3% to 6% in the general population. Spondylolytic defects involving multiple vertebral levels, on the other hand, are extremely rare. Only a handful of reports have examined the outcomes of surgical treatment of multi-level spondylolysis. Here, we present one case of bilateral pars defects at L3, L4, and L5. The patient, a 46-year-old female, presented with lower back pain radiating into the left lower extremity. Radiographs and CT scans of the lumbar spine revealed bilateral pars defects at L3-L5. The patient underwent lumbar discectomy and interbody fusion of L4-S1 as well as direct repair of the pars defect at L3. There were no postoperative complications, and by seven months the patient had improved clinically. While previous reports describe the use of either direct repair or fusion in the treatment of spondylolysis, we are unaware of reports describing the use of both techniques at adjacent levels.

  13. ENRAF gauge reference level calculations

    Huber, J.H., Fluor Daniel Hanford

    1997-02-06

    This document describes the method for calculating reference levels for Enraf Series 854 Level Detectors as installed in the tank farms. The reference level calculation for each installed level gauge is contained herein.

  14. Insignificant levels of dose

    Webb, G.A.M.; McLean, A.S.

    1977-01-01

    The procedures recommended by the International Commission on Radiological Protection (ICRP) for making decisions concerning controllable sources of radiation exposure of the public include 'justification' and 'optimisation'. The tool recommended by the ICRP for reaching these decisions is collective dose or dose commitment supplemented by consideration of doses to individuals. In both these considerations the practical problem arises of whether very small doses to large numbers of people should contribute to the final decision-making process. It may be that at levels of dose which are small increments on natural background, the relationship between dose and effect is linear even though the slope may be close to zero. If so, collective dose is a meaningful concept and the calculation of total detriment for the purpose of justification could legitimately include all doses. In the calculation of collective doses for the purpose of optimisation, which involves decisions on how much money or resource should be allocated to dose reduction, it is necessary to appraise radiation detriment realistically. At low levels of dose to the individual such as those small by comparison with variations in natural background within the UK, the risk to the individual is such that his well-being will not be significantly changed by the presence or absence of the radiation dose. These small doses, which are well below the point at which an individual attaches significance, should not carry a societal significance. Societal acceptance of risk is analysed with a view to assessing a level of possible risk, and hence dose, below which resources should not in general be diverted to secure further reduction. A formulation for collective dose commitment is proposed incorporating a cut-off to exclude insignificant doses. The implications of this formulation in practical situations are discussed

  15. ALICE High Level Trigger

    Alt, T

    2013-01-01

    The ALICE High Level Trigger (HLT) is a computing farm designed and build for the real-time, online processing of the raw data produced by the ALICE detectors. Events are fully reconstructed from the raw data, analyzed and compressed. The analysis summary together with the compressed data and a trigger decision is sent to the DAQ. In addition the reconstruction of the events allows for on-line monitoring of physical observables and this information is provided to the Data Quality Monitor (DQM). The HLT can process event rates of up to 2 kHz for proton-proton and 200 Hz for Pb-Pb central collisions.

  16. Global physical activity levels

    Hallal, Pedro C; Andersen, Lars Bo; Bull, Fiona C

    2012-01-01

    To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years......-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes......-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high...

  17. Water level detection pipeline

    Koshikawa, Yukinobu; Imanishi, Masatoshi; Niizato, Masaru; Takagi, Masahiro

    1998-01-01

    In the present invention, water levels of a feedwater heater and a drain tank in a nuclear power plant are detected at high accuracy. Detection pipeline headers connected to the upper and lower portions of a feedwater heater or a drain tank are connected with each other. The connection line is branched at appropriate two positions and an upper detection pipeline and a lower detection pipeline are connected thereto, and a gauge entrance valve is disposed to each of the detection pipelines. A diaphragm of a pressure difference generator is connected to a flange formed to the end portion. When detecting the change of water level in the feedwater heater or the drain tank as a change of pressure difference, gauge entrance valves on the exit side of the upper and lower detection pipelines are connected by a connection pipe. The gauge entrance valve is closed, a tube is connected to the lower detection pipe to inject water to the diaphragm of the pressure difference generator passing through the connection pipe thereby enabling to calibrate the pressure difference generator. The accuracy of the calibration of instruments is improved and workability thereof upon flange maintenance is also improved. (I.S.)

  18. Bacteraemia and acute phase proteins in Nigerian women with ...

    C-reactive protein, alpha–2-macroglobulin, transferrin and bacteraemia were studied in women with recurrent abortion and compared with the pregnant women as well as non-pregnant women with no history of abortion (controls). The results showed a significantly reduced level of transferrin but significantly raised levels of ...

  19. Mechanism and developmental changes in iron transport across the blood-brain barrier.

    Morgan, Evan H; Moos, Torben

    2002-01-01

    Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

  20. LHC Report: Level best

    Mike Lamont for the LHC team

    2012-01-01

    The LHCb experiment is special: there is a limit to the number of the events the detector can handle per bunch crossing. Consequently the maximum luminosity provided in 2012 has been around 4 x1032 cm-2s-1 (compared to the maximum of 7.7 x1033 cm-2s-1 seen by ATLAS and CMS). Nonetheless LHCb still wants to integrate as much luminosity as possible.    To meet LHCb's requirements a luminosity leveling technique is used. A machine setup is chosen that would give a peak luminosity well above the required maximum if the beams are collided head-on at LHCb's interaction point. This peak luminosity is then reduced to the required maximum by moving the two beams transversely apart at the interaction point. As the beam current goes down during a fill, the beams can be moved together in small increments to keep the collision rate constant throughout the fill. In practice, when the LHC goes into collisions in LHCb, the initial luminosity is safely below LHCb's demanded le...

  1. Monitoring Your Blood Sugar Level

    ... and NutritionHealth Insurance: Understanding What It CoversHigh Homocysteine Level: How It Affects Your Blood VesselsUnderstanding Your Medical ... Health Resources Healthcare Management Monitoring Your Blood Sugar Level Monitoring Your Blood Sugar Level Share Print What ...

  2. Role of Breastfeeding and Complementary Food on Hemoglobin and Ferritin Levels in a Cambodian Cross-Sectional Sample of Children Aged 3 to 24 Months.

    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

  3. Fasting and nonfasting lipid levels

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  4. Science Curriculum Guide, Level 4.

    Newark School District, DE.

    The fourth of four levels in a K-12 science curriculum is outlined. In Level 4 (grades 9-12), science areas include earth science, biology, chemistry, and physics. Six major themes provide the basis for study in all levels (K-12). These are: Change, Continuity, Diversity, Interaction, Limitation, and Organization. In Level 4, all six themes are…

  5. Emotion-driven level generation

    Togelius, Julian; Yannakakis, Georgios N.

    2016-01-01

    This chapter examines the relationship between emotions and level generation. Grounded in the experience-driven procedural content generation framework we focus on levels and introduce a taxonomy of approaches for emotion-driven level generation. We then review four characteristic level generators of our earlier work that exemplify each one of the approaches introduced. We conclude the chapter with our vision on the future of emotion-driven level generation.

  6. Level density of 57Co

    Mishra, V.; Boukharouba, N.; Brient, C.E.; Grimes, S.M.; Pedroni, R.S.

    1994-01-01

    Levels in 57 Co have been studied in the region of resolved levels (E 57 Fe(p,n) 57 Co neutron spectrum with resolution ΔE∼5 keV. Seventeen previously unknown levels are located. Level density parameters in the continuum region are deduced from thick target measurements of the same reaction and additional level density information is deduced from Ericson fluctuation studies of the reaction 56 Fe(p,n) 56 Co. A set of level density parameters is found which describes the level density of 57 Co at energies up to 14 MeV. Efforts to obtain level density information from the 56 Fe(d,n) 57 Co reaction were unsuccessful, but estimates of the fraction of the deuteron absorption cross section corresponding to compound nucleus formation are obtained

  7. Reactor water level control device

    Hiramatsu, Yohei.

    1980-01-01

    Purpose: To increase the rapid response of the waterlevel control converting a reactor water level signal into a non-linear type, when the water level is near to a set value, to stabilize the water level reducting correlatively the reactor water level variation signal to stabilize greatly from the set value, and increasing the variation signal. Constitution: A main vapor flow quality transmitter detects the vapor flow generated in a reactor and introduced into a turbine. A feed water flow transmitter detects the quantity of a feed water flow from the turbine to the reactor, this detected value is sent to an addition operating apparatus. On the other hand, the power signal of the reactor water level transmitter is sent to the addition operating apparatus through a non-linear water level signal converter. The addition operation apparatus generates a signal for requesting the feed water flow quantity from both signals. Upon this occasion, the reactor water level signal converter makes small the reactor water level variation when the reactor level is close the set value, and when the water level deviates greatly from the set value, the reactor water level variation is made large thereby to improve the rapid response of the reactor coater level control. (Yoshino, Y.)

  8. Specified assurance level sampling procedure

    Willner, O.

    1980-11-01

    In the nuclear industry design specifications for certain quality characteristics require that the final product be inspected by a sampling plan which can demonstrate product conformance to stated assurance levels. The Specified Assurance Level (SAL) Sampling Procedure has been developed to permit the direct selection of attribute sampling plans which can meet commonly used assurance levels. The SAL procedure contains sampling plans which yield the minimum sample size at stated assurance levels. The SAL procedure also provides sampling plans with acceptance numbers ranging from 0 to 10, thus, making available to the user a wide choice of plans all designed to comply with a stated assurance level

  9. Digital Levelling in Subterranean Spaces

    Tomáš Jiřikovský

    2007-06-01

    Full Text Available For precision levelling works are now more often used digital levels and code-scale staffs. Advantages in (and problems with their application to the regular line-levelling are well known and described. However, when using the digital levelling for measurements in specific local geodetic networks, monitoring networks and inside of buildings and underground spaces, new problems appear with the signalisation of the observed points, readability of the code (non-uniform illumination, temperature changes etc. The article informs about the application of two types of digital levels (Sokkia SDL-2, Trimble Zeiss DiNi 12T in the experimental subterranean levelling network for the basement settlement monitoring of a ten-floor building; the solution of marking of the points, field calibration and the system calibration of digital levels.

  10. Liquid level measurement in high level nuclear waste slurries

    Weeks, G.E.; Heckendorn, F.M.; Postles, R.L.

    1990-01-01

    Accurate liquid level measurement has been a difficult problem to solve for the Defense Waste Processing Facility (DWPF). The nuclear waste sludge tends to plug or degrade most commercially available liquid-level measurement sensors. A liquid-level measurement system that meets demanding accuracy requirements for the DWPF has been developed. The system uses a pneumatic 1:1 pressure repeater as a sensor and a computerized error correction system. 2 figs

  11. 'Level-level correlation and absorption in nuclear reactions'

    Hussein, M.S.

    Level-level correlation (LLC) in nuclear reactions is discussed in general and it is shown that in the presence of LLC, N sub(μ) = Σ/g μa/ 2 > divided by gamma μ T tilde, where T tilde is the average absorption in the eigen channels [pt

  12. Comments About a Chameleon Theory: Level I/Level II.

    Horn, John; Stankov, Lazar

    1982-01-01

    Jensen's ideas about two levels of intellectual abilities are criticized as being oversimplified. More than two levels of intellectual abilities and relationships between variables reflecting more than racial and socioeconomic status (SES) differences are suggested, arguing that Jensen's statements about race and SES differences are not properly…

  13. Low-level waste management

    Levin, G.B.

    1980-01-01

    An overview of the current situation in the United States and a look to the future of low-level waste management are presented. Current problems and challenges are discussed, such as: the need of additional disposal sites in the future; risks and costs involved in transport of low-level wastes; reduction of low-level waste volume through smelting, incineration, and storage for wastes containing nuclides with short half lives; development of a national policy for the management of low-level waste, and its implementation through a sensible system of regulations. Establishing a success with low-level waste management should provide the momentum and public confidence needed to continue on and to resolve the technical and politically more difficult low-level waste problems

  14. Culture at the Country Level

    Maseland, R.K.J.; Hoorn, A.A.J. van; Herk, H. van; Torelli, C.J.

    2017-01-01

    This chapter introduces and critically discusses the idea of measuring the culture of countries and cross-national differences therein. We start by elaborating the theoretical foundations for studying culture at the country level. We highlight the use of countries or nations as a unit of analysis and pay special attention to the way in which a group-level construct such as culture has implications at lower levels of analysis, affecting the values and beliefs of individuals. After briefly trac...

  15. Nucleonic level control in industries

    Eapen, A.C.; Rao, S.S.; Nair, R.S.

    1979-01-01

    The paper elicits the particular advantages of nucleonic level control methods in certain applications. The technique used is described briefly. Normal radioactive sources used and their selection for any application based on their characteristic emissions is explained. Level controller developed by the Bhabha Atomic Research Centre, Bombay, is described including details regarding electronic circuitry and the radiation detector used. Its application in zinc powder plant to measure powder level in a hopper is described. Some of the typical applications of gamma-ray level controllers are mentioned. (auth.)

  16. On 165Ho level scheme

    Ardisson, Claire; Ardisson, Gerard.

    1976-01-01

    A 165 Ho level scheme was constructed which led to the interpretation of sixty γ rays belonging to the decay of 165 Dy. A new 702.9keV level was identified to be the 5/2 - member of the 1/2 ) 7541{ Nilsson orbit. )] [fr

  17. Background noise levels in Europe

    Gjestland, Truls

    2008-01-01

    - This report gives a brief overview of typical background noise levels in Europe, and suggests a procedure for the prediction of background noise levels based on population density. A proposal for the production of background noise maps for Europe is included.

  18. Sea Level Rise Data Discovery

    Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

    2016-12-01

    Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

  19. Sea level and climate variations

    Oerlemans, J.

    1985-01-01

    Review paper, ESA Symposium on Application of Satellite Data to Climate Modelling. Alpbach (Austria) Sea level is an essential component of the climate system, on which many human activities in the coastal zone depend. Climate variations leading to changes in relative sea level are

  20. Enhanced Waste Tank Level Model

    Duignan, M.R.

    1999-06-24

    'With the increased sensitivity of waste-level measurements in the H-Area Tanks and with periods of isolation, when no mass transfer occurred for certain tanks, waste-level changes have been recorded with are unexplained.'

  1. Evaluations of average level spacings

    Liou, H.I.

    1980-01-01

    The average level spacing for highly excited nuclei is a key parameter in cross section formulas based on statistical nuclear models, and also plays an important role in determining many physics quantities. Various methods to evaluate average level spacings are reviewed. Because of the finite experimental resolution, to detect a complete sequence of levels without mixing other parities is extremely difficult, if not totally impossible. Most methods derive the average level spacings by applying a fit, with different degrees of generality, to the truncated Porter-Thomas distribution for reduced neutron widths. A method that tests both distributions of level widths and positions is discussed extensivey with an example of 168 Er data. 19 figures, 2 tables

  2. Noise levels in Damascus city

    Al-Oudat, M.; Maslmani, Y.

    2004-01-01

    Outdoor noise levels were measured at 22 sites in Damascus city. Sound level meter model NC-10 with a 20-140 dBA selectable range was used in the current investigation. At each site noise data were collected from 7 to 21 o'clock. The results showed that the noise levels were higher than WHO (World Health Organization) standard by 5-24.7 dB, 10-16 dB, 10-11 dB and 12-17 dB in residential, commercial, Commercial-industrial, and Heavy traffic streets respectively. Indoor and outdoor noise levels in some hospitals were higher than WHO standard by 15-28 dB and 19-23 dB respectively. The study showed that the authorities administration must take necessary procedures to reduce the noise levels in residential regions and in the regions surrounding the hospitals. (author)

  3. The CDF level-3 trigger

    Devlin, T.

    1993-01-01

    The Collider Detector at Fermilab (CDF) has been operating at the Tevatron and collecting data on proton-antiproton interactions with collision rates above 250,000 Hz. Three levels of filtering select events for data logging at a rate of about 4 Hz. The Level 3 trigger provides most of the capabilities of the offline production programs for event reconstruction and physics analysis. The type of physics triggers, application of cuts, and combinations of logical requirements for event selection are controlled at run time by a trigger table using a syntax fully integrated with the Level 1 and Level 2 hardware triggers. The level 3 software operates in 48 RISC/UNIX processors (over 1000 mips) served by four 20-MByte/sec data buses for input, output and control. The system architecture, debugging, code validation, error reporting, analysis capabilities and performance will be described

  4. Relationships between the school-level and classroom-level ...

    education; school-level environment; science education; South Africa. Introduction .... instrument to the primary school students (N = 1,077) of 31 distance-education primary school teachers ..... Centre for Curriculum, Transfer and Technology.

  5. The Barbados Sea Level Record

    Fairbanks, R. G.; Mortlock, R. A.; Abdul, N. A.; Wright, J. D.; Cao, L.; Mey, J. L.

    2013-12-01

    Additional offshore drill cores, nearly 100 new radiometric dates, and more than 1000 kilometers of Multibeam mapping greatly enhance the Barbados Sea Level record. Extensive Multibeam mapping around the entire island covers approximately 2650 km2 of the sea bottom and now integrates the offshore reef topography and Barbados Sea Level Record with the unparalleled onshore core collection, digital elevation maps, and Pleistocene sea level record spanning the past one million years. The reef crest coral, Acropora palmata, remains the stalwart indicator of sea level for many reasons that are validated by our redundant sea level records and redundant dating via Th/U and Pa/U analyses. Microanalysis and densitometry studies better explain why Acropora palmata is so well preserved in the Pleistocene reef records and therefore why it is the species of choice for sea level reconstructions and radiometric dating. New drill cores into reefs that formed during Marine Isotope Stage 3 lead us to a model of diagenesis that allows us to better prospect for unaltered coral samples in older reefs that may be suitable for Th/U dating. Equally important, our diagenesis model reinforces our rigorous sample quality criteria in a more quantitative manner. The Barbados Sea Level record has a sampling resolution of better than 100 years throughout much of the last deglaciation showing unprecedented detail in redundant drill cores. The Melt Water Pulses (MWP1A and MWP1B) are well resolved and the intervening interval that includes the Younger Dryas reveals sea level changes in new detail that are consistent with the terrestrial records of ice margins (see Abdul et al., this section). More than 100 paired Th/U and radiocarbon ages place the Barbados Sea Level Record unambiguously on the radiocarbon time scale for direct comparisons with the terrestrial records of ice margin changes.

  6. Optimum Safety Levels for Breakwaters

    Burcharth, H. F.; Sørensen, John Dalsgaard

    2005-01-01

    Optimum design safety levels for rock and cube armoured rubble mound breakwaters without superstructure are investigated by numerical simulations on the basis of minimization of the total costs over the service life of the structure, taking into account typical uncertainties related to wave...... statistics and structure response. The study comprises the influence of interest rate, service lifetime, downtime costs and damage accumulation. Design limit states and safety classes for breakwaters are discussed. The results indicate that optimum safety levels are somewhat higher than the safety levels...

  7. Farmers as Employers. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of farmers as employers: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with employment of agriculture…

  8. Farm Management and Leadership. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in farm management and leadership: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with farm management. SMAT materials can…

  9. Occupational Health and Safety. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of occupational health and safety: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication skills needed…

  10. Occupational Health and Safety. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of occupational health and safety: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with occupational safety and…

  11. Farmers as Employers. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of farmers as employers: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication and numeracy skills…

  12. Agricultural Production. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in agricultural production: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication skills needed to deal with…

  13. Agricultural Production. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in agricultural production: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with agricultural production. SMAT materials…

  14. Farm Management and Leadership. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in farm management and leadership: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner with the reading, writing, and spoken communication skills needed to deal with…

  15. Acceptance criteria for deposition of low-level and intermediate-level radiation levels radioactive wastes

    2002-09-01

    This norm establishes the criteria for acceptance low and intermediate radiation level for safe deposition in repositories, for assuring the protection of workers, population and environment against the hazardous effects of the ionizing radiations. The criteria of this norm applies to the low and intermediate radiation levels

  16. Level best : drilling seasonal load leveling business case : final report

    2005-10-01

    Drilling and seismic costs in Western Canada are as much as 35 per cent higher during winter months. Favourable commodity pricing has prompted aggressive expansion of drilling programs in the Western Canada Sedimentary Basin (WCSB), and capacity is becoming a significant issue. Many operators are turning to load leveling in order to secure rigs and crew availability. However, many operators still adhere to the traditional view that drilling of oil and gas wells is best accomplished during the winter. The purpose of the project discussed in this paper was to develop and present a business case for greater seasonal load leveling in the WCSB and spreading it more evenly throughout the year. Using calendar year quarters, publicly available data for a 5 year period from 2000-2004 for drilling activity, safety, weather, and environmental restrictions were examined. A list of candidate fields with high levels of activity and a good representation of well depths was selected. Well cost and rig data from 14 different companies was used. A variety of industry participants, drilling contractors, load leveling technology suppliers and provincial agencies were consulted to supplement well cost analyses. The financial impacts of load leveling were examined. Benefits included lower well costs; advanced production; avoided rig construction; reduced incident rates; and reduced turnover. While the focus of the business case for load leveling was based on hard cost data, many indirect benefits were identified, including First Nations sustainability and greater job security and comfort for workers. Various policies and incentives that encouraged load leveling in British Columbia and Alberta were reviewed. 57 figs

  17. Atomic-level computer simulation

    Adams, J.B.; Rockett, Angus; Kieffer, John; Xu Wei; Nomura, Miki; Kilian, K.A.; Richards, D.F.; Ramprasad, R.

    1994-01-01

    This paper provides a broad overview of the methods of atomic-level computer simulation. It discusses methods of modelling atomic bonding, and computer simulation methods such as energy minimization, molecular dynamics, Monte Carlo, and lattice Monte Carlo. ((orig.))

  18. High-level-waste immobilization

    Crandall, J.L.

    1982-01-01

    Analysis of risks, environmental effects, process feasibility, and costs for disposal of immobilized high-level wastes in geologic repositories indicates that the disposal system safety has a low sensitivity to the choice of the waste disposal form

  19. MOVES regional level sensitivity analysis

    2012-01-01

    The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

  20. Association in Level 2 Fusion

    Kokar, Mieczyslaw M; Matheus, Christopher J; Letkowski, Jerzy A; Baclawski, Kenneth; Kogut, Paul

    2004-01-01

    ... system, this cannot be said about the number of possible relations, which can grow exponentially. To alleviate the problems of computational complexity in Level 2 processing, the authors of this paper have suggested the use of ontologies...

  1. Processing TES Level-2 Data

    Poosti, Sassaneh; Akopyan, Sirvard; Sakurai, Regina; Yun, Hyejung; Saha, Pranjit; Strickland, Irina; Croft, Kevin; Smith, Weldon; Hoffman, Rodney; Koffend, John; hide

    2006-01-01

    TES Level 2 Subsystem is a set of computer programs that performs functions complementary to those of the program summarized in the immediately preceding article. TES Level-2 data pertain to retrieved species (or temperature) profiles, and errors thereof. Geolocation, quality, and other data (e.g., surface characteristics for nadir observations) are also included. The subsystem processes gridded meteorological information and extracts parameters that can be interpolated to the appropriate latitude, longitude, and pressure level based on the date and time. Radiances are simulated using the aforementioned meteorological information for initial guesses, and spectroscopic-parameter tables are generated. At each step of the retrieval, a nonlinear-least-squares- solving routine is run over multiple iterations, retrieving a subset of atmospheric constituents, and error analysis is performed. Scientific TES Level-2 data products are written in a format known as Hierarchical Data Format Earth Observing System 5 (HDF-EOS 5) for public distribution.

  2. Intermediate Levels of Visual Processing

    Nakayama, Ken

    1998-01-01

    ...) surface representation, here we have shown that there is an intermediate level of visual processing, between the analysis of the image and higher order representations related to specific objects; (2...

  3. Nuclear systems of level measurement

    Lara, A.J.; Cabrera, M.J.

    1992-01-01

    In the industry there are processes in which is necessary to maintain the products level controlled which are handled for their transformation. The majority of such processes and by the operation conditions, they do not admit measure systems of level of invasive type then the application of nuclear techniques for level measurement results a big aid in these cases, since all the system installation is situated beyond frontiers of vessels that contain the product for measuring. In the Department of Nuclear Technology Applications of Mexican Petroleum Institute was developed a level measurement system by gamma rays transmission which operates in the Low Density Polyethylene plant of Petrochemical Complex Escolin at Poza Rica, Veracruz, Mexico. (Author)

  4. Levels of radioactivity in Qatar

    Al-Thani, A.A.; Abdul-Majid, S.; Mohammed, K.

    1995-01-01

    The levels of natural and man-made radioactivity in soil and seabed were measured in Qatar to assess radiation exposure levels and to evaluate any radioactive contamination that may have reached the country from fallout or due to the Chernobyl accident radioactivity release. Qatar peninsula is located on the Arabian Gulf, 4500 km from Chernobyl, and has an area of ∼11,600 km 2 and a population of ∼600,000

  5. Level structure in 123Xe

    Luukko, A.; Hattula, J.; Helppi, H.; Knuuttila, O.

    1980-09-01

    The level structure of 123 Xe has been studied with 122 Te( 3 He,2n) and 123 Te( 3 He,3n) reactions using in-beam γ-ray spectroscopic methods. Band-like level structures based on the unique-parity hsub(11/2) neutron state and different low-j states are observed. The isomeric state proposed earlier is established at 185.4 keV with a half-life of 5.6+-0.3 μs, and a new spin assignment of 7/2 - is proposed for this level. A triaxial-rotor-model calculation has been performed to interprete the negative-parity level system. Because of the 7/2 - state, we do not obtain a consistent description of the negative-parity states with the triaxial rotor model, unlike the heavier odd-A Xe nuclei. On the other hand, the positive-parity level structures are interpreted in terms of the core-quasiparticle model supposing a vibrational core. This indicates different core shapes for the positive- and negative-parity level systems. (author)

  6. Intermittent sea-level acceleration

    Olivieri, M.; Spada, G.

    2013-10-01

    Using instrumental observations from the Permanent Service for Mean Sea Level (PSMSL), we provide a new assessment of the global sea-level acceleration for the last ~ 2 centuries (1820-2010). Our results, obtained by a stack of tide gauge time series, confirm the existence of a global sea-level acceleration (GSLA) and, coherently with independent assessments so far, they point to a value close to 0.01 mm/yr2. However, differently from previous studies, we discuss how change points or abrupt inflections in individual sea-level time series have contributed to the GSLA. Our analysis, based on methods borrowed from econometrics, suggests the existence of two distinct driving mechanisms for the GSLA, both involving a minority of tide gauges globally. The first effectively implies a gradual increase in the rate of sea-level rise at individual tide gauges, while the second is manifest through a sequence of catastrophic variations of the sea-level trend. These occurred intermittently since the end of the 19th century and became more frequent during the last four decades.

  7. Serum gonadotropins levels in childhood

    Hertogh, R. De; Vankrieken, L.; Wolter, R.; Vliet, G. Van

    1989-01-01

    The complex changes in serum LH and FSH levels from infancy to adulthood are diversely evaluated by radioimmunoassays or bioassays. The relative lack of sensitivity and specificity of radioimmunoassay, using polyclonal antibodies, could possibly be overcome by new immunoradiometric assays, using specific antibodies to LH and FSH. Significant differences were indeed observed between radioimmunoassays and immunoradiometric assays. During the prepubertal period, LH levels, measured by the immunoradiometric assays, were below the sensitivity of the method in the majority of the samples. LH levels were, however, well detectable when measured with radioimmunoassay, showing the heterogeneity of circulating LH structures. At the onset of puberty, LH levels increased at least 3 to 4 times in both sexes, when measured with immunoradiometric assays, whereas their increase was only 20 to 60% with the radioimmunoassays. FSH levels remained well detectable in the prepubertal period whether measured by immunoradiometric or radioimmunoassays. At pubertal onset, FSH increase in both sexes was more important in the immunoradiometric assays. The results obtained with immunoradiometric assays give a better insight into the quantitative and qualitative function of the gonadotropes during childhood. The almost complete absence of LH during the prepubertal period and the steep increase at the onset of puberty better reflects the reported data obtained with bioassays. The persistance of significant levels of FSH in the prepubertal ages, and the lesser increase at the onset of puberty, when compared with LH, illustrates that the individual regulation of LH and FSH secretion vary over time and is influenced by developmental factors. (author)

  8. Reactor water level control device

    Utagawa, Kazuyuki.

    1993-01-01

    A device of the present invention can effectively control fluctuation of a reactor water level upon power change by reactor core flow rate control operation. That is, (1) a feedback control section calculates a feedwater flow rate control amount based on a deviation between a set value of a reactor water level and a reactor water level signal. (2) a feed forward control section forecasts steam flow rate change based on a reactor core flow rate signal or a signal determining the reactor core flow rate, to calculate a feedwater flow rate control amount which off sets the steam flow rate change. Then, the sum of the output signal from the process (1) and the output signal from the process (2) is determined as a final feedwater flow rate control signal. With such procedures, it is possible to forecast the steam flow rate change accompanying the reactor core flow rate control operation, thereby enabling to conduct preceding feedwater flow rate control operation which off sets the reactor water level fluctuation based on the steam flow rate change. Further, a reactor water level deviated from the forecast can be controlled by feedback control. Accordingly, reactor water level fluctuation upon power exchange due to the reactor core flow rate control operation can rapidly be suppressed. (I.S.)

  9. Low-level toxicity of chemicals: No acceptable levels?

    Bruce P Lanphear

    2017-12-01

    Full Text Available Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at the lowest dose or levels of exposure. These results, which are contrary to the way the United States Environmental Protection Agency (EPA and other regulatory agencies assess the risk of chemicals, indicate that we have underestimated the impact of toxic chemicals on death and disease. If widely disseminated chemicals and pollutants-like radon, lead, airborne particles, asbestos, tobacco, and benzene-do not exhibit a threshold and are proportionately more toxic at the lowest levels of exposure, we will need to achieve near-zero exposures to protect public health.

  10. Promoting system-level learning from project-level lessons

    Jong, Amos A. de; Runhaar, Hens A.C.; Runhaar, Piety R.; Kolhoff, Arend J.; Driessen, Peter P.J.

    2012-01-01

    A growing number of low and middle income nations (LMCs) have adopted some sort of system for environmental impact assessment (EIA). However, generally many of these EIA systems are characterised by a low performance in terms of timely information dissemination, monitoring and enforcement after licencing. Donor actors (such as the World Bank) have attempted to contribute to a higher performance of EIA systems in LMCs by intervening at two levels: the project level (e.g. by providing scoping advice or EIS quality review) and the system level (e.g. by advising on EIA legislation or by capacity building). The aims of these interventions are environmental protection in concrete cases and enforcing the institutionalisation of environmental protection, respectively. Learning by actors involved is an important condition for realising these aims. A relatively underexplored form of learning concerns learning at EIA system-level via project level donor interventions. This ‘indirect’ learning potentially results in system changes that better fit the specific context(s) and hence contribute to higher performances. Our exploratory research in Ghana and the Maldives shows that thus far, ‘indirect’ learning only occurs incidentally and that donors play a modest role in promoting it. Barriers to indirect learning are related to the institutional context rather than to individual characteristics. Moreover, ‘indirect’ learning seems to flourish best in large projects where donors achieved a position of influence that they can use to evoke reflection upon system malfunctions. In order to enhance learning at all levels donors should thereby present the outcomes of the intervention elaborately (i.e. discuss the outcomes with a large audience), include practical suggestions about post-EIS activities such as monitoring procedures and enforcement options and stimulate the use of their advisory reports to generate organisational memory and ensure a better information

  11. Promoting system-level learning from project-level lessons

    Jong, Amos A. de, E-mail: amosdejong@gmail.com [Innovation Management, Utrecht (Netherlands); Runhaar, Hens A.C., E-mail: h.a.c.runhaar@uu.nl [Section of Environmental Governance, Utrecht University, Utrecht (Netherlands); Runhaar, Piety R., E-mail: piety.runhaar@wur.nl [Organisational Psychology and Human Resource Development, University of Twente, Enschede (Netherlands); Kolhoff, Arend J., E-mail: Akolhoff@eia.nl [The Netherlands Commission for Environmental Assessment, Utrecht (Netherlands); Driessen, Peter P.J., E-mail: p.driessen@geo.uu.nl [Department of Innovation and Environment Sciences, Utrecht University, Utrecht (Netherlands)

    2012-02-15

    A growing number of low and middle income nations (LMCs) have adopted some sort of system for environmental impact assessment (EIA). However, generally many of these EIA systems are characterised by a low performance in terms of timely information dissemination, monitoring and enforcement after licencing. Donor actors (such as the World Bank) have attempted to contribute to a higher performance of EIA systems in LMCs by intervening at two levels: the project level (e.g. by providing scoping advice or EIS quality review) and the system level (e.g. by advising on EIA legislation or by capacity building). The aims of these interventions are environmental protection in concrete cases and enforcing the institutionalisation of environmental protection, respectively. Learning by actors involved is an important condition for realising these aims. A relatively underexplored form of learning concerns learning at EIA system-level via project level donor interventions. This 'indirect' learning potentially results in system changes that better fit the specific context(s) and hence contribute to higher performances. Our exploratory research in Ghana and the Maldives shows that thus far, 'indirect' learning only occurs incidentally and that donors play a modest role in promoting it. Barriers to indirect learning are related to the institutional context rather than to individual characteristics. Moreover, 'indirect' learning seems to flourish best in large projects where donors achieved a position of influence that they can use to evoke reflection upon system malfunctions. In order to enhance learning at all levels donors should thereby present the outcomes of the intervention elaborately (i.e. discuss the outcomes with a large audience), include practical suggestions about post-EIS activities such as monitoring procedures and enforcement options and stimulate the use of their advisory reports to generate organisational memory and ensure a better

  12. State level operations and interaction with facility level systems

    Bellinger, J.

    1989-01-01

    The role of the State System of Accounting for and Control of Nuclear Materials at the State level, particularly the role of the National Authority, in ensuring that both national and international safeguards objectives are met is discussed. The legislative basis for the National Authority is examined. The activities of Australia's National Authority - the Australian Safeguards Office - are described

  13. Level densities in nuclear physics

    Beckerman, M.

    1978-01-01

    In the independent-particle model nucleons move independently in a central potential. There is a well-defined set of single- particle orbitals, each nucleon occupies one of these orbitals subject to Fermi statistics, and the total energy of the nucleus is equal to the sum of the energies of the individual nucleons. The basic question is the range of validity of this Fermi gas description and, in particular, the roles of the residual interactions and collective modes. A detailed examination of experimental level densities in light-mass system is given to provide some insight into these questions. Level densities over the first 10 MeV or so in excitation energy as deduced from neutron and proton resonances data and from spectra of low-lying bound levels are discussed. To exhibit some of the salient features of these data comparisons to independent-particle (shell) model calculations are presented. Shell structure is predicted to manifest itself through discontinuities in the single-particle level density at the Fermi energy and through variatons in the occupancy of the valence orbitals. These predictions are examined through combinatorial calculations performed with the Grover [Phys. Rev., 157, 832(1967), 185 1303(1969)] odometer method. Before the discussion of the experimenta results, statistical mechanical level densities for spherical nuclei are reviewed. After consideration of deformed nuclei, the conclusions resulting from this work are drawn. 7 figures, 3 tables

  14. Space elevator systems level analysis

    Laubscher, B. E. (Bryan E.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. It involves new, untried technologies in most of its subsystems. Thus the successful construction of the SE requires a significant amount of development, This in turn implies a high level of risk for the SE. This paper will present a systems level analysis of the SE by subdividing its components into their subsystems to determine their level of technological maturity. such a high-risk endeavor is to follow a disciplined approach to the challenges. A systems level analysis informs this process and is the guide to where resources should be applied in the development processes. It is an efficient path that, if followed, minimizes the overall risk of the system's development. systems level analysis is that the overall system is divided naturally into its subsystems, and those subsystems are further subdivided as appropriate for the analysis. By dealing with the complex system in layers, the parameter space of decisions is kept manageable. Moreover, A rational way to manage One key aspect of a resources are not expended capriciously; rather, resources are put toward the biggest challenges and most promising solutions. This overall graded approach is a proven road to success. The analysis includes topics such as nanotube technology, deployment scenario, power beaming technology, ground-based hardware and operations, ribbon maintenance and repair and climber technology.

  15. Nuclear level mixing resonance spectroscopy

    Coussement, R.; Put, P.; Scheveneels, G.; Hardeman, F.

    1985-01-01

    The existent methods for measuring quadrupole interactions are not suited to nuclei with lifetimes in the micro-seconds to minutes region. AD/NQR, a possible candidate in this lifetime gap, has not yet succeeded in overcoming its predicted difficulties. A new resonant method, recently developed and based on the principles of level mixing (cfr atomic spectroscopy) covers this less accessible lifetime range. Many other kinds of resonances can be described according to the level mixing formalism. The particular example of NMR as a level mixing resonance (LMR) is discussed. The underlying theory of LMR and its important consequences, leading to some interesting features of the method, is briefly formulated. Two successfully performed measurements demonstrate the feasibility and the predicted characteristics of this new promising method. (orig.)

  16. Low-level Radioactivity Measurements

    Churtgen, C.

    2007-01-01

    The low-level radioactivity measurements service performs measurements of alpha or beta emitters on various types of low-radioactivity samples (biological and environmental) from internal and external clients. to maintain and develop techniques concerning the measurement of low-level radioactivity of alpha and beta emitting radionuclides in environmental or biological samples; to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters and alpha-spectrometers); to support and advise the nuclear and non-nuclear industry on problems of radioactive contamination or low level radioactivity measurements; to maintain the quality assurance system according to the ISO17025 standard for which we obtained the Beltest accreditation in 1998; to assess the internal dose from occupational intakes of radionuclides for workers of the nuclear industry;

  17. High Level Radioactive Waste Management

    1991-01-01

    The proceedings of the second annual international conference on High Level Radioactive Waste Management, held on April 28--May 3, 1991, Las Vegas, Nevada, provides information on the current technical issue related to international high level radioactive waste management activities and how they relate to society as a whole. Besides discussing such technical topics as the best form of the waste, the integrity of storage containers, design and construction of a repository, the broader social aspects of these issues are explored in papers on such subjects as conformance to regulations, transportation safety, and public education. By providing this wider perspective of high level radioactive waste management, it becomes apparent that the various disciplines involved in this field are interrelated and that they should work to integrate their waste management activities. Individual records are processed separately for the data bases

  18. High-level Petri Nets

    various journals and collections. As a result, much of this knowledge is not readily available to people who may be interested in using high-level nets. Within the Petri net community this problem has been discussed many times, and as an outcome this book has been compiled. The book contains reprints...... of some of the most important papers on the application and theory of high-level Petri nets. In this way it makes the relevant literature more available. It is our hope that the book will be a useful source of information and that, e.g., it can be used in the organization of Petri net courses. To make......High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...

  19. Low-level Radioactivity Measurements

    Hurtgen, C.

    2002-01-01

    The objectives of the research performed in the area of low-level radioactivity measurements are (1) to maintain and develop techniques for the measurement of low-level environmental and biological samples, (2) to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters, alpha spectrometry), (3) to support and advise the nuclear and non-nuclear industry on problems of radioactive contamination and low-level radioactivity measurements; (4) to maintain and improve the quality assurance system according to the ISO17025 standard; and (5) to assess the internal dose from occupational intakes of radionuclides of workers of the nuclear industry. Progress and achievements in these areas in 2001 are reported

  20. Integrated at the neighbourhood level

    Putri, Prathiwi Widyatmi

    2017-01-01

    Cities in the Global South are generally vast due to urban sprawl. They are characterised by a varying level of density, and enclaves of informal settlements. Within this context, this article addresses the limits of large-scale and centralised water systems. It seeks to understand, qualitatively......-spatial characteristics of local communities can be accommodated. Smaller-scale development intervention also means stimulating creativity in planning and policy-making processes to address water-infrastructure needs at local levels and opens possibilities for integrating water-infrastructures with public space....... Such a decentralised approach matters to improve the overall socio-spatial quality of a neighbourhood, however it requires, in parallel, new institutional mechanisms to provide a coherent water and environmental management system at the urban level. This article argues for a synergy of two axes: the water sector...

  1. Low-level Radioactivity Measurements

    Hurtgen, C.

    2001-01-01

    The objectives of the research performed in the area of low-level radioactivity measurements are (1) to maintain and develop techniques for the measurement of low-level environmental and biological samples, (2) to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters, alpha spectrometry), (3) to support and advice the nuclear and non-nuclear industry in matters concerning radioactive contamination and/or low-level radioactivity measurements; (4) to maintain the quality assurance system according to the EN45001/ISO17025 standard; and (5) to assess the internal dose from occupational intakes of radionuclides of workers of the nuclear industry. Progress and achievements in these areas in 2000 are reported

  2. Modeling Multi-Level Systems

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  3. Deafness and motor abilities level

    A Zwierzchowska

    2008-09-01

    Full Text Available The audition injury hinders some motor motions and the organised coordination at the higher level and may be a cause of disturbances and disorder in some motor abilities adoption. It was assumed that deafness including its aetiology and injury mechanism may significantly influence the motor development of human being. The study aimed in checking if the deafness, as a result of various unfavourable factors, determines the motor development of children and youngsters. Consequently the dependency between qualitative features i.e.: signed motor level and aetiology, audition injury mechanism and the deafness degree was examined. The mechanism and aetiology of hearing correlated with the motor abilities displayed statistically significant dependencies in few motor trials only. Revealed correlations regarded mostly the coordination trials excluding the flexibility one. Statistically significant dependencies between the audition diminution and the motor abilities level were not found.

  4. Is sea-level rising?

    Unnikrishnan, A.S.

    correction in the estimation of trends obtained for tide gauge records. The altimeter data permits to prepare spatial maps of sea-level rise trends. We present a map prepared for the Indian Ocean (Figure 4) north of 10oS , which shows a fairly uniform... drawn information from research papers published by the author and report of the IPCC AR5 WG1 Chapter 13: Sea Level Changes, in which the author has served as a ‘Lead Author’. Figure1 is prepared using data from the University of Colorado. Nerem, R...

  5. Levels of Outsourcing and Offshoring

    Madsen, Erik Skov; Slepniov, Dmitrij

    2011-01-01

    The purpose of this paper is to examine the evolution of offshoring and outsourcing over time and highlight strategic considerations underpinning this process in companies. On the basis of four case studies of Danish and German industrial companies, this paper develops a holistic framework...... conceptualizing various levels of outsourcing and offshoring as well as factors driving the transition between these levels. The framework adds to better understanding of the process and challenges the linear nature of it and suggests that ‘backsourcing’ and repatriation of activities should receive more...

  6. Transferrin Polymorphism in Four Local Breeds of Goat in Central Java, Indonesia

    Kurnianto, E; Sutopo, S; Samsudewa, D; Purbowati, E; Dewanti, D.R; Brata, G.D

    2012-01-01

    The objectives of this study were to determine the gene frequency and individual heterozygosity oftransferrin in four local breeds of goat in Central Java-Indonesia. The number of blood samples weretaken from 96 heads of goat, in which each of breeds were 24 samples, those were Kejobong(Purbalingga regency), Ettawa Grade (Purworejo regency), Kacang (Grobogan regency) and Jawarandu(Pemalang regency). Polyacrilamide Gel Electrophoresis was performed to detect the bands of bloodplasm protein. Ge...

  7. The Transferrin Receptor at the Blood-Brain Barrier - exploring the possibilities for brain drug delivery

    Visser, Corine

    2005-01-01

    There are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain. However, treatment is difficult since many drugs cannot reach the brain in sufficient quantities due to

  8. Pitfalls in Assessing Specific and Affinity of Non-Transferrin-Bound from Uptake

    Brunner-Dopper, L.; Kriegerbecková, Karin; Kovář, Jan; Goldenberg, H.

    1998-01-01

    Roč. 261, č. 1 (1998), s. 128-130 ISSN 0003-2697 Grant - others:Austrian Research Fund (AT) 11594; Austrian Research Fund (AT) 12162; Česko-americký vědeckotechnický program(XC) 95011 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.991, year: 1998

  9. Covalent modification of serum transferrin with phospholipid and incorporation into liposomal membranes

    Afzelius, P; Demant, E J; Hansen, Gert Helge

    1989-01-01

    A method is described for incorporation of water-soluble proteins into liposomal membranes using covalent protein-phospholipid conjugates in detergent solution. A disulfide derivative of phosphatidylethanolamine containing a reactive N-hydroxysuccinimide ester group is synthesized, and the deriva......A method is described for incorporation of water-soluble proteins into liposomal membranes using covalent protein-phospholipid conjugates in detergent solution. A disulfide derivative of phosphatidylethanolamine containing a reactive N-hydroxysuccinimide ester group is synthesized...

  10. Expression of the neuronal transferrin receptor is age dependent and susceptible to iron deficiency

    Moos, Torben; Oates, Phillip S.; Morgan, Evan H.

    1998-01-01

    Blood-brain barrier, choroid plexus, developing brain, metabolism, nutrition, neurodegenerative disorders......Blood-brain barrier, choroid plexus, developing brain, metabolism, nutrition, neurodegenerative disorders...

  11. Colloids related to low level and intermediate level waste

    Ramsay, J.D.F.; Russell, P.J.; Avery, R.G.

    1991-01-01

    A comprehensive research investigation has been undertaken to improve the understanding of the potential role of colloids in the context of disposal and storage of low level and intermediate level waste immobilized in cement. Several topics have been investigated which include: (a) the study of the formation and characteristics of colloids in cement leachates; (b) the effects of the near-field aqueous chemistry on the characteristics of colloids in repository environments; (c) colloid sorption behaviour; (d) interactions of near-field materials with leachates; (e) characteristics of near-field materials in EC repository simulation tests; and (f) colloid migration behaviour. These experimental investigations should provide data and a basis for the development of transport models and leaching mechanisms, and thus relate directly to the part of the Task 3 programme concerned with migration and retention of radionuclides in the near field. 114 Figs.; 39 Tabs.; 12 Refs

  12. High-Level Radioactive Waste.

    Hayden, Howard C.

    1995-01-01

    Presents a method to calculate the amount of high-level radioactive waste by taking into consideration the following factors: the fission process that yields the waste, identification of the waste, the energy required to run a 1-GWe plant for one year, and the uranium mass required to produce that energy. Briefly discusses waste disposal and…

  13. Beyond macrocognition : The transaction level

    Schraagen, J.M.C.

    2017-01-01

    The purpose of this paper is to respond to a number of developments in the past 15 years in the areas of NDM and macrocognition. In my view, these developments necessitate the definition of a new systems level, extending and modifying Newell’s (1990) "bands of cognition". I will argue that what has

  14. Cultural Understanding: Spanish Level 1.

    Scott, Reid

    The teacher's attention is focused on selected elements of Spanish culture which may be taught integrally with instructional materials found in the first-year Spanish texts "Entender y Hablar", "La Familia Fernandez", and "A-LM Spanish, Level One". Items are cross-referenced for 42 cultural concepts ranging from nicknames to streets, roads, and…

  15. Level Design as Model Transformation

    Dormans, Joris

    2011-01-01

    This paper frames the process of designing a level in a game as a series of model transformations. The transformations correspond to the application of particular design principles, such as the use of locks and keys to transform a linear mission into a branching space. It shows that by using rewrite

  16. Biocards and Level of Abstraction

    Lenau, Torben Anker; Keshwani, Sonal; Chakrabarti, Amaresh

    2015-01-01

    Biocards are formal descriptions of biological phenomena and their underlying functional principles. They are used in bioinspired design to document search results and to communicate the findings for use in the further design process. The present study explored the effect of abstraction level used...

  17. Time orientation and construal level

    Beek, van Jannette; Handgraaf, Michel J.J.; Antonides, Gerrit

    2017-01-01

    Eating and exercising behaviour are both characterized by immediate and future consequences. Consequently, consideration of these consequences (i.e. time orientation) predicts eating and exercising behaviour. We investigate whether construal level acts as an underlying mechanism of these

  18. Engineering at the Elementary Level

    McGrew, Cheryl

    2012-01-01

    Can engineering technology be taught at the elementary level? Designing and building trebuchets, catapults, solar cars, and mousetrap vehicles in a west central Florida elementary class was considered very unusual in recent years. After a review of current research on failing schools and poor curriculum, the author wondered what her school could…

  19. Energy levels of 56Mn

    Van Assche, P. H. M.; Baader, H. A.; Koch, H. R.

    1971-01-01

    The low-energy spectrum of the 55Mn(n,γ)56 Mn reaction has been studied with a γ-diffraction spectrometer. These data allowed the construction of a level scheme for 56Mn with two previously unobserved doublets. High-energy γ-transitions to the low-energy states have been measured for different...

  20. Transportable type neutron level indicators

    Khatskevich, M.V.; Kalinin, O.V.; Moskovkin, V.N.; Molchanov, A.V.; Bobkov, A.D.; Rabotnov, Yu.A.

    1979-01-01

    Some peculiarities of designing level neutron converters (LNC) for portable indicators or level neutron relays are considered. The effect of the LNC geometry and other factors on measurement errors has been studied. Calibration results of the LNC with a neutron reflector and without it are presented. It is shown that the problem of level monitoring with the help of portable indicators can be solved practically for any volume, provided two LNC modifications with reflectors are available: the NPU-G modification with horizontal location of a counter for large volumes and the NPU-V with vertical location of a counter for lesser volumes. A possibility of perfecting LNC performances by shielding the counter with thermal neutron absorbers has been studied. The design of the NPU-V modification for the NIUP-2 level indicator is described. It is intended for tubes and cylinders 30-100 mm in diameter. Measurements carried out on different steel and aluminium vessels with a diameter ranging from 300 to 100 mm and a wall thickness of up to 16 mm with the help of the NPU-V and NPU-G modifications proved the efficiency of the LNC to control a variety of products (kerosine, gasoline, oils, acids, alkalis) [ru

  1. Visualizing attitudes towards service levels

    K.Y. Lam (Kar Yin); M. van de Velden (Michel); Ph.H.B.F. Franses (Philip Hans)

    2011-01-01

    textabstractTo assess the attitudes with respect to the quality of banks’ service levels, we use survey data amongst more than 250 Chief Financial Officers (CFOs) of a range of Netherlands-based companies. These companies range from small to very large (including multinationals as Philips and Shell)

  2. Selfishness Level of Strategic Games

    Apt, K.R.; Schäfer, G.

    2014-01-01

    We introduce a new measure of the discrepancy in strategic games between the social welfare in a Nash equilibrium and in a social optimum, that we call selfishness level. It is the smallest fraction of the social welfare that needs to be offered to each player to achieve that a social optimum is

  3. Logical Entity Level Sentiment Analysis

    Petersen, Niklas Christoffer; Villadsen, Jørgen

    2017-01-01

    We present a formal logical approach using a combinatory categorial grammar for entity level sentiment analysis that utilizes machine learning techniques for efficient syntactical tagging and performs a deep structural analysis of the syntactical properties of texts in order to yield precise resu...

  4. RPython high-level synthesis

    Cieszewski, Radoslaw; Linczuk, Maciej

    2016-09-01

    The development of FPGA technology and the increasing complexity of applications in recent decades have forced compilers to move to higher abstraction levels. Compilers interprets an algorithmic description of a desired behavior written in High-Level Languages (HLLs) and translate it to Hardware Description Languages (HDLs). This paper presents a RPython based High-Level synthesis (HLS) compiler. The compiler get the configuration parameters and map RPython program to VHDL. Then, VHDL code can be used to program FPGA chips. In comparison of other technologies usage, FPGAs have the potential to achieve far greater performance than software as a result of omitting the fetch-decode-execute operations of General Purpose Processors (GPUs), and introduce more parallel computation. This can be exploited by utilizing many resources at the same time. Creating parallel algorithms computed with FPGAs in pure HDL is difficult and time consuming. Implementation time can be greatly reduced with High-Level Synthesis compiler. This article describes design methodologies and tools, implementation and first results of created VHDL backend for RPython compiler.

  5. Middle Level Learning Number 47

    Lapham, Steven S.; Hanes, Peter; Turner, Thomas N.; Clabough, Jeremiah C.; Cole, William

    2013-01-01

    This issue's "Middle Level Learning" section presents two articles. The first is "Harriet Tubman: Emancipate Yourself!" (by Steven S. Lapham and Peter Hanes). "Argo," which won the 2012 Oscar for best picture, was about a daring escape of six U.S. diplomats from Iran during the 1979 hostage crisis. Now imagine the…

  6. Legitimizing differentiated flood protection levels

    Thomas, Hartmann; Spit, Tejo

    2016-01-01

    The European flood risk management plan is a new instrument introduced by the Floods Directive. It introduces a spatial turn and a scenario approach in flood risk management, ultimately leading to differentiated flood protection levels on a catchment basis. This challenges the traditional sources of

  7. Reduction of parathyoid hormone levels

    2011-01-01

    A method of acutely reducing the plasma level of PTH of a patient having an elevated PTH comprising the administration of a pharmaceutical composition comprising a GLP-2, or a variant, an analogue, or derivative of GLP-2 having the ability to bind and activate a GLP-2 receptor such as GLP-2 1-34...

  8. High-level radioactive wastes

    Grissom, M.C.

    1982-10-01

    This bibliography contains 812 citations on high-level radioactive wastes included in the Department of Energy's Energy Data Base from January 1981 through July 1982. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number

  9. Very low level radioactive material

    Schaller, K.H.; Linsley, G.; Elert, M.

    1993-01-01

    Man's environment contains naturally occurring radionuclides and doses from exposures to these radionuclides mostly cannot be avoided. Consequently, almost everything may be considered as very low level radioactive material. In practical terms, management and the selection of different routes for low level material is confined to material which was subject to industrial processing or which is under a system of radiological control. Natural radionuclides with concentrations reaching reporting or notification levels will be discussed below; nevertheless, the main body of this paper will be devoted to material, mainly of artificial origin, which is in the system involving notification, registration and licensing of practices and sources. It includes material managed in the nuclear sector and sources containing artificially produced radionuclides used in hospitals, and in industry. Radioactive materials emit ionising radiations which are harmful to man and his environment. National and international regulations provide the frame for the system of radiation protection. Nevertheless, concentrations, quantities or types of radionuclide may be such, that the material presents a very low hazard, and may therefore be removed from regulatory control, as it would be a waste of time and effort to continue supervision. These materials are said to be exempted from regulatory control. Material exempted in a particular country is no longer distinguishable from ''ordinary'' material and may be moved from country to country. Unfortunately, criteria for exempting radioactive materials differ strongly between countries and free trade. Therefore there is a necessity for an international approach to be developed for exemption levels

  10. FINANCIAL CRISIS FROM THE MACROECONOMIC LEVEL TO THE MICROECONOMIC LEVEL

    SANDA GHEORGHE GABRIEL; ENEA CONSTANTA

    2014-01-01

    The current economic and financial crisis, beyond the problems it generates both at micro and macro level, should determine an adaptation of the mechanisms, institutions and monetary / financial policies to the real economy we are facing. The issue of financial crises is extremely complex, including a series of quantitative and qualitative factors, financial, economic, social, ethical, technological and human, which can intervene and influence the financial operations in a...

  11. Disposal of high level and intermediate level radioactive wastes

    Flowers, R.H.

    1991-01-01

    The waste products from the nuclear industry are relatively small in volume. Apart from a few minor gaseous and liquid waste streams, containing readily dispersible elements of low radiotoxicity, all these products are processed into stable solid packages for disposal in underground repositories. Because the volumes are small, and because radioactive wastes are latecomers on the industrial scene, a whole new industry with a world-wide technological infrastructure has grown up alongside the nuclear power industry to carry out the waste processing and disposal to very high standards. Some of the technical approaches used, and the Regulatory controls which have been developed, will undoubtedly find application in the future to the management of non-radioactive toxic wastes. The repository site outlined would contain even high-level radioactive wastes and spent fuels being contained without significant radiation dose rates to the public. Water pathway dose rates are likely to be lowest for vitrified high-level wastes with spent PWR fuel and intermediate level wastes being somewhat higher. (author)

  12. Leptin levels in infertile males

    Jahan, S.; Bibi, R.; Ahmed, S.

    2011-01-01

    Objective: To determine the leptin levels in the serum of normal, sub fertile and infertile men. Study Design: Analytical study. Place and Duration of Study: Department of Animal Sciences Quaid-e-Azam University, Islamabad, National Institute of Health (NIH), Islamabad and Dr. Salma and Kafeel Medical Centre, Islamabad, from April to December 2009. Methodology: Serum leptin levels hormonal concentrations (LH, FSH and testosterone) were determined by EIA in 154 males including 24 (15.58%) fertile, 19 (12.34%) polyzoospermic (PZs), 26 (16.88%) teratozoospermic (TZs), 27 (17.53%) astheno-teratozoospermic (ATZs), 18 (11.69%) oligozoospermic (OZs), 18 (11.69%) oligo-astheno-teratozoospermic (OATZs), 11 (7.14%) obstructive azoospermic (OBST-AZOOs) and 11 (7.14%) non-obstructive azoospermic (NON-OBST-AZOOs). BMI was also determined, divided into groups of greater than 24. Hormonal concentrations were compared by ANOVA and correlation was performed by using Graph pad prism version 5. Results: Significantly high levels of leptin concentrations were found in fertile (p 24 compared to fertile and infertile male patients with BMI 24. Leptin showed a significant positive correlation with LH (p < 0.01) and FSH (p < 0.002) and a significant negative correlation with testosterone (p < 0.001). Conclusion: Abnormal leptin level was significantly associated with fertility problems in males. Providing a link between leptin and reproduction factors contributing in control of testosterone and gonadotropins secretion in many aspects depending on fertility status in male subjects. BMI appears to have significant association with serum leptin levels. (author)

  13. Level gauge using neutron radiation

    Mathew, P.J.

    1985-01-01

    Apparatus for determining the level of a solid or liquid material in a container comprises: a vertical guide within or alongside the container; a sensor positioned within the guide; means for moving the sensor along the guide; and means for monitoring the position of the sensor. The sensor comprises a source of fast neutrons, a detector for thermal neutrons, and a body of a neutron moderating material in close proximity to the detector. Thermal neutrons produced by fast neutron irradiation of the solid or liquid material, or thermal neutrons produced by irradiation of the neutron-moderating material by fast or epithermal neutrons reflected by the solid or liquid material, are detected when the sensor is positioned at or below the level of the material in the container

  14. Radon levels in Oslo schools

    Birovlev, A.

    2004-01-01

    Radon measurements using passive CR-39 detectors have been conducted in all schools in Oslo municipality during winter 2003/2004. Results are presented and discussed in the light of qualitative and quantitative factors, some of which are specific for schools as workplaces. Analysis is conducted with respect to factors relating to building construction type, ventilation principle, age of building, building size etc. The influence of ventilation type on radon levels is studied, and problems of investigations based purely on conventional passive radon detectors are noted. Over-estimation of radon concentration by passive detectors and day-night variations of indoor radon levels in buildings with mechanical ventilation systems are discussed. Several guiding principles for planning similar investigations based on above discussions are outlined. (author)

  15. Technology Performance Level Assessment Methodology.

    Roberts, Jesse D.; Bull, Diana L; Malins, Robert Joseph; Costello, Ronan Patrick; Aurelien Babarit; Kim Nielsen; Claudio Bittencourt Ferreira; Ben Kennedy; Kathryn Dykes; Jochem Weber

    2017-04-01

    The technology performance level (TPL) assessments can be applied at all technology development stages and associated technology readiness levels (TRLs). Even, and particularly, at low TRLs the TPL assessment is very effective as it, holistically, considers a wide range of WEC attributes that determine the techno-economic performance potential of the WEC farm when fully developed for commercial operation. The TPL assessment also highlights potential showstoppers at the earliest possible stage of the WEC technology development. Hence, the TPL assessment identifies the technology independent “performance requirements.” In order to achieve a successful solution, the entirety of the performance requirements within the TPL must be considered because, in the end, all the stakeholder needs must be achieved. The basis for performing a TPL assessment comes from the information provided in a dedicated format, the Technical Submission Form (TSF). The TSF requests information from the WEC developer that is required to answer the questions posed in the TPL assessment document.

  16. Mission Level Autonomy for USSV

    Huntsberger, Terry; Stirb, Robert C.; Brizzolara, Robert

    2011-01-01

    On-water demonstration of a wide range of mission-proven, advanced technologies at TRL 5+ that provide a total integrated, modular approach to effectively address the majority of the key needs for full mission-level autonomous, cross-platform control of USV s. Wide baseline stereo system mounted on the ONR USSV was shown to be an effective sensing modality for tracking of dynamic contacts as a first step to automated retrieval operations. CASPER onboard planner/replanner successfully demonstrated realtime, on-water resource-based analysis for mission-level goal achievement and on-the-fly opportunistic replanning. Full mixed mode autonomy was demonstrated on-water with a seamless transition between operator over-ride and return to current mission plan. Autonomous cooperative operations for fixed asset protection and High Value Unit escort using 2 USVs (AMN1 & 14m RHIB) were demonstrated during Trident Warrior 2010 in JUN 2010

  17. Students as Math Level Designers

    Jensen, Erik Ottar; Hanghøj, Thorkild; Schoenau-Fog, Henrik

    The short paper presents preliminary findings from a pilot study on how students become motivated through design of learning games in math. The research is carried out in a Danish public school with two classes of 5th graders (N = 42 students). Over the course of two weeks, the students work...... with a design template for a runner game in the Unity 3D game design engine. The students are introduced to the concept of “flow” (Csikszentmihalyi, 1991) as a game design principle and are asked to design levels for a math runner game, which are both engaging as well as a meaningful way of learning math....... In this way, the students are positioned as “math level designers”, which means that they both have to redesign the difficulty of the runner game as well as the difficulty of the mathematical questions and possible answers....

  18. Feature-level domain adaptation

    Kouw, Wouter M.; Van Der Maaten, Laurens J P; Krijthe, Jesse H.

    2016-01-01

    -level domain adaptation (flda), that models the dependence between the two domains by means of a feature-level transfer model that is trained to describe the transfer from source to target domain. Subsequently, we train a domain-adapted classifier by minimizing the expected loss under the resulting transfer...... modeled via a dropout distribution, which allows the classiffier to adapt to differences in the marginal probability of features in the source and the target domain. Our experiments on several real-world problems show that flda performs on par with state-of-the-art domainadaptation techniques.......Domain adaptation is the supervised learning setting in which the training and test data are sampled from different distributions: training data is sampled from a source domain, whilst test data is sampled from a target domain. This paper proposes and studies an approach, called feature...

  19. Low-level radioactive waste

    McLaren, L.H.

    1983-03-01

    This bibliography contains information on low-level radioactive waste included in the Department of Energy's Energy Data Base for January through December 1982. The abstracts are grouped by subject category as shown in the table of contents. Entries in the subject index also facilitate access by subject, e.g., Low-Level Radioactive Wastes/Transport. Within each category the arrangement is by report number for reports, followed by nonreports in reverse chronological order. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes, each proceded by a brief description, are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number. 492 references

  20. Multiple Level Crowding: Crowding at the Object Parts Level and at the Object Configural level.

    Kimchi, Ruth; Pirkner, Yossef

    2015-01-01

    In crowding, identification of a peripheral target in the presence of nearby flankers is worse than when the target appears alone. Prevailing theories hold that crowding occurs because of integration or "pooling" of low-level features at a single, relatively early stage of visual processing. Recent studies suggest that crowding can occur also between high-level object representations. The most relevant findings come from studies with faces and may be specific to faces. We examined whether crowding can occur at the object configural level in addition to part-level crowding, using nonface objects. Target (a disconnected square or diamond made of four elements) identification was measured at varying eccentricities. The flankers were similar either to the target parts or to the target configuration. The results showed crowding in both cases: Flankers interfered with target identification such that identification accuracy decreased with an increase in eccentricity, and no interference was observed at the fovea. Crowding by object parts, however, was weaker and had smaller spatial extent than crowding by object configurations; we related this finding to the relationship between crowding and perceptual organization. These results provide strong evidence that crowding occurs not only between object parts but also between configural representations of objects. © The Author(s) 2015.

  1. Level-3 Calorimetric Resolution available for the Level-1 and Level-2 CDF Triggers

    Canepa, A.; Liu, T.; Cortiana, G.; Flanagan, G.; Frisch, H.; Krop, D.; Pilcher, C.; Rusu, V.; Cavaliere, V.; Greco, V.; Giannetti, P.; Piendibene, M.; Sartori, L.; Vidal, Miguel

    2008-01-01

    As the Tevatron luminosity increases sophisticated selections are required to be efficient in selecting rare events among a very huge background. To cope with this problem, CDF has pushed the offline calorimeter algorithm reconstruction resolution up to Level 2 and, when possible, even up to Level 1, increasing efficiency and, at the same time, keeping under control the rates. The CDF Run II Level 2 calorimeter trigger is implemented in hardware and is based on a simple algorithm that was used in Run I. This system has worked well for Run II at low luminosity. As the Tevatron instantaneous luminosity increases, the limitation due to this simple algorithm starts to become clear: some of the most important jet and MET (Missing ET) related triggers have large growth terms in cross section at higher luminosity. In this paper, we present an upgrade of the Level 2 Calorimeter system which makes the calorimeter trigger tower information available directly to a CPU allowing more sophisticated algorithms to be impleme...

  2. System-level musings about system-level science (Invited)

    Liu, W.

    2009-12-01

    In teleology, a system has a purpose. In physics, a system has a tendency. For example, a mechanical system has a tendency to lower its potential energy. A thermodynamic system has a tendency to increase its entropy. Therefore, if geospace is seen as a system, what is its tendency? Surprisingly or not, there is no simple answer to this question. Or, to flip the statement, the answer is complex, or complexity. We can understand generally why complexity arises, as the geospace boundary is open to influences from the solar wind and Earth’s atmosphere and components of the system couple to each other in a myriad of ways to make the systemic behavior highly nonlinear. But this still begs the question: What is the system-level approach to geospace science? A reductionist view might assert that as our understanding of a component or subsystem progresses to a certain point, we can couple some together to understand the system on a higher level. However, in practice, a subsystem can almost never been observed in isolation with others. Even if such is possible, there is no guarantee that the subsystem behavior will not change when coupled to others. Hence, there is no guarantee that a subsystem, such as the ring current, has an innate and intrinsic behavior like a hydrogen atom. An absolutist conclusion from this logic can be sobering, as one would have to trace a flash of aurora to the nucleosynthesis in the solar core. The practical answer, however, is more promising; it is a mix of the common sense we call reductionism and awareness that, especially when strongly coupled, subsystems can experience behavioral changes, breakdowns, and catastrophes. If the stock answer to the systemic tendency of geospace is complexity, the objective of the system-level approach to geospace science is to define, measure, and understand this complexity. I will use the example of magnetotail dynamics to illuminate some key points in this talk.

  3. Biosafety Level 3 Recon Training

    Dickens, Brian Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chavez, Melanie Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Heimer, Donovan J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Knudsen, Ryan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Velasquez, Celina Carmelita [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-04-12

    The Biosafety Level 3 Recon training is a 3D virtual tool developed for the Counter WMD Analysis Cell (CWAC) and the Asymmetric Warfare Group (AWG) by the Application Modeling and Development Team within the NEN-3 International Threat Reduction Group. The training simulates a situation where friendly forces have secured from hostile forces a suspected bioweapons development laboratory. The trainee is a squad member tasked to investigate the facility, locate laboratories within the facility, and identify hazards to entrants and the surrounding area. Before beginning the 3D simulation, the trainee must select the appropriate MOPP level for entering the facility. The items in the simulation, including inside and outside the bioweapon facility, are items that are commonly used by scientists in Biosafety Level (BSL) laboratories. Each item has clickable red tags that, when activated, give the trainee a brief description of the item and a controllable turn-around view. The descriptions also contain information about potential hazards the item can present. Trainees must find all tagged items in order to complete the simulation, but can also reference descriptions and turn-around view of the items in a glossary menu. Training is intended to familiarize individuals whom have little or no biology or chemistry background with technical equipment used in BSL laboratories. The revised edition of this simulation (Biosafety Level 3 Virtual Lab) changes the trainee into a investigator instead of a military combatant. Many doors now require a virtual badge swipe to open. Airlock doors may come in sets such that the open door must be closed before the next door in the set can be opened. A user interface was added so that the instructor can edit the information about the items (the brief descriptions mentioned above) using the simulation software instead of the previous method of manually entering the material in xml settings files. Facility labels, such as "No Parking" and "Men

  4. Low level photoneutron detection equipment

    Ji Changsong; Zhang Yuqin; Li Yuansui

    1991-01-01

    A low level photoneutron detection equipment has been developed. The photoneutrons produced by interaction of 226 Ra gamma quanta and deutron (D) target are detected with n-n discrimination detector made up of 3 He proportional counter array. The D-content information in the target can be obtained from the measured photoneutron counts. The equipment developed is mainly used for nondestructive D-content measurement of D-devices

  5. Level structure of 154Ho

    Moon, Chang-Bum; Komatsubara, Tetsuro; Furuno, Kohei

    2013-10-01

    The excited states of the odd-odd 154Ho nucleus have been studied by using in-beam γ-ray spectroscopy with the 141Pr (16O, 3n) 154Ho reaction at Elab=75 MeV. The beam was provided by the 12UD Pelletron accelerator at the University of Tsukuba. In this work, the complicated decay pattern of low energy transitions just above the T1/2=3.10 min isomer have been established. In addition, a number of new states and γ-ray transitions, especially those associated with energetically favored band termination, have been observed for the first time in 154Ho. A negative collective band and its signature partner built on the 11- level are interpreted as being based on the πh11/2⊗νi13/2 configuration. A positive band built on the 10+ level is based on the πh11/2⊗νh9/2 configuration while another positive band built on the 9+ level is being associated with the πh11/2⊗νf7/2 configuration. An energetically favored level Jπ=19- can be interpreted as being attributed to the πh11/2⊗νi13/2 configuration coupled to the 8+ state in neighboring core 152Dy, namely, a four-quasiparticle alignment based on the [πh11/2νi13/2]11-⊗[ν(h9/2f7/2)]8- configuration. Another energetically favored state at Jπ=27- is assigned the six-quasiparticle [π(h11/2)3]27/2-⊗[ν(f7/2h9/2i13/2)]27/2- configuration.

  6. Parathyroid Hormone Levels and Cognition

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  7. Landau levels on a torus

    Enrico OnofriDipartimento di Fisica, Universita` di Parma, and INFN, Gruppo Collegato di Parma, Parma, Italy

    2015-01-01

    Landau levels have represented a very rich field of research, which has gained widespread attention after their application to quantum Hall effect. In a particular gauge, the holomorphic gauge, they give a physical implementation of Bargmann's Hilbert space of entire functions. They have also been recognized as a natural bridge between Feynman's path integral and Geometric Quantization. We discuss here some mathematical subtleties involved in the formulation of the problem when one tries to s...

  8. System level modeling and component level control of fuel cells

    Xue, Xingjian

    This dissertation investigates the fuel cell systems and the related technologies in three aspects: (1) system-level dynamic modeling of both PEM fuel cell (PEMFC) and solid oxide fuel cell (SOFC); (2) condition monitoring scheme development of PEM fuel cell system using model-based statistical method; and (3) strategy and algorithm development of precision control with potential application in energy systems. The dissertation first presents a system level dynamic modeling strategy for PEM fuel cells. It is well known that water plays a critical role in PEM fuel cell operations. It makes the membrane function appropriately and improves the durability. The low temperature operating conditions, however, impose modeling difficulties in characterizing the liquid-vapor two phase change phenomenon, which becomes even more complex under dynamic operating conditions. This dissertation proposes an innovative method to characterize this phenomenon, and builds a comprehensive model for PEM fuel cell at the system level. The model features the complete characterization of multi-physics dynamic coupling effects with the inclusion of dynamic phase change. The model is validated using Ballard stack experimental result from open literature. The system behavior and the internal coupling effects are also investigated using this model under various operating conditions. Anode-supported tubular SOFC is also investigated in the dissertation. While the Nernst potential plays a central role in characterizing the electrochemical performance, the traditional Nernst equation may lead to incorrect analysis results under dynamic operating conditions due to the current reverse flow phenomenon. This dissertation presents a systematic study in this regard to incorporate a modified Nernst potential expression and the heat/mass transfer into the analysis. The model is used to investigate the limitations and optimal results of various operating conditions; it can also be utilized to perform the

  9. Serum zinc level in thalassemia

    Keikhaei, B.; Badavi, M.; Pedram, M.; Zandian, K.

    2010-01-01

    To compare serum zinc level between Thalassemia Major (TM) patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine (DFO) and 31 were on the combination of DFO and deferiprone (DEF) protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15+- 5 years. Mean serum zinc level was 68.97+- 21.12 mu g/dl, 78.10-28.50 mu g/dl, and 80.16+- 26.54 mu g/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran. (author)

  10. [Alternative nutrition and glutathione levels].

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Brtková, A; Magálová, T; Barteková, S

    1999-08-30

    Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P vegan diet also in adult age.

  11. Level of Sexual Myths Level in Premature Ejaculation Cases

    Mehmet Gunes

    2016-06-01

    Full Text Available Objective: The aim of this study is to determine level of belief in sexual myths in the cases of premature ejacula­tion (PE which is the most common sexual dysfunction in men. Methods: This study included 100 cases who applied Di­cle University Faculty of Medicine hospitals meet prema­ture ejaculation criteria of DSM-5 and 70 healthy controls. Sociodemographic data form, Hamilton Depression Rat­ing Scale (HDS, Hamilton Anxiety Rating Scale (HAS, Arizona Sexual Experience Scale (ASES-Men form and Sexual Myths Evaluation Form were applied to partici­pants. Results: In the study, rate of belief in sexual myths in PE cases was found significantly higher than healthy controls. In the PE cases, education time less than 10 years, the presence of comorbid sexual dysfunction were found to be statistically significant factors that increase the level of belief in sexual myths in the PE cases, HDS (p=0.0002, HAS (p=0.0001, ASES (p=0.0004 scores were statisti­cally significantly higher than the control group. In the loss of sexual desire in men with comorbid ASES (p=0.0001, with ED, ASES (p=0.001 and HDS (p=0.040 scores were found statistically significantly higher. Conclusions: Sexual information should be given in the appropriate age by educated person in educational insti­tutions.

  12. Parathyroid Hormone Levels and Cognition

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, plevels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  13. Ground level cosmic ray observations

    Stephens, S.A. [Tata Institute of Fundamental Research, Bombay (International Commission on Radiation Units and Measurements); Grimani, C.; Brunetti, M.T.; Codino, A. [Perugia Univ. (Italy)]|[INFN, Perugia (Italy); Papini, P.; Massimo Brancaccio, F.; Piccardi, S. [Florence Univ. (Italy)]|[INFN, Florence (Italy); Basini, G.; Bongiorno, F. [INFN, Laboratori Nazionali di Frascati, Rome (Italy); Golden, R.L. [New Mexico State Univ., Las Cruces, NM (United States). Particle Astrophysics Lab.; Hof, M. [Siegen Univ. (Germany). Fachbereich Physik

    1995-09-01

    Cosmic rays at ground level have been collected using the NMSU/Wizard - MASS2 instrument. The 17-hr observation run was made on September 9. 1991 in Fort Sumner, New Mexico, Usa. Fort Sumner is located at 1270 meters a.s.l., corresponding to an atmospheric depth of about 887 g/cm{sup 2}. The geomagnetic cutoff is 4.5 GV/c. The charge ratio of positive and negative muons and the proton to muon ratio have been determined. These observations will also be compared with data collected at a higher latitude using the same basic apparatus.

  14. Low level radioactive waste disposal

    Balaz, J.; Chren, O.

    2015-01-01

    The Mochovce National Radwaste Repository is a near surface multi-barrier disposal facility for disposal of processed low and very low level radioactive wastes (radwastes) resulting from the operation and decommissioning of nuclear facilities situated in the territory of the Slovak Republic and from research institutes, laboratories, hospitals and other institutions (institutional RAW) which are in compliance with the acceptance criteria. The basic safety requirement of the Repository is to avoid a radioactive release to the environment during its operation and institutional inspection. This commitment is covered by the protection barrier system. The method of solution designed and implemented at the Repository construction complies with the latest knowledge and practice of the repository developments all over the world and meets requirements for the safe radwaste disposal with minimum environmental consequences. All wastes are solidified and have to meet the acceptance criteria before disposal into the Repository. They are processed and treated at the Bohunice RAW Treatment Centre and Liquid RAW Final Treatment Facility at Mochovce. The disposal facility for low level radwastes consists of two double-rows of reinforced concrete vaults with total capacity 7 200 fibre reinforced concrete containers (FCCs) with RAW. One double-row contains 40 The operation of the Repository was started in year 2001 and after ten years, in 2011 was conducted the periodic assessment of nuclear safety with positive results. Till the end of year 2014 was disposed to the Repository 11 514 m 3 RAW. The analysis of total RAW production from operation and decommissioning of all nuclear installation in SR, which has been carried out in frame of the BIDSF project C9.1, has showed that the total volume estimation of conditioned waste is 108 thousand m 3 of which 45.5 % are low level waste (LLW) and 54,5 % very low level waste (VLLW). On the base of this fact there is the need to build 7

  15. NASA Technology Readiness Level Definitions

    Mcnamara, Karen M.

    2012-01-01

    This presentation will cover the basic Technology Readiness Level (TRL) definitions used by the National Aeronautics and Space Administration (NASA) and their specific wording. We will discuss how they are used in the NASA Project Life Cycle and their effectiveness in practice. We'll also discuss the recent efforts by the International Standards Organization (ISO) to develop a broadly acceptable set of TRL definitions for the international space community and some of the issues brought to light. This information will provide input for further discussion of the use of the TRL scale in manufacturing.

  16. Biopower at the molar level

    Frandsen, Martin; Triantafillou, Peter

    2011-01-01

    Over the last decade or so much social science research on the developments in the life sciences and biomedicine seems to be focusing too narrowly on individualization or, more recently, on geneticization, that is, the ‘molecular’ level. This article argues that current public health policies......, the society and ‘its’ population today serves as a benchmark for a wide array public interventions seeking to make individuals and groups live a life that is longer and of a better quality. This new strategy, which goes well beyond reducing mortality and sickness, seems in principle to be without political...

  17. Radiation Levels around the LHC

    Mala, P; Calviani, M; Nordt, A

    2013-01-01

    This work discuss on the radiation levels measured around the LHC machine during the 2012 operational year. The doses and particle fluences are measured primarily by RadMon detectors – about 300 RadMons are installed around the accelerator – and by thermoluminescent detectors. In addition, BLMs, IG5/PMI ionisation chambers as well as FGCs can be used for corresponding cumulated dose evaluations. The probability of SEE depends directly on the high-energy hadron (HEH) fluence, so this is the main parameter that is calculated based on RadMons counts.

  18. Macroeconomic level of technology transfer

    Smirnova Nadezhda

    2016-04-01

    Full Text Available World practice of economic management has proved that the best indicator of competitiveness is achieved by that economic system, the economic units of which timely and adequately update the resource and technical base, thus achieving higher financial and economic indicators. Ensuring that sustainable development becomes possible due to the transfer of technological innovations, namely the diffusion from the developer to the customer on both commercial and free of charge basis. The article focuses on functioning of technology transfer at the macro level, namely the creation of its domestic models.

  19. Business plan: LevelUp

    Zhak, Viktor; Sokolov, Ilya

    2013-01-01

    The following thesis was created to enable the writers to produce a business plan for LevelUp Company, gaming café that is going to operate in the center of Helsinki and provide customers playing hours on PC, PS4 and X-box One. The entire business plan describes all aspects concerning marketing analysis, financial data and basic information on the gaming café as location, number of staff, prices open hours etc. The theoretical framework was based on the most reliable marketing and finance...

  20. Level Scheme of 223Fr

    Gaeta, R.; Gonzalez, J.A.; Gonzalez, L.; Roldan, C.

    1972-01-01

    A study has been made of the decay of 2 27 Ac at levels of 223 F r, means of alpha Spectrometers of Si barrier detector and gamma Spectrometers of Ge(Li). The rotational bands 1/2-(541 ↓ ] , 1/2-(530 ↑ ) and 3/2-(532 ↓ ) have been identified, as well as two octupolar bands associated with the fundamental one. The results obtained indicate that the unified model is applicable in this intermediate zone of the nuclide chart. (Author) 150 refs

  1. Developing State Level Approaches under the State Level Concept

    Budlong Sylvester, K.; Murphy, C.L.; Boyer, B.; Pilat, J.F.

    2015-01-01

    With the pursuit of the State-Level Concept (SLC), the IAEA has sought to further evolve the international safeguards system in a manner which maintains (or improves) the effectiveness of the system in an environment of expanding demands and limited resources. The IAEA must not remain static and should continuously examine its practices to ensure it can capture opportunities for cost reductions while adapting to, and staying ahead of, emerging proliferation challenges. Contemporary safeguards have been focused on assessing the nuclear programme of the State as a whole, rather than on the basis of individual facilities. Since the IAEA's integrated safeguards program, State-level Approaches (SLAs) have been developed that seek to optimally combine the measures provided for by the Additional Protocol with those of traditional safeguards. This process resulted in facility specific approaches that, while making use of a State's broader conclusion, were nonetheless prescriptive. Designing SLAs on a State-by-State basis would avoid the shortcomings of a one-size-fits-all system. It would also enable the effective use of the Agency's information analysis and State evaluation efforts by linking this analysis to safeguards planning efforts. Acquisition Path Analysis (APA), along with the State Evaluation process, can be used to prioritize paths in a State in terms of their attractiveness for proliferation. While taking advantage of all safeguards relevant information, and tailoring safeguards to individual characteristics of the State, paths of the highest priority in all States will necessarily meet the same standard of coverage. Similarly, lower priority paths will have lower performance targets, thereby promoting nondiscrimination. Such an approach would improve understanding of safeguards implementation under the SLC and the rational for safeguards resource allocation. The potential roles for APA and performance targets in SLA development will be reviewed

  2. Why control blood glucose levels?

    Rossini, A A

    1976-03-01

    The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined. The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: (1) ketoacidosis and hyperosmolar coma; (2) intracellular dehydration; (3) electrolyte imbalance; (4) decreased phagocytosis; (5) immunologic and lymphocyte activity; (6) impairment of wound healing; and (7) abnormality of lipids. The long-term disadvantages of uncontrolled diabetes melitus include the following: (1) nephropathy; (2) neuropathy; (3) retinopathy; (4) cataract formation; (5) effect on perinatal mortality; (6) complications of vascular disease; and (7) the evaluation of various clinical studies suggesting the relationship of elevated blood glucose levels and complications of diabetes mellitus. It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.

  3. Parathyroid Hormone Levels and Cognition

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  4. Low level radiation: biological effects

    Loken, M.K.

    1983-01-01

    It is imperative that physicians and scientists using radiations in health care delivery continue to assess the benefits derived, vs. potential risk, to patients and radiation workers being exposed to radiation in its various forms as part of our health delivery system. Insofar as possible we should assure our patients and ourselves that the benefits outweigh the potential hazards involved. Inferences as to the possible biological effects of low level radiation are generally based on extrapolations from those effects observed and measured following acute exposures to considerably higher doses of radiation. Thus, in order to shed light on the question of the possible biological effects of low level radiation, a wide variety of studies have been carried out using cells in culture and various species of plant and animal life. This manuscript makes reference to some of those studies with indications as to how and why the studies were done and the conclusions that might be drawn there from. In addition reference is made to the handling of this information by scientists, by environmentalists, and by the news media. Unfortunately, in many instances the public has been misled by what has been said and/or written. It is hoped that this presentation will provide an understandable and reasonable perspective on the various appropriate uses of radiation in our lives and how such uses do provide significant improvement in our health and in our quality of life

  5. Humidity level In psychrometric processes

    Mojsovski, Filip

    2008-01-01

    When a thermal engineer needs to control, rather than merely moderate humidity, he must focus on the moisture level as a separate variable - not simply an addition of temperature control. Controlling humidity generally demands a correct psychrometric approach dedicated to that purpose [1].Analysis of the humidity level in psychrometric thermal processes leads to relevant data for theory and practice [2]. This paper presents: (1) the summer climatic curve for the Skopje region, (2) selected results of investigation on farm dryers made outside laboratories. The first purpose of such activity was to examine relations between weather conditions and drying conditions. The estimation of weather condition for the warmest season of the year was realized by a summer climatic curve. In the science of drying, basic drying conditions are temperature, relative humidity and velocity of air, thickness of dried product and dryer construction. The second purpose was to realize correct prediction of drying rates for various psychrometrics drying processes and local products. Test runs with the dryer were carried out over a period of 24 h, using fruits and vegetables as experimental material. Air flow rate through the dryer of 150 m3/h, overall drying rate of 0.04 kg/h and air temperature of 65 oC were reached. Three types of solar dryers, were exploited in the research.

  6. International harmonization of intervention levels

    Jensen, P.H.

    1994-05-01

    A summary is given on international guidance on intervention levels in circumstances in which remedial actions might be considered in nuclear accident situations. The nature and limitations of international work and their effect on the resulting guidance are discussed. The basic international principles recommended can be expressed in the following compressed form: (1) serious deterministic effects should be avoided by intervention, (2) each protective measure should be justified, i.e. do more good than harm, (3) the level at which the protective measures are to be introduced should be optimized, i.e. do most good, and (4) each protective measure should be optimized separately and independent of all other countermeasures. It is of great importance that decision makers inform the public of all aspects of their decisions in order to make the decisions transparent, especially when the interventions chosen are mainly for political or social reason rather than health protection grounds. Otherwise the public may be misled and the radiological protection community will be mistrusted. 17 refs., 6 tabs

  7. The JET level-1 software

    McCullen, P.A.; Farthing, J.W.

    1998-01-01

    The complex nature of the JET machine requires a large amount of control parameter preparation, selection and validation before a pulse may be started. Level-1 is defined as the centralized, cross-subsystem control of JET. Before it was introduced over 10 years ago, the Session Leader (SL) who is responsible for specifying the parameter settings for a JET pulse, had virtually no software available to help him except for a simple editor used for the creation of control waveforms. Most of the required parameter settings were calculated by hand and then passed on either verbally or via hand-written forms. These parameters were then set by a large number of people - Local Unit Responsible Officers (LUROs) and CODAS Duty Officers (CDOs) using a wide selection of dedicated software. At this time the Engineer in Charge (EiC) would largely depend on the LUROs to inform him that conditions were ready. He never set control parameters personally and had little or no software available to him to see what many of the settings were. The first implementation of Level-1 software went some way towards improving the task of pulse schedule preparation in that the SL could specify his requirements via a computer interface and store them in a database for later use. At that time the maximum number of parameters that could be handled was 500. (author)

  8. MIPAS level 2 operational analysis

    P. Raspollini

    2006-01-01

    Full Text Available The MIPAS (Michelson Interferometer for Passive Atmospheric Sounding instrument has been operating on-board the ENVISAT satellite since March 2002. In the first two years, it acquired in a nearly continuous manner high resolution (0.025 cm−1 unapodized emission spectra of the Earth's atmosphere at limb in the middle infrared region. This paper describes the level 2 near real-time (NRT and off-line (OL ESA processors that have been used to derive level 2 geophysical products from the calibrated and geolocated level 1b spectra. The design of the code and the analysis methodology have been driven by the requirements for NRT processing. This paper reviews the performance of the optimized retrieval strategy that has been implemented to achieve these requirements and provides estimated error budgets for the target products: pressure, temperature, O3, H2O, CH4, HNO3, N2O and NO2, in the altitude measurement range from 6 to 68 km. From application to real MIPAS data, it was found that no change was needed in the developed code although an external algorithm was introduced to identify clouds with high opacity and to exclude affected spectra from the analysis. In addition, a number of updates were made to the set-up parameters and to auxiliary data. In particular, a new version of the MIPAS dedicated spectroscopic database was used and, in the OL analysis, the retrieval range was extended to reduce errors due to uncertainties in extrapolation of the profile outside the retrieval range and more stringent convergence criteria were implemented. A statistical analysis on the χ2 values obtained in one year of measurements shows good agreement with the a priori estimate of the forward model errors. On the basis of the first two years of MIPAS measurements the estimates of the forward model and instrument errors are in general found to be conservative with excellent performance demonstrated for frequency calibration. It is noted that the total retrieval

  9. Low-level radwaste solidification

    Naughton, M.D.; Miller, C.C.; Nelson, R.A.; Tucker, R.F.

    1983-01-01

    This paper reports on a study of ''Advanced Low-Level Radioactive Waste Treatment Systems'' conducted under an EPRI contract. The object of the study is to identify advanced lowlevel radwaste treatment systems that are commercially available or are expected to be in the near future. The current state-ofthe-art in radwaste solidification technology is presented. Related processing technologies, such as the compaction of dry active waste (DAW), containers available for radwaste disposal, and the regulatory aspects of radwaste transportation and solidification, are described. The chemical and physical properties of the currently acceptable solidification agents, as identified in the Barnwell radwaste burial site license, are examined. The solidification agents investigated are hydraulic cements, thermoplastic polymers, and thermosetting polymers. It is concluded that solidification processes are complex and depend not only on the chemical and physical properties of the binder material and the waste, but also on how these materials are mixed

  10. Symmetry and Asymmetry Level Measures

    Angel Garrido

    2010-04-01

    Full Text Available Usually, Symmetry and Asymmetry are considered as two opposite sides of a coin: an object is either totally symmetric, or totally asymmetric, relative to pattern objects. Intermediate situations of partial symmetry or partial asymmetry are not considered. But this dichotomy on the classification lacks of a necessary and realistic gradation. For this reason, it is convenient to introduce "shade regions", modulating the degree of Symmetry (a fuzzy concept. Here, we will analyze the Asymmetry problem by successive attempts of description and by the introduction of the Asymmetry Level Function, as a new Normal Fuzzy Measure. Our results (both Theorems and Corollaries suppose to be some new and original contributions to such very active and interesting field of research. Previously, we proceed to the analysis of the state of art.

  11. Reactor Emergency Action Level Monitor

    Touchton, R.A.

    1987-01-01

    The Reactor Emergency Action Level Monitor (REALM) Expert System is designed to provide assistance in the identification of a nuclear power plant emergency situation and the determination of its severity. REALM has been developed to operate in a real-time processing environment. REALM embodies a hybrid architecture utilizing both rule-based reasoning and object-oriented programming techniques borrowed from the Artificial Intelligence discipline of Computer Sciences. The rulebase consists of event-based rules and symptom-based rules. The symptom-based rules go beyond the current EAL structure to address the more problematic scenarios and entail a more symbolic representation of the plant information. The results to date have been encouraging that expert system technology can provide improved emergency decision-making capability in nuclear power plants

  12. Excited levels of Pa-233

    Vara Cuadrado, J. M.

    1969-01-01

    A study of Pa-233 excited levels from the alpha decay of Np-237 and from beta decay of Th-233 has been performed. The alpha decay spectrum was measured with a semiconductor spectrometer of 18 keV effective resolution (FWHM). Over 13 new lines were identified. The gamma ray spectra of Np-237 and Th-233 were obtained with a Ge-Li detector low and medium range energy lines, and with Si-Li detector for the low energy region. A continuous purification method of Np-237 from its comparatively short-lived daughter Pa-233 was applied. A high number of new lines were identified in both spectra. The gamma-gamma coincidence spectra were obtained with INa(T 1 ) detectors. (Author) 54 refs

  13. Sentence-Level Attachment Prediction

    Albakour, M.-Dyaa; Kruschwitz, Udo; Lucas, Simon

    Attachment prediction is the task of automatically identifying email messages that should contain an attachment. This can be useful to tackle the problem of sending out emails but forgetting to include the relevant attachment (something that happens all too often). A common Information Retrieval (IR) approach in analyzing documents such as emails is to treat the entire document as a bag of words. Here we propose a finer-grained analysis to address the problem. We aim at identifying individual sentences within an email that refer to an attachment. If we detect any such sentence, we predict that the email should have an attachment. Using part of the Enron corpus for evaluation we find that our finer-grained approach outperforms previously reported document-level attachment prediction in similar evaluation settings.

  14. Wafer level packaging of MEMS

    Esashi, Masayoshi

    2008-01-01

    Wafer level packaging plays many important roles for MEMS (micro electro mechanical systems), including cost, yield and reliability. MEMS structures on silicon chips are encapsulated between bonded wafers or by surface micromachining, and electrical interconnections are made from the cavity. Bonding at the interface, such as glass–Si anodic bonding and metal-to-metal bonding, requires electrical interconnection through the lid vias in many cases. On the other hand, lateral electrical interconnections on the surface of the chip are used for bonding with intermediate melting materials, such as low melting point glass and solder. The cavity formed by surface micromachining is made using sacrificial etching, and the openings needed for the sacrificial etching are plugged using deposition sealing methods. Vacuum packaging methods and the structures for electrical feedthrough for the interconnection are discussed in this review. (topical review)

  15. Principles for system level electrochemistry

    Thaller, L. H.

    1986-01-01

    The higher power and higher voltage levels anticipated for future space missions have required a careful review of the techniques currently in use to preclude battery problems that are related to the dispersion characteristics of the individual cells. Not only are the out-of-balance problems accentuated in these larger systems, but the thermal management considerations also require a greater degree of accurate design. Newer concepts which employ active cooling techniques are being developed which permit higher rates of discharge and tighter packing densities for the electrochemical components. This paper will put forward six semi-independent principles relating to battery systems. These principles will progressively address cell, battery and finally system related aspects of large electrochemical storage systems.

  16. Ionizing radiation: levels and effects. Volume I. Levels

    1972-01-01

    This is the sixth substantive report of the United Nations Scientific Committee on the Effects of Atomic Radiation to the General Assembly. It reviews the levels of radiation received from all sources to which man is exposed and, among the effects of ionizing radiation, it considers the genetic effects, the effects on the immune response and the induction of malignancies in animals and man. These are not the only effects of ionizing radiation. The acute consequences of massive amounts of radiation that may be received accidentally or during nuclear warfare are not reviewed here (the short discussion of this subject in the 1962 report is still largely valid, at least as an introduction), nor are the effects on the nervous system and the induction of chromosome anomalies in somatic cells, which were both considered by the Committee in its 1969 report. Unlike previous reports of the Committee, the present report is submitted to the General Assembly without the technical annexes in which the evidence considered by the Committee is discussed in detail and in which the bases for the Committee's conclusions, which are stated in the report, are fully documented. However, the annexes are being made available at the same time as the report in a separate publication, issued in two volumes and the Committee wishes to draw the attention of the General Assembly to the fact that the separation of the report from the annexes is for convenience only and that major importance attaches to the scientific evidence given in the annexes.

  17. Colloids related to low level and intermediate level waste

    Ramsay, J.D.F.; Russell, P.J.; Avery, R.G.

    1991-03-01

    A comprehensive investigation has been undertaken to improve the understanding of the potential role of colloids in the context of disposal and storage of low and intermediate level waste immobilised in cement. Several topics have been investigated using a wide range of advanced physico-chemical and analytical techniques. These include: (a) the study of formation and characteristics of colloids in cement leachates, (b) the effects of the near-field aqueous chemistry on the characteristics of colloids in repository environments, (c) colloid sorption behaviour, (d) interactions of near-field materials with leachates, and (e) preliminary assessment of colloid migration behaviour. It has been shown that the generation of colloids in cement leachates can arise from a process of nucleation and growth leading to an amorphous phase which is predominantly calcium silicate hydrate. Such colloidal material has a capacity for association with polyvalent rare earths and actinides and these may be significant in the source term and processes involving radionuclide retention in the near field. It has also been shown that the near-field aqueous chemistry (pH, Ca 2+ concentration) has a marked effect on colloid behaviour (deposition and stability). A mechanistic approach to predict colloid sorption affinity has been developed which highlights the importance of colloid characteristics and the nature of the ionic species. (author)

  18. Nuclear power: levels of safety

    Lidsky, L.M.

    1988-01-01

    The rise and fall of the nuclear power industry in the United States is a well-documented story with enough socio-technological conflict to fill dozens of scholarly, and not so scholarly, books. Whatever the reasons for the situation we are now in, and no matter how we apportion the blame, the ultimate choice of whether to use nuclear power in this country is made by the utilities and by the public. Their choices are, finally, based on some form of risk-benefit analysis. Such analysis is done in well-documented and apparently logical form by the utilities and in a rather more inchoate but not necessarily less accurate form by the public. Nuclear power has failed in the United States because both the real and perceived risks outweigh the potential benefits. The national decision not to rely upon nuclear power in its present form is not an irrational one. A wide ranging public balancing of risk and benefit requires a classification of risk which is clear and believable for the public to be able to assess the risks associated with given technological structures. The qualitative four-level safety ladder provides such a framework. Nuclear reactors have been designed which fit clearly and demonstrably into each of the possible qualitative safety levels. Surprisingly, it appears that safer may also mean cheaper. The intellectual and technical prerequisites are in hand for an important national decision. Deployment of a qualitatively different second generation of nuclear reactors can have important benefits for the United States. Surprisingly, it may well be the nuclear establishment itself, with enormous investments of money and pride in the existing nuclear systems, that rejects second generation reactors. It may be that we will not have a second generation of reactors until the first generation of nuclear engineers and nuclear power advocates has retired

  19. Involve women at many levels.

    Huq, N

    1995-03-01

    The organizers of the 1994 International Conference on Population and Development (ICPD) realize that slowing the rate of population growth requires the involvement of women at many levels. The planning processes in countries leading up to the ICPD were required to include women, and funds became available for women to attend regional and international preparatory meetings. National delegations at the ICPD also included many more women than the previous two world population conferences in 1974 and 1984. Space was also provided at the ICPD for the involvement of nongovernmental organizations. Naripokkho, a women's advocacy organization in Bangladesh, was therefore able to communicate its message at the conference. In preparation, the organization held consultations and workshops with grassroots women in thirteen regions of Bangladesh. Approximately one third of the women in the workshops had more children than they desired, many felt that they had to have at least two sons, poor services led women to discontinue contraceptive use, and very few women reported that a lack of access to contraception or method failure was responsible for their large families. It was also determined during the preparatory phase that environmental damage cannot be linked to population in a simplistic manner, history, politics, geography, business, and economics play important roles. Once at the ICPD, Naripokkho they negotiated and lobbied the governments to influence the ICPD program of action. Gains for women were made in both language and substance. Indeed, the program of action is the most progressive population document ever issued by a mainstream institution, gives women's goals new legitimacy, and is a powerful tool for groups working at the grassroots level. Governments must now be held to their commitments made in the program.

  20. Low-level Radioactive waste Management

    1991-01-01

    This meeting describes low-level radioactive waste management problems and contains 8 papers: 1 Low-level radioactive waste management: exemption concept and criteria used by international organizations. 2 Low-level radioactive waste management: french and foreign regulations 3 Low-level radioactive waste management in EDF nuclear power plants (FRANCE) 4 Low-level radioactive waste management in COGEMA (FRANCE) 5 Importance of low-level radioactive wastes in dismantling strategy in CEA (FRANCE) 6 Low-level radioactive waste management in hospitals 7 Low-level radioactive waste disposal: radiation protection laws 8 Methods of low-level radioactive materials measurements during reactor dismantling or nuclear facilities demolition (FRANCE)